Modern Organic Synthesis with Î±-Diazocarbonyl Compounds

Review pubs.acs.org/CR

Modern Organic Synthesis with α‑Diazocarbonyl Compounds Alan Ford,† Hugues Miel,§ Aoife Ring,† Catherine N. Slattery,† Anita R. Maguire,*,†,‡ and M. Anthony McKervey*,∥ †

Department of Chemistry and ‡School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland § Almac Discovery Ltd., David Keir Building, Stranmillis Road, Belfast BT9 5AG, United Kingdom ∥ Almac Sciences Ltd., Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, United Kingdom 3.1.1. Reactions of Ketenes from Wolff Rearrangement 3.2. Cyclopropanation Reactions 3.2.1. Cyclopropanation of Alkenes 3.2.2. Cyclopropenation of Alkynes 3.3. Reactions with Aromatics 3.3.1. Aromatic Cycloaddition Reactions (the Buchner Reaction) 3.3.2. Aromatic Substitution Reactions 3.4. Catalytic Asymmetric C−H Insertion Reactions 3.4.1. Intramolecular C−H Insertion Reactions 3.4.2. Intermolecular C−H Insertion Reactions 3.5. X−H Insertion Reactions of Diazocarbonyl Compounds 3.5.1. N−H Insertion Reactions 3.5.2. O−H Insertion Reactions 3.5.3. Si−H Insertion Reactions 3.5.4. S−H Insertion Reactions 3.5.6. Insertions Involving Halogens 3.6. Ylide Formation from α-Diazocarbonyls 3.6.1. Oxonium Ylides 3.6.2. Sulfonium Ylides 3.6.3. Ammonium Ylides 3.6.4. Carbonyl Ylide 1,3-Dipolar Cycloaddition 4. Concluding Remarks Author Information Corresponding Authors Notes Biographies Acknowledgments Abbreviations References

CONTENTS 1. Introduction 2. Synthesis of α-Diazocarbonyl Compounds 2.1. Acylation of Diazoalkanes 2.1.1. Preparation and Improved Management of Diazomethane: Continuous Processing 2.1.2. Recent Developments in Batch Preparation of Diazoketones 2.2. Diazo Transfer Reactions 2.3. Electrophilic Substitution and Cross-Coupling at the Diazo Carbon Atom 2.3.1. Aldol-Type C−C Coupling of Terminal Diazocarbonyls with Aldehydes and Imines 2.3.2. C−C Coupling of Terminal Diazocarbonyls with Other Electrophiles 2.3.3. Electrophilic Substitution with Silyl Chlorides as a Protecting Group Strategy 2.3.4. Electrophilic Halogenation of Diazocarbonyls 2.3.5. Palladium-Catalyzed C−C Coupling at the Diazo Function 2.4. Dehydrohalogenation of Hydrazine Derivatives: A Diazomethane-Free Conversion of Acid Chlorides to Terminal Diazoketones 2.5. Substituent Modification 2.5.1. Preparation of Terminal α,β-Unsaturated Diazocarbonyl Compounds 2.5.2. Preparation of Vinyldiazoesters 2.6. Conclusion and Outlook 3. Diazocarbonyl Reactions: Introduction 3.1. Wolff Rearrangement © 2015 American Chemical Society

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1. INTRODUCTION In 1994, Ye and McKervey published a paper in Chemical Reviews entitled “Organic Synthesis with α-Diazocarbonyl Compounds”.1 Our intention then was to draw attention to the enormous influence that the proximal combination of two simple functional groups, “keto” and “diazo”, have had on the practice of organic synthesis. At that time, 20 years ago, diazocarbonyl chemistry was already a mature science, but what

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DOI: 10.1021/acs.chemrev.5b00121 Chem. Rev. 2015, 115, 9981−10080

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and (6) substituent modification at either side of the diazocarbonyl group. Selecting the most appropriate synthetic strategy usually depends on the nature of the substituents attached to the diazocarbonyl group.

struck us forcibly then was the level of interest in the topic that had persisted over almost a century. Now, if anything, the level of interest is even greater, and the expansion into new application areas during the past two decades has been such that we feel justified in again reviewing the topic with the same focus that characterized our earlier review, namely, the application of diazocarbonyl compounds to organic synthesis.1−7 Not all aspects of diazocarbonyl chemistry have prospered equally, but the areas that continue to attract the most attention are preparation of diazocarbonyl substrates, including diazomethane synthesis, the Wolff rearrangement, cyclopropanation of alkenes, reactions with aromatics, C−H insertion, X−H insertion, and formation and reactions of ylides. In addition, there have been significant developments with the use of diazocarbonyl reactions in biological environments, e.g., structure-selective alkylation of DNA and RNA. The areas of cyclopropanation and aliphatic C−H insertion have been reviewed extensively elsewhere; only a selection of the most significant developments are treated here.

2.1. Acylation of Diazoalkanes1,2

Acylation of diazomethane is the most widely used route to acyclic terminal diazoketones. The process is frequently referred to as the Arndt−Eistert reaction (Scheme 2), and Scheme 2. Synthesis of a Terminal Diazoketone by Acylation of Diazomethane

although there are examples of its use with higher alkanes, e.g., diazoethane, its principal use applies to diazomethane to form diazomethyl products. The acylating agent is an activated carboxylic acid derivative, usually an acyl chloride or mixed anhydride. 2.1.1. Preparation and Improved Management of Diazomethane: Continuous Processing. Diazomethane is a highly toxic9 and explosive10 gas. Its permissible exposure limit is 0.2 ppm.11 Despite these safety concerns, it is widely used as a reagent in dilute solution, on a laboratory and a manufacturing scale.10,12−14 Much recent effort has concentrated on safe handling of diazomethane. The classical preparation of diazomethane by base-promoted decomposition of an N-nitroso derivative, typically N-methyl-N-nitroso-p-toluenesulfonamide (Diazald), involves its isolation by distillation as a solution in an organic solvent.15,16 The resulting diazomethane solution is collected in a flask which is then manually handled by the chemist for subsequent use. Recent developments in the preparation of diazomethane have focused on minimizing the risk of exposure to the user, by generating and reacting the diazomethane in situ. This can be done either in batch reactions or under continuous-flow conditions.17 The in situ batch preparation of diazomethane was recently developed by Carreira and co-workers18 using a biphasic system and a water-soluble derivative of Diazald engineered by Almac Sciences Ltd. (Scheme 3).19 The diazomethane is generated in the strongly basic aqueous layer and transferred into an organic layer where cyclopropanation takes place in the presence of an iron porphyrin catalyst. This in situ batch approach offers a considerable advantage in terms of safety and simplicity over the current methods, though its use thus far has been demonstrated only in cyclopropanation, which tolerates the strongly basic aqueous conditions. Continuous processing presents another approach to control the hazards associated with the synthesis of diazomethane. Diazomethane and diazoketones have been produced on an industrial scale by specialist companies, but only recently has this technology been adapted to microreactor technology, with a view to making it more accessible to the chemical community. Maggini and co-workers have developed a system whereby diazomethane generation and subsequent ester formation are carried out in a single-channel flow reactor.20 This system can generate up to 19 mol/day of diazomethane using N-methyl-Nnitrosourea (MNU) as a diazomethane precursor. MNU and other diazomethane precursors such as Diazald are all

2. SYNTHESIS OF α-DIAZOCARBONYL COMPOUNDS8 Use of diazocarbonyl compounds as reaction intermediates relies on the availability of simple and reliable methods of synthesis, and although several well-documented methods already exist, diazocarbonyl synthesis remains an active research area. This is largely driven by the need to improve safety considerations by minimizing risks in handling reagents while extending the ability to access new molecules through chemoselective synthesis. The classical routes to diazocarbonyl compounds (Scheme 1) are (1) amine diazotization, (2) Scheme 1. Common Approaches to Diazocarbonyl Compounds

modification of oximes, hydrazones, and tosylhydrazones, (3) acylation of diazoalkanes, and (4) diazo transfer to an acid derivative or a ketone. Of these, the first two are still used, but there have been no significant recent innovations in these methods. However, methods for diazoalkane acylation and diazo transfer, routes 3 and 4, continue to evolve with new reagents and procedures. To this list we can now add approaches whereby a diazocarbonyl compound is converted into another one with retention of the diazo function. These include (5) substitution and cross-coupling at the diazo carbon 9982


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allowing the preparation of diazoketone from water-sensitive precursors. While this reactor allows the preparation of diazomethane and diazoketone in a continuous process, its output remains very small (1 mmol/day). It is also not compatible with common organic solvents such as diethyl ether, dichloromethane, and THF as they can cause swelling of the PDMS polymer. These two main limitations have been recently overcome by Kappe and co-workers,23 using a tube-in-tube (TiT) reactor (initially developed in the Steven Ley laboratory)24 where the inner tube of the device is made of Teflon AF-2400. This semipermeable, more robust membrane allows gases to permeate but not liquids. Using a commercially available TiT device, Kappe and co-workers were able to safely conduct the Arndt−Eistert reaction and produce diazoketone in a continuous process. For example, Cbz-protected phenylalanine is first activated as a mixed anhydride with ethyl chloroformate in a tubular reactor.25 Diazomethane is generated in situ from an aqueous solution of Diazald and potassium hydroxide in the inner chamber of the TiT reactor. It then diffuses into the outer chamber of the reactor through the permeable membrane, where it reacts with the mixed anhydride. The resulting enantiopure diazoketone is obtained in 82% yield after column chromatography (Scheme 5).

Scheme 3. In Situ Diazomethane Formation and Cyclopropanation

hazardous materials. Struempel et al. have also developed a microreactor system capable of generating both diazomethane and Diazald in a continuous manner.21 Both the microreactors developed by Struempel and Maggini generate diazomethane in a single channel containing all the reactants and solvents. This setup is effective for the subsequent alkylation of carboxylic acids with diazomethane but is not suited to diazoketone synthesis as the starting acyl chlorides and other activated acyl derivatives are all water sensitive. Kim and co-workers have developed a more advanced microreactor which does allow the continuous production of both diazomethane and diazoketones.22 It consists of two parallel channels separated by a PDMS membrane. Diazald reacts with potassium hydroxide in the bottom channel to generate diazomethane, which diffuses out through the membrane and into the upper channel where it reacts with the main reactants (Scheme 4). By contrast with the in situ batch processing of diazomethane, the organic phase in the microreactor remains completely separated from the aqueous phase by the PDMS membrane, thus

Scheme 5. Continuous-Flow Arndt−Eistert Reaction Using the Tube-in-Tube Reactor

The setup was further extended to in situ conversion of amino acid-derived diazoketones into the corresponding chloroketones, which are key intermediates in the preparation

Scheme 4. Production of Diazomethane and Downstream Products in a Dual-Channel Flow Reactora

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of protease inhibitors. This latest work by Kappe constitutes a significant safety improvement in the preparation of diazomethane on a laboratory scale and its use to produce diazoketones compared to the traditional batch process.26 It avoids the distillation and handling of large amounts of diazomethane and therefore considerably reduces the risk of accidental exposure. The continuous-flow setup is also reported to be robust and easy to operate and could be expected to find its place in the future as a useful alternative to the Diazald kit. Finally, production of diazoketone under continuous processing has also been carried out using (trimethylsilyl)diazomethane.27 (Trimethylsilyl)diazomethane was originally developed as a safer, commercially available alternative to diazomethane. While it is deemed to be more thermally stable and less explosive, its toxicity by oral exposure remains acute. This reagent has been directly implicated in the death of two chemists in 2008 and 2009 in two separate incidents where it was used under batch conditions.28 2.1.2. Recent Developments in Batch Preparation of Diazoketones. One of the main drawbacks for the conversion of acyl chlorides to diazoketones is the need to employ an excess of diazomethane (2−6 equiv): the excess reagent acts as a trap for the hydrogen chloride byproduct, thus preventing it from reacting with diazoketone, the intended product. The alternative of using a tertiary amine such as triethylamine to trap the hydrogen halide byproduct is only effective with nonenolizable acyl halides. Enolizable acyl halides tend to give only a low yield of diazoketone due to competing ketene formation. De Kimpe and co-workers recently made the discovery that the use of calcium oxide as a hydrogen halide scavenger does not result in ketene formation but does give excellent yields of diazoketone when using diazomethane in stoichiometric amounts (Scheme 6).29 Calcium oxide was also found to give better yields with nonenolizable acyl halides than classical basic scavengers.

Scheme 7. Hindered Diazoketones Made from Diazomethane and Acyl Mesylates

smooth diazoketone formation in good yields and mild conditions (Scheme 8).31 Scheme 8. Diazoketone Formation from Acylphosphonium Salts

Scheme 6. Improved Arndt−Eistert Synthesis with Calcium Oxide

In the case of amino acids, which are popular substrates for diazoketone formation, activation of the carboxylate function requires protection of the amino group prior to the acylation of diazomethane. Liguori and co-workers have found that [(fluorenylmethyl)oxy]carbonyl chloride is an effective reagent for the one-pot protection and activation of amino acids and subsequent conversion to diazoketones (Scheme 9).32 Scheme 9. One-Pot Protection and Diazoketone Formation from an Amino Acid

Although acyl halides are usually the preferred acyl derivatives for diazoketone formation, conversion of highly hindered carboxylic acids to the corresponding acyl chlorides can sometimes prove difficult or impossible. Nicolaou and coworkers found that acyl mesylates were more suitable intermediates for the synthesis of highly hindered diazoketones (Scheme 7).30 Some aromatic and heteroaromatic diazoketones were reported to be difficult to prepare using both the standard mixed anhydride activation and the acyl mesylate. Acylphosphonium salts, generated from a carboxylic acid, triphenylphosphine, and N-bromosuccinimide, were found to undergo

2.2. Diazo Transfer Reactions

Formation of diazocarbonyl compounds via diazo transfer is applicable to a wide range of active methylene compounds, typically ketones and carboxylic acid derivatives. Diazo transfer is most usually carried out with a sulfonyl azide in the presence of a base (Scheme 10). Simple ketones, having no additional electron-withdrawing/ aromatic group at the β-position, can be converted to the 9984


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Thermal stability of the transfer agent and ease of removal of the sulfonamide byproduct are two key parameters in the development of novel diazo transfer reagents, the former being the more imperative. There have been many attempts to design the “ideal” sulfonyl azide for this purpose, though none has met this specification entirely. One of the more recent additions to the list is imidazolesulfonyl azide hydrochloride (1).38 It was reported to be “prepared in a one-pot reaction on large scale from inexpensive materials, is shelf-stable and is conveniently crystalline”. Further stability studies were conducted by Klapötke and co-workers, who found that replacing the hydrochloride counterion in 1 with tetrafluoroborate in 2 or hydrogen sulfate in 3 significantly improved the stability of this reagent in relation to shock sensitivity (Scheme 13).39

Scheme 10. Diazo Transfer Preparation of Diazocarbonyl Compounds

corresponding diazocarbonyl compound in a two-step process involving a trifluoroacetyl activation followed by a diazo transfer reaction.33 This methodology reported by Danheiser is particularly interesting for preparing α,β-unsaturated diazoketones. These diazocarbonyl compounds cannot be obtained through acylation of diazomethane due to competing dipolar cycloaddition of the conjugated double bond. Although the scope of the Danheiser protocol has been mainly limited to simple, α,β-unsaturated ketones as well as aromatic methyl ketones, recent reports have demonstrated the utility of this transformation for more complex intermediates in natural product synthesis (Scheme 11).34−36

Scheme 13. Imidazolesulfonyl Azide Salts

However, in addition to the putative relative stability of the hydrochloride 1, serious concerns were raised regarding the safety of its preparation.40 The first step involves the addition of sodium azide to sulfuryl dichloride to form intermediate 4 (Scheme 14). Sulfuryl dichloride can generate hydrogen chloride upon exposure to moisture, which in turn may react with sodium azide to form the highly explosive hydrazoic acid. Intermediate 4 may also react with another equivalent of sodium azide to form the equally explosive sulfuryl diazide (6). In view of these serious safety concerns, Wang and coworkers developed a two-step alternative synthesis using sulfuryl diimidazole as the starting material under nonacidic conditions (Scheme 15). They also recommend that compound 5 (free base, not the hydrochloride salt) be used as the final diazo transfer reagent and that this compound should be prepared in situ.40 While this new protocol has been safely scaled up to 100 g, reagent 5 may not be as attractive as the widely used, and commercially available, acetamidobenzenesulfonyl azide. Another recent diazo transfer reagent is benzotriazole-1-sulfonyl azide (7) developed by Katritzky and co-workers (Scheme 16).41 It is both crystalline and stable. Similar safety concerns may however be raised regarding its preparation, which also starts from sulfuryl dichloride and sodium azide.42 Another recent reagent, nonafluorobutanesulfonyl azide (8), is reported to be shelf-stable, and its synthesis does not require the hazardous combination of sulfuryl dichloride and sodium azide. The advantage of this reagent is that the sulfonamide byproduct can be easily eliminated by a mildly basic wash during the workup.43 Finally, Kumar and co-workers have reported the first example of the synthesis and application of ionic liquidsupported sulfonyl azide (Scheme 17).44 In addition to the now wide range of sulfonyl azides available, 2-azido-1,3-dimethylimidazolinium salts were introduced by Kitamura and co-workers as a novel class of diazo transfer reagents (Scheme 18).45−47 2-Azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) tested negative in impact and sensitivity tests. Its decomposition temperature, 200 °C, is the highest of all the reported diazo transfer reagents. The byproduct of the diazo transfer reaction is a highly watersoluble imidazolinone.

Scheme 11. Trifluoracetylation/Detrifluoroacetylation Diazo Transfer

Simple carboxylic esters can also be converted to the corresponding diazocarbonyl compounds using the Danheiser methodology. The required strongly basic and cryogenic conditions may sometimes be problematic. A more recent procedure was developed by Taber to address these issues; activation of the ester by a titanium chloride-mediated benzoylation is followed by diazo group transfer under mild conditions (Scheme 12).37 Scheme 12. Benzoylation/Debenzoylation Diazo Transfer

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Scheme 14. Safety Issues in the Preparation of Azide 1

Scheme 15. Alternative Preparation of Azide 5

Scheme 18. 2-Azido-1,3-dimethylimidazolinium Hexafluorophosphate (ADMP)

Scheme 16. Benzotriazolesulfonyl Azide and Nonafluorobutanesulfonyl Azide

The two-step sequence (Scheme 19) represents a useful alternative to the traditional diazo transfer of β-dicarbonyl compounds. It can also be conveniently carried out in one pot when DBU is employed as the base. Asymmetric versions of the aldol reaction of diazoketoesters have been reported by several authors.51−54 The best yield and enantioselectivity were achieved by Trost and co-workers, with a dinuclear magnesium complex (Scheme 20).53,54 Base-mediated coupling of diazocarbonyls was also reported with electron-deficient imines such as N-acyl and N-sulfonyl imines (Scheme 21 and Scheme 22).48,55−62 2.3.2. C−C Coupling of Terminal Diazocarbonyls with Other Electrophiles. Deprotonation of diazocarbonyls and subsequent C−C bond formation has been carried out with electrophiles other than aldehydes and imines, such as chloroformates, pyrocarbonates, and sulfonyl chlorides (Scheme 23).63 Diazoketones derived from protected enantiopure amino acids were also successfully condensed (Scheme 24) with acyl imidazolide in the presence of LDA to afford the corresponding bis(N-protected α-amino)diazo-α-diketones.64 2.3.3. Electrophilic Substitution with Silyl Chlorides as a Protecting Group Strategy. Substitution of a diazocarbonyl azomethine proton with a silyl derivative was recently reported as a protecting group strategy. In their sequential double cross-aldolization of diazoacetone (Scheme 25), Gosselin and co-workers needed to carry the first aldolization on the methyl side of the diazoketone.65 As the azomethine proton is more acidic than the methyl protons, they protected this position with a silyl group. 2.3.4. Electrophilic Halogenation of Diazocarbonyls. α-Halodiazoacetates have traditionally been prepared via silver or mercury diazoacetate intermediates. Recently, a metal-free, less hazardous preparation of halodiazoacetates was developed

Scheme 17. Diazo Transfer Using Ionic Liquid-Supported Sulfonyl Azide

2.3. Electrophilic Substitution and Cross-Coupling at the Diazo Carbon Atom

2.3.1. Aldol-Type C−C Coupling of Terminal Diazocarbonyls with Aldehydes and Imines. Aldol-type additions of diazocarbonyls with aldehydes and ketones have been historically carried out with strong bases, LDA being by far the most widely employed. Weaker bases such as DBU in particular have more recently been shown to also be effective.48 Mild oxidation of the resulting α-diazo-β-hydroxycarbonyl adducts to the corresponding diazodicarbonyl compound has been reported with both IBX49 and Dess−Martin periodinane.50 9986


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Scheme 19. Two-Step and One-Pot Preparation of Diazoketoesters

Scheme 21. Mannich-Type Coupling of Diazocarbonyl Compounds with Imines

Scheme 22. Asymmetric Mannich-Type Coupling of Diazocarbonyl Compounds with Imines

Scheme 23. Coupling of Diazocarbonyls with Various Electrophiles

Scheme 20. Asymmetric Aldol Reaction with Ethyl Diazoacetate

Scheme 24. Coupling of Diazocarbonyls with Acyl Imidazolides

Scheme 25. Silyl Protection Strategy for the Bisaldolization of a Diazoketone

by Bonge-Hansen and co-workers.66−68 It involves the treatment of the diazocarbonyl with N-halosuccinimide in the presence of DBU (Scheme 26). Halodiazoacetates are less stable than nonhalogenated diazoacetates (they decompose within hours at room temperature) but are conveniently handled at 0 °C in solution. 2.3.5. Palladium-Catalyzed C−C Coupling at the Diazo Function. Cross-coupling is another process that allows the transformation of one diazocarbonyl compound into another.

Vinyl and aryl iodides, for example, were coupled to ethyl diazoacetate under relatively mild conditions to generate 9987


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Scheme 26. Formation of Halogenated EDA Analogues

Scheme 29. Palladium-Catalyzed Carbonylative Coupling of Aryl Iodides with EDA

unsaturated diazoesters (Scheme 27, Scheme 28, and Scheme 29).69 Scheme 27. Palladium-Catalyzed Cross-Coupling of Vinyl Iodides with EDA

Scheme 30. Diazomethane-Free Conversion of Acyl Chlorides to Diazoketones

Scheme 28. Palladium-Catalyzed Cross-Coupling of Aryl Halides with EDA

2.5. Substituent Modification

Due to its high reactivity under a broad range of conditions, the diazocarbonyl functionality is usually transformed in the step that follows its preparation. In a limited number of cases, diazocarbonyl compounds carrying other functionalities can be modified while leaving the diazocarbonyl functionality intact (Scheme 31). The diazocarbonyl group is usually stable under Scheme 31. Functional Modification of Diazocarbonyl Compounds

mild neutral and basic conditions (room temperature or below). Most of the reactions that convert one diazocarbonyl compound into another one are carried out under these conditions. Diazodicarbonyl compounds are more stable than diazomonocarbonyl compounds and can therefore be converted to other carbonyl compounds under a wider range of conditions. 2.5.1. Preparation of Terminal α,β-Unsaturated Diazocarbonyl Compounds. The standard diazomethane acylation with acid chlorides is not suited to α,β-unsaturated

2.4. Dehydrohalogenation of Hydrazine Derivatives: A Diazomethane-Free Conversion of Acid Chlorides to Terminal Diazoketones

A diazomethane-free new protocol was reported employing Nisocyanotriphenylphosphoranimine as a CN2 synthetic equivalent. It involves the formation of a hydrazidoyl intermediate which is subsequently converted to the diazoketone under mild conditions (Scheme 30).70 9988


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substrates because of competing dipolar cycloaddition to the conjugated double bond. Burtoloso and co-workers have developed an alternative method based on the Horner− Wadsworth−Emmons methodology (Scheme 32).71 This

Scheme 35. Reactions of Vinyldiazoesters

Scheme 32. Synthesis of E- and Z-α,β-Unsaturated Diazoketones from Aldehydes

method was extended to the preparation of the Z isomers by employing Ando-type phosphonates (Scheme 32).72 α,βUnsaturated diazoketones can be converted to other diazocarbonyl compounds by Michael addition with amines (Scheme 33).73

was reported by Barluenga and co-workers.76 Formylation of the terminal alkene afforded enal diazocarbonyl compounds, precursors to unprecedented electrophilic rhodium enal carbenes.77 Finally, a triflic acid-catalyzed Povarov reaction of alkenyldiazoesters allowed the preparation of various six- and seven-membered rings.78 In his 2009 review,8 Maas identified six compounds/classes of compounds as suitable scaffolds for building other diazocarbonyl compounds (Scheme 36). Only the last two

Scheme 33. Michael Addition of Amines onto α,βUnsaturated Diazoketones

Scheme 36. Scaffolds for Functional Modification of Diazocarbonyl Compounds

2.5.2. Preparation of Vinyldiazoesters. A series of diazoesters having a substituted vinyl group α to the diazo group were prepared by treating the corresponding hydroxydiazoester with trifluoroacetic anhydride in the presence of triethylamine at room temperature (Scheme 34).74,75 Vinyldiazoesters are themselves versatile intermediates for the preparation of other diazocarbonyl compounds (Scheme 35). Notably, a copper-catalyzed oxidative rearrangement involving an unprecented 1,2-shift of the diazoacetate function classes of compounds (I and II) have been widely used since 2009 (the numbers in parentheses represent the number of related papers in the past 6 years). Group I is more a reflection of the range of synthetic transformations that have been carried out at a remote center of diazoketoesters than a homogeneous class of diazocarbonyl compounds; on the other hand, group II compounds are all enol diazoacetate C4 nucleophilic building blocks which have found a wide range of applications as demonstrated by Doyle79−85 and Davies.86,87 Representative examples of the versatility of enol diazoacetates are shown in Scheme 37. They include Mukaiyama aldol reactions with aldehydes, Mukaiyama−Michael reactions with α,β-enones, and Mannich reactions with imines and nitrones. Most recently, Doyle has developed a general Lewis acid-catalyzed carbocationic C−C coupling reaction of an enol diazo compound with benzydryl, allylic, and oxonium carbocations.

Scheme 34. Preparation of Vinyldiazoesters

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Other notable advances include newly developed palladium cross-coupling at the diazo function, a wider range of electrophiles employed in substitution reactions, chemoselective oxidation of the hydroxyl group in the presence of the diazo group, and the use of vinyldiazoacetate and vinyldiazoacetoacetate as key building blocks to prepare novel diazocarbonyl substrates. It is also worth noting that some of these advances offer alternative routes to the diazo transfer methodology for the preparation of diazoketoesters, as shown in Scheme 39. Finally, the scope for transformation of one diazocarbonyl compound into another with retention of the diazo functionality has been greatly extended.

Scheme 37. Reactions of Enol Diazoacetate Ester

Scheme 39. Scope of Functionalization of Diazocarbonyl Compounds

2.6. Conclusion and Outlook

The preparation of diazocarbonyl compounds continues to be an active research area and that has progressesed significantly in recent years. Improving safety remains the key driver in both diazomethane acylation and diazo transfer strategies (Scheme 38). For example, a diazomethane-free route has been Scheme 38. Scope of Transformations of Diazocarbonyl Compounds

With regard to safety in the preparation of diazocarbonyl compounds, we reiterate the following two key points which were made following accidents with (trimethylsilyl)diazomethane and benzotriazolesulfonyl azide: (1) “It seems that an unfortunate consequence of labelling TMSD as ‘safe’ in terms of reduced explosion hazards has resulted in a widespread impression that it is also nontoxic.” 28 (Trimethylsilyl)diazomethane was once suggested to be a “safer” alternative to diazomethane. It may be less explosive but remains an acutely toxic reagent and should be handled accordingly. (2) “When it comes to exploring potential hazards of azides, one needs to consider more than just its thermal stability on melting. The properties of thermal stability, shock sensitivity, and explosivity are related, but not in a direct manner. For example, picric acid melts at 122 °C without decomposition but is shock-sensitive and explosive. Some compounds are shocksensitive but not explosive, and others are explosive but only mildly shock-sensitive.” 88

developed as an alternative to the Arndt−Eistert methodology. The most significant developments in the safer preparation and use of diazomethane have been achieved in the area of flow chemistry. Commercial equipment, using the tube-in-tube technology, has been very recently and successfully applied to the preparation of a wide range of diazoketones on a gram scale and can be expected to be more widely used in the future by the chemistry community. While flow chemistry has also been employed in the diazo transfer methodology, most of the work in this area has focused on the development of novel sulfonyl azide reagents with improved stability.

3. DIAZOCARBONYL REACTIONS: INTRODUCTION The most significant reactions of α-diazocarbonyl compounds are those that proceed with loss of nitrogen which can be brought about thermally, photochemically, or catalytically: the N2 release acts as an entropically driven trigger for many potentially useful applications in synthesis. Diazocarbonyls react stoichiometrically with many Brønsted acids and electrophiles, and catalytically with numerous transition metals and 9990


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found that decomposition of aryldiazoesters and aryldiazoketones (Scheme 40) in the presence of styrene in trifluor-

their salts. Reactive intermediates include free carbenes, carbenoids (complexed or metal carbenes), ylides, and diazonium cations. A notable feature of the development of these reactions is the broad range of metal−chiral ligand combinations now known to be catalytically active in enantioselective reactions. There are also a growing number of reactions which are exclusively organocatalytic. In this review, as before, we have chosen to group diazocarbonyl reactions not on the basis of common intermediates or mechanisms, but rather according to product type since the latter arrangement makes it much easier to appreciate their versatility in synthesis.

Scheme 40. Thermally Induced Cycloadditions of Aryldiazoesters and Aryldiazoketones

3.1. Wolff Rearrangement

otoluene (bp 102 °C) produced cycloadducts with high chemoselectively, favoring cyclopropane in the case of aryldiazoesters and cyclobutane via a ketene intermediate in the case of aryldiazoketones.103 Another recent example of the use of thermolysis to effect Wolff rearrangement is the synthesis of uracil derivatives from cyclic precursors in the presence of amines.104 The initially formed ketene combines with the amine to produce a βaminoamide which on condensation with triphosgene yields a uracil derivative, 11 (Scheme 41).

In a review entitled “100 Years of the Wolff Rearrangement”, published in 2002, Kirmse highlighted a century-old fascination with a reaction that has contributed much to the growth of chemical synthesis.89 Quite apart from the ongoing use of the Wolff rearrangement of diazocarbonyl compounds in the Arndt−Eistert reaction, and in ring contraction methodology, there are aspects of the Wolff rearrangement which continue to attract theoretical and practical interest, namely, the discovery of new ways to exploit synthetically the reactive ketene intermediates,90,91 and the application of sophisticated spectroscopic and computational techniques to probe the sequential mechanistic details of events between diazocarbonyls and ketenes. Traditionally, the mechanistic sequence of events in the Wolff rearrangement has been viewed as: α-diazocarbonyl substrate → α-oxocarbene → ketene → final product. Although the actual rearrangement step is frequently viewed as concerted, there is much evidence for an alternative stepwise process involving the discrete formation of reactive carbonylcarbenes on thermal or photochemical loss of nitrogen. The evidence comes from matrix isolation and low-temperature time-resolved spectroscopy supported by computation and trapping studies.92−97 In metal-catalyzed reactions, the reactive intermediate is generally presumed to be a metal-complexed carbene (metal carbene). There is also evidence for the existence of a noncarbene route to ketenes.98 Although light-promoted decomposition of diazocarbonyls is usually accomplished using a medium-pressure mercury vapor lamp, there are reports that a 100 W compact fluorescent light source, operating in a continuous-flow reactor, can also be effective.99 Apart from photolysis, silver ion catalysis remains a popular choice for effecting Wolff rearrangement of diazoketones; the combination of silver benzoate and triethylamine has been used successfully for more than 50 years. The addition of silica gel to catalytic amounts of silver trifluoroacetate has been used by Podlech to prepare β-amino acids very efficiently.100 Other forms of silver catalysis include the use of silver nanoclusters (Agn), generated in situ from silver oxide or other silver salts via reduction.101,102 Initially, there was a widely held view that although rhodium complexes were very successful for several other diazocarbonylcarbene transfer processes, they tended to suppress Wolff rearrangement. In fact, there are a growing number of cases where rhodium complexes have been identified as very effective catalysts for this reaction (vide infra). One of the earliest methods of diazocarbonyl decomposition involves pyrolysis, and although excessive heat can lead to unselective reaction, there are recent instances where simple thermolysis is effective. For example, Davies and co-workers

Scheme 41. Thermolytic Wolff Contraction

The substrate 10 is a 2-diazo-1,3-dicarbonyl derivative, a particularly popular type for Wolff rearrangement, since such substrates bearing two proximal carbonyl functions produce αoxoketenes with a rich synthetic potential (Scheme 42). Scheme 42. Generation of an α-Oxoketene from a 2-Diazo1,3-dicarbonyl Derivative

There are several other examples of nucleophilic additions to α-oxoketenes which we shall illustrate below. Recent improvements in decomposition modes include the application of microwave and ultrasound, which have beneficial effects on reaction rates; base-free Ag+-catalyzed Wolff rearrangement is also facilitated by sonication, which is useful for base-sensitive substrates. 3.1.1. Reactions of Ketenes from Wolff Rearrangement. 3.1.1.1. Arndt−Eistert Homologation. Notwithstanding the inherent hazards in handling diazomethane (see section 2), the Arndt−Eistert reaction continues to be a popular method of 9991


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reaction with diazophosphonate and N-protected prolinal, a process that was shown to be free of racemization.71 Although several silver salts were active catalysts for the rearrangement, they were otherwise unsatisfactory due to the need to use high loadings of catalyst added intermittently throughout the reaction; however, application of photochemical conditions led to clean reaction, furnishing the homologated ester 17 in essentially quantitative yield.73 Among other examples of Arndt−Eistert homologation in synthesis are those involving functionalized peroxides. Dussault and Xu found that diazoketones containing peroxy substituents undergo Wolff rearrangement to afford homologated peroxyalkanoates to an extent that was reaction condition dependent (Scheme 46).107 Thus, reaction of diazoketones 18 and 19 with

homologation of carboxylic acids, and although the majority of diazoketones employed in homologations have been prepared from acid chlorides and diazomethane, there are instances where this approach failed. Such an example is found with the diazoketone 13 (Scheme 43) where reaction of the bis(acid Scheme 43. Synthesis of a Homologated Diester Using (Trimethylsilyl)diazomethane

Scheme 46. Wolff Rearrangement of PeroxideFunctionalized Diazoketones

chloride) 12 with diazomethane failed to produce reproducible results.105 However, a simple switch to (trimethylsilyl)diazomethane did produce the diazoketone 13, and use of silver benzoate in ethanol completed the synthesis of the homologated diester 14. The Arndt−Eistert reaction has been used to produce molecules capable of acting as fluorescent probes. For example, Wolff rearrangement of the nonfluorescent diazoketone 15 in ethanol produces the fluorescent ethyl ester 16 (Scheme 44).106 This reaction has been studied as a model for labeling reactions performed with biomolecules. Scheme 44. Wolff Rearrangement of a Nonfluorescent Diazoketone

silver benzoate and triethylamine in methanol furnished homologated peroxy products in excellent yield. These conditions were much less successful when applied to substrates 20 and 21. However, use of photolysis in methanol did produce the homologated products in good yield. These results demonstrate the ability of peroxy groups to withstand the conditions of the Arndt−Eistert process and suggest that this methodology offers new possibilities for the introduction of natural or unnatural peroxy-containing groups onto polymers and biomolecules. The Arndt−Eistert process has also been used in solid-phase synthesis. Fehrentz and co-workers anchored phenylalanine to Wang resin via the amino function, leaving the carboxyl group free for activation prior to reaction with diazomethane.108 Homologation was then effected by silver benzoate with benzylamine to produce a resin-bound benzyl amide. Use of water in place of the amine led to the corresponding βhomologated amino acid (Scheme 47). In its original form, the Arndt−Eistert reaction defines the one-carbon extension of a carboxylic acid into a homologous acid (or the corresponding ester or amide) using a ketene intermediate generated from a diazocarbonyl derivative via the Wolff rearrangement. Mechanistically, the process involves addition of an oxygen, sulfur, or nitrogen nucleophile to the ketene intermediate. This is in fact now recognized as one of a broad range of useful reactions of this functionality which encompasses addition of carbon nucleophiles, both inter- and intramolecular, and numerous pericyclic reactions.

There are several recent examples of the Arndt−Eistert homologation, most of which relate to saturated substrates. Much less common are reactions based on unsaturated diazoketones such as that in Scheme 45. Pinho and Burtoloso prepared this diazoketone via a Horner−Wadsworth−Emmons Scheme 45. Combined Horner−Wadsworth−Emmons and Arndt−Eistert Homologation

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employed in an earlier route to the same substrate based on an amino acid.110 Treatment of the diazoketone with catalytic silver benzoate in dichloromethane induced Wolff rearrangement, producing the ketene with an appropriately placed pendant vinylogous amide for nucleophilic C−C bond-forming cyclization to a six-membered enaminone. Yet another example of the addition of carbon nucleophiles is the reaction of isocyanides with ketenes generated by thermally induced Wolff rearrangement. Yu and co-workers found that thermolysis of α-diazoketoesters in xylene at 140 °C in the presence of α-isocyanoacetamides led to formation of 5aminooxazoles.112 The process is viewed as nucleophilic addition of the carbon end of the isocyanide dipole to the electrophilic center of the ketene to produce a nitrilium intermediate. Tautomerization of the nitrilium ion followed by cyclization through a carbonyl oxygen atom forms the oxazole (Scheme 50).

Scheme 47. Solid-Phase Arndt−Estert Homologation

3.1.1.2. Intramolecular Capture of Ketenes Generated by Wolff Rearrangement. There have been a number of imaginative examples of intramolecular capture of ketenes by oxygen and nitrogen nucleophiles. Zhang and Romo devised a route to bicyclic and tricyclic fused γ-lactones via Wolff rearrangement coupled with O−H insertion.109 The diazocarbonyl precursors were prepared by addition of ethyl lithio-αdiazoacetate to a β-lactone (Scheme 48). The resulting δ-

Scheme 50. Formation of 5-Aminooxazoles via Thermal Wolff Rearrangement

Scheme 48. Coupled Wolff Rearrangement and O−H Trapping

hydroxy-α-diazo-β-ketoester was then subjected to Wolff rearrangement conditions (either photolytic or thermolytic in toluene) to form a ketene that was trapped efficiently by the pendant alcohol to form a γ-lactone. A similar sequence of reactions could be used to convert β-lactones into phosphonate γ-lactones. 3.1.1.2.1. Carbon Nucleophiles. More recently, the additions have been extended to include inter- and intramolecular addition of carbon nucleophiles. A notable example of the latter process is the synthesis of cyclic six-membered enaminones by Seki and Georg.110,111 These workers prepared an appropriate diazoketone from diazobromoacetone, benzylamine, and ethyl propiolate (Scheme 49). This route was chosen to avoid the use of diazomethane which had been

Among other notable examples of intermolecular addition of carbon nucleophiles to ketenes generated by Wolff rearrangement are annulation reactions of trialkylsilyl ketenes, labeled “TAS-ketenes” by Danheiser and co-workers. Several aspects of the chemical behavior of silyl ketenes were already known from earlier work of Maas and co-workers, who had shown that silyl diazoketones could be decomposed to silyl ketenes photochemically or by copper catalysis.113 The Maas group later showed that aryl silyl ketenes could be similarly produced by catalysis by triflic acid.114 In particular, trialkylsilyl vinyl ketenes and trialkylsilyl aryl ketenes could be produced conveniently by photolysis of trialkylsilyl diazoketones in benzene at room temperature.115,116 Photolysis appears to be the method of choice for producing alkyl-, aryl-, and alkenyl-substituted silyl ketenes from silyl diazoketones. Independently, Marsden and Pang demonstrated for a range of silylated diazoketones that use of rhodium(II) octanoate also mediates Wolff rearrangement very efficiently, producing isolable silyl ketenes which could be isolated as such or derivatized to α-silyl benzyl amides.117 These trialkylsilyl ketenes exhibit remarkable stability: the silyl substituent suppresses the tendency to undergo dimerization and [2 + 2]-cycloaddition, allowing them to express their underlying reactivity as reactive dienes in Diels−Alder cycloadditions and as reactive carbonyl compounds in annulation reactions. An example of the latter use of a trialkylsilyl vinyl ketene is a

Scheme 49. Combined Wolff Rearrangement and Nucleophilic Cyclization

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2,3-disilylcyclopropanone in equilibrium with an oxyallylic cation, electrocyclic ring closure of which leads to a cyclopentenone.118 In a significant recent extension of the benzannulation process, Danheiser and co-workers have combined the Wolff rearrangement of α,β-unsaturated diazoketones with other ketenophilic partners, including N-carbomethoxy, N-sulfonyl, and N-phosphoryl ynamides to produce polycyclic aromatic and heteroaromatic molecules (Scheme 53).119

benzannulation strategy employing C-acylation of a lithium ynolate, leading, via electrocyclic ring closure, to a cyclohexadienone and ultimately to a highly substituted phenol (Scheme 51). This regiocontrolled benzannulation strategy Scheme 51. Benzannulation via Trialkylsilyl Vinyl Ketene

Scheme 53. Benzannulation of α,β-Unsaturated Diazoketones with N-Substituted Ynamides

Annulation processes involving the combination of Wolff rearrangement and aza-Wittig reactions have been used to construct several nitrogen heterocycles. For example, reaction of a diazocarbonyl compound with an azidoacrylate in the presence of triphenylphosphine produces pyridines (Scheme 54).120 Triphenylphosphine forms a phosphazene with the azide in a Staudinger−Meyer reaction, while the diazocarbonyl component undergoes a thermal Wolff rearrangement to a ketene. The subsequent combination of these two reactive components leads to an aza-Wittig reaction followed by electrocyclic ring closure and ultimately a pyridine. This

provides access to several ortho-substituted phenols suitable for further useful transformations leading to benzo-fused oxygen heterocycles.116 The Danheiser group has also used trialkylsilyl aryl ketenes as four-carbon components in stereoselective [4 + 1]-annulations for the synthesis of cyclopentenones (Scheme 52). This annulation process is believed to involve the formation of a Scheme 52. [4 + 1]-Annulation of Aryl Ketenes

Scheme 54. Sequential Wolff Rearrangement, Aza-Wittig, and Electrocyclization Reactions

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annulation process can be extended to the production of isoquinolines through the use of aryl acrylates (Scheme 55).121

Scheme 57. Three-Component Wolff Rearrangement, Imine Trapping, and Cycloaddition

Scheme 55. Isoquinoline Synthesis

There are several reactions of α-oxoketenes which have been classified as “multicomponent” in the sense that they involve Wolff rearrangement combined with at least two other reactive components, typically an aldehyde or ketone and an amine. Several of these reactions have been devised by Coquerel and Rodriguez and their co-workers.122 For example, microwaveassisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones in the presence of aldehydes and primary amines provides access to oxazinones and oxazinediones (Scheme 56). The success of

hyde yielded an α-spiro-δ-lactam as a single diastereomer in 74% yield, resulting from formal [2 + 4]-cycloaddition of the double bond of the acyl ketene acting as the dienophile to the azadiene from the aldehyde and amine (Scheme 58).123 Scheme 58. Three-Component Wolff Rearrangement, Imine Trapping, and Electrocyclic Ring Closure

Scheme 56. Wolff Rearrangement Combined with Imine Trapping

this reaction rests on nucleophilic addition of an imine to the ketene, with the proviso that the rate of imine formation from amine and aldehyde is faster than is Wolff rearrangement of the diazoketone to avoid direct nucleophilic addition of the amine to the ketene. Variation in the nature of the aldehyde and ketone permits access to a diverse range of bicyclic products (Scheme 56). These workers were able to extend the scope of these threecomponent reactions by choice of aldehyde and amine partners capable of postcondensation cycloaddition reactions. For example, the combination of furfural or an oxazole with allylamine led to the formation of the pentacyclic adducts, the process having terminated in an intramolecular Diels−Alder reaction (Scheme 57). A new aspect of the reactivity of oxoketenes was uncovered when this study was extended to include unsaturated aldehydes, e.g., cinnamaldehyde. Microwave irradiation of the same diazoketone in the presence of benzylamine and cinnamalde-

A more involved but equally effective use of α-oxoketenes is the condensation with hydrazones to form spirooxindoles.124 From a fundamental point of view, this reaction introduces αoxoketenes as effective dipolarophiles in 1,3-dipolar cycloadditions. Microwave irradiation of a 1:1:1 mixture of benzaldehyde, phenylhydrazine, and 2-diazocyclohexane-1,3dione produced the spiropyrazolidin-3-one 22 in up to 80% yield as a single diastereomer. This reaction was found to be quite general, accommodating a broad range of each of the three components (Scheme 59). This approach provides access to stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3-ones by a three-component reaction. The cascade involves the rapid formation of hydrazone, which undergoes a [1,2]-hydrogen shift to give the corresponding azomethine imine 1,3-dipole; Wolff rearrangement of diazocyclohexanedione provides the 9995


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Scheme 61. Photolytic Formation of a β-Lactam via N−H Trapping of a Ketene

Scheme 59. Wolff Rearrangement and Hydrazone Trapping

workers on synthetic approaches to the marine natural product diazonamide A. The suitably N-protected diazo precursor was prepared from a serine-based imidazolide and N-benzylacetanilide (Scheme 62).126 Scheme 62. Rh(II)-Catalyzed Formation of β-Lactams via N−H Trapping of a Ketene

second partner for the 1,3-dipolar cycloaddition leading to the pyrazolidinone. The reaction allows the creation of four covalent bonds and two contiguous chiral quaternary centers with excellent diastereoselectivity, in a single catalyst/additivefree, highly atom-economical transformation. Yet another demonstration of the reactivity of α-oxoketenes is illustrated by the behavior of the indanyl system shown in Scheme 60. Photolysis of the diazo-1,3-dicarbonyl indanone 23 in water yields an α-ketenylbenzocyclobutenone susceptible to hydration and ultimately to cleavage of the cyclobutane ring.125 Scheme 60. Wolff Rearrangement and Subsequent Cleavage of the Cyclobutane Ring

Other examples of intramolecular addition of nitrogen nucleophiles to oxoketenes occur in substrates of the type illustrated in Scheme 63. Wang and co-workers found that chiral δ-(N-sulfinylamino)-α-diazo-β-ketoesters of the type 25 could be synthesized by addition of the lithium enolate of αdiazoacetoacetate to chiral N-sulfinylimines.127 The intention was to use these substrates to generate oxoketenes by photolytic Wolff rearrangement and thereby bring about intramolecular N−H insertion leading to 2-oxopyrrolidines. In the event, however, the expected result was not observed, leading to the conclusion that the N-sulfinyl group was not compatible with the photolysis conditions. Replacement of the N-sulfinyl group by a Boc group produced the corresponding N-Boc-diazoester, which on photolysis did produce the 2oxopyrrolidine 26 in excellent yield. A further observation from this study was that N−H insertion with the same substrate

3.1.1.2.2. Nitrogen Nucleophiles. The combination of Wolff rearrangement with intramolecular addition of a nitrogen nucleophile constitutes a powerful way of making nitrogen heterocycles, especially β-lactams. For example, it constitutes a central feature of a recent synthesis of an enantiopure β-lactam from D-serine. A suitably protected serine was elaborated into the α-diazo-β-dicarbonyl derivative 24, which was subjected to photochemical Wolff rearrangement under CFL conditions. Intramolecular addition of the trityl-protected amine on the ketene thus afforded the product β-lactam (Scheme 61).99 Another recent example, also based on serine as the amino acid building block, is from the work of Konopelski and co9996


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There are related examples which demonstrate that the outcome of the reactions of these diazocarbonyl substrates depends not only on the nature of the heterocyclic ring but also on the length of the aliphatic tether linking the diazo moiety to the aromatic fragment. Wolff rearrangements of thienyldiazocarbonyl substrates have been used to produce diverse bicyclic thienopyrroles for medicinal chemistry discovery programs. Kim and co-workers devised novel thiophene substrates suitable for Wolff rearrangement using novel methodology based on reaction of thioaroyl ketene S,N-acetals with carbenes (Scheme 66).130

Scheme 63. Combined Wolff Rearrangement and N−H Trapping

Scheme 66. Combined Wolff Rearrangement and N−H Trapping of Thienyldiazocarbonyl Substrates

could also be effected by rhodium(II) catalysis whereupon the product was the corresponding 2-oxopyrrolidine again with excellent enantioselectivity. There has been considerable interest in Wolff rearrangement of diazoketones attached as side chains to five-membered ring heterocycles, notably pyrrole, furan, and thiophene. Pyrrolyl ketenes have been studied by Tidwell’s group for their potential as synthetic intermediates.128 N-Pyrrolyl ketene, a nonconjugated heteroaryl ketene, offering the feature of attachment of a heteroaryl nitrogen directly to a ketene, was of particular stability, structural, and theoretical interest (Scheme 64). NScheme 64. Photolysis of N-(Diazoacetyl)pyrrole in Methanol

The substrates were prepared by exposure of the ketene S,Nacetal 35 to mercuric acetate followed by addition of the trimethylsilyl enol ether of an alkyl α-diazoacetoacetate to yield thiophenes with suitably positioned amino- and diazocarbonyl side chains. Exposure of the thiophene diazoketone 36 to rhodium(II) acetate in benzene produced in 99% yield the thienopyrrolone 37 as a mixture of keto and enol forms. The exclusive formation of this product was interpreted as indicating a cis relationship between the rhodium carbene and the keto end of the β-dicarbonyl group of the side chain with an intramolecular hydrogen bond between the carbonyl oxygen and the proximal alkylamino group as depicted. The cis form represents the preferred arrangement of the rhodium carbene for Wolff rearrangement to ketene. To complete the synthesis, the ketene is trapped by the proximal amino group to form the nitrogen ring. 3.1.1.3. Cycloaddition Reactions of Ketenes from in Situ Wolff Rearrangement. In principle, the [2 + 2]-cycloaddition of ketenes from Wolff rearrangement with alkenes and alkynes constitutes the most direct method for the synthesis of cyclobutanones and cyclobutenones.90 Unfortunately, however, this process is truly general only for highly nucleophilic ketenophiles such as conjugated dienes and enol ethers. In general, unactivated alkenes and alkynes fail to react in good yield with either alkyl- or aryl-substituted ketenes, or with ketene itself. A notable and useful exception to this lack of reactivity is illustrated by the behavior of thio-substituted ketenes. Danheiser and co-workers have uncovered a new method for the generation of thio-substituted ketenes as well as their surprisingly facile cycloaddition with both activated and

(Diazoacetyl)pyrrole (27) was obtained from the acid by reaction with isobutyl chloroformate and diazomethane. Upon photolysis at 300 nm in methanol, N-(diazoacetyl)pyrrole produced not only the expected normal Wolff rearrangement methyl ester 28 but also the ketocarbene-derived O−H insertion product 29 and a new rearranged methyl ester, 30, in a 28:25:47 ratio. The new product appears to result from a rearranged ketene, 31, formed by vinylogous Wolff rearrangement. Previous examples of such rearrangements include the proposal that 1-diazo-3-(2-furyl)-2-propanone (32) furnishes the methyl ester 34 via the ketene 33 (Scheme 65).129 Scheme 65. Vinylogous Wolff Rearrangement of a FuranFunctionalized Diazoketone

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unactivated alkenes and alkynes.131 These workers found that exposure of α-diazothioesters to the action of catalytic rhodium(II) acetate leads to a remarkably facile “thia-Wolff rearrangement”, producing thio-substituted ketenes which combine with a variety of ketenophiles to provide access to α-thiocyclobutanones, cyclobutenones, and β-lactams. Reductive desulfurization of these cycloadducts takes place under mild conditions and in excellent yield, and this sequence thus represents a useful new alternative to the existing dichloroketene-based methodology for the synthesis of fourmembered carbocycles and heterocycles. Aryl thioesters proved to be superior to the tert-butyl derivative as substrates, and most studies were conducted with the phenylthio or mesitylthio derivative (Scheme 67). Scheme 68 summarizes the results of a

atom in the thiol ester to capture the rhodium carbene in a process leading to the cyclic sulfonium ylide (Scheme 69). The Scheme 69. Rh(II)-Catalyzed Thia-Wolff Rearrangement of an α-Diazothioester

formation of cyclic sulfonium ylides by intramolecular attack of sulfides on rhodium carbenes is well documented, although prior examples that involve thiol esters or that lead to the formation of three-membered rings are apparently without precedent. In contrast to the ability of rhodium to initiate the thia-Wolff rearrangement, the photochemical version of this reaction proved to be a much less efficient reaction. Several prior reports have described the generation of thio-substituted ketenes via the photochemical Wolff rearrangement.132−134 For example, irradiation (300 nm) of a solution of diazo phenylthiol ester and methylenecyclohexane in benzene led to polymeric products with no cyclobutanone detectable by 1H NMR analysis of the crude product mixture.131 Photolysis or microwave pyrolysis of amino acid- and peptide-derived diazoketones in the presence of imines has been used by Linder and Podlech in [2 + 2]-cycloaddition reactions leading to β-lactams.135−137 A typical example is shown in Scheme 70.

Scheme 67. Combined Thia-Wolff Rearrangement and [2 + 2]-Cycloaddition Involving Alkenes

Scheme 70. Combined Wolff Rearrangement and [2 + 2]Cycloaddition via Microwave Pyrolysis

Scheme 68. Combined Thia-Wolff Rearrangement and [2 + 2]-Cycloaddition Involving Alkynes A final example which illustrates the power of combining the Wolff rearrangement with other bond-forming events is taken from the work of Stoltz and co-workers on the synthesis of fused bicycles containing seven-membered rings.138 These workers, recognizing that cycloheptadienones of the type 38 (Scheme 71) might be accessible by a tandem Wolff/Cope rearrangement with concomitant opening of a strained cyclopropane ring, studied reaction conditions for decomposition of diazoketones of the type shown. Although most standard Wolff protocols produced evidence of Arndt−Eistert homologated acid formation, the concomitant strain-release Cope rearrangement required an additional push in the form of silver benzoate and sonication, under which conditions the desired Wolff/Cope product was obtained in 95% yield. 3.1.1.4. Ring Contraction via Wolff Rearrangement. Ring contraction in cyclic systems continues to enjoy widespread use as one of the most effective ways of producing highly strained molecules. One of the great strengths of the Wolff rearrangement in this regard is its independence of ring-opening/ringclosure sequences. There are numerous examples of its power in changing ring sizes rather than making rings from acyclic precursors. Photolysis is the method of choice for ring contraction. In general, the difference in strain energy between

companion study of [2 + 2]-cycloaddition of arylthio ketenes with acetylenic ketenophiles, again using catalytic rhodium acetate. The utility of these thia-Wolff [2 + 2]-cycloaddition products lies primarily in the ease of their production and the ease with which they can be converted into a variety of useful sulfur-free products.131 Another notable feature of this thia-Wolff rearrangement is the use of rhodium catalysis. Danheiser suggests that the unusual facility of the Wolff rearrangement of these thiosubstituted diazo substrates is due to the ability of the sulfur 9998


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of a ketene. Thus, it appears that under matrix isolation conditions Wolff rearrangement of the tricycloheptyl nucleus to tricyclohexyl is indeed possible. Several diazoacenaphthenones have been studied by Shechter and co-workers in a search for ring contraction leading to 1Hcyclobuta[de]naphthalenes.141 This study was prompted by the earlier discovery of Chapman and co-workers that the parent diazonaphthenone 40 on photolysis in a frozen argon matrix at 10−15 K produces a triplet oxocarbene which undergoes Wolff rearrangement to ketene 41, detectible in the matrix by IR methods (Scheme 73).142

Scheme 71. Tandem Wolff/Cope Rearrangement

Scheme 73. Photolytic Wolff Rearrangement in a Frozen Argon Matrix

a substrate and product, ΔEstrain, appears to be the deciding factor in determining the success of ring contraction. In general, it is known that a reaction where the ring strain increase is not more than about 35 kcal/mol is likely to be successful. However, yields do not correlate directly with the strain energies of the products. Wiberg and co-workers have used the Wolff rearrangement to great effect in bridged-ring spiro hydrocarbons to probe the effects of angle strain on molecular stability.139,140 Their study was based on the ring contraction of tricyclo[4.1.0.0]heptane as a route to tricyclo[3.1.0.0]hexane, whose strain energy had been estimated to be approximately 37 kcal/mol greater than that of its tricycloheptane analogue (Scheme 72).

The Schechter study chose a series of disubstituted diazoacenaphthenones for photochemical and thermal decomposition under less extreme conditions in alcohol and amine solvents at various temperatures in a search for ketenes or their adducts with solvent. The compounds chosen were four 5,6disubstituted derivatives, 42−45, and one 3,8-disubstituted derivative, 46, in the expectation that repulsive interactions between the peri-5,6-substituents in the former and crowding effects of the methoxy groups in the latter might lead to Wolff rearrangement by compressing, twisting, and reducing the stabilizing delocalization in their incipient five-membered ring α-oxocarbenes (Scheme 74). Furthermore, conversion to

Scheme 72. Synthesis of Bridged-Ring Spiro Hydrocarbons via Ring Contraction

Scheme 74. Photolysis and Thermolysis of Disubstituted Diazoacenaphthenones

Photolysis of the tricycloheptyl diazoketone derivative 39 in methanol produced exclusively the tricycloheptyl methoxy ketone rather than ring contraction (Scheme 72). Since the diazoketone was known to be stable in methanol, it was concluded that its photoexcited state was sufficiently basic to abstract a proton from the solvent, leading to a diazonium ion and hence the methoxy derivative. Photolysis in dimethylamine produced a new dimethylamino adduct identified as that of a rearrangement but not of Wolff contraction. This adduct may result from a ketocarbene which fragments prior to capture by Michael addition of dimethylamine. However, photolysis in a Nujol matrix at 15 K led to the formation of an unstable nitrogen-free product with the IR spectral features characteristic

ketenes should be facilitated by electronic effects resulting from the presence of the nitro/methoxy groups. In the event, none of the substituted diazoacenaphthenones produced ketenes 47 or their solvolysis products 48. However, this study did provide useful information on the generation and fate of nonrearranging α-oxocarbenes. For example, photolysis of 42 in methanol yielded the 2-methoxy adduct 49 and the reduction product 50; reaction in tert-butyl alcohol also produced the tert-butyl ether and larger amounts of the 9999


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an intermediate carbene generated so close to neighboring olefinic bonds and a ring junction. The marine antibiotic acanthodoral (58) is a sesquiterpene aldehyde possessing a highly strained bridged bicyclo[3.2.1]heptane. Photo-Wolff rearrangement of a bicyclo[3.2.1]diazoketone, 57, provided the key to a successful synthesis by Zhang and Koreeda (Scheme 77).145

reduction product. Photolysis in cyclohexane resulted in carbenic C−H insertion in the solvent to form 51 rather than reduction. Thermolysis studies revealed yet another aspect of the α-oxocarbene: when the diazoketone was heated in primary and secondary amines at 140−180 °C, again there was no evidence of ketene formation, but a novel N−H insertion reaction occurred, leading to an indole 52. Thus, diazoketones failed to undergo Wolff rearrangement in methanol, though ring-contracted ketenes were observed in photolysis in an argon matrix at 10−15 K. The literature of the past 30 years is replete with examples of ring contractions in strained systems; many are explorations of the limits of distortions that tetrahedral carbon atoms can sustain and still constitute isolable molecules. A comprehensive account of these systems is available in Kirmse’s review.89 3.1.1.5. Examples in Synthesis. We have selected an illustrative few examples of ring contractions in total synthesis to demonstrate the variety of ring types that are now accessible. A recent example of an already strained system is provided by the synthesis of an aminobicyclo[2.1.1]hexane derivative (Scheme 75) from a simple norbornane precursor.143 The

Scheme 77. Synthesis of Acanthodoral

Scheme 75. Wolff Rearrangement of a Norbornane Derivative

A striking example of the efficacy of the Wolff rearrangement in strained ring synthesis is found in the Corey synthesis of pentacycloanammoxic acid (59), a naturally occurring fatty acid consisting of a linear fusion of five cyclobutane rings in the form of a ladder (a “ladderane”). The accumulation of so many small rings within a single molecule results in excessive strain energy and severely limits the possible synthetic approaches. Previous syntheses of unnatural ladderanes have employed nonspecific oligomerization of cyclobutadienes or photochemical [2 + 2]-cycloaddition processes. There are two versions of the Corey synthesis, first the racemate146 and later the optically active form.147 Both rely on a photochemical Wolff rearrangement to introduce a four-membered ring by ring contraction, at a late stage in the racemate version and at an earlier stage in the single-enantiomer version (Scheme 78). The alkaloid dibromopalau’amine (60) contains a highly strained and unusual trans- azabicyclo[3.3.0]octane embedded within a dense array of functionality. Feldman and Nuriye have assembled the pentacyclic core of dibromopalau’amine using a combination of two intramolecular reactions: (a) a Pummerer

ultimate target was an unnatural amino acid, 2aminobicyclo[2.1.1]hexane-2,5-carboxylic acid, a potent mGluR agonist. The key step in the synthesis involved elaboration of a readily available norbornane derivative into a suitably functionalized diazoketone which was a mixture of regioisomers 53 and 54. Separation of the mixture was unnecessary as irradiation of both isomers in methanol at room temperature produced the same ring-contracted bicyclo[2.1.1]hexane product. In seeking to take advantage of the power of the Diels−Alder reaction to construct bicyclic structures of the dolabellane-type marine natural products, Snyder and Corey synthesized an advanced intermediate which required a final ring contraction.144 In the event, photolysis in methanol of the diazocyclohexenone 55 (Scheme 76) followed by thermal treatment with DBU generated the required ring-contracted ester 56 in 68% yield. The success of this Wolff rearrangement is noteworthy, given the number of potential side reactions of

Scheme 78. Synthesis of Pentacycloanammoxic Acid

Scheme 76. Wolff Rearrangement of a Diazocyclohexenone Derivative

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reaction-mediated oxidative bicyclization to deliver the pentacyclic core with a trans-bicyclo[4.3.0]nonene moiety, the double bond of which allowed access to a diazoketone suitable for (b) photochemical Wolff contraction of the six-membered ring to deliver the strained trans-azabicyclo[3.3.0]octane. The success of this synthesis again demonstrates one of the great strengths of the Wolff rearrangement: the avoidance of alternative, problematic ring-opening/ring-closure sequences (Scheme 79).148

Irradiation of 2-diazo-3-oxochlorins in the presence of nucleophilic and biomimetic substrates 1-butanol, tosylhydrazine, or tetrahydrofurfuryl alcohol generates Wolff-rearranged, pyrrole ring-contracted azeteoporphyrinoids in 11−34% yield, with the corresponding hydroxyporphyrins in up to 55% yield. For metalated diazooxochlorins, these products compete with intramolecular exocyclic ring formation by meso-phenyl ring alkylation, which occurs in up to 76% yield in the absence of a substrate. The dependence of the product distribution on the substrate is established by photolysis in neat dichloromethane. Under these conditions, formation of the Wolff-rearranged product is inhibited and the phenyl alkylation product dominates (76%) due to the absence of a good nucleophile. A conceptually analogous dependence is also observed for the free-base derivative, with the exocyclic ring-containing dimerization product isolated in 42% yield. The third reaction pathway, formation of the hydroxyporphyrin, is enhanced by the presence of non-nucleophilic, oxidizable substrates such as 1,4-cyclohexadiene (M = Cu, 55%); however, in the presence of the bulky and oxidatively more stable tert-butyl alcohol, intramolecular exocyclic ring-quenching is observed in 51% yield with no detection of the hydroxyporphyrin. All porphyrinoid photoproducts possess intense absorption bands throughout the visible spectral region, indicating that ringcontracted substrate adducts, as well as phenyl ring addition products, maintain porphyrinoid aromaticity. Overall, the ability of these chromophores to react photochemically under substrate control may make unimolecular porphyrinoid photoreagents such as these useful for applications in photobiology or O2-independent photodynamic therapy. Both carbene and ketene intermediates formed may find potential as in situ alkylating agents in phototherapeutic applications. Contraction of rings leading to severe angle strain can occur in systems containing triple bonds (Scheme 81). The behavior of the 11-membered ring enediyne 62 on photolysis provides an illustrative example of the use of ring contraction to induce subsequent reaction, e.g., Bergman cyclization. Typically, the

Scheme 79. Synthesis of Dibromopalau’amine

Wolff rearrangement resulting in ring contraction has been observed in an impressive array of biochemical frameworks, some with biochemical implications: the N2 release acts as a trigger for several potentially useful biological applications. Biology provides a variety of potential nucleophiles such as the sugar backbone of DNA and other basic substrates. The behavior of diazooxochlorins on photolysis provides a case in point. Irradiation of the diazooxochlorin 61 in the presence of biomimetic nucleophiles generated a ring-contracted azeteoporphyrinoid resulting from Wolff rearrangement and ketene capture by the external nucleophile. Other products included the hydroxyporphyrin and the product resulting from intramolecular addition to the meso-benzene ring (Scheme 80).149

Scheme 81. Wolff Contraction and Bergman Cyclization

Scheme 80. Wolff Rearrangement and Ketene Capture of a Diazooxochlorin

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Bergman cyclization is a cycloaromatization process of a 1,5diyne that is induced thermally or photochemically. Most cyclizations have high activation energy barriers, and therefore, temperatures in excess of 200 °C are needed: compare the behavior of this 11-membered ring enediyne 62 incorporating an α-diazo-β-diketone moiety which on light-induced Wolff contraction produces two isomeric 10-membered ring enediyne ketenes, 63 and 64, the extra ring strain of which is sufficient to trigger spontaneous Bergman cyclization at or below room temperature, leading to aromatic products. In the photochemical or thermal contraction, the alkyl substituent migrates ca. 2.5 times faster than the alkynyl group.150 Transition-metal organometallic versions of the Wolff contraction were apparently unknown until the recent discovery that certain five-membered metallacycles exhibit rearrangement. Although carbon migration is the source of ring contraction in conventional Wolff rearrangements, this is not the case for reaction of substrates containing a transition metal within the ring. This unusual behavior is illustrated by αformyl-3-iridacyclopentanone (Scheme 82), which on treat-

Masamune, and Evans have led to highly efficient and enantioselective intermolecular cyclopropanation reactions.160−166 In particular, the development of novel bidentate ligands such as 65−67 which are suitable for coordination to copper salts proved critical for achieving high enantiocontrol and high trans selectivity (Scheme 83).

Scheme 82. Reaction of an Iridacycle

The copper(I) bisoxazoline complex 67 pioneered by Evans in the 1990s is still a standard to which new bisoxazoline ligands are compared. Due to the success of bisoxazoline ligands for cyclopropanation reactions, many new ligands investigated are based on the bisoxazoline moiety.167−169 Below are a select number of examples of ligands 68−71 which have been recently applied to Cu(I/II)-catalyzed intermolecular cyclopropanation reactions and have reported high enantioand/or diastereocontrol (Scheme 84).170−174

Scheme 83. Bidentate Oxazoline-Containing Ligands

Scheme 84. Examples of Recently Reported Bisoxaline Ligands for Cyclopropanation

ment with tosyl azide yielded the four-membered iridacycle, rather than the expected diazoketone.151 The latter appears to be only a reactive intermediate on the Wolff pathway to a ringcontracted product whose structure suggests that migration of the iridium center to the carbenic carbon atom in the presumed intermediate is preferred to migration of the carbon atom. The Wolff product exhibited unusual reactivity: despite its α,βunsaturated ketone constitution, it readily undergoes electrophilic epoxidation with peracids. 3.2. Cyclopropanation Reactions

3.2.1. Cyclopropanation of Alkenes. This area has been extensively reviewed in recent years,3,4,152−155 and thus, only selected significant contributions will be discussed in this review, with particular attention being paid to the use of chiral catalysts and applications in natural product synthesis. The cyclopropanation of alkene bonds by α-diazocarbonyl compounds is one of the most extensively studied transformations in organic chemistry. The cyclopropane ring itself is found in a number of natural products as well as being a versatile synthetic building block which can be converted into a range of functionalities.156−159 Although a number of transition metals are used for cyclopropanation, including rhodium, ruthenium, and cobalt, among others, copper catalysts remain at the forefront, particularly for intermolecular reactions. In particular, complexes containing semicorrin or C2-symmetric bisoxazoline ligands demonstrate some of the highest chemoand enantioselectivities. 3.2.1.1. Intermolecular Alkene Cyclopropanation by αDiazocarbonyl Compounds. Since Nozaki’s pioneering studies in the 1960s, major advancements in the area by Aratani, Pfaltz,

Intermolecular copper-catalyzed cyclopropanation reactions involving α-diazocarbonyl compounds have not been widely reported in the total or formal synthesis of natural products.158,175 However, the cyclopropanation of methyl 3furancarboxylate with tert-butyl diazoacetate involving a copper bisoxazoline complex was recently used as a key step in the total synthesis of (−)-paeonilide (Scheme 85).176 In general, rhodium(II) catalysts do not achieve the high enantiocontrol displayed by copper complexes.177 However, catalysts such as 72−74 have proven to be superior to copper for the cyclopropanation reactions of aryl- and styryldiazoacetates (Scheme 86).178 The rhodium(II)-catalyzed tandem cyclopropanation/Cope rearrangement or [4 + 3]-cycloaddition reaction has been extensively investigated by Davies and co-workers. It has been found to be highly diastereoselective, with the capability for 10002


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rhodium(I) N-heterocyclic iminocarbene-type catalyst, 77, in the cyclopropanation of various alkenes and α-diazoacetates (Scheme 88).

Scheme 85. Furan Cyclopropanation Route to (−)-Paeonilide

Scheme 88. Cis-Selective Rh(I)-Catalyzed Cyclopropanation

Scheme 86. Rhodium-Catalyzed Cyclopropanation with Donor−Acceptor Diazo Compounds In comparison to rhodium- and copper-based catalysts, ruthenium and cobalt have only recently garnered attention as highly efficient catalysts for this type of reaction.155,195 Ruthenium(II) complexes bearing multidentate ligands such as Nishiyama’s pybox ligand have demonstrated both high enantio- and diastereocontrol for the cyclopropanation reactions of styrene with a range of α-diazoacetates.196−199 Porphyrin, Schiff base, salen, and diphosphine ligands have also been found to be highly efficient in terms of both enantio- and diastereoselectivities.197,200−204 Recently, ruthenium(II) pheoxazoline catalysts such as 78 have emerged as highly enantioselective catalysts for the cyclopropanation reactions involving both terminal alkenes and vinyl carbamates with αdiazoacetates (Scheme 89).205−207

complete diastereocontrol at up to three stereogenic centers. This process has been utilized in the synthesis of a number of natural products such as (+)-barekoxide (75) and (+)-barekol (76) (Scheme 87).179

Scheme 89. Ru-Pheox-Catalyzed Cyclopropanation

Scheme 87. Cyclopropanation/Cope Rearrangement in Natural Product Synthesis

For cobalt-catalyzed cyclopropanation reactions, both Schiff base and porphyrin ligands have emerged as the most frequently used classes of ligands.208 Katsuki developed both trans-selective and cis-selective cobalt salen catalysts 79 (Scheme 90) and 80 (Scheme 91), respectively.209−211 Both were found to exhibit high diastereo- and enantiocontrol; however, 80 was found to be limited in scope to arylsubstituted alkenes. Zhang and co-workers have reported major successes in intermolecular alkene cyclopropanation reactions using cobalt(II) porphyrin metalloradical catalysts.212−216 A recent example involves the use of a Co(II) catalyst bearing a D2-symmetric chiral porphyrin ligand, 81, to induce high diastereo- and enantiocontrol in the cyclopropanation reactions involving

Charette and co-workers have reported numerous successes using rhodium(II) catalysts in alkene cyclopropanation involving α-diazocarbonyl compounds bearing two electronwithdrawing groups α to the diazo carbons (acceptor/acceptor types).180−189 A number of rhodium catalysts have been reported to give high diastereoselectivity for formation of the cis isomer.190−194 A recent example involves the use of a 10003


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Scheme 90. Katsuki’s Trans-Selective Cobalt Salen Catalyst

Scheme 93. Synthesis of (+)-Colletoic Acid

Scheme 91. Katsuki’s Cis-Selective Cobalt Salen Catalyst

Scheme 94. Synthesis of (±)-Nemorosone and (±)-Hyperforin

electron-rich and electron-poor alkenes and α-cyano-αdiazocarbonyl compounds (Scheme 92).217 Scheme 92. Cobalt Porphyrin-Catalyzed Cyclopropanation

copper-catalyzed intramolecular cyclopropanation reaction as the key step (Scheme 95).246 Scheme 95. Synthesis of Indole Alkaloid Intermediates

Other metals have also found success in these types of reactions. These include complexes of iridium,218 iron,219 gold,220 and mercury.221 3.2.1.2. Intramolecular Alkene Cyclopropanation by αDiazocarbonyl Compounds. Intramolecular cyclopropanation reactions provide a useful route to both simple and complex cyclopropane-fused systems.222 As with the intermolecular version of the reaction, both copper and rhodium have been extensively used; however, in recent times, other transition metals such as ruthenium and cobalt have been reported to be applicable.200,202,223−227 Nakada and co-workers have demonstrated the utility of copper catalysts for the intramolecular cyclopropanation of αdiazo-β-ketosulfones, -esters, and -phosphine oxides.228−234 This methodology has also been adopted for the synthesis of a range of natural products.228,235−245 Some recent examples include the total synthesis of (+)-colletoic acid (82) (Scheme 93), (±)-nemorosone (83), and (±)-hyperforin (84) (Scheme 94). Qin and co-workers recently developed a biomimetic approach to the pentacyclic substructures of the indole alkaloids perophoramidine and communesin, utilizing a

Copper catalysts are also effective at facilitating macrocyclization of α-diazoacetates. This has most recently been investigated using diazoacetates tethered to allyl groups via a number of ethylene glycol linkers (0−3).247−249 In general, enantioselectivity is seen to increase with increasing ring size, with enantioselectivities up to 85% ee reported for the largest ring (Scheme 96). Unlike the intermolecular version of the reaction, chiral rhodium(II) catalysts are usually superior to chiral copper complexes for intramolecular cyclopropanation reactions.177 Rhodium(II) carboxamidates have been reported to be superior catalysts for the intramolecular cyclopropanation reactions of 10004


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Both ruthenium(II) catalysts and cobalt(II) catalysts have proven particularly successful in intramolecular cyclopropanation reactions involving α-diazoacetate-based substrates. High enantiocontrol has been reported for ruthenium(II) salenbased,223 ruthenium(II) Schiff base-based,202 ruthenium(II) porphyrin-based,200,224,225 cobalt(II) porphyrin-based,226 and cobalt(II) salen-based227 catalysts. 3.2.2. Cyclopropenation of Alkynes. The cyclopropenation of alkynes by means of α-diazocarbonyl compounds is a powerful transformation which leads to the formation of unsaturated cyclopropene products.2−4 These cyclopropene products possess high strain energy and are highly reactive synthetic intermediates.254,255 Both rhodium carboxylate and carboxamidate catalysts have proven effective at intermolecular cyclopropenation reactions involving α-diazoester substrates.256−260 Rh2(DOSP)4 has proven particularly successful in the cyclopropenation reactions of terminal alkynes with aryl- and vinyldiazoacetates, affording cyclopropene products bearing a quaternary stereocenter in high enantioselectivities and moderate yields.257,261 Pérez and co-workers investigated the use of a copper(I) trispyrazolylborate complex in cyclopropenation reaction involving ethyl diazoacetate and both terminal and internal alkynes. The desired cyclopropene products were obtained in yields of up to 94%.262 Copper-catalyzed reactions of aryldiazoacetates with terminal alkynes were seen to undergo formal [3 + 2]-cycloaddition leading to indenes rather than [2 + 1]-cycloaddition to give the corresponding cyclopropene products (Scheme 99).263

Scheme 96. Formation of Cyclic Polyether Cyclopropanes

diazoacetates and diazoacetamides, achieving high yields and enantioselectivities.250 Rhodium(II) catalysts containing azetidinone carboxylate ligands have been found to be highly effective catalysts for intramolecular cyclopropanation reactions involving diazomalonates, vinyldiazoacetates, and aryldiazoacetates, achieving high yields and moderate enantioselectivities.251 Rh2(DOSP)4 has successfully been utilized as a catalyst for the tandem intramolecular cyclopropanation/Cope rearrangement reactions of allyl vinyldiazoacetates; this methodology was adopted for the synthesis of 5-epi-tremulenolide (85) in 93% ee (Scheme 97).252 Scheme 97. Synthesis of 5-epi-Tremulenolide via Intramolecular Cyclopropanation/Cope Rearrangement

Scheme 99. Formal [3 + 2]-Cycloaddition of Aryldiazoacetates with Terminal Alkynes

Wang investigated the copper-catalyzed reactions of terminal alkynes with α-diazoesters, and reported a cascade coupling/ cyclization reaction to give 2,3,5-trisubstituted furan derivatives rather than the expected cyclopropene-type product (Scheme 100).264

Rh(II)-catalyzed intramolecular cyclopropanation reactions of α-diazocarbonyls have been reported as key steps in a number of syntheses of other natural products,158 including (+)-coronafacic acid (86) (Scheme 98).253

Scheme 100. Cascade Coupling/Cyclization Reaction

Scheme 98. Synthesis of Coronafacic Acid

Zhang reported high yields and high enantiocontrol (up to 98% ee), using a cobalt(II)-based metalloradical catalyst, 81.265 This D2-symmetric chiral cobalt porphyrin complex was found to successfully mediate cyclopropenation reactions between a wide range of terminal and conjugated alkynes with cyanodiazoacetamides and -diazoacetates (Scheme 101). Other metals have recently proved successful for cyclopropenation reactions. Katsuki and co-workers demonstrated that iridium salen complexes can efficiently catalyze enantioselective cyclopropenation reactions between terminal alkynes and donor/acceptor and acceptor/acceptor diazo compounds.266 Recently, Davies reported success in the cyclo10005


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ketocarbene or a metal carbene. The initial product is an acylnorcaradiene, 87, which is prone to spontaneous, though reversible, electrocyclic ring opening to form an acylcycloheptatriene, 88 (Scheme 103). 271,272 This initially formed

Scheme 101. Co(II)-Catalyzed Cyclopropenation with Cyano-Substituted Diazo Species

Scheme 103. Transition-Metal-Catalyzed Buchner Reaction

propenation of internal alkynes with donor/acceptor diazo compounds using silver and gold catalysts.267,268 Initial studies were carried out using silver triflate, producing cyclopropenes in up to 98% yield. Extension of the work to nonracemic versions of the reaction using silver catalysis failed. However, use of a binuclear gold catalyst, (S)-xylyl-BINAP(AuCl2), activated by AgSbF6 led to high enantioselectivites (up to 97% ee). Although intramolecular cyclopropenation reactions are possible depending on the position of the alkenyl group, the resulting cyclopropene products are frequently not isolable, although exceptions do exist. The cyclopropene intermediates can undergo rearrangement to vinylcarbenes which then partake in further reactions.2,269 In addition to demonstrating highly enantioselective coppercatalyzed macrocyclic cyclopropanation reactions,247−249 Doyle and co-workers have also reported success in the preparation of macrocyclic lactones with a fused cyclopropene ring.270 In this case, Rh2((S)-IBAZ)4 was found to demonstrate the highest enantiocontrol (>99% ee) and also high yields (73−92%) (Scheme 102).

acylcycloheptatriene 88 may undergo sigmatropic rearrangements to give a thermodynamic mixture of cycloheptatrienes 90.273 The acylnorcaradiene intermediate may also be susceptible to acid-catalyzed rearomatization to form an alkylbenzene, 89.274 There are several cases known where the norcaradiene intermediate is stable and isolable due to prevention of the electrocyclic ring-opening process by geometric (Scheme 104)275,276 or electronic (Scheme 105) constraints.277−281 Scheme 104. Predominance of Norcaradiene

Scheme 105. Stabilization of Norcaradiene

Scheme 102. Macrocyclic Cyclopropenation Transition-metal-catalyzed Buchner reactions were initially carried out using various copper salts, but were found to produce complex product mixtures. This led to the conclusion that the Buchner reaction was likely to be of only limited use in synthesis. Problems associated with isolation and identification of products from these complex reaction mixtures were largely solved in the 1980s following the introduction of rhodium(II) catalysts.1,2,271,272,282,283 Although rhodium(II) catalysts are the most widely reported catalysts for intermolecular aromatic cycloaddition reactions, in recent years, other transition metals such as iron284 and silver285 have been investigated as potentially useful catalysts. For example, Lovely and co-workers investigated the use of a silver trispyrazolylborate (scorpionate) ligand complex, 91, as a catalyst for the reaction of benzene derivatives and ethyl diazoacetate (Scheme 106).285 Reactions involving electron-rich and electron-poor benzene derivatives were found to proceed with good efficiencies, particularly in the case of more electron-rich systems. However, better yields were achieved for the parent benzene substrate. The electronic nature of substituents on the aromatic substrate can have a pronounced effect on the reactivity of the substrate as well as the regioselectivity of cycloheptatriene formation.286,287 Although the Buchner reaction can tolerate a

3.3. Reactions with Aromatics

There are two principal types of reaction of diazocarbonyl substrates with aromatics: aromatic cycloaddition (otherwise known as the Buchner reaction) and aromatic alkylation. The latter have been persistently and probably incorrectly described as aromatic C−H insertion; in fact, these processes are more likely to be examples of C−H functionalization via aromatic electrophilic substitution. 3.3.1. Aromatic Cycloaddition Reactions (the Buchner Reaction). Of the two reaction types described above, Buchner reactions are the longest standing and best studied. Although thermolytic and photolytic versions of this reaction are known, the metal-catalyzed version is by far the most useful, and thus will be the focus of this section. The process is believed to involve cyclopropanation of a benzenoid double bond by an α10006


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fluorobenzene yielded a mixture of three fluorocycloheptatrienes, 93−95 (Scheme 109), in a ratio of 80:12:8, which

Scheme 106. Silver-Catalyzed Buchner Reaction

Scheme 109. Buchner Reaction of Fluorobenzene

corresponds to reaction across the three different π-bonds of the aromatic system with a preference for the bond most remote to the fluoro substituent.286 Under similar conditions, reaction of this substrate with ethyl diazoacetate produced a comparable product distribution. The formation of substituted cycloheptatrienes was further investigated with a selection of disubstituted dihalobenzenes. 1,4-Difluorobenzene has the potential to produce two isomeric products (Scheme 110). However, only a single isomer, 96, was formed.

broad range of substituent types, increased reactivity has been reported for substrates with electron-donating substituents; conversely, decreased reactivity was observed for substrates containing electron-withdrawing groups. These observations may be consistent with the notion that the transient carbene is essentially electrophilic. With regard to the regioselective manner by which the reactions proceed, a number of sites of attack may be available depending on the substitution pattern of the aromatic substrate. For example, for a monosubstituted aromatic substrate, there are three different sites of attack on the three unequal double bonds (Scheme 107).

Scheme 110. Buchner Reaction of 1,4-Difluorobenzene

Scheme 107. Regioselectivity in Buchner Reaction of Monosubstituted Aromatic Substrates Finally, a selection of 1,2-dihalobenzenes 97 (X = F, Cl, Br) were subjected to the Buchner process, summarized in Scheme 111.287 These substrates have the potential to generate four Scheme 111. Buchner Reactions of 1,2-Dihalobenzenes

In an attempt to investigate the steric and electronic factors associated with the intermolecular Buchner reaction, Spring and co-workers conducted a systematic study of rhodium(II)catalyzed reactions between ethyl diazoacetate and various mono-, di-, and trisubstituted aromatic halides.287 Initial studies were conducted using 1,3,5-trifluorobenzene as the aryl component as only a single unconjugated cycloheptatriene, 92, can result (Scheme 108). The study continued with other fluorobenzenes with the potential to yield two or more isomeric products. Anciaux and co-workers had previously established that rhodium(II) trifluoroacetate-mediated reaction of methyl diazoacetate with

possible cycloheptatriene isomers corresponding to cycloaddition across four different bonds of the aromatic ring. All three dihalobenzenes displayed a preference for formation of the C(4)−C(5) addition product 101; the next in order of preference was the C(3)−C(4) product 100, and the least favored was the C(1)−C(2) product 98. Overall, the general conclusion was that the metal carbene species generated in situ is believed to be highly electrophilic, and thus, cycloaddition is presumed to be favored at the more nucleophilic π-bonds of the aromatic substrate, i.e., those remote from the electronegative halogen substituent.

Scheme 108. Buchner Reaction of 1,3,5-Trifluorobenzene

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Since the original report by McKervey274,283 in the early 1990s that an o-methoxy substituent favors cyclization toward itself, the issue has been ultimately resolved by independent reports by Manitto300 and Maguire.302 The initial product of the reaction is indeed formed by addition away from the methoxy substituent to form the kinetic product 106, the 5-substituted azulenone, but this kinetic product is thought to rearrange to the thermodynamic product 105 by means of spiro intermediate 107. Subsequent treatment of either azulenone product with trifluoroacetic acid results in the corresponding tetralone product (Scheme 114).

Polybenzenoid molecules such as fullerenes are also capable of partaking in intermolecular aromatic addition reactions involving α-diazocarbonyl compounds.288−295 In general, these reactions are carried out thermally, and reactions with C60 fullerene result in a mixture of three regioisomers, identified as the [6,6]-closed methanofullerene and the two [5,6]-open fulleroids.296 Recently, Tuktarov and co-workers investigated cycloaddition of diazothioates to C60 under thermal and catalytic conditions.295 It was found that, in the presence of a palladium-based three-component catalyst, the selective formation of methanofullerenes was observed. However, in the absence of a catalyst, a mixture of stereoisomeric homofullerenes was obtained. For intramolecular Buchner reactions, the structure of the αdiazocarbonyl can have a dramatic effect on the ensuing reaction, in terms of both chemo- and regioselectivities. Intramolecular aromatic cycloaddition reactions are typically favored in systems having a three-atom spacer between the aromatic ring and the diazo carbon since an alternative C−H insertion would produce a four-membered ring (Scheme 112).

Scheme 114. Effect of a Methoxy Substituent on the Intramolecular Buchner Reaction

Scheme 112. Buchner Reaction vs C−H Insertion

However, the C−H insertion process becomes competitive in substrates containing four-atom spacers since five-membered ring formation is now permitted.283,297 The nature of the substituent Y on the diazo carbon, and the identity of the catalyst and its attendant ligands, can also affect the outcome.283 The first intramolecular system studied, in the 1990s, was 1diazo-4-phenylbutan-2-one (103), a terminal diazoketone (Y = H) possessing a three-atom spacer.283 Prior to the advent of rhodium catalysts, the intramolecular Buchner reaction of 103 under copper catalysis had been observed to produce an azulenone, 102, in low yield.298 However, the promise implicit in this potentially new direct route to azulenes only became apparent when this reaction was reinvestigated under rhodium catalysis and was found to yield the isomeric kinetic azulenone 104 in high yield (Scheme 113).274,283

Although substitution on the aromatic moiety can have a dramatic effect, other substituent effects such as the presence of a methyl group α to the diazo carbon or introduction of a substituent into the three-carbon spacer do not inhibit aromatic addition.301 Diastereocontrol in the intramolecular Buchner reaction was found to be heavily influenced by the presence of substituents at the 3-position in the α-diazocarbonyl substrate.301−303 Generally, the presence of such substituents resulted in high diastereocontrol, with preferential formation of the trans-azulenone. It was also found that, as the steric bulk of the substituent at the 3-position increased, so too did the trans selectivity of the reaction.302 The presence of a methoxy substituent on the aromatic ring was found to result in reduced diastereoselectivity. Introduction of the methoxy group was found to have induced a cis−trans isomerism which resulted in a larger proportion of cis-azulenone to be present.301,304 Recent studies have demonstrated that the reactivity of the Rh(II) catalyst can dramatically alter the diastereoselectivity of the ensuing reaction; reduced diastereocontrol is observed for more reactive rhodium(II) carboxylate catalysts such as Rh2(pfb)4 and Rh2(tfa)4.303 However, this effect can be counteracted through the presence of bulky substituents at the 2- and 3positions of the carbon chain. This allows aromatic addition reactions to proceed essentially independent of the catalyst in terms of efficiency and diastereocontrol. An exception to the ability of most arenes to engage in the Buchner reaction is the behavior of metal-complexed arenes. Merlic and co-workers have examined the reactivity of chromium arene complexes toward metal carbenes derived from selected α-diazoesters and α-diazoketones, raising the following questions: will aromatic

Scheme 113. Copper vs Rhodium Catalysis

As with its intermolecular counterpart, the intramolecular version of the Buchner reaction tolerates a range of substituents on the aromatic ring ranging from nitro to alkyl with a significant degree of regiocontrol: ortho substitution on the aromatic ring generally tends to direct cyclization away from the substituent. There has been some debate in the literature on the directive effect of an o-methoxy substituent.274,283,299−301 10008


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cycloaddition be observed, will complexation provide protection and diminish or prevent reaction with inherently electrophilic carbenes, or will the enhanced acidity of aryl and benzylic protons activate C−H insertion at these positions?305 The behavior of a pseudo-C2-symmetric N-benzyldiazoacetamide, 108, on exposure to rhodium(II) acetate provided a comparative answer in favor of reaction exclusively at the uncomplexed site with no reaction detected at the complexed site (Scheme 115).

facilitate formation of the norcaradiene core of 109 (Scheme 116).307 In addition to clarifying the effect of various electronwithdrawing groups as α-substituents, it was found that substitution on the aryl component could affect the product obtained from the reaction.308 In most cases, substrates bearing electron-donating groups in the ortho or para position reacted efficiently with low catalyst loadings to produce norcaradienes in moderate to high yields in most cases (Scheme 117).308

Scheme 115. Buchner Reaction of Chromium-Complexed Arenes

Scheme 117. Buchner Reactions of Cyano-Substituted Diazoketones

Reisman and co-workers have conducted a detailed study of intramolecular Buchner reactions with diazocarbonyl substrates possessing electron-withdrawing groups as α-substituents (acceptor/acceptor type) and a four-carbon linker arrangement with a view ultimately to assemble the polycyclic norcaradiene core of the naturally occurring diterpene salvileucalin B (109) (Scheme 116).306,307 This molecule is striking in that it

However, in the case of electron-donating groups in the meta position, the resulting norcaradienes were found to be unstable, rearomatizing easily to benzo-fused cycloheptanones (up to 93% yield) (Scheme 118).308 Substrates bearing electronScheme 118. Buchner Reactions of Cyano-Substituted Diazoketones: Effect of Meta Substitution

Scheme 116. Synthesis of (+)-Salvileucalin B

withdrawing groups on the aromatic ring also produced stable norcaradienes, though less efficiently and generally in lower yields (Scheme 117). An analogous series of α-diazo-βcyanoamides behaved similarly when subjected to rhodium(II) catalysis, forming stable norcaradiene products, though yields were typically lower because of increased formation of carbene dimer products. Reisman’s study is the latest demonstration of the power and versatility of the Buchner cycloaddition reaction in fused- and bridged-ring carbocyclic synthesis. Among other notable examples of intramolecular aromatic cycloaddition reactions is Danheiser’s approach to substituted azulenes.309,310 Defined as a “ring expansion−annulation strategy”, this approach seeks to combine metal-catalyzed cycloaddition with a β-elimination and concomitant enolization to complete the pentaene array so characteristic of the azulene nucleus; it also seeks to address the limitation of many earlier azulene syntheses, namely, the ability to introduce substituents into both the seven- and five-membered rings (Scheme 119). The Sugimura group has devised a rare example of the use of the intramolecular Buchner reaction as a template for an asymmetric synthesis of an acyclic polyketide unit.311,312 The approach is based on the use of an optically active 2,4pentanediol as a chiral auxiliary to act as a stereocontrolling

possesses a stable norcaradiene unit that is geometrically constrained from isomerizing to a cycloheptatriene. Initial studies were carried out using an acceptor-type α-diazocarbonyl substrate bearing a four-carbon linker, and reactions were found to be dependent on the catalyst: Rh(II) catalysts displayed a preference for C−H insertion, while Cu(II) catalysts provided promising levels of aromatic addition.306 Following this, the scope of the study was extended to include α-diazocarbonyl substrates bearing a range of electron-withdrawing αsubstituents. Only the substrate containing the α-diazo-βketonitrile moiety was found to successfully undergo aromatic addition; all others favored C−H insertion. Aromatic addition of the α-diazo-β-ketonitrile was subsequently utilized to 10009


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Scheme 119. Ring Expansion−Annulation

Scheme 122. Synthesis of Harringtonolide (112)

linker in a substrate (110 in Scheme 120) consisting of a benzenoid moiety and a diazocarbonyl reaction center. Scheme 120. 2,4-Pentanediol-Tethered Buchner Reaction

Scheme 123. Synthesis of Gibberellin Derivatives

The intramolecular Buchner reaction has also found great applicability in the area of bicyclic sesquiterpenoid synthesis.313,314 One example involves use of the intramolecular Buchner reaction to synthesize a key intermediate in the formal synthesis of (±)-confertin (111) in the early 1990s (Scheme 121).313 Scheme 121. Formal Synthesis of (±)-Confertin

For example, in reactions involving N-tert-butyl-N-phenethyldiazoacetamides, Rh2(pfb)4 formed exclusively the aromatic cycloaddition product, while Rh2(cap)4 formed the γ-lactam product with only a small amount of the cycloaddition product detected.318 Doyle and co-workers reported competitive pathways for the Rh(II)-catalyzed cyclizations of diazoacetatetype substrates bearing naphthalene-1,8-dimethanol groups.319 In reactions where macrocyclic cyclopropenation or ylide formation (followed by [2,3]-sigmatropic rearrangement) competes with intramolecular aromatic addition, remarkable catalyst-dependent chemoselectivity was observed (Scheme 124 and Scheme 125). McKervey and co-workers reported the first example of enantioselectivity in the intramolecular Buchner reaction in the cyclization of 2-diazo-5-phenylpentan-3-one to the azulenone 113, achieving enantioselectivities up to 33% ee with a rhodium(II) prolinate-based catalyst (Scheme 126).283 Copper bisoxazoline complexes have recently emerged as successful catalysts for intramolecular Buchner reaction of αdiazoketones, obtaining enantioselectivities up to 95% ee (Scheme 127).321 This is the highest enantioselectivity to date reported for this transformation. Further work determined that the presence of additives such as Na(BARF) or K(BARF) enhanced the enantiocontrol of the reaction, particularly in the case of α-diazoketones bearing electron-withdrawing groups in the para position of the aryl ring.322,323

The elegant work of Mander and co-workers has demonstrated the power of the intramolecular Buchner reaction in the construction of highly functionalized polycyclic molecules.315−317 A case in point is the synthesis of the bioactive diterpenoid harringtonolide (112), which contains a cycloheptatrienone ring bearing four contiguous substituents (Scheme 122).317 Additionally, Mander also used a similar strategy in the total synthesis of gibberellin derivatives, where the molecular architecture prevented isomerization of the norcaradiene (Scheme 123).315 High chemoselectivity in intramolecular Buchner reactions has been found to be strongly dependent on the catalyst choice. This has been demonstrated in intramolecular aromatic addition reactions involving α-diazoacetamide-type,318 αdiazoacetate-type,319 and α-diazoketone-type320 substrates. 10010


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Scheme 124. Buchner Reaction vs Ylide Rearrangement

Scheme 127. Enantioselective Copper-Catalyzed Buchner Reaction

discussion below, we will refer to it simply as aromatic substitution or aromatic C−H functionalization. These types of reactions, which can proceed both in an intermolecular and in an intramolecular fashion, are a powerful synthetic tool by which C−C bonds can be formed between two sp2-hybridized carbons under relatively mild conditions. These reactions have been traditionally carried out in the presence of a transition-metal catalyst, usually rhodium or copper,2 and have been found to be dependent on the substrate structure as well as the catalyst used. However, it is probably significant that protonic and Lewis acids have also been found to be catalytically active in many of these aromatic substitutions. The early examples of the reaction were intramolecular in scope,1 but the area of intermolecular aromatic substitution has received increased attention in recent years. Tayama and coworkers reported high yields in the intermolecular reactions of α-diazoesters with N,N-disubstituted anilines (Scheme 128).326 Reactions were carried out in the presence a range of Lewis acid catalysts, and were found to proceed efficiently and with high yields in the presence of Cu(OTf)2.

Scheme 125. Buchner Reaction vs Cyclopropenation

Scheme 128. Copper-Catalyzed Intermolecular Aromatic Substitution Reaction Scheme 126. Enantioselective Rhodium-Catalyzed Buchner Reaction

Recently, gold complexes have emerged as potentially useful catalysts for intermolecular aromatic substitution reactions.327−330 In reactions where one or more reaction pathways are possible, gold catalysts have displayed preferential formation of the aromatic C−H functionalization product in all cases. The group of Diaz-Requejo and Pérez have recently conducted a detailed study of the incidence of aromatic C−H functionalization versus aromatic cycloaddition (Buchner reaction) with benzene and alkylbenzenes using gold-based catalysts, following their discovery that certain gold complexes with N-heterocyclic carbene (NHC) ligands, with the composition (NHC)AuCl, were capable of alkane C−H functionalization with metal carbenes.327,328 These workers found that that the complex IPrAuCl in the presence of Na(BARF) as a halide scavenger promoted the conversion of toluene and ethyl diazoacetate into a 4:1 mixture of aromatic C−H functionalization product and cycloheptatriene product (Scheme 129). Extension of the study to include a range of

3.3.2. Aromatic Substitution Reactions. Reactions of αdiazocarbonyl compounds with aromatic substrates leading to aromatic substitution products is a significant pathway which, depending on the substrate structure, can compete effectively with the aromatic cycloaddition process. In some cases, exclusive aromatic substitution is observed, while in others mixtures of products are formed. Although incorrectly termed C−H insertion, the process differs mechanistically from aliphatic C−H insertion in that aromatic C−H insertion is believed to involve formation of a zwitterionic intermediate from electrophilic addition of a metal carbene to the aromatic ring and a subsequent rapid proton transfer.324,325 In the 10011


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styryldiazoacetates and the proline-based Rh2((S)-DOSP)4.332 The overall process constitutes a C−H functionalization resulting in cyclopentannulation of the indole ring with high levels of asymmetric induction (up to 99% ee). Two typical examples are shown in Scheme 132.

Scheme 129. Gold-Catalyzed Reaction of EDA with Toluene

Scheme 132. C−H Functionalization Resulting in Cyclopentannulation

Au(I) and Au(III) complexes revealed that Au(III) complexes bearing IPr or SIPr ligands provided exclusively the aromatic C−H functionalization product. The conclusion drawn from these studies was that the process involved electrophilic addition of a metal carbene intermediate to the aromatic ring followed by a 1,2-proton migration. Zhang and co-workers reported a gold-catalyzed, highly chemoselective, and high-yielding reaction between α-diazoesters and phenols (Scheme 130).330 What is remarkable about Scheme 130. Gold-Catalyzed Aromatic Substitution Reactions of Unprotected Substituted Phenols

A general Rh-catalyzed method of enantioselective C−H functionalization of indoles was later described by Fox and coworkers using α-alkyl-α-diazoacetates with a range of substituted indoles and a tert-leucine-based rhodium catalyst, Rh2((S)-NTTL)4.333 High yields (82−96%) and enantioselectivities (79−99% ee) were obtained for a range of substituted indoles. It was found that use of a low temperature (toluene at −78 °C) was essential for optimal chemical yields and enantioselectivities (Scheme 133). Scheme 133. Enantioselective C−H Functionalization of Indoles this reaction is that no O−H insertion reaction is observed for the phenolic substrates. This is the first example of aromatic substitution reactions of unprotected phenols with diazo compounds. Among other examples of intermolecular aromatic C−H functionalization are Li and co-workers’ rhodium(III)-catalyzed reactions of diazocarbonyl compounds with aromatics bearing azacycle directing groups. The range of azacycle directing goups included pyrazoles, pyrimidines, and oxazoles (Scheme 131).331 C−H functionalization of indoles using metal carbenes derived from diazocarbonyl substrates has attracted recent attention. Davies and co-workers were among the first to develop an enantioselective version of indole alkylation using

The intramolecular aromatic substitution reaction has been more extensively investigated than its intermolecular counterpart. It represents a versatile method of annulation of a benzene nucleus and has much appeal in medicinal heterocyclic chemistry. A number of successful reactions involving formation of [6,5]-bicyclic systems have been reported, allowing formation of both carbocyclic and heterocyclic systems such as indanones,334 oxindoles,335−340 benzofuranones,341 and sultams.342 Formation of other bicyclic systems, such as [6,6]bicycles, is possible; however, competition between reaction pathways may occur in such cases.343−345 Hu and co-workers have reported on the preparation of nitrogen- and oxygencontaining [6,6]-bicyclic compounds via this route. In relation to the nitrogen-based heterocycles, it was found the reaction chemoselectivity was dependent on the transition-metal catalyst used, with rhodium-based catalysts selectively forming the

Scheme 131. Catalyzed Azacycle-Directed Intermolecular Aromatic C−H Functionalization

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Traditionally, intramolecular aromatic substitution reactions have been carried out in the presence of rhodium(II) or copper catalysts. However, in recent times other metals have emerged as potentially useful catalysts for this type of transformation, although, in most instances, these catalysts have seen themselves restricted to certain diazocarbonyl substrates. Rhodium,326,335,347 copper,339 ruthenium,338 and silver337 catalysts have all found applicability in reactions involving αdiazo-β-ketoanilides forming [6,5]-bicyclic products. A titanium complex has also recently been reported as a successful catalyst for these types of substrates.340 The reactions were found to proceed efficiently, resulting in oxindoles in both high yields and high enantioselectivities (Scheme 137). Mechanistically,

aromatic substitution product, while silver-based catalysts promoted Wolff rearrangement (Scheme 134).344 The Scheme 134. Wolff Rearrangement vs Aromatic C−H Functionalization

Scheme 137. Titanium BINOLate-Catalyzed Enantioselective Intramolecular Aromatic C−H Functionalization

reactions of α-diazo-β-ketoesters leading to 4-carbonylchromane derivatives were also investigated, and were found to be more selective than their nitrogen-based counterparts, achieving yields up to 97%. These reactions were found to be dependent on catalyst selection, and displayed some sensitivity to substitution of the aromatic ring (Scheme 135).345 Scheme 135. Rhodium(II)-Catalyzed Aromatic Substitution Reactions of α-Diazo-β-ketoesters

this reaction is believed to proceed differently from the accepted aromatic substitution reaction, although the product formed is the same. It is believed that the reaction is initiated by enantioselective protonation of the α-carbon followed by the intramolecular electrophilic aromatic substitution, with the TiBINOLate complex acting as a chiral Lewis acid-assisted Brønsted acid. The intramolecular aromatic substitution has also been applied to natural product synthesis.348−350 For example, Stoltz and co-workers reported selective aromatic substitution reaction as a key step in the total synthesis of (+)-amurensinine (115) (Scheme 138).350 As with other diazocarbonyl reaction types, three-component reactions initiated by aromatic functionalization have also begun to emerge. Hu and co-workers reported the first asymmetric functionalization of aromatic C−H bonds through a three-component reaction of N,N-disubstituted anilines with α-diazoesters and imines in the presence of Rh(II)/chiral phosphoric acid cocatalysts. The presence of the imine as the third component in this reaction allows it to participate as a reactive electrophile and trap the zwitterion intermediate formed through electrophilic addition of the metal carbene to the aromatic ring. The densely substituted β-aminoester products were formed with high enantio- and diastereoselectivities in most cases (Scheme 139).324 The three-component approach has also been used by the Hu group to effect C−H alkylation of several indoles and oxindoles, again using imines as the electrophilic trap in a highly efficient, integrated rhodium/chiral Bronsted acidcocatalyzed approach.351 For the oxindole synthesis, the five-

Intramolecular aromatic substitution has been used to construct isoquinolines by Jung and co-workers. The challenge here was to construct a six-membered ring while avoiding competition by cycloheptatriene formation via Buchner reactions (Scheme 136).346 The reaction was found to be heavily influenced by the α-substituent; in cases where sulfonyl or phosphoryl groups were present as α-substituents, exclusive aromatic substitution was observed. Scheme 136. Effect of the α-Substituent

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Scheme 138. Synthesis of (+)-Amurensinine

Scheme 140. Oxindole Formation via C−H Functionalization/Trapping Reactions

Scheme 139. Trapping of Zwitterionic Intermediates Formed by Rh(II)-Catalyzed Intermolecular Aromatic Substitution Reactions

Scheme 141. Enantioselective Intermolecular C−H Functionalization of Indoles

membered heterocyclic component was constructed in situ from N,N-disubstituted diazoacetamides via a rhodium(II)catalyzed intramolecular C−H functionalization leading to a zwitterion intermediate which in the presence of the cocatalystactivated imine proceeded to the ultimate product. Rhodium acetate was selected as the catalyst for the carbene initiation step, and several chiral PPAs were screened to catalyze the imine activation. The preferred combination of reactants is shown in Scheme 140. A similar strategy was next applied to the formation of 3-substituted indoles by intermolecular C−H functionalization of native indoles using phenyldiazoacetates and a PPA-activated imine again using rhodium(II) catalysis (Scheme 141). 3.4. Catalytic Asymmetric C−H Insertion Reactions

The area of C−H insertion has been extensively reviewed in recent years,352−363 and therefore, this review focuses only on a selection of examples to demonstrate the continuing expansion of this important area of diazocarbonyl compound chemistry. As the majority of reports since the early 1990s have concerned enantioselective C−H insertion reactions, this topic is the primary focus of this section. Early work in this area was 10014


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conducted by Taber and Wenkert, who demonstrated that C− H insertion reactions may occur with high levels of regio- and diastereoselectivities.364−371 A number of key trends were identified during these initial studies: reactions proceed with a high propensity for trans-substituted five-membered ring formation,364,366,371 with retention of configuration,372 and with reactivity generally following the order of tertiary > secondary ≫ primary.365 Highly diastereoselective insertions were also described for reactions employing enantiomerically pure β-ketoesters369,370 and β-ketoesters with chiral auxiliaries.367,368 A common side reaction in C−H insertion processes is β-hydride elimination, and it has been demonstrated that the use of Rh2(tfa)4 can encourage this pathway, leading to a useful synthesis of Z-α,β-unsaturated ketones and esters.373 Since these early developments in the area, numerous examples of substrate-controlled intramolecular C−H insertion reactions have been reported in the literature. Selected recent examples in natural product syntheses include kainic acids such as (−)-α-allokainic acid (117) and (−)-α-kainic acid (118),374 bakuchiol (119),375 and (−)-cameroonan-7-α-ol (120) (Scheme 142, Scheme 143, and Scheme 144).376

Scheme 144. Synthesis of (−)-Cameroonan-7-α-ol (120)

Scheme 145. Formation of Arylcyclohexanone in Preference to Arylcyclopentanone

Scheme 142. Synthesis of Kainic Acids 117 and 118

3.4.1. Intramolecular C−H Insertion Reactions. The first examples of catalyst-controlled asymmetric induction in C−H insertion processes were reported independently by the groups of Hashimoto and Ikegami380 and McKervey381 in 1990. Both studies employed chiral rhodium(II) carboxylate catalysts formed from N-protected amino acids, with 12% ee recorded by McKervey for insertion of an α-diazo-β-ketosulfone substrate and 24% ee obtained by Hashimoto and Ikegami for C−H insertion with a related α-diazo-β-ketoester. Later work by Hashimoto and Ikegami demonstrated that increased levels of enantiocontrol may be achieved by the following means: through insertion into benzylic sites, through use of substrates possessing sterically bulky ester alkoxy groups, and by decreasing the electron density at the target C−H bond.382,383 In 2001, Lahuerta and co-workers examined the C−H insertion reactions of terminal α-diazoketones, and reported moderate to good asymmetric induction for cyclopentanone synthesis in the presence of orthometalated arylphosphine catalysts.384 Hashimoto and co-workers have also reported the highly enantioselective synthesis of 1,2disubstituted cyclopentanes for reactions catalyzed by the tertleucinate-derived carboxylate Rh2((S)-PTTL)4 and a polymersupported version of Rh2((S)-PTTL)4.385,386 Doyle’s chiral rhodium(II) carboxamidate catalysts have shown exceptional success in the asymmetric synthesis of lactone products. Early studies in this area demonstrated the ability of Rh 2 (MEPY)4 to provide enantioenriched γbutyrolactones (up to 90% ee). 387 A wide range of carboxamidate species have since been proven effective for intramolecular C−H insertions with diazoacetates. In particular, Rh2(MPPIM)4 has shown great success for the cyclization of simple alkyl diazoacetates with high levels of enantioselectivity, and as a result, this catalyst has been employed in the total synthesis of a number of natural lignan lactones,388 the necine

Scheme 143. Synthesis of Bakuchiol (119)

Taber and co-workers have also shown that, in favorable cases, α-aryldiazoketones will cyclize to form cyclohexanones in preference to cyclopentanones, due to the more electronically discriminating nature of the derived metal carbenes, when compared with carbenes derived from α-diazoesters (Scheme 145).377 The formation of six-membered rings by C−H insertion has also been reported in specific cases, and in cases where five-membered ring formation is not possible.378,379 10015


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base (−)-turneforcidine,389 and the platelet-aggregration inhibitor (S)-(+)-imperanene (121) (Scheme 146).390

Scheme 148. Synthesis of (+)-Conocarpan

Scheme 146. Synthesis of (S)-(+)-Imperanene (121)

The imidazolidinone catalyst Rh2(MACIM)4 has emerged as the optimal catalyst for C−H insertion reactions of tertiary alkyl and cycloalkyl diazoacetates, outperforming alternative rhodium(II) carboxamidates in terms of overall regio-, diastereo-, and enantiocontrol.391−393 The production of βlactone products has also been described for the C−H insertion reactions of phenyl diazoacetates, albeit with lower levels of enantioselectivity (up to 63% ee) than those typically observed for γ-lactone synthesis.394 This methodology has been successfully applied to the C−H insertion reactions of steroidal diazoacetates.395 The enantioselective construction of additional oxygencontaining heterocyclic species via intramolecular C−H insertion has also been described. In 1992, McKervey and Ye reported the first application of C−H insertion chemistry for the asymmetric synthesis of chromanones from α-diazoketone precursors, with up to 82% ee achieved (Scheme 147).396

and (−)-serotobenine,403 although in these studies chiral auxiliaries were used to achieve preferential formation of the trans isomer during the C−H insertion step. Early studies examining the enantioselective synthesis of nitrogen-containing heterocycles were conducted by Doyle and co-workers. The production of both β- and γ-lactam products was shown to be possible for the intramolecular reactions of various diazoacetamides, with the product distribution dependent on both the catalytic species employed and the nature of the diazo substrate.404 Moderate to good levels of enantiocontrol were recorded for these initial investigations, with Rh2((S)MEOX)4 generally found to provide superior asymmetric induction compared to Rh2((S)-MEPY)4. While the production of five-membered ring products is typically favored in C−H insertion chemistry, β-lactam formation is observed in many instances due to the activating effect of the nitrogen atom adjacent to the C−H insertion site. In particular, diazo substrates possessing an N-tert-butyl group or an N,O-acetal moiety have shown a propensity toward βlactam formation in studies employing both achiral and chiral rhodium catalysts.405−410 This trend has been exploited by Hashimoto and co-workers for the production of key intermediates in the synthesis of carbapenem (Scheme 149)410 and trinem (Scheme 150)409 antibiotics.

Scheme 147. Asymmetric Synthesis of Chromanones

The synthesis of dihydrobenzofuran products has been investigated by the groups of Hashimoto,397 Corey,398 and Davies,399,400 with a range of rhodium(II) catalysts, primarily carboxylate species. Good levels of enantiocontrol were obtained (up to 96% ee) for the C−H insertion reactions of various aryldiazoacetates. In 2009, this methodology was successfully employed by Hashimoto and co-workers for the asymmetric synthesis of the neolignans (−)-epi-conocarpan (123) and (+)-conocarpan (122) (Scheme 148).401 In this work the newly developed rhodium(II) carboxylate complex Rh2((S)-PTTEA)4 was found to be the catalyst of choice, providing 2-aryl-5-bromo-3-(methoxycarbonyl)-2,3-dihydrobenzofuran with excellent diastereoselectivity [97% de (cis)] and high enantioselectivity for the cis isomer (84% ee). A similar synthetic strategy has also been adopted by Fukuyama and co-workers for the total syntheses of (−)-ephedradine402

Scheme 149. Synthesis of Carbapenem Antibiotics

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Scheme 150. Synthesis of Trinem Antibiotics

Scheme 152. Copper-Catalyzed Thiopyran and Cyclopentanone Formation

The same research group has also reported the enantioselective synthesis of the phosphodiesterase type IV inhibitor (R)-(−)-rolipram via intramolecular C−H insertion.411 In this study, the benzene-fused rhodium(II) carboxylate Rh2((S)BPTTL)4 was found to be the catalyst of choice, providing the desired γ-lactam product in good yield and with high levels of enantiocontrol. The effectiveness of the N-bis(trimethylsilyl)methyl (N-BTMSM) group as a conformational control element for the C−H insertion reactions of tertiary diazoamides has been demonstrated by Wee and co-workers.412−415 It was found that use of BTMSM as a nitrogen protecting group provided superior results in terms of chemo-, regio-, and enantiocontrol over alternative groups such as NCHPh2.414 In addition, the N-BTMSM group may be easily removed in subsequent synthetic steps, allowing for employment of this chemistry in total synthesis (Scheme 151).412,414

copper bisoxazoline−Na(BARF) catalyst system was very recently applied to intramolecular C−H insertion reactions of 2-sulfonyl-2-diazoacetamides, resulting in the formation of trans-γ-lactams in a highly chemoselective and regioselective manner. High yields (∼70−90%) and moderate to high enantioselectivities (up to 82% ee) were also observed.419 3.4.2. Intermolecular C−H Insertion Reactions. While early reports do exist of intermolecular carbenoid C−H insertions employing achiral rhodium catalysts,420−423 these reactions were generally not regarded as synthetically useful owing to poor regioselectivities and high levels of competing dimer formation.2 In the late 1990s, Davies and co-workers reported that highly chemo- and regioselective intermolecular C−H insertions could be achieved for reactions of donor/ acceptor-type carbenoids.424 In addition to excellent chemoand regiocontrol, high levels of enantioselectivity could also be achieved for these reactions through use of the chiral rhodium(II) tetraprolinate catalyst Rh2((S)-DOSP)4 (Scheme 153). Since this initial publication,424 numerous examples of highly enantioselective intermolecular C−H insertions employing Rh2((S)-DOSP4) have been reported by the Davies group, including complementary reactions to several classic C−C

Scheme 151. Use of the N-BTMSM Protecting Group

Scheme 153. Use of Rh2(DOSP)4 for Intermolecular C−H Insertion While rhodium catalysts have dominated the field of asymmetric C−H insertion over the past two decades, examples do exist of the application of copper complexes in this area. Indeed, in some instances copper catalysts can outperform their rhodium rivals in terms of enantiocontrol, as demonstrated by Lim and Sulikowski in a study examining the synthesis of 1,2disubstituted mitosenes.416 Recently, the synthetic utility of copper complexes for achieving highly enantioselective intramolecular C−H insertions with α-diazosulfones has been demonstrated by Maguire and co-workers.323,417,418 In this work thiopyran and cyclopentanone products were prepared in up to 98% and 91% ee, respectively (Scheme 152), representing the highest levels of enantiocontrol reported to date for copper-catalyzed C−H insertion. Reactions were conducted in the presence of various copper salts and bisoxazoline ligands, with the addition of an additive species such as Na(BARF) or K(BARF) found to be critical for achieving highly enantioselective insertions. The 10017


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bond-forming reactions such as the aldol reaction,425−427 the Claisen rearrangement,428 the Mannich reaction,429 the Michael reaction,430 and the Claisen condensation,431 and examples of selective insertion into primary432−434 and tertiary435 C−H bonds. In addition, this methodology has been applied as the key C−C bond-forming step in several syntheses of natural products and compounds of pharmaceutical interest such as (−)-α-conidendrin (125), (+)-imperanene (121), and (S)venlafaxine (126) (Scheme 154).432,434,436−440

Scheme 155. Tandem C−H Insertion/Cope Rearrangement Applied to Synthesis

Scheme 154. Intermolecular C−H Insertions in Total Synthesis

combined C−H insertion/Cope rearrangement has recently been applied as a surrogate reaction for the vinylogous Mukaiyama aldol reaction, producing a range of 1,2disubstituted alkene products in high yield (67−89%) and with excellent enantioselectivity (93−99% ee).444 Additional rhodium catalyst species, including Rh2((S)biDOSP) 4 ,439 Rh 2 ((S)-biTISP) 4 , 429 Rh 2 ((S)-MEPY) 4 , 445 Rh 2 ((S)-PTTL) 4 , 4 4 6 an d rho dium(II ) ( S)-N -((nperfluorooctyl)sulfonyl)prolinate,447 have also been applied to intermolecular C−H insertion reactions, providing high levels of enantiocontrol in many instances. In 2007, Fraile and co-workers reported the first successful application of chiral copper bisoxazoline and azabisoxazoline catalysts for enantioselective intermolecular C−H insertion.448 Interestingly, the reaction of methyl phenyldiazoacetate and tetrahydrofuran proceeded with good enantiocontrol (up to 88% ee) only for catalysts immobilized onto Laponite clay. This study was later extended to include a wider range of ether substrates, with the immobilized copper complexes again outperforming their homogeneous counterparts in terms of enantioselectivity in the majority of cases examined.449 Recently, Fraile and co-workers have also reported the use of copper catalysts supported on silica or silica−alumina for

In 1999, Davies and co-workers observed a novel reaction pathway during studies toward the synthesis of 4,4-diarylbutanoates.86 The reaction of vinyldiazoacetates and cyclohexadienes did not undergo predicted C−H insertion but instead was found to proceed via a formal combined C−H insertion/Cope rearrangement, with high levels of enantiocontrol recorded (84−99% ee). The synthetic utility of this novel transformation has since been demonstrated by its utilization in formal asymmetric syntheses of the antidepressant (+)-sertraline,86 the diterpene natural products (−)-colombiasin A (128),441 (−)-elisapterosin B (127) (Scheme 155),441 (+)-elisabethadione,442 and (+)-erogorgiaene,443 and a series of selective monoamine reuptake inhibitors.440 Additionally, the 10018


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diazomethane and produces α-haloketone building blocks in a multistep synthesis in excellent yields. Of the many X−H combinations, N−H and O−H insertion reactions have been the most studied and the most highly developed. Much improvement has occurred during the past two decades in the efficacy of these insertion reactions catalyzed by transition metals, and there now exists a large family of reactions involving various nitrogen and oxygen base functionalities. The full potential of these processes in organic synthesis has become recognized only recently. Not only has the trend to increase the complexity of the diazocarbonyl substrates become more challenging, requiring greater levels of chemo- and regioselectivities, but there has been a concomitant expansion of the range of catalytically active metals accessible. Furthermore, the ability to incorporate asymmetric synthesis and enantioselectivity into several of these processes has finally been raised to synthetically competitive levels. This is particularly significant for N−H and O−H insertion reactions when one considers the importance of these functional groups in modern organic synthesis. An exception to the general perception that O−H insertion of carboxylic acids with diazocarbonyl substrates usually requires metal or Lewis acid catalysis has been described by Crousse and co-workers, who found that such reactions could occur smoothly at room temperature in fluorinated alcohols as solvent in the absence of metal salts.454 These workers established that ethyl diazoacetate is stable in hexafluoroisopropyl alcohol (HFIP) or trifluoroethanol (TFE) at room temperature or at reflux, showing no decomposition, dimerization, or Wolff rearrangement. However, addition of a carboxylic acid causes rapid reaction with formation of an acetoxyester in excellent yield (Scheme 158). That the role of

intermolecular C−H insertion reactions, with up to 59% ee achieved for the insertion of methyl phenyldiazoacetate in tetrahydrofuran.450 In recent years, the choice of transition-metal catalysts for enantioselective intermolecular C−H insertion has been extended to include iridium complexes.451,452 Both iridium(III) salen and porphyrin catalyst complexes have been successfully applied to intermolecular C−H insertion reactions involving αdiazoacetates. 3.5. X−H Insertion Reactions of Diazocarbonyl Compounds

In our earlier review, we defined reactions of diazocarbonyl compounds in which the diazo function is replaced by two new substituents, X and Y, as α,α-substitution (Scheme 156).1 Scheme 156. α,α-Substitution, or X−Y Insertion

Although the term accurately summarizes this chemical change, the alternative description of X−Y insertion has become more widely accepted, and we shall adopt the latter in this discussion. By far the most significant combinations of new substituents are when X is a hydrogen atom and Y a heteroatom (O, N, S, Si, P, Hal) or heteroatom-based group (the category of C−H insertion is reviewed in section 3.4). There is a less extensive group of X−Y insertion reactions where neither X nor Y is a hydrogen atom, e.g., molecular halogen.453 Although the adduct produced by H−X insertion is formally the result of insertion of a carbene into the H−X bond, mechanistically there probably exists a broad spectrum of processes ranging from uncatalyzed electrophilic attack on the diazocarbonyl group to catalyzed metal carbene formation leading to either concerted H−X insertion or ylide formation between a heteroatom and a metal carbene in situations where metal catalysis is employed. There is a consensus that ylide formation is the more common pathway; only under thermolytic or photolytic conditions are free carbenes likely to be implicated. The X−H insertion processes of recent significance have involved hydrogen halides, amines, alcohols, including water, and carboxylic, sulfur-based, and phosphorus-based acids. Not all of these processes require external catalysis, a notable case in point being the reaction of diazoketones with hydrogen chloride to form α-chloroketones which Kappe and co-workers have recently developed into a fully continuous process allowing the synthesis of α-chloroketones without racemization from the respective N-protected amino acids,25 illustrated in Scheme 157 for a phenylalanine derivative. This continuous process eliminates the need to store, transport, or handle

Scheme 158. Metal-Free O−H Insertion in Fluorinated Alcohol Solvents

fluorinated alcohols was unique in promoting this reaction was established by the observation that other solvents, notably dichloromethane, diethyl ether, and ethanol, were completely ineffective. This O−H insertion reaction was equally effective with a range of carboxylic acids, including aromatic acids and amino acids, producing (acyloxy)esters in 75−98% yields; it was also successful with sulfonic, phosphoric, and boronic acids. 3.5.1. N−H Insertion Reactions. 3.5.1.1. Intermolecular N−H Insertion with Amines. The thermal decomposition of ethyl diazoacetate in the presence of aniline to form Nphenylglycine ethyl ester (Scheme 159) is one of the earliest reactions recorded for a diazocarbonyl compound. The introduction of copper catalysis increased awareness of the potential of this reaction as an example of a N−H insertion process with applications to the synthesis of amino acids. The

Scheme 157. Formation of an α-Chloroketone via a Diazoketone

Scheme 159. Intermolecular N−H Insertion Reaction of Aniline

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alkanediones to an extent that could be controlled by the ratio of the reactants. For example, a 1:1 ratio of 2-diazo-1,3cyclohexanedione and m-cyanoaniline furnished a mixture of the monoinsertion product and the bisinsertion product in about equal amounts; a 2:1 ratio in favor of the diazo partner gave largely the bisinsertion product. Subsequent treatment of the bisinsertion product with ammonium acetate followed by sodamide produced the tricyclic dihydropyrazine (Scheme 161) The N−H insertion route has been proposed as a solution to the general problem of synthesizing triarylamines and arylalkylamines. This approach, due to Livant and co-workers,457 is based on the union of a diaryl- or arylalkylamine and a diazocyclohexanedione, the latter providing the additional aryl ring via an aromatization reaction. These workers found that, under rhodium(II) catalysis, 2-diazo-1,3-cyclohexanedione undergoes N−H insertion with a range of disubstituted amines to produce adducts in which the cyclohexane moiety could be aromatized subsequently. In general, the insertion process was performed with neat amine if this reactant was a liquid at room temperature. The most effective aromatization procedure involved conversion of the N−H insertion adduct into an enol silyl ether (not isolated) which underwent dehydrogenation on exposure to the palladium reagent Pd(CH3CN)2Cl2 (Scheme 162). By its nature, the new aryl ring amine must be trisubstituted.

earliest studies employed aniline as the preferred substrate and various copper salts as catalysts. Although aniline remains the most popular choice for exploring new catalysts and new diazocarbonyl substrates, the range of N−H-containing substrates has since been expanded to include substituted anilines, alkylamines, amides, carbamates, indoles, sulf inimines, hydrazides, ureas, imines, and peptides. Very recently, N−H insertion has been used to effect bioconjugation via selective alkylation of nucleic acids, peptides, and proteins using several diazoesters. However, the first successful N−H insertion with ammonia, the simplest of all nitrogen sources, was not reported until 2006 when Aviv and Gross found that iron porphyrins were excellent catalysts for the insertion of ammonia into ethyl diazoacetate.455 Using gaseous ammonia as the nitrogen source, the product consisted of the glycine ester and the tripleinsertion product, whereas, using ammonium acetate, the latter product was obtained exclusively (Scheme 160). Scheme 160. Intermolecular N−H Insertion of Ammonia/ Ammonium Acetate

Scheme 162. N−H Insertion and Subsequent Aromatization

Generally speaking, rhodium(II) salts have emerged as the most studied catalysts for the promotion of these reactions. However, there have been several recent reports of the generation of reactive metal carbenes with other metals that are more readily available than rhodium, such as silver, ruthenium, cobalt, palladium, iron, copper, and scandium. These metals are capable of accessing synthetically useful challenging or privileged structural motifs. As with most diazocarbonyl reactions, both intermolecular and intramolecular versions are known. Aspects of intermolecular N−H insertion with aniline continue to attract attention, frequently either to evaluate the efficacy of new catalyst systems or to access novel structures with potential in medicinal chemistry. An example of the latter is the recent work of Zhang and Sui on the production of novel tricyclic 1,4-dihydropyrazines (Scheme 161).456 These workers found that rhodium(II) acetate catalyzed the reaction of anilines with 2-diazo-1,3-cyclo-

The vast majority of published studies of catalyzed N−H insertion reactions relate to diazoesters and diazoketones. Much less attention has been given to other diazo substrates, e.g., diazoamides, which offer attractive direct routes to αaminoamides. Iwasa and co-workers have developed an efficient protocol for the synthesis of a wide range of α-aminoamides from amines, including aniline, and diazoacetamides using ruthenium(II) pheoxazoline catalyst 129.458 A limited catalyst screen revealed that the ruthenium complex was marginally superior to rhodium(II) acetate and copper iodide; the process worked efficiently with electron-withdrawing and electrondonating arylamines and simple secondary amines such as dibenzyl- and dipropylamine, and in a range of solvents including water, affording the insertion products in 48−97% yield (Scheme 163). Notwithstanding this growing emphasis on metal catalysis, there have been notable recent successes with purely thermal or photochemical decomposition. For example, Davies and coworkers have demonstrated metal-free, thermal N−H insertion with aryldiazoacetates and a range of primary and secondary aliphatic amines and arylamines in trifluorotoluene, a solvent chosen for its inertness toward reactive carbene intermediates.459 Aryldiazoacetates act as precursors for thermally generated donor/acceptor carbenes which undergo direct N−

Scheme 161. Intermolecular N−H Reaction of mCyanoaniline

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Scheme 163. Ru(II)-Catalyzed Intermolecular N−H Insertion

Scheme 165. Organocatalyzed N−H Insertion

as a carbon nucleophile. The proposed catalytic cycle is shown in Scheme 166. H insertion with amines via transient aza-ylide intermediates to afford a variety of α-aminoesters (Scheme 164).

Scheme 166. Proposed Catalytic Cycle of Organocatalyzed N−H Insertion

Scheme 164. Thermal N−H Insertion Reactions of Aryldiazoacetates and Amines

Very recently, the possibility of using an organocatalytic approach to N−H insertion has been realized. The success of this approach is essentially based on the use of intermolecular, noncovalent bonding to promote diazo decomposition and ultimately coupling. Mattson and co-workers demonstrated this idea very nicely through the use of hydrogen bonds to activate the α-nitrodiazoester 130 in the presence of the urea catalyst 131 (Scheme 165).460,461 The ability of ureas to recognize nitro groups through intermolecular hydrogen bond interactions forms the basis of a new catalytic process, termed hydrogen bond donor (HBD) activation, which exploits the urea nitro group recognition to facilitate the loss of nitrogen gas and thereby generates a reactive intermediate capable of N−H insertion. These authors made the initial observation that α-nitro-α-diazoesters such as 130 and aniline in the presence of 20 mol % 131 in toluene yielded the α-amino-α-arylester 132. Since the product did not contain a nitro group, they concluded that the initial product of N−H insertion was unstable to the reaction conditions and was converted into the observed product via nucleophilic displacement of the NO2 group by a second molecule of aniline acting

Overall, the process constitutes an HBD-catalyzed, twocomponent coupling of an aniline and an α-nitro-α-diazoester, with the aniline providing both the initial N−H insertion partner and the subsequent carbon-based nucleophile. Mattson was subsequently able to develop the process into a threecomponent coupling through the use of one amine for the N− H insertion stage and a different nucleophilic amine for the second stage capable of providing access to a wide range of αaminoesters in excellent yield (Scheme 167). An organocatalytic system in the form of a cinchona alkaloid has recently been used by Miyairi and co-workers to promote N−H insertion of anilines into phenyldiazoacetates in a thermally induced reaction.462 A typical example is illustrated in Scheme 168. The additional fact that the product was formed with modest enantiocontrol confirmed that the alkaloid was involved, at least in part, in the insertion process. This suggests that the thermally produced carbene formed an ammonium ylide with 10021


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Scheme 167. Examples of α-Aminoesters Prepared via Three-Component Coupling

Scheme 169. Combined Rh(II)-SPA-Catalyzed N−H Insertion

Scheme 168. Cinchona Alkaloid-Induced Asymmetry in Thermal N−H Insertion Reactions

transition-metal catalysts. Wang and co-workers have developed this idea very successfully for the combination of C−N bond formation via catalytic N−H insertion and catalytic alkyne hydroamination using a single copper-based catalyst.464 A phenyldiazoacetate analogue bearing an o-alkynyl group was chosen as a suitable substrate. In the event, the (oalkynylphenyl)diazoacetate 134 was subjected to tetrakis(acetonitrile)copper(I) hexafluorophosphate in the presence of aniline to yield isoindole 135 in 90% yield (Scheme 170).

aniline which underwent a [1,2]-proton shift assisted by intermolecular hydrogen bond formation with dihydrocinchonine (Scheme 168). Interestingly, a degree of cooperative catalysis was observed when the reaction was conducted in the presence of dihydrocinchonine (1 mol %) and rhodium trifluoroacetate (1 mol %) inasmuch as the product yield increased to 90% though the extent of chiral induction remained unchanged. The increase in chemical yield was believed to be due to suppression of the carbene dimer in favor of product formation by the metal catalyst. That the metal catalyst had no effect on the extent of chiral induction was taken as evidence for no involvement of the metal in the proton transfer process. The concept of cooperative catalysis has been successfully applied to N−H insertion processes by Zhou and co-workers, who combined rhodium carboxylates with chiral spiro phosphoric acids (SPAs) to produce an entirely new type of N−H insertion catalyst system.463 These workers, working on the assumption that rhodium-catalyzed reaction most likely proceeds via an ylide intermediate (Scheme 169), proposed that the subsequent proton transfer process could be facilitated by an SPA, leading to chiral induction in the product. Thus, reaction of methyl α-diazo-α-phenylacetate and tert-butyl carbamate as the N−H donor using rhodium triphenylacetate [Rh2(tpa)4] and chiral SPA 133 as the catalyst combination led to rapid formation of the N−H insertion product with 92% ee. An emerging area of research within the field of N−H insertion involving diazocarbonyl substrates is the development of reaction systems in which a single catalyst mediates two or more different reactions in tandem in a chemoselective manner. Such a kind of sequential or concurrent catalysis is particularly attractive in synthesis given the potential of many different reactions that can be catalyzed by the same or similar

Scheme 170. Combined N−H Insertion and Alkyne Hydroamination

The N−H Insertion step of this two-stage process occurred efficiently for a range of substituted anilines. Both p-NO2- and p-MeO-substituted anilines produced isoindole products in excellent yield. However, with aliphatic amines as substrates, only trace amounts of products were formed. Other copper catalysts were effective in promoting reaction, but none was found to be as effective as [Cu(MeCN)4]PF6. Although the use of two catalytic reactions in tandem employing a single catalyst must be considered the ideal combination, the alternative of two catalytic reactions employing two different catalysts is also an option providing the catalysts are compatible to the extent that they can be employed in a one-pot process. The combination of a catalytic reaction and a thermal process is also an option. Examples of both these processes have been published. Catalytic N−H insertion and ring-closing metathesis have been used in tandem to produce a range of nitrogen heterocycles. McMills and co-workers have demonstrated that several five- to eight-membered nitrogen heterocycles can be prepared by an efficient one-pot, two-component sequence featuring rhodium(II)-catalyzed N−H insertion of vinyl10022


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substituted α-diazocarbonyls into Boc-protected amines followed by ring-closing metathesis catalyzed by Grubbs or Hoveyda−Grubbs second-generation catalysts (Scheme 171).465

Scheme 173. Tandem N−H Insertion and Diels−Alder Reaction

Scheme 171. Two-Component N−H Insertion and RingClosing Metathesis

produced from diazocarbonyl intermediates and amines under metal catalysis, could be intercepted by external electrophiles before intramolecular [1,2]-proton transfer occurs, leading to stable N−H insertion products, has proved to be a very productive way of generating numerous polyfunctional molecules. The challenge is to trap irreversibly the highly reactive ammonium ylide intermediate with a third electrophilic component and thereby prevent its neutralization of charge by fast proton transfer. There is a growing list of this type of threecomponent combination of diazocarbonyl, amine, and electrophile, often classed as multicomponent reactions (MCRs). The range of electrophiles that have been found to function in MCRs include aldehydes, imines, Michael acceptors, alkynals, and α-dicarbonyls. For example, Doyle, Hu, and co-workers studied the rhodium-catalyzed reaction of phenyldiazoacetate in the presence of an arylamine and an imine.468 It was already known that catalyzed reaction of diazoacetate with imines led to aziridines via an iminium ylide intermediate. The addition of an arylamine to this combination produced a three-component reaction resulting in the formation of an ammonium ylide from arylamine and diazoacetate, followed by product formation through two competitive reaction pathways: (A) [1,2]-hydrogen shift giving the normal N−H insertion product and (B) nucleophilic addition to imine to form a diamine (Scheme 174). Related examples of three-component reactions involving an amine, a diazocarbonyl substrate, and an azodicarboxylate have

Among other successful examples of one-pot, twocomponent sequences initiated by N−H insertion is the Moody synthesis of indoles (Scheme 172).466 This synthesis Scheme 172. Combined N−H Insertion and Bischler Cyclization

combines the rhodium-catalyzed N−H insertion of Nmethylaniline with the Bischler cyclization of the resulting α(N-arylamino)ketone intermediates. Initially it was hoped that the Lewis acidic nature of rhodium(II) carboxylates would effect both transformations in a single operation in one pot, but this proved not possible, and although rhodium acetate did satisfactorily catalyze the N−H insertion step, copper(II) trifluoroacetate proved to be generally more efficient with respect to yields of α-(N-arylamino)ketone intermediates. The optimized conditions for cyclization proved to be acidic Amberlyst resin in hot toluene, which produced indoles in 30−81% yield. Moody and co-workers have explored the combination of N−H insertion leading to 1,2,4-triazines with thermal Diels− Alder reactions in their synthesis of pyridines (Scheme 173).467 Two routes were explored for the N−H insertion stage. The first involved the known insertion of an α-diazo-β-ketoester into a carboxamide N−H bond followed, successively, through reaction with hydrazine and aromatization to form a 1,2,4triazine-5-carboxylate. The second used hydrazine as the N−H insertion partner to form an acyclic adduct which cyclizes with ammonia to yield the isomeric triazine-6-carboxylate after aromatization. The product of the latter route was combined in a thermal cycloaddition in chlorobenzene with norbornadiene to complete a simple three-step route from a hydrazide to a pyridine. 3.5.1.2. Three-Component Reactions of Diazocarbonyls, Amines, and Electrophiles. The idea that ammonium ylides,

Scheme 174. Competitive [1,2]-Hydrogen Shift and Nucleophilic Addition in Three-Component Reactions Involving an Aryldiazoester, an Imine, and an Arylamine

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been developed by Hu and his co-workers.469 Here the competition between [1,2]-hydrogen shift in the ammonium ylide leading to N−H insertion directly or nucleophilic addition to the electrophilic azodicarboxylate leading to an aminal strongly favors the latter (Scheme 175).

Scheme 177. N−H Insertion, Oxidative Dehydrogenation, and [3 + 2]-Cycloaddition

Scheme 175. Three-Component Reactions Involving an Amine, a Diazocarbonyl Substrate, and an Azodicarboxylate

Hu and co-workers have recently described a rhodium(I)catalyzed three-component reaction involving an aromatic amine, an aryldiazoacetate, and a β-nitroacrylate. The optimal conditions were established as 2 mol % [Rh(C2H4)2Cl]2 with 4.1 mol % chiral ligand in toluene at room temperature. The product was the γ-nitro-α-aminosuccinate, illustrated in Scheme 176.470

Scheme 178. Three-Component Reactions Involving Diazooxindoles, Formaldehyde, and Aniline/Water

Scheme 176. Rhodium(I)-Catalysed Three-Component Reaction Involving an Amine, a Diazoester, and a Nitroacrylate

Although rhodium remains the metal of choice for N−H insertion reactions, interest has continued to grow in other metals prompted by concerns about high catalyst loadings (as high as 10 mol %), catalyst poisoning, long reaction times, and poor chemical yields. Aviv and Gross,473 and independently Woo and co-workers,474 have championed a switch to iron(III) corroles and porphyrins as superior catalysts for reaction of diazoacetates with nitrogen-containing nucleophilic substrates. With the reaction of aniline with ethyl diazoacetate as a test case, Aviv and Gross compared the potency of iron corroles/ porphyrins with other rhodium-, ruthenium-, copper-, silver-, gold-, and rhenium-based complexes and concluded that the iron(III) complexes were clearly unmatched by all others in terms of yield of isolated product (>90%), catalyst loading (0.1 mol %), reaction time (minutes vs hours), conditions (room temperature, aerobic), and reactant dosing (single portion). Similar behavior was observed with several substituted anilines. Much more coordinating amines, such as piperidine, morpholine, 2-methylindoline, and propylamine, also gave corresponding products in excellent yields under similar conditions. The relatively poor performance of rhodium(II) acetate in comparison reflects catalyst poisoning, which clearly is not an issue with the iron corrins and porphyrins. 3.5.1.3. Bioconjugation Reactions Involving N−H Insertion. The chemical modification of complex biomolecules via bioconjugation presents major challenges in efficiency and selectivity. This is particularly so for biomolecules as complex as nucleic acids and proteins. Nevertheless, progress has been

Yet another example of a three-component process is the recent combination of a diazoketone, an amine, and a nitroalkene described by Wang and co-workers.471 The process, which culminated in the formation of polysubstituted pyrroles, commenced with a N−H insertion reaction of a diazoketone and benzylamine catalyzed by copper(I) triflate (Scheme 177). There followed a copper-catalyzed oxidative dehydrogenation to form an imine (air was not excluded) through activation of the C−H bond adjacent to nitrogen. Deprotonation of the imine generated an azomethine ylide which is trapped by a [3 + 2]-cycloaddition, also catalyzed by copper, by the transnitroalkene. Completion of the process involved thermal extrusion of HNO2 and dehydrogenation with formation of the pyrrole. The most recent example of a three-component process is the reaction of diazooxindoles and formaldehyde with either anilines or water (Scheme 178).472 In this atom- and stepeconomic transformation, the rhodium(II)-catalyzed reaction of diazooxindole 136 with aniline or water produced the corresponding ammonium or oxonium ylide which was trapped by formaldehyde (or formalin) to yield an amino alcohol or diol, respectively. Both processes tolerate a range of substituents in the oxindole and in the amino alcohol version in the aniline. 10024


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groups present on the surface of the proteins. Che and coworkers have described the site-selective modification of the Nterminus of proteins by N−H insertion reactions of diazoesters and primary arylamines using a water-soluble metalloporphyrin catalyst (Scheme 180).225 The catalyst 138 was a ruthenium porphyrin rendered water-soluble by covalently attaching sugar moieties such as β-D-glucosyl (Glc) to the meso-aryl rings of a porphyrin ligand, in the expectation that its water solubility might be enhanced and also the presence of the sugar residues on the periphery might be able to direct the ruthenium catalyst to approach a specific site of substrate biomolecules via hydrogen-bonding and dipole−dipole interactions. Catalytic activity of 138 in aqueous solution could be established by efficient N−H insertion of arylamines into ethyl diazoacetate in 76−83% yields. The challenge in applying this reaction to bioconjugation processes with peptides is to achieve high site selectivity and chemoselectivity for the reaction of a diazo compound with peptides that contain multiple reactive X−H (X = C, N, O, S) sites as is the case with many amino acid residues. The diazo substrate selected was (dansylamino)ethyl diazoacetate 140, to act as a fluorophoric monitor, and peptide YTSSSKNVVR 139 was chosen as a model substrate since it possesses various types of O−H (primary, secondary, and phenolic) and N−H (terminal, ε, and guanidinyl) sites available for carbene insertion (Scheme 181). Reaction of 140 with 139 in phosphate-buffered saline containing a catalytic amount of catalyst 138 at room temperature afforded product 141 with 93% substrate conversion with only a trace of the doubleinsertion product 142. Neither other N−H insertion nor O−H insertion products were detected. This and similar studies involving variation in the temperature and pH confirmed that the glycosylated porphyrin catalyst 138 is a highly selective catalyst for modification of the N-terminus of peptide 139 in an aqueous medium via carbene N−H insertion. An additional interesting feature of the process is the observation that reaction occurred at the N-terminal amine (pKa = 7.6−8.0) rather than the more basic internal lysine ε-amine (pKa = 9.3− 9.5), a distinction that may reflect the influence of the pH on the reaction: at pH 7.4−8.4 most of the lysine ε-amino groups will be protonated in aqueous media, rendering these amino groups unavailable for catalyzed N−H insertion. The absence of O−H insertion products in the reaction may be due to the lower nucleophilicity of the hydroxyl groups compared with the terminal amino groups. The 138-catalyzed insertion reaction proved to be useful for selective modification of the N-terminal tyrosine of peptide 139 and other N-terminal amino acids such as glycine, alanine, and histidine. Under the optimum conditions (pH 7.4), a variety of other peptides (YLSGANLNL, PPGFSPFR, GGG, ALILTLVS, HDMNKVLDL, TYGPVFMSL, and DRVYIHPFHL) reacted with diazoester 140 in the presence of catalyst 138 to produce N-terminal modifications via N−H insertion with 21−95% conversions. Through choice of the peptide, these workers were able to extend their study of X−H insertion reactions to include S−H bonds. Competition between N−H and S−H bonds in carbene insertion reaction is commonly encountered in peptide modification. In the event, treatment of peptide AYEMWCFHQK 143, which contains both N-terminal amine and internal S−H groups, with diazoester 140 in the presence of catalyst 138 afforded S−H insertion product 144 exclusively with complete substrate conversion, indicating that a thiol insertion reaction is more rapid than an amine insertion; the

made in bioconjugation using transition-metal-catalyzed diazocarbonyl transformations. Nucleic acids and proteins share the functional feature of having nucleophilic N−H groups which are available to combine with diazocarbonyl substrates via reactive ketenes from Wolff rearrangement or N− H insertion reactions with reactive metal carbenes: the nitrogen release in the process provides a trigger for reactivity, leading to potential biological applications with both these macromolecules. Despite the obvious complication of having to use an aqueous environment, and thereby competition from O−H insertion, Gillingham and co-workers have found that a variety of nucleic acids can be catalytically alkylated with rhodium carbenes generated from diazo compounds in aqueous buffer through a N−H insertion process.475 A proof-of-concept study showed that simple tetradeoxynucleotide d(ATGC) on reaction with diazoester 137 in the presence of Rh2(OAc)4 produced singly and doubly alkylated products whose structures established that the purine bases were the sites of chemical modification (Scheme 179). Scheme 179. Rh(II)-Catalyzed N−H Insertion Reaction of a Tetradeoxynucleotide

A more comprehensive investigation of the reaction was carried out with a series of hairpin sequences (Table 1), chosen because they contain a number of common nucleic acid structural elements in a single molecule, and revealed the following features. This study established the feasibility of using carbenoid N−H insertion reactions to achieve direct alkylation of native nucleic acids with a predictable selectivity profile that allows the strategic targeting of unpaired nucleobases such as those present in single strands, bulge regions, and overhangs. Given the enormous excess of water present, the preference for N−H insertion observed here as with protein-labeling studies is striking. As with structure-selective catalytic alkylation of DNA and RNA, site-selective modification also represents formidable challenges in the application of metal-catalyzed carbene transfer to bioconjugation reactions of proteins. In principle, the metalcatalyzed approach to protein modification can selectively target the natural amino acid side chains that are inaccessible to modification by conventional methods or incorporate suitable unnatural functional groups into the amino acid side chains. The challenge lies in that the bioconjugation of proteins has to be performed in aqueous media without interference from carbenoid reactions with the solvent; in addition, the reaction conditions must be sufficiently mild to allow proteins to retain their activity or structural features yet be highly efficient at the protein concentration levels and, crucially, permit single modification of a single group or of many similar or the same groups in different sites with tolerance for various functional 10025


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Table 1. Rh(II)-Catalyzed N−H Insertion Reactions of Nucleic Acids

Scheme 180. Water-Soluble Ruthenium(II) Porphyrin Catalyst

Scheme 181. N−H Insertion Reaction Involving a DansylFunctionalized Diazocarbonyl Substrate and Peptide YTSSSKNVVR

catalyst.476 Excellent tryptophan chemoselectivity was demonstrated with peptide and protein substrates. 3.5.1.4. N−H Insertion with Other Nitrogen-Containing Molecules. Although the bulk of N−H insertion studies have been conducted with amines, principally anilines, there has been a significant development with other N−H substrates, e.g., amides. One of the attractions of amides is the possibility for the use of the adducts in subsequent transformations, in particular five-membered heterocycle formation. Moody’s group has conducted a detailed study of the use of N−H insertion reactions of a wide range of primary amides with αdiazo-β-ketoesters to produce 1,4-dicarbonyl compounds preeminently suited as precursors for 1,3-azole synthesis.477−479 This N−H insertion reaction has been used extensively to

thioether group of methionine in the same peptide remained intact throughout the reaction. Under the same conditions, porphyrin 138 catalyzed the insertion of diazoester 139 with SSCSSCPLSSK 145, a peptide containing a disulfide link and both N-terminal and internal amine bonds, to yield exclusively the N-terminal N−H insertion product 146 without cleavage of the disulfide bond (Scheme 182). Chemoselective labeling of tryptophan residues in selected proteins has also been realized (Scheme 183) using a diazoester derived from styrylacetic ester and rhodium(II) acetate as the 10026


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Scheme 182. Reactions of Dansyl-Functionalized Diazoesters and Sulfur-Containing Peptides

Scheme 185. Rh(II)-Catalyzed Reactions of Benzamide with α-Diazo-β-ketoesters

Scheme 183. Rh(II)-Catalyzed Reaction of Styrylacetic Ester-Derived Diazoesters and a Tryptophan Residue

the unexpected isomeric oxazole-5-carboxylate 152. The failure of the above reaction to deliver a single oxazole prompted a search for alternative rhodium catalysts. Dirhodium tetrakis(heptafluorobutyramide), a catalyst with fluorinated carboxamide ligands with superior catalytic activity for other diazocarbonyl reactions, proved also to be active in the reaction of benzamides with diazoketoesters, producing an oxazole directly though not the same oxazole isolated from the rhodium(II) acetate−cyclodehydration combination. The product formed was found to be the isomeric oxazole-5carboxylate 154. Though the yields were modest at best (18− 38%), evidently the catalyst switch from acetate to hexafluorobutyramide caused a dramatic change in reactivity that resulted in the formation of the isomeric oxazoles. The effect of the catalyst was not limited to α-diazo-βketocarboxylate esters, since α-diazo-β-ketophosphonates behaved similarly. Thus, rhodium(II) acetate-catalyzed reaction of dimethyl (1-diazo-2-oxopropyl)phosphonate (156) with benzamide in dichloromethane gave the N−H insertion product 157 in 62% yield; subsequent cyclodehydration produced the oxazole-4-phosphonate 159. In contrast, use of the perfluorobutyramide catalyst in toluene gave directly the 5phosphonate 158 (Scheme 186). Although ligand effects in rhodium(II)-catalyzed diazocarbonyl reactions are well documented, the changes in regioselectivity in oxazole formation described above are striking and are presumed to be electronic in nature, reflecting a change in electrophilicity of the intermediate rhodium carbene caused by a change in the ligand from acetate to perfluorobutyrate. Clearly, the 5-substituted oxazoles arise from O−H insertion of the rhodium carbene intermediate into the imino tautomer of the carboxamide followed by cyclization, notwithstanding the availability of a N−H bond in the primary carboxamide. There are other examples involving the formation of a C−O bond in the reaction of a carboxamide with a rhodium carbene even where a N−H bond is available for insertion, though these examples all involve lactam or imine N−H groups. In the course of their extensive study of the amide approach to oxazole synthesis via N−H metal carbene insertion, the Moody group encountered situations where

access oxazole and thiazole building blocks for cyclic peptides using single-enantiomer amides derived from amino acids.480,481 A representative example involving a simple alkanamide and diazoketoester 147 with rhodium(II) acetate catalysis is shown in Scheme 184. The resulting dicarbonyl Scheme 184. Synthesis of Azoles Involving N−H Insertion

adduct was readily dehydrated to form an oxazole, 149; alternatively, treatment with Lawesson’s reagent formed the corresponding thiazole 148, and exposure to ammonium acetate completed the five-membered heterocyclic trio by forming imidazole 150. In the course of these studies using substituted benzamides as the N−H partner, an unexpected catalyst effect was observed.482 Reaction of benzamide with 147 (Scheme 185), again under rhodium(II) acetate catalysis, furnished, after dehydration, oxazole 155 as expected. A similar reaction sequence applied to the chloromethyl derivative 151 also gave the expected oxazole-4-carboxylate 153 and smaller amounts of 10027


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Scheme 186. Rh(II)-Catalyzed Reactions of Benzamide with α-Diazo-β-ketophosphonates

Scheme 188. Effect of N-Substitution on Reactions of 3Indolyldiazoesters

Among other recent examples of catalyzed N−H insertion with amides are those employed by Moody’s group in their approach to the tryptophan core of stephanotic acid.484 N-Bocvalinamide (164) and Boc-Ile-Val-NH2 (165) provided the single-enantiomer building blocks (Scheme 189), each reacting Scheme 189. Synthesis of the Tryptophan Core of Stephanotic Acid (169) chemoselectivity became an important issue, notably in the behavior of certain 3-indolyldiazoesters as precursors to certain naturally occurring indolyloxazoles.483 3-Indolyl-α-diazo-βketoester 161 was selected as a suitable precursor for the natural alkaloid martefragin A (160). A model study using this diazoester and hexanoic amide in the presence of dirhodium tetraoctanoate produced a mixture of two products, the minor of which was the expected N−H insertion product 162 (39%), but surprisingly the major product (55%) 163 was that of Wolff rearrangement (Scheme 187). Scheme 187. Rh(II)-Catalyzed Reactions of 3Indolyldiazoesters

This partial switch in chemoselectivity with diazoketoesters in favor of Wolff rearrangement under the influence of dirhodium catalysis was unexpected but not unprecedented, and was traced to the electronic influence of the indole heterocycle. A series of indolyldiazoesters in which the electronic properties were modified by a chloro substituent at position 2 or attenuated by different substituents on the indole nitrogen atom (Me, Boc, Bs, Ns), when exposed to the same combination of catalyst and amide, revealed that Wolff rearrangement is suppressed in favor of N−H insertion by more electron-withdrawing substituents on the indole nitrogen: the N-methyl derivative produced Wolff rearrangement exclusively, whereas the Ns (2-nitrobenenesulfonyl) led only to N−H insertion (Scheme 188).

with a diazophosphonate to give a phosphonodipeptide, 166, and a phosphonotripeptide, 167, respectively. Although the yield of the tripeptide was modest, the chemoselectivity of its formation is notable considering the alternative N−H insertion options available to the rhodium carbene. Peptides 166 and 167 were subsequently elaborated into C6-substituted tryptophan analogues 168 representing the tryptophan core of stephanotic acid (169). The Moody group has demonstrated another aspect of amide N−H insertion reactions in a metal carbene approach to peptide synthesis. This approach is unusual in that it does not involve the formation of the peptide bond itself, and while it is unlikely to supplant traditional peptide coupling methodology, it may find uses in the synthesis of peptide sequences that 10028


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incorporate noncoded amino acids such as N-methyl and dehydro derivatives.485 N-Protected amino acid amides provide the building blocks of the N−H insertion sites for rhodiumcatalyzed coupling with (a) diazoesters or (b) diazophosphonates. The former will lead directly to dipeptides and the latter indirectly via Wadsworth−Emmons reaction to dehydrodipeptides amenable to stereoselective hydrogenation (Scheme 190).

Scheme 192. N−H Insertion on a Solid Support

Scheme 190. Reactions of N-Protected Amino Acid Amides with Diazoesters or Diazophosphonates

amidation reactions could be used to release the oxazole from the polymer. The Janda group also included Boc-amino acid amides in their study of N−H insertion of polymer-bound α-diazo-βketoesters and demonstrated the extension of this approach to the construction of pyrazinones and pyrazines.488 Among other N−H functionalized insertion partners for diazocarbonyl substrates that have the potential to generate diverse heterocycles are ureas. Janda and co-workers have explored such reactions in solution and in the solid phase with a view to preparing libraries of small heterocycles for application in combinatorial-type screening programs for drug discovery.489,490 From the initial screening, these workers discovered that primary ureas were excellent substrates in N−H insertion reactions of α-diazo-β-ketoesters catalyzed by rhodium(II) octanoate (Scheme 193). The best results were obtained using

Among other nitrogen-containing molecules amenable to catalytic N−H insertion are indoles and benzotriazoles. Muthusamy and Srinivasan found that both these heterocycles engage in rhodium(II)-catalyzed insertion with several 3diazopiperidinones of the type shown in Scheme 191.486 Scheme 191. Rh(II)-Catalyzed Reaction of Diazopiperidinone with Indole/Benzotriazole

Scheme 193. Rh(II)-Catalyzed N−H Insertion Reactions of Primary Ureas

Having shown that aniline and the parent 3-diazopiperidin-2one (171) combine to produce the (phenylamino)piperidinone adduct in high yield, they were able to show that indole and benzotriazole behaved similarly to form adducts 170 and 172, respectively, with high degrees of chemoselectivity. N−H insertion has been extended to solid-phase synthesis employing α-diazo-β-ketoesters as substrates. Janda and coworkers prepared polymer-bound acetoacetate substrates by reaction of a ketene with hydroxybutyl JandaJel resin (Scheme 192).487 Diazo transfer was accomplished with dodecylbenzenesulfonyl azide to produce the resin-bound α-diazo-βketoester, the intention being to use the reaction with diverse primary amide coupling partners to produce oxazoles. For example, exposure to benzamide in the presence of rhodium(II) octanoate in toluene gave the N−H insertion product in 99% yield. Oxazole synthesis was completed by cyclodehydration of the insertion product on the solid phase using dichlorotriphenylphosphine. Reduction, transesterification, or

a mixed solvent system of toluene/1,2-dichloroethane (1:1) with slow addition of the catalyst. Cyclization of the N−H insertion product to the corresponding imidazolone was easily achieved by brief treatment with TFA. 3.5.1.5. Intramolecular N−H Insertion. The intramolecular N−H insertion reaction is a now-well-established approach to a variety of monocyclic and bicyclic heterocycles; a highlight of its power in synthesis is its use to construct the five-membered ring in the Merck synthesis of thienamycin in 1978. The intramolecular N−H insertion reaction catalyzed by transition metals provides a powerful strategy for nitrogen heterocycle 10029


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synthesis, especially five-membered cycles. Among more recent demonstrations of its versatility is the Wang and Zhu synthesis of a range of polyfunctional fluoropyrroles (Scheme 194).491

Scheme 195. Intramolecular N−H Insertion Reaction of a Glucose-Derived α-Diazo-β-ketoester

Scheme 194. Synthesis of Polyfunctional Fluoropyrroles via N−H Insertion

Scheme 196. Copper(II)-Catalyzed Intramolecular N−H Insertion Reactions of Diazocarbonyl Substrates Derived from α- and β-Amino Acids

Scheme 197. Diastereoselective Rh(II)-Catalyzed N−H Insertion of a Boc-Protected α-Diazophosphonate

3.5.1.6. Asymmetric N−H Insertion Reactions. Throughout the 1990s, efforts to promote enantioselective or diastereoselective intermolecular N−H insertion using either chiral dirhodium catalysts or chiral amines met with only limited success, unlike asymmetric C−H insertion, which had already become an established route for enantioselective C−C bond formation. The first glimmer of hope with chiral catalysis came with the 1996 report by Garcia, McKervey, and Ye that the reaction of the diazoketoester 180 could be catalyzed by dirhodium(II) tetra-(S)-mandelate, forming N-Boc-pipecolic acid methyl ester 181 in 45% ee (Scheme 198).495

Using ethyl 4-bromo-4,4-difluoroacetoacetate as the building block, these workers first inserted a δ-amino function at the terminal carbon atom, prior to introducing the diazo group via diazo transfer. Intramolecular reaction of 173 was effected using rhodium(II) acetate (0.5 mol %) in toluene, forming a mixture of the N−H insertion product 175 and its H−F elimination product, β-fluoropyrrole 177. Prolonging the reaction time from 30 min to 6−12 h caused complete conversion of the former product into the latter, which was eventually isolated in 90−95% yield. To further elaborate the utility of this intramolecular N−H insertion process, the authors modified the diazo precursor by adding additional functionality in the form of a cyanomethylene group via a Wittig reaction to form diazoester 174, which produced pyrrole 176 on cyclization. Intramolecular N−H insertion reactions of glucose-derived δ-amino-α-diazo-β-ketoesters have been used to construct pyrrolidine iminosugars.492 The requisite N-protected glucose-derived precursor bearing a diazoketoester side chain, 178, was constructed by standard methods and subjected to rhodium(II) catalysis in benzene to yield a bicyclic pyrrolidinone, 179, in 78% yield (Scheme 195). Wang has used copper-catalyzed N−H insertion to produce oxoazetidine, oxopyrrolidine, and oxopiperidine derivatives in moderate to good yields (Scheme 196).493 Compared to previous studies where rhodium catalysts were used, no competing C−H insertion products were detected with the copper catalyst. Diastereoselective formation of 2,5-disubstitued pyrrolidines was also reported via intramolecular N−H insertion of a diazophosphonate (Scheme 197).494

Scheme 198. Enantioselective Rh(II)-Catalyzed N−H Insertion Reaction of an α-Diazo-β-ketoester

Significant progress was to follow over the next decade:496 there are now a number of catalyst systems capable of producing intermolecular N−H insertion at >95% ee over a diverse range of structural types. Zhou and co-workers have been particularly successful in developing this approach to chiral aminoesters.497−499 Using a catalyst generated in situ, from CuCl, spiro bisoxazoline ligand 182, and Na(BARF), the N−H insertion reaction between aniline and ethyl diazopro10030


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readily removable group, which anilines clearly are not. Lee and Fu independently made a significant advance in the search for asymmetric N−H insertion reactions for amino acid synthesis by the introduction of carbamates as ammonia equivalents (Scheme 202).500 Whereas Zhou had focused on a copper/ chiral bisoxazoline catalyst combination, Lee and Fu developed a copper/planar-chiral bipyridine 184 combination.

panoate produced (R)-N-phenylalanine ethyl ester in 94% yield with 98% ee (Scheme 199). Scheme 199. Enantioselective Cu(II)-Catalyzed N−H Insertion Reaction of Aniline

Scheme 202. Enantioselective Cu(I)-Catalysed N−H Insertion

Besides α-diazopropionates, other α-alkyl-α-diazoacetates underwent the insertion reaction smoothly, with excellent yields and high enantioselectivities.498 A selection of representative examples of (N-phenylamino)esters produced in this way is shown in Scheme 200; its application to the synthesis of the herbicide (R)-flamprop-M-isopropyl (183) is shown in Scheme 201.

A very recent example of significant asymmetric synthesis in N−H insertion is contained in the report of Doyle and coworkers of enantioselective vinylogous reactions of vinyldiazoacetates and aldehyde-derived hydrazones (Scheme 203).82

Scheme 200. Enantioenriched (N-Phenylamino)esters from Asymmetric N−H Insertion

Scheme 203. Asymmetric Vinylogous N−H Insertion

3.5.2. O−H Insertion Reactions. The history of O−H insertion reactions of diazocarbonyl substrates parallels closely that of their N−H counterparts. Catalyzed and uncatalyzed reactions of diazoesters, diazoketones, and diazophosphonates with water, alcohols, phenols, and carboxylic, sulfonic, and phosphonic acids offer direct routes to α-substituted oxygenated derivatives (including oxygen-containing heterocycles) and, potentially, through asymmetric catalysis, their optically active analogues. In fact, the most significant recent developments in this area have occurred in the catalyzed asymmetric version of O−H insertion. As with N−H insertion, the catalyzed O−H insertion process with alcohols and phenols is widely believed to proceed through transient-metal carbenes, leading to oxonium ylides which decay to product via a [1,2]-proton shift. With diazocarbonyl substrates, the electron-withdrawing nature of the carbonyl group should stabilize the alcohol-derived ylide and thus favor this pathway. Furthermore, the carbonyl group provides a convenient spectroscopic label which Platz and coworkers were able to use to monitor the progress of O−H insertion via time-resolved infrared spectroscopy.501 These workers used ultrafast photolysis of ethyl diazoacetate in methanol to generate transient IR bands consistent with the direct intervention of a carbene−alcohol ylide intermediate (Scheme 204). The ylide is believed to form in a nearly diffusion-controlled process, and its decay is governed by a

Scheme 201. Synthesis of (R)-Flamprop-M-isopropyl

For the Zhou methodology to fulfill its full potential in the synthesis of single-enantiomer amino acids, it needs to be general with respect to both the range of diazoester substrates and the N−H component. In its present form, it is deficient in respect to the latter in that it performs poorly or not at all with amines other than anilines. Ideally, the N−H component needs to be an “ammonia equivalent” amine, RNH2, where R is a 10031


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Scheme 204. Photolytic O−H Insertion

Scheme 207. Sequential O−H Insertion and Sharpless− Huisgen [3 + 2]-Cycloaddition

bimolecular reaction with an additional alcohol molecule or a hydrogen bond network of molecules. The synthesis of an ether from an alcohol by O−H insertion usually presumes the availability of the alcohol, but as Corey and Busch-Petersen have recently demonstrated,502 this is not necessarily so when the alcohol is a very minor component of a mobile tautomeric pair, a classic example being the 2hydroxypyridine/2-pyridone pair, where the keto form predominates in aqueous solution, with the enol form existing only as a very minor component in the gas phase. Nevertheless, treatment of 2-pyridone with tert-butyl diazoacetate under rhodium acetate catalysis produced the enol ether in 84% yield (Scheme 205), a result attributed to transfer of the carbene Scheme 205. Rh(II)-Catalyzed O−H Insertion Reaction of 2-Pyridone

of Moody and co-workers, on the use of α-diazophosphonates as substrates for O−H insertion with simple alcohols,505 forms the backdrop for similar reactions of several nucleosides bearing a free 5′-hydroxy group with a diazophosphonoacetate (Scheme 206).506,507 These reactions were catalyzed by rhodium(II) acetate, and the products were epimeric mixtures of phosphononucleosides in yields of 28−86%. We saw earlier how the N−H insertion process can be exploited to facilitate bioconjugation reactions with molecules as complex as nucleic acids and proteins. Similarly, the O−H insertion process can be applied to complex biomolecules containing hydroxyl groups (Scheme 207). Romo and coworkers have used the rhodium-catalyzed O−H insertion reaction to “arm” alcohol-containing natural products with a tethered alkyne.508 Subsequent copper-catalyzed Sharpless− Huisgen [3 + 2] cycloaddition allows attachment of various probes useful for chemical genetics experiments. The general approach is illustrated graphically in Scheme 207. 3.5.2.2. Enantioselective Intermolecular O−H Insertion Reactions. The most significant advances in catalytic enantioselective O−H insertion reactions with diazocarbonyls and alcohols have been made in the past decade, earlier efforts by Moody and others to devise enantioselective or diastereoselective processes having met with only limited success. The first effective method was reported in 2006 by Maier and Fu, using copper bisazaferrocene catalyst 185 (Scheme 208).509 These workers made a detailed study of the coupling of simple alcohols with α-aryl-α-diazoesters to form α-alkoxyesters in high yields and up to 98% ee. They also made the serendipitous discovery, as yet unexplained, that small amounts of water enhanced the enantioselectivity of this catalyst system. The example shown in Scheme 208 relates to coupling of the parent phenyldiazoester with 2-(trimethylsilyl)ethanol, a particularly attractive combination since the insertion product could be easily deprotected to provide the α-hydroxyester in high yield without racemization.

from the initially formed rhodium(II) carbene intermediate to the oxygen atom of 2-pyridone to form an an oxonium ylide which upon 1,4-hydrogen shift forms the enol ether. 2-Thiopyridone reacted smoothly with ethyl diazoacetate with Rh(II) catalysts to afford the corresponding thioether, paralleling the behavior of 2-pyridone, and ε-caprolactam produced the corresponding imino ether when similarly treated, even though negligible amounts of this enol tautomer can exist at equilibrium. 3.5.2.1. Intermolecular O−H Insertion Reactions with Alcohols. The types of alcohols now known to engage in catalyzed O−H insertion reactions range from simple monofunctional derivatives to multifunctional molecules with complex structures. Similarly, the range of catalysts and catalyst−ligand combinations continues to expand; recent examples include the use of indium chloride503 with ethyl diazoacetate and a ruthenium−diimine combination504 with an α-diazo-β-dicarbonyl substrate. The general applicability of these new catalyst systems is difficult to assess as they have not been tested for a range of substrates. Examples of the increasing complexity in alcohol structure are illustrated in Scheme 206 and Scheme 207. The earlier work Scheme 206. Syntheseis of Phosphononucleosides via O−H Insertion

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enantioselective O−H insertions (see the iron-catalyzed examples in Scheme 210) under mild conditions.

Scheme 208. Enantioselective Cu(II)-Catalyzed Intermolecular O−H Insertion of 2-(Trimethylsilyl)ethanol

Scheme 210. Enantioselective Fe(II)-Catalyzed O−H Insertion of Water

Those aryldiazoacetates bearing a coordinating substituent at the ortho position gave higher enantioselectivities in ironcatalyzed reaction than in copper-catalyzed reaction. For example, the iron-catalyzed insertion of α-diazo(2chlorophenyl)acetate with water and the spiro oxazoline catalyst produced the mandelate product with 96% ee; the analogous reaction with the copper catalyst gave the same product with a much lower enantiomeric excess (36% ee). The chloromandelate was subsequently used as a precursor for the drug clopidogrel (187) (Scheme 211).

A more simple and direct approach to asymmetric synthesis of chiral α-aryl-α-hydroxy/alkoxyesters was subsequently uncovered by Zhou and co-workers with the discovery that both copper and iron complexes of spiro bisoxazoline ligands are effective catalysts for O−H insertion of water, alcohols, and phenols.499,510 From a comprehensive study in which these workers compared various salts of iron, cobalt, nickel, silver, and rhodium, a clear preference emerged for copper and iron in terms of yield and enantioselectivity: an iron catalyst prepared in situ from FeCl2·4H2O and the chiral spiro bisoxazoline ligand 186 was most effective in promoting highly enantioselective O−H insertion for a range of primary, secondary, and allylic alcohols. A selection of examples is shown in Scheme 209. Collectively, this reaction constitutes one of the most effective methods for synthesis of chiral α-alkoxyphenylacetates.

Scheme 211. Synthesis of Clopidogrel (187)

Scheme 209. Enantioselective Fe(II)-Catalyzed Intermolecular O−H Insertion Reaction of Alcohols

Saito and co-workers have described an entirely different approach to asymmetric intermolecular O−H insertion with water. These workers found that O−H insertion of phenyldiazoacetates with water could be observed with enantioselectivities up to 50% through the combined catalytic effect of rhodium(II) complexes and the alkaloid quinine.511 3.5.2.3. Intramolecular O−H Insertion Reactions of Alcohols. The early work of Rapoport and Moody had established the catalytic intramolecular O−H insertion process as a viable route for the construction of five-, six-, and sevenmembered cyclic ethers and esters. The power of the intramolecular process in highly complex cases is beautifully demonstrated by the recent total synthesis by Li and Yang and their co-workers of maoecrystal V (190), a diterpenoid natural product of Chinese herb origin.512 This molecule possesses a highly congested pentacyclic carbon framework with six stereocenters, three of which are contiguous quaternary carbon atoms. The focus of the key step in the synthesis was a hydroxyl group deeply embedded in the center of this array containing a distal diazoester moiety. Rhodium(II)-catalyzed reaction of 188 led to intramolecular O−H insertion, forming a sevenmembered ether, 189, in 60% yield suitable for eventual conversion to the natural product 190 (Scheme 212). Much of the focus of recent studies of intramolecular O−H insertion with alcohols has been on asymmetric reactions employing chiral ligands. The Zhou group has optimized a copper-based catalyst system capable of forming a broad range

The extension of the O−H insertion approach to reactions with water was equally successful despite initial reservations about the ability of a reacting species with a molecular structure as small as that of water to engage in chiral discrimination. In fact, a range of ortho-, meta-, and para-substituted α-aryl-αdiazoacetate substrates with iron and copper catalysis assisted by the spiro oxazoline ligand 182 produced several highly 10033


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of substituted phenols, and it is unclear if the inefficiency was associated with the formation of the intermediate (aryloxy)ketones or with the subsequent dehydration step. The O−H insertion between α-diazopropionates and phenols constitutes a direct and efficient route to α-(aryloxy)propionates with wide applications in pharmaceuticals and agrochemicals. The synthesis of single-enantiomer α-(aryloxy)propionates poses significant challenges: the high acidity of the α-hydrogen atom renders these products so susceptible to racemization that mild neutral reaction conditions are essential. The metal-catalyzed O−H insertion reaction with phenols meets these conditions ideally. Originally, the Zhou group used copper complexes of chiral spiro bisoxazolines as catalysts and observed the formation of α-(aryloxy)carboxylic esters in high yield with enantioselectivities of >99% ee for a diverse range of substituted phenols.514 An alternative copper complex based on a chiral imidazoindolylphosphine was evaluated for the same process by Uozumi and co-workers and found to be less effective in enantioselectivity.515 The Zhou group has recently extended the catalytically active metals for enantioselective O−H insertion to include palladium.516 Following their success with copper and iron complexes of spiro bisoxazolines, these workers found that these ligands combine with palladium salts to catalyze the insertion of phenols with α-aryl-α-diazoacetates. Aryloxy adducts were obtained in highly enantioselective and chemoselective yield. The nature of the palladium precursor affected strongly both the product yield and enantioselectivity, [Pd(PhCN)2Cl2] and [Pd(CH3CN)2Cl2] proving to be the most effective and the most stable under the reaction conditions. It provides an easy synthetic route to chiral α-aryl-α-(aryloxy)acetates in good yields (up to 87%) and excellent enantioselectivity (96−99% ee) (Scheme 215).

Scheme 212. Synthesis of Maoecrystal V

of cyclic ethers with different ring sizes and substituent patterns.513 High enantioselectivities were observed for cyclization of ω-hydroxy-α-diazoesters with CuOTf and the spiro bisoxazoline ligand 191 in dichloromethane. Scheme 213 contains several examples of cyclic ethers produced. Scheme 213. Enantioenriched Cyclic Ethers via Cu(I)Catalyzed O−H Insertion

Scheme 215. Pd(II)-Catalyzed O−H Insertion Reaction of Phenol

An application of the method to the synthesis of tomoxetine (192), a chiral drug used in the treatment of psychiatric disorders, is shown in Scheme 216.

3.5.2.4. O−H insertion Reactions of Phenols. Just as with alcohols, intermolecular and intramolecular insertion reactions of phenols are known and constitute effective routes from diazocarbonyls to aryloxy derivatives and benzofurans. Moody and co-workers combined rhodium(II) catalysis with poly(phosphoric acid) to convert a range of phenols and methyl 2diazo-3-oxobutyrate into benzofurans in a one-pot process (Scheme 214).466 Yields were modest (19−67%) over a range

Scheme 216. Synthesis of Tomoxetine (192)

Scheme 214. Synthesis of Benzofurans via Rh(II)-Catalyzed O−H Insertion of Phenols

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The authors tested several bisoxazoline ligands; the best results were achieved with ligand 182. Molecular sieves are added to absorb adventitious water. The reaction tolerates a broad range of substrates and meets the conditions that are necessary to avoid byproduct formation. It is easily performed at the gram scale. The Zhou group have extended this very successful approach to several chiral oxygen heterocycles using their spiro bisoxazoline ligands for enantioselective copper-catalyzed intramolecular phenol insertion.513,517 The approach, summarized in Scheme 217, provides access to chiral 2-carboxydihy-

Scheme 219. Three-Component Reaction Involving an Aryldiazoester, a Benzyl Alcohol, and an Imine

Scheme 217. Enantioselective Cu(I)-Catalyzed O−H Insertion Reactions of Phenolic α-Diazoesters the form of a β-amino alcohol with high diastereoselectivity (dr 97:3), although minor amounts of the two-component product, that of direct O−H insertion, were also formed. The high chemoselectivity (three-component vs two-component) and excellent diastereoselectivity were observed for most examples of the reaction regardless of the electronic effect of substituents in the imine; the chemoselectivity could be influenced to a limited extent (to 94:6) by adding an electron-withdrawing substituent to the benzyl alcohol. Overall, the process provides ready access to β-amino-α-hydroxyesters through the simultaneous construction of quaternary stereocenters by C−O and C−C bond formation in a single step. Incorporation of enantioselectivity into the overall process could be achieved through the use of imines bearing chiral auxiliaries, e.g., N-(tertbutylsulfinyl)imines. An alternative to incorporation of a chiral auxiliary into the imine component is the use of a chiral Brønsted acid as a cocatalyst to activate the imine through iminium ion formation and thereby minimize the undesired direct proton transfer process. The group of Hu has been particularly active in this area in combining metal catalysis with Brønsted catalysis to produce polyfunctional chemo- and stereodefined molecules, many of significant biological interest.519 This strategy of cocatalysis involving a chiral phosphoric acid and rhodium acetate has also been applied to the synthesis of the paclitaxel side chain.520 The Hu group has developed this synergistic approach involving both Brønsted and Lewis acids in combination with rhodium catalysis in a quite general way for several MCRs.519 There are now several recent examples of MCRs involving oxonium ylides and carbonyl electrophiles ranging from simple aldehydes to more highly functionalized ketones. Among the former, Hu and co-workers studied the MCR of aryldiazoacetates, alcohols, and substituted benzaldehydes under rhodium(II) catalysis.521 A representative example is shown in Scheme 220. The reaction thus provides a convenient route to α,β-dihydroxy acid derivatives. All the evidence of this and related control experiments suggests that it involves oxonium ylide formation followed by nucleophilic addition to the aldehyde. The formation of a small amount of the direct O−H insertion product indicates that the alternative 1,2-hydrogen shift process is still operating. A zirconium-based Lewis acid was identified as an effective cocatalyst to suppress the direct O−H insertion process.522 Two examples involving α-dicarbonyls are illustrated in Scheme 221 and Scheme 222. In the first, the components were phenyldiazoacetate and benzyl alcohol with isatin as the ylidetrapping electrophile.523 The product, isolated in 93% yield,

drobenzofurans, -dihydrobenzopyrans, and -tetrahydrobenz[b]oxepines in high yields and excellent enantioselectivities. The utility of this cyclization reaction was further demonstrated by the formal total synthesis of the dihydrobenzofuran (R,S,S,S)(−)-nebivolol (194) (Scheme 218). Scheme 218. Synthesis of (−)-Nebivolol (194)

3.5.2.5. Three-Component Reactions of Diazocarbonyls, Alcohols, and Electrophiles. The development of multicomponent reactions in O−H insertion chemistry mirrors that of its N−H insertion counterpart. A case in point is the combination of a diazoester, an alcohol, and an imine as illustrated in Scheme 219.518 Treatment of an equimolar mixture of methyl phenyldiazoacetate, benzyl alcohol, and an imine derived from o-aminophenol with rhodium(II) acetate (1 mol %) yielded predominantly the three-component product in 10035


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Scheme 220. Three-Component Synthesis of α,β-Dihydroxy Acid Derivatives

Both these processes are believed to commence with oxonium ylide formation. 3.5.2.6. O−H Insertion Reactions of Hydroperoxides. Very recently, Fisher and Mattson have extended the concept of hydrogen bond donor (HBD) organocatalysis to O−H insertion of hydroperoxides with α-aryldiazoesters (Scheme 223).530 The organocatalyst used was the disubstituted urea Scheme 223. HBD-Organocatalyzed O−H Insertion of Hydroperoxides

Scheme 221. Three-Component Formation of Highly Functionalized Indolinones

131 which these authors had earlier shown was effective in N− H insertion reactions; its role here is believed to enhance the acidity of the hydroperoxide via N−H bonding in advance of proton transfer to the diazoester. Displacement of dinitrogen by the peroxy anion completes the insertion process. This method is applicable to a diverse set of substrates, and the corresponding α-peroxyesters are typically isolated in high yield. 3.5.3. Si−H Insertion Reactions. Although insertion reactions of diazocarbonyls into silicon−hydrogen and sulfur−hydrogen bonds were already well-known by 1994, they have received much less recent attention compared with their N−H and O−H counterparts. There have however been a few notable recent developments, particularly with asymmetric reactions where chiral copper and rhodium catalysts have shown the most promise. Jacobsen and co-workers used a copper(I) salt combined with a chiral C2-symmetric Schiff base derived from trans-1,2-diaminocyclohexane to catalyze insertion of trialkylsilanes into diazoarylacetates, leading to adducts with enantioselectivities up to 84%; in favorable cases, the ee could be improved to up to 99% by recrystallization (Scheme 224).531

Scheme 222. Three-Component Synthesis of β-Lactams

Scheme 224. Enantioselective Cu(I)-Catalyzed Intermolecular Si−H Insertion

was a highly functionalized 3-substituted 3-hydroxyindolin-2one with two vicinal quaternary stereocenters, with an isomer ratio of 98:2 in favor of the erythro isomer. The reaction proceeded efficiently for a range of substituted phenyldiazoacetates and N-protected and unprotected isatins. Second, a similar study using azetidine-2,3-diones as trapping agents has been conducted by Alcaide et al.524 The product (Scheme 222) was an epimeric mixture of densely functionalized β-lactams. Other electrophiles capable of acting as oxonium ylidetrapping agents include chalcones, 525 alkynals, 526 and (alkynylaryl)aldimines.527 There are intramolecular versions of MCRs involving prior oxonium ylide formation. Hatakeyama and co-workers found that homopropargyl alcohols combine with diazocarbonyl in a tandem process characterized as formal [4 + 1]-cycloaddition catalyzed cooperatively by rhodium(II) acetate and zinc chloride to afford tetrahydrofurans.528 Another route to tetrahydrofurans involving allyl alcohols and aryldiazoacetates has been described by the Hu group.529

The Davies group working with the now familiar (arylsulfonyl)prolinate catalyst observed very high enantioselectivities for the asymmetric Si−H insertion reactions of several vinyldiazoesters and aryldiazoesters with dimethylphenylsilane (Scheme 225).532 This work confirmed the beneficial effect of the choice of pentane as the reaction solvent. A later study by Ge and Corey of Si−H insertion reactions of diazocycloalkenyl substrates found similarly high levels of 10036


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and thiols using copper catalysts based on Zhou’s chiral spiro bisoxazoline ligands.535 Representative examples using benzyl and phenyl mercaptans are shown in Scheme 228, demonstrat-

Scheme 225. Enantioselective Rh(II)-Catalyzed Si−H Insertion Reaction Involving α-Diazoesters

Scheme 228. Enantioselective Cu(I)-Catalyzed S−H Insertion Reactions of α-Diazoesters and Thiols

enantioselectivity using several rhodium(II) N-sulfonylproline carboxylates such as Rh2(196)4 as catalysts (Scheme 226).533 Scheme 226. Enantioselective Synthesis of 6-Silylated 2Cyclohexenones

ing good enantioselectivities for a range of propionates and arylacetates. Other mercaptans were less effective for asymmetric S−H insertion, though a trityl analogue could be obtained in 77% ee. The trityl group could be removed reductively without compromising the stereochemistry of the product (Scheme 228). 3.5.6. Insertions Involving Halogens. It has been known for almost a century that molecular chlorine, bromine, and iodine displace nitrogen from diazocarbonyls, furnishing α,αdihalogenated products. Similarly, the hydrogen halides, though not hydrogen iodide, react to produce α-halocarbonyl adducts. Collectively, these reactions do not require external catalysis; some have acquired an enduring usefulness in chemical synthesis, e.g., for the production of single-enantiomer αchloroketones from amino acids. The example illustrated in Scheme 229 relating to formation of an α-bromoketone from

The most recent study of the asymmetric Si−H insertion reaction by the Zhou group contains a comparison of the catalytic efficacy of various copper−ligand combinations for a series of diazoarylacetate substrates.534 In general, the results demonstrated that a series of spiro diimine ligands displayed a much higher activity and enantioselectivity than their spiro bisoxazoline counterparts. Within the spiro diimine series, compound 197 was the most effective. Thus, the insertion reaction with dimethylphenylsilane and methyl α-diazophenylacetate in the presence of the copper complex of this ligand was complete in 1 h, affording the product in 95% yield with 93% ee (Scheme 227). Similar high yields (85−95%) and enantioselectivities (90−99% ee) were observed with a variety of α-diazo-α-phenylacetates and several aryl- and alkylsilanes. Scheme 227. Enantioselective Cu(II)-Catalyzed Si−H Insertion Reaction with Dimethylphenylsilane

Scheme 229. Formation of an α-Bromoketone

aspartic acid is unusual in that it employs simultaneous protection of one carboxy group and its adjacent amino function by conversion to an oxazolidinone with hexafluoroacetone.536 The other carboxy group was then converted into an α-diazocarbonyl function in the usual way. Treatment with HBr at low temperature caused spontaneous release of nitrogen, forming the α-bromoketone, and deprotection was achieved by warming in aqueous acetonitrile. More recently, the emphasis has been largely on exploration of alternative ways of delivering halogen substituents to diazocarbonyl substrates. There are many ways by which the

3.5.4. S−H Insertion Reactions. S−H insertion with thiols offers a versatile way of placing sulfur-containing substituents adjacent to carbonyl groups in ketones and esters; metalcatalyzed versions have become the norm, replacing earlier photolytic and free radical reactions. The most significant recent examples are asymmetric versions between α-diazoesters 10037


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bonds in a chemoselective fashion. Investigations comparing product distributions for photochemical carbene transformations versus carbenoid reactions demonstrated that increased levels of ylide-derived products were obtained for the metalcatalyzed process, thus paving the way for the development of additional catalytic methods. In general, rhodium(II) carboxylates are the catalysts of choice for the formation of oxonium ylides; however, examples employing copper complexes have also been reported, particularly for reactions in which competing C−H insertion can occur.544−548 3.6.1.1. [2,3]-Sigmatropic Rearrangement. In 1986, Pirrung549 and Johnson550 reported the first rhodium-catalyzed intramolecular reactions of oxonium ylides generated from αdiazoketones and α-diazo-β-ketoesters. These studies demonstrated the potential of cyclic oxonium ylides for the synthesis of five-, six-, and eight-membered oxygen heterocycles, while also establishing standard procedures for subsequent studies examining transition-metal-mediated oxonium ylide production. Pirrung subsequently applied this methodology to the substrate-controlled synthesis of the antifungal agent (+)-griseofulvin.551 Another early example of the application of [2,3]sigmatropic rearrangement of oxonium ylides in total synthesis is the preparation of (±)-decarestrictine (198), reported by Clark and co-workers.545 This synthesis involved the coppercatalyzed cyclization of an α-diazoketone substrate to produce a diastereomeric mixture of products, the major product of which could be transformed to the target natural product in four synthetic steps (Scheme 232).

diazo group of diazocarbonyl substrates can be replaced by one or two halogen atoms. Many of these are long-standing and have been reviewed at length. More recent approaches include the use of iodobenzene dichloride to convert diazoacetates into gem-dichlorinated products, in high yield in dichloromethane, a process activated by pyridine (Scheme 230).537 Scheme 230. Synthesis of Gem-Dichlorinated Derivatives

Methods for introduction of a single fluorine substituent continue to attract attention. Moody and co-workers have developed an approach based on nucleophilic fluorination rather than the more commonly used electrophilic reagents.538 Treatment of α-diazo-β-ketoesters with HBF4 in dichloromethane resulted in monofluorination by the usually inert and stable tetrafluoroborate anion. 3.6. Ylide Formation from α-Diazocarbonyls

The realization in the 1950s that carbenes and carbenoids could engage in ylide formation has had a profound effect on the development of diazocarbonyl compounds as synthetic intermediates. Carbenes derived from diazocarbonyl compounds exhibit highly electrophilic properties which dictate one of their most characteristic reactions: ylide formation with heteroatomic species. Metal carbenes may thus readily form adducts by reaction with Lewis bases (B:). The most common Lewis bases utilized to generate ylides include ethers, sulfides, amines, and carbonyl compounds, forming oxonium, sulfur, nitrogen, and carbonyl ylides, respectively.1,2,539 The adduct generated may either dissociate from the catalytic species to form a “free ylide” or react as a metal-ligated ylide complex (Scheme 231). While the stereochemistry of this trans-

Scheme 232. Synthesis of Decarestrictine (198)

Scheme 231. Ylide Formation

[2,3]-Sigmatropic rearrangements of oxonium ylide intermediates may proceed with high levels of diastereoselectivity, as described in early studies by Johnson,550 Clark,544 and Doyle,552 for the reactions of ylides generated from allyl ethers and α-diazoketones. In the last example,552 a large excess of the erythro isomer was recorded for reactions with trans-alkenes, while the threo isomer was found to dominate for cis-alkenes (Scheme 233). Yakura has recently reported the application of stereoselective rhodium(II)-catalyzed oxonium ylide formation/[2,3]-sigmatropic rearrangement of α-diazo-β-ketoesters for the synthesis of 2-allyl-3-oxotetrahydrofurans553 and tetrahydrofuran-3-ones.554 The first example of catalyst-induced asymmetric induction in a [2,3]-sigmatropic rearrangement of a carbenoid-derived ylide was reported by McKervey and co-workers in 1992 (Scheme 234).406 In this seminal study, enantioselectivity of up to 30% ee was achieved for intramolecular oxonium ylide generation from an α-diazo-β-ketoester. In a later more extensive study, McKervey reported 60% ee for the analogous

formation can be affected through substrate control, in cases involving metal-ligated ylide complexes, asymmetric induction is also possible under the influence of enantiopure ligands on the metal, generally rhodium carboxylates or homogeneous copper complexes. These ylides are usually highly reactive species and readily undergo further reactions, both inter- and intramolecularly, to give stable products. The most common reactions of catalytically generated ylides include [2,3]-sigmatropic rearrangement of allyl-substituted intermediates, [1,2]-insertion or Stevens rearrangement (typical of oxonium, sulfur, and nitrogen ylides), and dipolar cycloaddition (typical of carbonyl ylides). 3.6.1. Oxonium Ylides. Early work by Nozaki, Kirmse, and Ando540−543 provided indications of the synthetic utility of oxonium ylide rearrangements for the formation of new C−C 10038


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Scheme 233. Diastereoselectivity of [2,3]-Sigmatropic Rearrangement

Scheme 235. Enantioselective Construction of a 2,8Dioxabicyclo[3.2.1]octane Ring System

Scheme 234. Catalytic Asymmetric Oxonium Ylide Formation/[2,3]-Sigmatropic Rearrangement of α-Diazo-βketoesters

pathway (Scheme 236).559 Similar catalyst-dependent chemoselectivity has also been observed by Clark560 and West.547,561 Scheme 236. Chromanone vs Benzofuranone Formation

reaction with a closely related substrate using Rh2((S)-PTTL)4 in hexane.555 In 2001, Hashimoto556 and Hodgson557 reported independent studies examining the same ylide transformation. Hashimoto demonstrated that this reaction may be conducted in toluene at 0 °C without loss of enantiocontrol. Hodgson investigated ylide reactions in the presence of two rhodium(II) binaphthyl phosphate catalysts, Rh2((R)-BNP)4 and the dodecyl-substituted Rh2((R)-DDBNP)4, and obtained ee’s of up to 62% when the reaction was carried out in benzene at 25 °C. Despite the potential for asymmetric induction demonstrated in these early investigations, reports of enantioselective oxonium ylide [2,3]-sigmatropic rearrangements in the recent literature have been limited. In 2009, Hashimoto and coworkers described the enantioselective construction of a 2,8dioxabicyclo[3.2.1]octane ring system via [2,3]-sigmatropic rearrangement of an oxonium ylide using chiral rhodium(II) carboxylates.558 In this study, Rh2((S)-TFPTTL)4, was shown to be a highly efficient catalyst for the enantioselective tandem cyclic oxonium ylide formation and [2,3]-sigmatropic rearrangement from an α-diazo-β-ketoester, providing the 2,8dioxabicyclo[3.2.1]octane core structure of zaragozic acids in up to 93% ee (Scheme 235). Calter had previously investigated the same transformation, reporting 47% yield and 34% ee for the reaction employing Rh2((S)-TBSP)4 in refluxing benzene. Competitive C−H insertion is a common occurrence in intramolecular cyclic oxonium ylide formation reactions. Chemoselectivity can be controlled by catalyst choice, with rhodium species typically found to favor C−H insertion, while copper complexes generally provide the ylide-derived product as the major chemoisomer.2 Thus, reaction employing rhodium(II) acetate produced predominately the chromanone product arising from C−H insertion; however, reaction in the presence of Cu(acac)2 resulted in exclusive formation of the benzofuranone product formed from the oxonium ylide

In 2010, Davies described highly enantioselective C−C bond formation via rhodium-catalyzed tandem ylide formation/[2,3]sigmatropic rearrangement between donor/acceptor carbenoids and allylic alcohols (Scheme 237a).562 By careful choice of substrates (highly substituted allyl alcohol and methyl phenyldiazoacetate or methyl styryldiazoacetate), catalyst [Rh2((S)DOSP)4], and solvent (pentane), [2,3]-sigmatropic rearrangement products were found to dominate over the formation of products from competing O−H insertion. High enantioselectivities (up to 98% ee) were achieved in this study for Scheme 237. Enantioselective Ylide Formation/[2,3]Sigmatropic Rearrangement

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intermolecular reactions with a variety of allylic substrates. Davies has recently extended this methodology to include the enantioselective synthesis of allenes by rhodium-catalyzed ylide formation/[2,3]-sigmatropic rearrangement between donor/ acceptor carbenoids and highly functionalized propargylic alcohols, with this process again dominating over alternative O−H insertion (Scheme 237b).563 The usefulness of the oxonium ylide/[2,3]-sigmatropic rearrangement has been highlighted in several recent publications describing the synthesis of complex ring systems. Examples include the synthesis of the A-ring fragment of gambieric acid as described by Clark and co-workers (Scheme 238),546 the iterative construction of polypyran domains

Scheme 240. Eight-Membered Oxacycle Formation

Scheme 238. Synthesis of a Gambieric Acid A Fragment

commonly found in polyether marine ladder toxins as reported by West and co-workers (Scheme 239),547 and Kumaraswamy’s highly diastereoselective preparation of eight-membered oxacycles (Scheme 240).548 Scheme 241. Synthesis of trans-Whisky Lactone Scheme 239. Iterative Polypyran Construction

3.6.1.2. [1,2]-Stevens Rearrangement. Early examples in this area include the copper-catalyzed tetrahydrofuran synthesis described by Nozaki and co-workers.540,564 This reaction was later explored by Katsuki and co-workers, who utilized tert-butyl diazoacetate and a chiral catalyst prepared from CuOTf and bipyridine ligand 199, providing a mixture of cis- and transtetrahydrofurans with enantioselectivities of up to 93% ee. The same ring expansion strategy has also been applied by Katsuki to the enantioselective synthesis of trans-whisky lactone (200) (Scheme 241).565 Catalyst-controlled [1,2]-rearrangement of oxonium ylides has also been demonstrated by Doyle, who reported enantioselective oxonium ylide formation/[1,2]-Stevens rearrangement of 1,3-dioxan-5-yl diazoacetates catalyzed by various chiral rhodium(II) carboxamidates.566 In this study, preferential formation of the ylide-derived product over the C−H insertion product could be achieved by careful choice of the catalyst (Scheme 242). The imidazolidinone catalyst Rh2 ((S)MPPIM)4 was found to provide the highest level of the

rearrangement product with moderate levels of enantiocontrol (65% ee). Competition between intramolecular [2,3]- and [1,2]rearrangements has also been described for reactions of cyclic allylic oxonium ylides.556,550 Brogan and co-workers have reported that cyclization of the six-membered ring ylide 201 provides exclusively the [1,2]-shift-derived product 202 in the presence of both rhodium and copper catalysts (Scheme 243).567 3.6.2. Sulfonium Ylides. Unlike oxonium ylides, the isolation of sulfur ylides is possible if the ylide carbon is flanked by two stabilizing electron-withdrawing groups and if the ylide generated is not prone to subsequent rapid rearrangement reactions. Both Porter568 and Tamura569 have reported the isolation of sulfonium ylides generated from 10040


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although poor yields were often obtained. Selected examples are highlighted in Scheme 246.

Scheme 242. Ylide Rearrangement vs C−H Insertion

Scheme 245. [2,3]-Sigmatropic Rearrangements of Sulfur Ylides

Scheme 243. [1,2]-Rearrangement of Ylide 201

Scheme 246. Copper-Catalyzed Reactions

thiophene and thioxanthene, respectively. The reaction of sulfoxides with diazocarbonyl compounds in the presence of a transition-metal catalyst has also been shown to produce stable sulfur ylides. The isolation of sulfoxonium ylides has been reported in the literature for both inter- and intramolecular processes,570,571 although in general rearrangements with sulfoxonium ylides have been less widely explored than those with their sulfonium counterparts (Scheme 244).

More recently, Wang and co-workers have reported the first example of rhodium-catalyzed sulfonium ylide generation for the Sommelet−Hauser rearrangement.573 The ylides required for this [2,3]-rearrangement reaction are typically generated by deprotonation of a sulfonium salt with a strong base; however, as shown in Scheme 247, the thia-Sommelet−Hauser rearrangement may also proceed under transition-metalcatalyzed conditions. Thus, the initially formed sulfur ylide 203 tautomerizes to generate ylide 204, which may subsequently undergo consecutive [2,3]-sigmatropic dearomatization and [1,3]-shift rearomatization to give the orthosubstituted aromatic product. Wang has used this methodology to prepare a series of 3-(arylthio)-1,3-disubstituted oxindoles by rhodium-catalyzed reaction of various α-diazoester compounds and sulfenamides (Scheme 247).574 The catalog of catalysts for the [2,3]-sigmatropic rearrangement of sulfur ylides has been extended beyond copper and rhodium to include a wider range of transition-metal complexes. Iron(III) corroles and porphyrins have been shown to be efficient catalysts for the [2,3]-sigmatropic rearrangement of ylides formed by reaction of sulfides with diazoacetates, with high yields and very short reaction times typically recorded (Scheme 248).473 Catalytic asymmetric [2,3]-sigmatropic rearrangements of sulfur ylides were first reported in 1995 by Uemura and co-

Scheme 244. Stable Sulfur Ylides

3.6.2.1. [2,3]-Sigmatropic Rearrangement. Metal-catalyzed sulfonium ylide [2,3]-sigmatropic rearrangements are highly versatile synthetic transformations and have been reported with a wide range of copper and rhodium species. Early examples include the reactions of 3,3,3-trifluoro-2-diazopropionate with allyl, propargyl, and allenic sulfides in the presence of rhodium(II) acetate to produce [2,3]-sigmatropic rearrangement products in high yield (Scheme 245).572 Coppercatalyzed processes are also common in the early literature, 10041


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Scheme 247. Rhodium-Catalyzed Thia-Sommelet−Hauser Rearrangement

Scheme 249. Catalytic Asymmetric [2,3]-Sigmatropic Rearrangement

Scheme 250. Effect of Sulfides on Enantioselectivity

While, typically, low-to-moderate levels of asymmetric induction are achieved for [2,3]-sigmatropic rearrangements with diazoacetate substrates, improved levels of enantiocontrol have been reported for reactions of aryldiazoacetates. Wang and co-workers observed good enantioselectivity for the reactions of various aryldiazoacetates with propargyl sulfides to give allene derivatives.578 Both copper and rhodium complexes were found to be efficient catalysts for the rearrangement reaction shown in Scheme 251, with copper bisoxazoline and Rh2((S)-DOSP)4

Scheme 248. Iron Porphyrin-Catalyzed [2,3]-Sigmatropic Rearrangement

Scheme 251. Rearrangements of Ylides from Aryldiazoacetates

workers (Scheme 249).575 Although stereoselectivities obtained in this early study were poor (≤20% ee), the potential to induce enantioselectivity in this transformation was successfully demonstrated, and this was subsequently exploited by several research groups. Katsuki and co-workers explored the reactions of related allyl aryl sulfides and diazoacetic acid esters, with up to 74% ee obtained for [2,3]-sigmatropic rearrangements of sulfur ylides in the presence of a cobalt(III) salen catalyst.576 In 2000, McMillen and co-workers demonstrated that the structure of the sulfide has an important influence on enantiocontrol in the [2,3]-rearrangement step. Thus, increasing asymmetric induction was recorded for increasing steric bulk of the sulfide substituent, with the highest levels of enantioselectivity obtained for reaction of the 2,6-dimethylphenyl and (+)-menthyl derivatives (Scheme 250).577

providing the allene products in 80% and 73% ee, respectively. Wang later examined this transformation using water as the reaction solvent, with good enantioselectivity again recorded for reactions in the presence of Rh2((S)-DOSP)4 and Rh2(4(S)MPPIM)4.579 In an effort to achieve even greater levels of enantiocontrol for the [2,3]-sigmatropic rearrangement of sulfur ylides, Wang and co-workers examined a double-asymmetric-induction approach using diazoacetamides derived from Oppolzer’s camphor sultam in conjunction with copper catalysts possessing bisoxazoline or Schiff base ligands.580 Such a strategy was found to result in high levels of enantioselectivity for reactions of various diazoacetamides and allyl 2-chlorophenyl sulfide 10042


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reaction of 1,3-oxathiolanes and diazomalonates in the presence of various copper bisoxazoline catalysts. Optimal results were achieved for reaction with dibenzyl-substituted diazomalonates, 1,3-oxathiolanes with an electron-withdrawing-group-substituted (X = Cl, Br, CF3) benzene ring, and a copper catalyst generated from Cu(OTf)2 and ligand 207 (Scheme 254).

(Scheme 252). Notably, similar enantiocontrol was observed in this study for reactions catalyzed by the enantiopure Schiff base Scheme 252. Rearrangements of Sultam-Derived Ylides

Scheme 254. Catalytic Asymmetric [1,2]-Stevens Rearrangement

ligand 195 and the achiral ligand 205, indicating that asymmetric induction is dominated by the sultam auxiliary. 3.6.2.2. [1,2]-Stevens Rearrangement. The formation of sulfur ylides and subsequent [1,2]-Stevens rearrangement has been applied as a key C−C bond forming strategy in several syntheses of natural products. Early examples include the preparation of the pyrrolizidine alkaloids (+)-heliotridine, (+)-retronecine,581,582 (±)-trachelanthamidine, (±)-isoretronecanol, and (±)-supinidine583,584 and the aromatic sesquiterpenes (±)-laurene and (±)-cuparene.585,586 Recently, Porter has described the synthesis of the core structure of the RNA polymerase inhibitor tagetitoxin utilizing intramolecular sulfur ylide formation followed by [1,2]rearrangement to give the nonane ring system (Scheme 253).587,588 Interestingly, attempts to induce thermal rearrange-

3.6.3. Ammonium Ylides. Reports of reactions of ammonium ylides generated from metal carbenoids are less frequent in the literature than those of their oxygen and sulfur counterparts. This is likely due to the strongly Lewis basic nature of the nitrogen atom of the amine precursors which can complex tightly to the transition metal, often rendering the catalyst inactive.590 Nonetheless, the synthetic potential of nitrogen ylides has been demonstrated for both inter- and intramolecular processes. 3.6.3.1. [2,3]-Sigmatropic Rearrangement. Rhodium-catalyzed [2,3]-sigmatropic rearrangement of ammonium ylides has been reported by Doyle and co-workers as an efficient method for the synthesis of substituted homoallylamines (Scheme 255).591 Good yields are achieved for reactions conducted with

Scheme 253. Synthesis of the Tagetitoxin Skeleton Scheme 255. [2,3]-Sigmatropic Rearrangement of Ammonium Ylides

excess amine and slow addition (24−30 h) of the diazo substrate, both of which help to suppress competing carbenoid dimerization. The first efficient and general copper-catalyzed [2,3]sigmatropic rearrangement of tetrahydropyridinium ylides was described in 2003 by Sweeney and co-workers.592 A large substrate scope was demonstrated in this study, with a range of diazoester and N-methyltetrahydropyridine components found to provide functionalized pyrrolidine products in good to excellent yields (Scheme 256). The nature of the α-substituent of the diazo substrate was found to be particularly important in these transformations, with electron-withdrawing substituents found to enhance product yields. In contrast to intermolecular reactions of ammonium ylides, intramolecular addition of tertiary amines to metal carbenes is a far more common process. There is no requirement for excess amine. The intramolecular [2,3]-rearrangement of ammonium ylides has been reported by Clark and co-workers as a general

ment of the sulfonium ylide intermediate 206 were unsuccessful, with the less commonly employed photochemically induced Stevens rearrangement instead providing the desired bicyclic core structure. In 2009, Tang and co-workers reported the first example of a catalytic asymmetric [1,2]-Stevens rearrangement of sulfur ylides.589 In this work, optically active 1,4-oxathianes were prepared in high yields and with excellent stereoselectivities by 10043


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copper(II) acetylacetonate again found to be the optimal catalyst in both studies. More recently, Sweeney has reported ene-endo-spirocyclic ylides as a new class of ammonium ylides for [2,3]-sigmatropic rearrangements.597 As shown in Scheme 259, the tetrahy-

Scheme 256. Cu-Catalyzed Rearrangement of Tetrahydropyridinium Ylides

Scheme 259. Reactions of Ene-Endo-Spirocyclic Ylides

route for the synthesis of cyclic aminoketones (Scheme 257).593 Copper(II) acetylacetonate was found to be the Scheme 257. Synthesis of Cyclic Aminoketones

superior catalyst over rhodium(II) acetate for this transformation, providing five- to seven-membered cyclic amines in high yield (73−84%) and eight-membered heterocycles in modest yield (39%). Clark has also described the synthesis of bicyclic amines using this methodology.594 The stereoselectivity of the [2,3]rearrangement of ammonium ylides in this study was found to be highly dependent on the structure of the diazo starting material. Thus, five-membered ring products were formed as a single diastereomer, while the homologous six-membered products were obtained as a mixture of cis and trans isomers formed via two different ylide intermediates (Scheme 258),

dropyridine-derived spiro[6,7]-ylides were found to undergo mainly [2,3]-rearrangement with minor amounts (23%) of the [1,2]-Stevens rearrangement-derived product also observed. In contrast, the analogous spiro[6,6]-ylides were observed to provide roughly equal amounts of the [2,3]- and [1,2]rearrangement products. This method represents a novel route for the synthesis of the core structures of a range of bicyclic alkaloids. 3.6.3.2. [1,2]-Stevens Rearrangement. Limited examples exist of the intermolecular generation/[1,2]-rearrangement of nitrogen ylides. West and co-workers have reported the synthesis of α-aminoketones and α-aminoesters via the intermolecular reaction of tertiary amines and α-diazoketones and α-diazoesters, respectively (Scheme 260).598 As previously described for the intermolecular [2,3]-sigmatropic rearrangement of ammonium ylides, a large excess of the amine is

Scheme 258. Formation of Five- and Six-Membered Rings

Scheme 260. Intermolecular Ammonium Ylide Formation/ [1,2]-Rearrangement although, notably, the cis isomer was found to epimerize to the thermodynamically more stable trans diastereomer upon contact with silica gel. The [2,3]-sigmatropic rearrangement of ammonium ylides generated from metal carbenoids has been exploited by Clark for the synthesis of novel α-substituted and α,α-disubstituted amino acids,595 and for the preparation of the skeleton of the polycyclic alkaloid manzamine A,596 with 10044


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required for successful product synthesis. Copper powder was found to be the optimal catalyst in this study, with rhodium(II) acetate proving ineffective due to likely complexation with nitrogen. West has carried out several studies examining intramolecular ammonium ylide formation/[1,2]-Stevens rearrangement, reporting the preparation of substituted piperidin-3-ones from acyclic 5-(dialkylamino)-1-diazopentan-2-ones,599 and the synthesis of substituted morpholin-2-ones from 2-(N,Ndialkylamino)ethyl diazoacetates.600 In 1994, West described a concise, enantioselective route to the alkaloid (−)-epilupinine (208) from proline ester using [1,2]-rearrangement of a spirocyclic ylide intermediate as the key C−C bond-forming step. As shown in Scheme 261, copper-catalyzed cyclization of

Scheme 262. Synthesis of the Cephalotaxane Ring Skeleton

Scheme 263. Synthesis of Isoindolobenzazepine Alkaloids

Scheme 261. Synthesis of (−)-Epilupinine (208)

Scheme 264. Synthesis of the Pyrrolo[1,2a][1,4]benzodiazepinone Ring System

(R1 = Ph; R2 = Me) gives a relatively soft nucleophilic ylide that undergoes 1,4-addition/cyclization with the α,β-unsaturated carbonyl substrate, while the hard ylide species generated from reaction of aniline and ethyl diazoacetate (R1 = H; R2 = Et) reacts preferentially at the carbonyl carbon in a 1,2-addition fashion. This methodology has also been described for oxonium ylides, which have been shown to undergo nucleophilic addition with a range of electrophiles, including aldehydes and activated ketones.523,608−610 3.6.4. Carbonyl Ylide 1,3-Dipolar Cycloaddition. Ylides formed by reaction of diazocarbonyl-derived carbenoids with carbon−oxygen double bonds are reactive intermediates which undergo further reactions such as 1,3-dipolar cycloaddition,269,611−621 cyclization to epoxides,353,622 and hydride transfer502 (Scheme 266). The 1,3-dipolar cycloaddition is the most common reaction pathway and is the focus of this section. The formation of ylides may be intra- or intermolecular, as can the 1,3-dipolar cycloaddition; thus, one-, two-, or three-component reactions are possible, usually leading to products with several stereocenters, often with a high degree of selectivity. This means that these reactions have

the proline-derived starting material generates two diastereomeric spirocyclic ylides which undergo subsequent [1,2]rearrangement to provide the quinolizidine products (84% yield), the major isomer of which is then converted to 208 in three steps.601,602 This methodology has been applied to the synthesis of several biologically active compounds, including the cephalotaxine ring skeleton (Scheme 262),603 isoindolobenzazepine alkaloids (Scheme 263),604 and the novel pyrrolo[1,2-a][1,4]benzodiazepinone system (Scheme 264).605 3.6.3.3. Nucleophilic Reactions of Ammonium Ylides. Recently, Hu and co-workers have demonstrated that ammonium ylides generated in situ from diazoacetates and anilines can react in a highly regiospecific manner with β,γunsaturated α-ketoesters to generate either β-hydroxy α-amino acid derivatives (via 1,2-addition) or substituted 2,3-dihydropyrroles (via tandem 1,4-addition/cyclization).606,607 The regioselectivity of this transformation is dependent on both the hard/soft nature of the ammonium ylide and the electronic nature of the diazoacetate. Thus, as shown in Scheme 265, reaction of aniline and a donor/acceptor-substituted carbenoid 10045


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Scheme 265. Reactions of Ylides from Aniline

Scheme 267. Formation of Dioxolanes and Dihydrofurans

dimethyl acetylenedicarboxylate, a mixture containing 213, 214, and some dioxolanes, 209−212, was obtained. The nature of the diazo compound also has a strong influence on the reaction pathway.624 While dimethyl diazomalonate reacted with aldehydes to form dioxolane 215 and/or epoxide 216, in ratios that were dependent on the electronic nature of the aldehyde, methyl diazoacetoacetate reacted with electron-rich and electron-poor aldehydes to form the dioxolene product 217 exclusively, through intramolecular trapping of the ylide (Scheme 268). Scheme 268. Formation of Dioxolanes, Epoxides, and Dioxolenes

Scheme 266. Generic Reactions of Carbonyl Ylides

found wide application in organic synthesis. As is the case with onium ylides, the reactions can take place either via a free ylide, in which case the catalyst has no influence on the stereochemical outcome of the reaction, or via a metal ylide, in which case asymmetric induction due to the influence of a chiral catalyst is possible. 3.6.4.1. Intermolecular Ylide Formation. Doyle and coworkers examined stereocontrol in the reaction of diazocarbonyl compounds with aldehydes to form dioxolanes, and reported that there is an influence of the catalyst on the diastereoselectivity of reactions involving p-nitrobenzaldehyde, but not in the case of p-anisaldehyde.623 Thus, reaction of anisaldehyde with ethyl diazoacetate afforded roughly equal amounts of the dioxolanes 209 and 210, and only trace amounts, if any, of 211 and 212. The reactions with pnitrobenzaldehyde provided mixtures containing all four diastereomers, indicating that a metal-stabilized ylide is involved (Scheme 267). When ethyl diazoacetate reacted in the presence of p-anisaldehyde and dimethyl acetylenedicarboxylate, the trans-dihydrofuran 213 was formed as the sole product, while in the presence of p-nitrobenzaldehyde and

Jiang and co-workers reported that methyl diazo(trifluoromethyl)acetate reacts with aryl aldehydes to form dioxolanes with high diastereoselectivity; for example, the di-pfluoro- and di-p-methoxy-substituted dioxolanes were isolated in 89% and 95% yields, respectively, as single diastereomers. The presence of an ortho substituent on the aldehyde led to a diastereomer ratio of ∼9:1 (Scheme 269).625 Although aryldiazoacetate esters generally react with aldehydes and ketones to give epoxides, Hu and co-workers Scheme 269. Dioxolane Formation via Methyl Diazo(trifluoromethyl)acetate

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ylides generated from aryl aldehydes and dimethyl diazomalonate, leading to moderate to good yields of substituted spirodioxolanes and tetrahydrofurans, respectively (Scheme 273).

found that methyl phenyldiazoacetate reacts in the presence of a mixture of electron-rich and electron-deficient aryl aldehydes to form the “crossed product” dioxolanes as the major product, with only two diastereomers observed.626 While p-nitrobenzaldehyde and p-anisaldehyde gave rise to 50% dioxolanes in a 45:55 ratio (accompanied by 13% and 11% methoxy and nitro epoxides, respectively), use of 2,4-dinitrobenzaldehyde gave 95% dioxolanes with an 81:19 dr. The reaction appears not to involve a metal-associated ylide as the dr is independent of the catalyst (Rh2(OAc)4, Rh2(cap)4, Rh2(DOSP)4) and the DOSP-catalyzed reaction gave racemic products (Scheme 270).

Scheme 273. Reactions of Ylides from Dimethyl Diazomalonate and Benzaldehyde

Scheme 270. Formation of “Crossed Product” Dioxolanes

Muthusamy and co-workers reported that diazooxindoles react in the presence of mixtures of aryl aldehydes substituted with electron-donating and electron-withdrawing groups to furnish a single isomer of the unsymmetrical spirodioxolanes (Scheme 271).627

Hu and Doyle reported the reaction of diazoindane-1,3-dione with aldehydes and maleimides to form structurally constrained tetrahydrofuran derivatives that were of interest as analogues of tRNA synthetase inhibitors. Good yields of the adducts were obtained, with a preference for the endo adduct (Scheme 274);

Scheme 271. Formation of Spirodioxolanes

Scheme 274. Reaction of Diazoindane-1,3-dione with Benzaldehyde and Maleimide

Jamison and co-workers reported that an aldehyde functionalized with a dicobalt hexacarbonyl cluster participates in highly diastereoselective three-component reactions with ethyl diazoacetate and dipolarophiles. The uncomplexed acetylenic aldehyde gave rise to a low yield of the other diastereomer, with lower selectivity (Scheme 272).628 Nair and co-workers have reported studies using quinones629 and nitrostyrenes630 as dipolarophiles in conjunction with adducts were also formed with dimethyl acetylenedicarboxylate and dimethyl fumarate.631 A more recent study by Hu described the reaction of phenyldiazoacetates with cinnamaldehydes and nitrostyrenes to give substituted tetrahydrofurans.632 Zhu and co-workers described the reaction of acceptor/ acceptor diazoesters with aromatic aldehydes and dimethyl acetylenedicarboxylate to obtain dihydrofurans in moderate to high yields and diastereoselectivities. The competing formation of dioxolanes could be suppressed by using bulkier ester groups, leading to better yields of dihydrofurans (Scheme 275). Higher diastereoselectivity was observed with electron-poor aldehydes.633 Fox reported the highly diastereoselective formation of dioxolanes from α-alkyl-α-diazoesters, accompanied by only minor amounts of β-elimination products.634 A subsequent

Scheme 272. Ylide Formation with Complexed and Uncomplexed Acetylenic Aldehydes

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Scheme 278. Formation of syn-β-Amino Alcohols

Scheme 275. Reaction of an Acceptor/Acceptor Diazocarbonyl Substrate with Benzaldehyde and DMAD

report described the formation of dihydro- and tetrahydrofuran products from three-component reactions (Scheme 276).635 In terms of yield, the catalyst of choice for these reactions was Rh2(piv)4, although the catalyst did not affect the diastereomer ratio of the product. Scheme 276. Reactions of α-Alkyl-α-diazoesters

Scheme 279. Formation of a Spiro[oxindole-3,4′oxazolidine]

Rh2(OAc)4 and CuCl gave predominantly exo selectivity, while more Lewis acidic Cu(OTf), or CuCl combined with Yb(OTf)3, gave greater endo selectivity. Reactions with Rh2(5(S)-MEPY)4 or Cu(OTf)−bisoxazoline afforded low levels of enantioselectivity, the first reported example of asymmetric induction in an intermolecular carbonyl ylide cycloaddition reaction (Scheme 280).640

Very recently, Suga described diastereoselective formation of tetrahydrofurans via reactions of α-alkyldiazoacetate esters, aldehydes, and crotonic acid derivatives. It was noted that including metal salts such as Co(BF4)2·6H2O, Ni(BF4)2·6H2O, or AgBF4 afforded high diastereoselectivities and suppressed dioxolane formation (Scheme 277).636

Scheme 280. Intramolecular Ylide Formation and Reaction with N-Phenylmaleimide

Scheme 277. Diastereoselective Formation of Tetrahydrofurans

The reaction of carbonyl ylides with aldimines to afford oxazolidines, which were hydrolyzed to syn-β-amino alcohols, has also been described. Reactions with chiral diazoacetates or aldimines proceed with moderate to good diastereoselectivity, while chiral catalysts afford modest enantioselectivity, indicating that in this instance a metal-associated ylide is involved (Scheme 278).637,638 The ylides formed from dimethyl diazomalonate and aromatic aldehydes react with isatin ketimines to form spiro[oxindole-3,4′-oxazolidine]s in high yields and with excellent diastereoselectivity (Scheme 279).639 3.6.4.2. Tandem Intramolecular Ylide Formation/Intermolecular Cycloaddition. Suga and Ibata examined the reactivity of the diazo compound 218 with maleimides and found that the exo/endo selectivity was strongly influenced by the catalyst.

Subsequent reports from Suga showed moderate enantioselectivity in reactions of diazoketone 218 with aldehydes, catalyzed by Rh2(OAc)4 and Yb(BNP)3,641 and later that high levels of enantioselectivity are possible through the combination of Rh2(OAc)4 with rare-earth triflates and pybox ligands.642−644 The combination of Rh2(OAc)4 and Lewis acid was also applied to inverse electron demand cycloadditions,645,646 and to the reactions of carbonyl ylides with imines.647 Garciá Ruano described the reaction of the ylide derived from diazoketone 218 with enantiopure vinyl sulfoxides as dipolarophiles, reporting very high regioselectivity, and that the resulting adducts can be isolated in moderate to good yields. 10048


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The sulfinylfuranone 219 reacts with complete facial selectivity to form a 76:24 mixture of the anti-exo and anti-endo adducts which were isolated in 51% and 23% yields, respectively. At 0 °C the exo:endo ratio was improved to 81:19 (Scheme 281).648

Scheme 283. Ruthenium Porphyrin-Catalyzed Reactions

Scheme 281. Reaction with a Vinyl Sulfoxide Dipolarophile

to be capable of over 5000 turnovers over several reaction runs.651 The nature of the ketone terminus was shown to have a strong effect on the diastereoselectivity of the reactions.652 The reactions of carbonyl ylides with allene carboxylates were described by Harned and co-workers. Yields of 50−90% with endo:exo ratios of 2.7:1 to 4:1 were obtained. The reactions could be carried out at 65 °C for 12 h, although it was found that the reaction times were considerably shorter when conducted at 150 °C under microwave irradiation; the same diastereomer ratio was obtained under these conditions (Scheme 284).653

Muthusamy and co-workers have described the intramolecular formation of carbonyl ylides followed by 1,3-dipolar cycloaddition reactions with aromatic aldehydes, α,β-unsaturated aldehydes, α,β-unsaturated ketones, and a dienone, which leads to a variety of epoxy-bridged tetrahydropyranone ring systems in a diastereoselective manner (Scheme 282). The

Scheme 284. Reaction with an Allene Carboxylate Dipolarophile

Scheme 282. Intramolecular Carbonyl Ylide Formation Reactions

Reactions with cyclopropenes have been described by Molchanov and co-workers, affording cyclopropane-fused adducts in moderate to good yield, with generally high exo selectivity. Electron-withdrawing groups attached to the cyclopropene ring dramatically reduced the yields.654,655 Reactions with methylenecyclopropanes as dipolarophiles were less selective (Scheme 285).656 Very recently, Chouraqui and Commeiras have demonstrated intermolecular cycloaddition reactions of alkylidene butenolides with carbonyl ylides, affording adducts with complete chemoand diastereoselectivity, in yields of 43−62% (Scheme 286).657 Harwood and co-workers described the reactions of chiral mesoionic isomünchnone dipoles with dipolarophiles, using chiral auxiliaries derived from phenylgycinol (Scheme 287). Moderate diastereofacial selectivity and good endo selectivity were observed in reactions with maleimides or dimethyl acetylenedicarboxylate, while excellent diastereofacial and exo selectivity were obtained in reactions with aldehydes, but with slightly lower yields.658,659 The aldehyde-derived adducts could be converted into enantiopure α,β-dihydroxy acids.660 Subsequently, reactions with imines were shown to give

reactions with α,β-unsaturated aldehydes and the dienone gave exclusive CO cycloaddition, while reactions with α,βunsaturated ketones afforded mixtures of CO and CC cycloaddition products.649 The formation of spirocarbocycles from α-methylene cyclic ketones was also described, in which the stereoselectivity was dependent on the ylide ring size.650 Che and co-workers have reported that ruthenium(II) tetraarylporphyrin complexes catalyze a broad range of reactions of ylides with carbon−carbon and carbon−oxygen double bonds, with results comparable to those of reactions catalyzed by Rh2(OAc)4. Two examples are shown in Scheme 283. A recyclable soluble PEG-supported complex was shown 10049


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Scheme 285. Reactions with Cyclopropene Dipolarophiles

Scheme 288. Adducts from Diazo Pyrrolidone-Derived Isomünchnones

selectivity (Scheme 289).663 The application of intermolecular cyclizations of isomünchnones to form pyridone,664−666 Scheme 289. Isomünchnone Adduct from an Amino AcidDerived Diazoester

Scheme 286. Reaction with an Alkylidene Butenolide Dipolarophile

carboline,667 and indolizinone668 ring systems have been described by Padwa and co-workers. The same group have also described intermolecular cyclizations of carbonyl ylides669−672 and push−pull carbonyl ylides.673,674 Savinov and Austin reported diastereoselective cycloaddition of vinyl ethers with isomünchnones,675 and later developed a substrate with a chiral auxiliary that delivered a diastereomeric excess of over 95% (Scheme 290).676 A solid-supported auxiliary was also used, affording the same level of diastereoselectivity as observed in the solution-phase reactions.677 Release of the products from the auxiliary for both the solution- and solid-phase reactions was achieved by aminolysis, affording products with high enantioselectivity. Hodgson and co-workers have described intermolecular reactions of carbonyl ylides with norbornene, styrenes, and phenylacetylene in the presence of various chiral rhodium catalysts (Scheme 291). Reactions catalyzed by Rh2(DOSP)4 gave yields of 40−83% and up to 81% ee, while reactions catalyzed by Rh2(DDBNP)4 gave yields of 40−75% and up to 82% ee. Reactions with Rh2(DDBNP)4 at lower temperatures gave lower yields but improved enantiocontrol (up to 92% ee).678−681 The use of allene or propargyl dipolarophiles, toward the synthesis of nemorensic acids, led to lower enantioselectivities (maximum 51% ee).682−684 High enantioselectivity was observed by Hashimoto and coworkers in Rh2(BPTV)4-catalyzed reactions of ylides derived from ketone-functionalized diazoketones with dimethyl acetylenedicarboxylate. For example, the diazo compound 221 gave rise to the adduct 222 in 79% yield and 90% ee.685 Reactions of related diazoesters were somewhat variable; under similar

Scheme 287. Phenylglycinol-Based Isomünchnone Dipole Reactions

enantiopure α-amino-β-hydroxy acids.661 The chiral auxiliary could be recovered and recycled. Padwa and Prien studied the facial selectivity of reactions of dipolarophiles with isomünchnones. The reaction of the pyrrolidone diazo compound 220 was found to give the exo adduct as the major diastereomer. Inclusion of a substituent in the pyrrolidone ring enhanced the exo selectivity; if the substituent was in the 5-position, the syn diastereomer was preferred, while a substituent in the 3-position led to the anti diastereomer preferentially (Scheme 288).662 The same workers also studied the stereocontrol in reactions of amino acid-derived isomünchnones and observed high exo-syn 10050


Chemical Reviews

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Scheme 290. Diastereoselective Cycloaddition of Ethyl Vinyl Ether with Isomünchnones

Scheme 292. Catalyst-Controlled Asymmetric Induction

Immobilized variants of Rh2(TCPTTL)3(PTTL) have also been studied in a continuous-flow system, and it was shown that good yields and excellent enantioselectivity are possible; in the extreme example, a turnover number of close to 12 000 was recorded.691 Very recently, Hashimoto has described the application of Rh2(TCPTTL)4 to reactions with allene dipolarophiles, obtaining products in up to 82% yield and 99% ee.692 3.6.4.3. Tandem Intramolecular Ylide Formation/Intramolecular Cycloaddition. The first example of catalystcontrolled asymmetric induction in a carbonyl ylide [3 + 2]cycloaddition was described by Hodgson and co-workers in 1997. A diazoketoester containing remote ketone and alkene groups was shown to undergo intramolecular ylide formation and cycloaddition in the presence of Rh2(DOSP)4 to afford the tricyclic adduct with an enantiomeric excess of 52%.693 It was subsequently demonstrated by the same group that the enantioselectivity could be improved to 90% ee by using Rh2(DDBNP)4 (Scheme 293).694−696 Further studies examined nonterminal alkenes and alkynes,697 aryl-terminated diazoke-



conditions in the presence of Rh2(PTTL)4, diazo compound 218 afforded the DMAD adduct 223 in 67% yield and 74% ee, while the benzo-fused analogue gave the adduct 224 in 71% yield and 93% ee. The benzoate-substituted diazoketone 225 afforded poor yields and enantioselectivity for the adduct 226 (Scheme 292).686 More recently, Hashimoto has also studied the use of aldehydes,687,688 styrenes and acetylenes,689 and indoles690 as dipolarophiles in conjunction with these catalysts. 10051


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tones,698 and diazosulfones.699 The sequential one-pot combination of cross-metathesis followed by ylide formation and cycloaddition was also described (Scheme 294).700,701

Scheme 296. Reactions of Vinyl Sulfonate Ylide Precursors

Scheme 294. Sequential Cross-Metathesis and Ylide Dipole Cycloaddition

Scheme 297. Reactions of Tethered γ-Alkylidenebutenolides

Chiu and co-workers have reported intramolecular reactions with allene-substituted ylide precursors; a single diastereomer of the oxatricyclic products was formed. Three- or four-carbon linkers led to the formation of five- or six-membered fused ring products in each case through reaction with the internal double bond of the allene. The shorter chain linked compound reacted with the terminal bond of the allene, leading to an endocyclic cycloalkene (Scheme 295).702 Chiu and Metz demonstrated intramolecular cyclizations of vinyl sulfonate-substituted diazo compounds leading to the formation of polycyclic sultones (Scheme 296).703

An interesting example of intermolecular ylide formation/ intramolecular cycloaddition was described by Johnson. For example, methyl phenylsulfonyldiazoacetate reacts with 5hexynal, affording the adduct 227, which readily loses phenylsulfinic acid to form the tetrahydrofuran 228 (Scheme 299).715 3.6.4.4. Examples in Synthesis. The highly regio- and stereoselective nature of carbonyl ylide 1,3-dipolar cycloadditions permits the rapid buildup of molecular complexity, with simultaneous establishment of multiple stereocenters. The examples that follow demonstrate that cascade reactions of diazocarbonyl compounds have been applied to good effect in the synthesis of complex natural products, using both substrate and catalyst control of stereochemistry. In some cases, careful substrate design or application of chiral catalysts is required to ensure formation of the desired stereochemistry. 3.6.4.4.1. Substrate-Controlled Reactions. The Padwa group has published several studies, including formal and total syntheses. Examples include studies toward aspidospermine (230)716,717 and kopsifolines718,719 from push−pull ylides formed from 229 and 231, respectively, approaches to the lysergic acid (232)720 and mersicarpine721 skeletons, via isomünchnones, and the preparation of a carbon analogue of ribasine722 and the skeleton of komaroviquinone (233).723,724 Formal syntheses include illudin M (234),725,726 lycopodine (236),727 via the Stork intermediate 235, and vallesamidine (238),728 via the Heathcock intermediate 237; the latter two intermediates were prepared via isomünchnone cycloadducts. The full syntheses of vinca alkaloids 3H-epivincamine (239), tacamonine (240), and apotacamine (241),729,730 and of (±)-aspidophytine (242), have been described.731,732 Selected examples of these natural products and key intermediates are collected in Schemes 300−307.

Scheme 295. Reactions of Allene-Substituted Ylide Precursors

Tethered γ-alkylidenebutenolides also undergo intramolecular cycloaddition with carbonyl ylides. The diastereoselectivity was found to depend on the length of the tether, although extending the tether beyond four carbon atoms leads to formation of 4H-pyran products due to 1,4-shift (Scheme 297).657 Extensive investigations by the Padwa group describe the intramolecular cyclizations of a variety of isomü n chnones704−707 and carbonyl ylides.708−714 Some representative examples are illustrated in Scheme 298. 10052


Chemical Reviews

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Scheme 298. Selected Examples from the Padwa Group

Scheme 300. Synthesis of Aspidospermine and Kopsifoline

Scheme 301. Synthesis of Lysergic Acid

Scheme 299. Intermolecular Ylide Formation/ Intramolecular Cyclization

Scheme 302. Komaroviquinone

Some of the earliest examples of the application of carbonyl ylide dipolar cycloadditions to complex natural product synthesis include Dauben’s synthesis of the tigliane skeleton (Scheme 308)733 and McMills’s approach to the unfunctionalized phorbol ring system (Scheme 309).734 Illudin M (234)

was also synthesized by Kinder,735 the key step using an ylide approach similar to that described by Padwa.725,726 Baldwin and co-workers reported the intramolecular cyclization of the alkyne-substituted diazo compound 243 10053


Chemical Reviews

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Scheme 303. Synthesis of Illudin M

Scheme 306. Synthesis of Vinca Alkaloids

Scheme 304. Synthesis of the Stork Intermediate and Lycopodine

Scheme 307. Synthesis of Aspidophytine

Scheme 305. Synthesis of the Heathcock Intermediate and Vallesamidine

Scheme 308. Synthesis of the Tigliane Skeleton

Scheme 309. Synthesis of an Unfunctionalized Phorbol Ring System

during the synthesis of some benzo analogues of tropolone natural products. The adduct was isolated in 74% yield (Scheme 310).736 Wood and co-workers described the synthesis of (±)-epoxysorbicillinol (244) via the intermolecular reaction of an acylmalonate-derived ylide with methyl propiolate as the key step. The adduct was formed as a single diastereomer (Scheme 311).737

The diazoester 245 reacts with 3-butyn-2-one in the presence of Rh2(OAc)4 to form the adduct 246, which is a key intermediate in Hashimoto’s synthesis of zaragozic acids A and C (Scheme 312).738−741 The same group have described the synthesis of polygalolides A and B via the intramolecular adduct 247 (Scheme 313).742,743 Carbonyl ylide strategies toward the 10054


Chemical Reviews

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Scheme 310. Benzotropolone Formation

Scheme 313. Synthesis of Polygalolides A and B

Scheme 311. Synthesis of the Epoxysorbicillinol Intermediate

Scheme 314. Synthesis of Colchicine

Scheme 312. Zaragozic Acid Synthesis

Scheme 315. Guaiane Approach

zaragozic acid core have also been reported by Hodgson744−746 and by researchers at Merck.747 The intramolecular reaction of an ylide derived from diazoketone 248 carrying a tethered alkyne function was applied by Schmalz and co-workers during the synthesis of (−)-colchicine (249) and (−)-isocolchicine, with a diastereomeric excess of >98% achieved for the key cyclization (Scheme 314).748 Related studies toward oxa-B-ring colchicine analogues were also described by Schmalz.749 The approach to an oxobridged guaiane sesquiterpenoid ring system was described by Maier and co-workers; however, the facial selectivity of the adduct formation, determined from the crystal structure of 250, led to the wrong stereochemistry to be carried forward to the natural product (−)-englerin A (251), which was the target of the study (Scheme 315).750

Another intramolecular cycloaddition was used by Lee and co-workers, in a formal synthesis of the broad-spectrum antibiotic (−)-platensimycin (259). Judicious heteroatom placement was required to promote the formation of the desired regioisomeric adduct 253, since in the absence of the halogen substituent the alternative regioisomer 257 predominated. Small amounts of the cyclopropane 255 or 258 were also formed, as a mixture of diastereomers (Scheme 316).751 The “undesired” regioisomer 254 was later carried forward to the analogue isoplatensimycin,752 and the route was further exploited to prepare several analogues of platensimycin.753 Kanazawa and co-workers have described approaches to the antitumor agent camptothecin (263) and related structures. 10055


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Chiu and co-workers described the synthesis of (−)-indicol (265) involving the cycloaddition of the ylide formed from the diazo compound 264; the single stereocenter of the starting diazoketone determines the stereochemistry in the major diastereomer (Scheme 318). The diastereoselectivity of the

Scheme 316. Synthesis of (−)-Platensimycin

Scheme 318. Synthesis of Indicol

reaction was relatively insensitive to the catalyst; several chiral catalysts were screened, but the influence on the diastereomer ratio was marginal, suggesting that the catalyst is weakly associated or may not be associated with the ylide.761 The synthesis of the tricyclic core of brownin F (267) was described by Chouraqui and Commeiras using a carbonyl ylidetethered butenolide approach to construct the adduct 266 containing four stereocenters, with the required relative stereochemistry, in 78% yield (Scheme 319).762

One approach was via the isomünchnone-derived intermolecular adduct 260754−758 (the formation of which was first described by Padwa and co-workers),665 and a second approach was via the intermolecular adduct 261.759 A third strategy involved the adduct 262 formed by intramolecular cycloaddition (Scheme 317).760 Scheme 317. Approaches to Camptothecin

Scheme 319. Synthesis of the Brownin F Skeleton

3.6.4.4.2. Catalyst-Controlled Reactions. Chiu and coworkers completed the synthesis of pseudolaric acid A (270) from the adduct 268.763−766 In this instance, the choice of catalyst was critical to override substrate-controlled stereoselectivity. The use of Rh2(OAc)4 gave a 60% yield of adducts 268 and 269 in a ratio of 1:4, while the use of Rh2(BPTV)4 gave an 82% yield with a ratio of 1.6:1 in favor of the desired adduct 268 (Scheme 320). Hashimoto and co-workers reported the use of catalystcontrolled enantioselectivity in the synthesis of the natural products 271 and descurainin (272), isolated from Ligusticum chuanxing Hort., an herb used in traditional Chinese medicine (Scheme 321).767,768 Hashimoto has also published approaches 10056


Chemical Reviews

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Scheme 320. Synthesis of Pseudolaric Acid A

Scheme 322. Synthesis of Tashiromine

Scheme 321. Synthesis of Natural Products Isolated from L. chuanxing Hort.

understanding of diazocarbonyl reactivity and the advent of new catalysts in parallel with increased ease of access and handling of diazo compounds, which has resulted in this chemistry being more widely adopted. This is exemplified by success in N−H, O−H, and C−H insertion, particularly in enantioselective intermolecular reactions; applications of the Wolff rearrangement have demonstrated new significant areas where ketenes function as reaction intermediates. The impact of continuous-flow chemistry and in situ methods has facilitated the use of this chemistry. Chemists are now better equipped to target much more elaborate molecules in total synthesis using diazocarbonyl methodology than was the case 20 years ago. Furthermore, selective bioconjugation in proteins and nucleic acids and carbohydrates exploiting diazocarbonyl reactivity is evident, offering new tools for use in drug discovery.

AUTHOR INFORMATION Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. Notes

The authors declare no competing financial interest. Biographies

to the core structures of psoracryfols with good diastereoselectivity and up to 87% ee,688 and also the aspidosperma alkaloid core, with up to 66% ee and with perfect endo diastereoselectivity.769 Suga and co-workers described the application of chiral Lewis acid-catalyzed asymmetric cycloadditions of carbonyl ylides generated from diazoimide derivatives to indolizidine alkaloids, exemplified by the total synthesis of (+)-tashiromine (274) (Scheme 322).770

4. CONCLUDING REMARKS The past 20 years have been the most productive in the history of α-diazocarbonyl chemistry, despite the fact that it has been in existence for over a century. The driving force for all of these recent developments has been high chemoselectivity in their reactions coupled with, where appropriate, high stereoselectivity. This has been accomplished through a better

Alan Ford was born in Gateshead, England, in 1972. He studied at the University of Hull, England, and received a B.Sc. in chemistry in 1993 and a Ph.D. in 1996. He has held postdoctoral positions in the Selective Synthesis Group, University of Hull, from 1997 to 1998, in the Department of Metal-Mediated Organic Synthesis, Debye Institute, University of Utrecht, The Netherlands, from 1998 to 10057


Chemical Reviews

Review

2000, and in the Organic and Pharmaceutical Synthesis Research Team, Department of Chemistry, University College Cork, Ireland, from 2000 to the present. His main research interests include development of novel rhodium catalysts for asymmetric carbene chemistry and the synthesis of nucleoside analogues as potential antiviral agents.

Catherine N. Slattery was born in 1985 in Limerick, Ireland. She received her B.Sc. degree from University College Cork (UCC) in 2008. During this time, she spent five months working as a research scientist in Pfizer Global Research and Development, Sandwich, U.K. She was awarded the Eli Lilly Chemistry Prize and the Pfizer Pharmaceuticals Prize for her undergraduate academic achievements. She obtained her Ph.D. from University College Cork in 2012. After 18 months working as a postdoctoral researcher supported by Eli Lilly

Hugues Miel was born in Caen, France, in 1967. He studied at the

at UCC, she took up a position at Merck, Sharpe and Dohme in

University of Caen and received a Ph.D. (organic and medicinal

County Tipperary, Ireland.

chemistry) in 1998. Following postdoctoral research at Queen’s University Belfast under the supervision of M. Anthony McKervey, he joined QuChem (chemistry contract research organization) in 1999, now part of the Almac Group. In 2010 he joined Almac Discovery, a drug discovery company focused on developing new treatments for cancer. Some of his interests include the design and development of new synthetic routes (he is the winner of three InnoCentive Challenges) and the application of diazocarbonyl chemistry to access unexplored chemical space in drug discovery.

Anita R. Maguire was born in 1964 in Cork. She undertook undergraduate and postgraduate studies at University College Cork (B.Sc., 1985; Ph.D., 1989), focusing during her Ph.D. studies on asymmetric catalysis in reactions of α-diazoketones. Following postdoctoral research in the Facultes Universitaires, Namur, Belgium, and subsequently at the University of Exeter, she returned to Cork in 1991 initially as a Lecturer in Organic Chemistry, then as Associate Professor of Organic Chemistry in 2002, and then as the first Professor of Pharmaceutical Chemistry in 2004. In 2011 she was appointed as Vice President for Research and Innovation at University College Aoife Ring was born in 1988 in Cork, Ireland. She received her B.Sc.

Cork. She is an Adjunct Professor at the University of Bergen. Her

degree from University College Cork in 2010. She is currently

research interests include the development of new synthetic methodology employing diazocarbonyl chemistry and organosulfur

undertaking Ph.D. studies under the supervision of Prof. Anita R.

chemistry, asymmetric synthesis, including biocatlaysis and transition-

Maguire. Her Ph.D. work focuses on enantioselective transition-metal-

metal catalysis, and the design and synthesis of bioactive compounds

catalyzed transformations of α-diazocarbonyl compounds, specifically

with pharmaceutical applications. She was elected a Member of the

C−H insertion and aromatic addition reactions.

Royal Irish Academy in 2014. 10058


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Review

N-(benzophthaloyl)valinate benzenesulfonyl bis(trimethylsilyl)methyl benzoyl caprolactamate carboxybenzyl compact fluorescent light diastereomer ratio 1,8-diazabicycloundec-7-ene 1,2-dichloroethane 6,6-didodecyl-1,1′-binaphthalene-2,2′-diyl phosphate de diastereomeric excess DMAD dimethyl acetylenedicarboxylate DMAP 4-(dimethylamino)pyridine DNA deoxyribonucleic acid DOSP dodecylbenzenesulfonyl prolinate EDA ethyl diazoacetate ee enantiomeric excess esp α,α,α′,α′-tetramethyl-1,3-benzenedipropionate EWG electron-withdrawing group Fmoc [(fluorenylmethyl)oxy]carbonyl HBD hydrogen bond donor hfacac 1,1,1,5,5,5-hexafluoroacetylacetonate HFIP 1,1,1,3,3,3-hexafluoroisopropyl alcohol HMDS hexamethyldisilazide HMPA hexamethylphosphoramide 2(S)-IBAZ isobutyl 4-oxoazetidine-2(S)-carboxylate IBX 2-iodoxybenzoic acid IPr 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene IR infrared (spectroscopy) LDA lithium diisopropylamide 4(S)-MACIM methyl 1-acetyl-2-oxoimidazolidine-4(S)-carboxylate Mand mandelate MCR multicomponent reaction 4(S)-MEOX methyl 2-oxazolidone-4(S)-carboxylate 5(S)-MEPY methyl 2-pyrrolidone-5(S)-carboxylate Mes mesityl, 2,4,6-trimethylphenyl mGluR metabotropic glutamate receptor MOM methoxymethyl 4(S)-MPPIM tetrakis[methyl (phenylpropyl)imidazolidine4(S)-carboxylate] MW microwave NMR nuclear magnetic resonance (spectroscopy) Ns 2-nitrobenzenesulfonyl NTTL N-(1,8-naphthaloyl)-tert-leucinate NXS N-halosuccinimide OAc acetate oct octanoate OTf trifluoromethanesulfonate PDMS poly(dimethylsiloxane) PEG polyethylene glycol pfb perfluorobutyrate pfm perfluorobutyramide PG protecting group piv pivalate PMB p-methoxybenzyl PMP p-methoxyphenyl PPA poly(phosphoric acid) PTAD 1-adamantyl-N-phthalimidoacetate PTTEA N-phthaloyltriethylalaninate BPTV Bs BTMSM Bz cap Cbz CFL dr DBU DCE DDBNP

Professor M. Anthony McKervey was born in County Fermanagh, Northern Ireland, in 1938. He received his university degrees, B.Sc. (1961), Ph.D. (1964), and D.Sc. (1972), from Queen’s University Belfast. Following a period in the United States, where he was a postdoctoral fellow with A. C. Cope and, later, Assistant Professor at the Massachusetts Institute of Technology, he returned to Queen’s to a lectureship in 1966 and, in 1973, a readership. In 1976 Professor McKervey was appointed to the Chair of Organic Chemistry at University College Cork (UCC), where he served three terms as Head of Department. He returned to Queen’s in 1990 as Professor of Organic Chemistry and Head of the Research Division of the Chemistry School. During 1986−2003, he was Adjunct Professor of Organic Chemistry at the Ecole Européenne Des Hautes Etudes Des Industries Chimique De Strasbourg (EHICS), University of Strasbourg. In 2013 he was appointed to an adjunct professorship at UCC. Professor McKervey served as Vice-President (1980−1982) and President (1982−1984) of the Institute of Chemistry of Ireland. Awards include The Astra award of the Royal Dublin Society, jointly with the Loctite Corp., in 1986, the ACE award of the Ciba-Geigy Foundation Trust in 1988, and the Boyle-Higgins Gold Medal of the Institute of Chemistry of Ireland in 1993. Professor McKervey was elected a Member of the Royal Irish Academy in 1983. After retiring from Queen’s in 1998, he continues to work in chemistry as a consultant. In 1992, Professor McKervey founded the University-based Custom Synthesis and Process Development Centre (QuChem), which later became Almac Sciences Ltd. as part of the Almac Group of pharmaceutical and health care companies.

ACKNOWLEDGMENTS Support from the Science Foundation Ireland for the Synthesis & Solid State Pharmaceutical Centre (Grant SFI SSPC 12/RC/ 2275) is gratefully acknowledged (A.R.M.). ABBREVIATIONS acac acetylacetonate ADMP 2-azido-1,3-dimethylimidazolinium hexafluorophosphate BARF tetrakis[3,5-bis(trifluoromethyl)phenyl]borate BiDOSP (2S,2′S),(5R,5′R)-5,5′-(1,3-phenylene)bis(1-(4dodecylbenzenesulfonyl)prolinate) BINOL 1,1′-bi-2-naphthol BiTISP (2S,2′S),(5R,5′R)-5,5′-(1,3-phenylene)bis(1(2,4,6-triisopropylbenzenesulfonyl)prolinate) BNP 1,1′-binaphthalene-2,2′-diyl phosphate Boc (tert-butyloxy)carbonyl BOX bisoxazoline bp boiling point BPTTL N-(benzophthaloyl)-tert-leucinate 10059


Chemical Reviews PTTL RNA rt SAR SPA TAS TBDPS TBPRO TBS TCPTTL TDCPP TFA tfa tfacac TFE tfm TFPTTL THF TiT TMS TMSE Tol tpa Tr Ts TTP xylyl-BINAP

Review

from Methylurea through N-Methyl-N-nitrosourea. US5854405A, 1998; Chem. Abstr. 1999, 130, 83188. (14) Warr, A. J.; Proctor, L. Process for the Preparation of Diazomethane. WO2001047869A1, 2001; Chem. Abstr. 2001, 135, 78221. (15) The Diazald kit available from Aldrich is a set of distillation glassware designed for the safe preparation of diazomethane (∼100 mmol). (16) Black, T. H. The Preparation and Reactions of Diazomethane. Aldrichimica Acta 1983, 16, 3−10. (17) Deadman, B. J.; Collins, S. G.; Maguire, A. R. Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds. Chem. - Eur. J. 2015, 21, 2298−2308. (18) Morandi, B.; Carreira, E. M. Iron-Catalyzed Cyclopropanation in 6 M KOH with in Situ Generation of Diazomethane. Science 2012, 335, 1471−1474. (19) Moody, D. Soluble Diazoalkane Precursors. WO2008040947A2, 2008; Chem. Abstr. 2008, 148, 428821. (20) Rossi, E.; Woehl, P.; Maggini, M. Scalable in Situ Diazomethane Generation in Continuous-Flow Reactors. Org. Process Res. Dev. 2012, 16, 1146−1149. (21) Struempel, M.; Ondruschka, B.; Daute, R.; Stark, A. Making Diazomethane Accessible for R&D and Industry: Generation and Direct Conversion in a Continuous Micro-Reactor Set-Up. Green Chem. 2008, 10, 41−43. (22) Maurya, R. A.; Park, C. P.; Lee, J. H.; Kim, D.-P. Continuous In Situ Generation, Separation, and Reaction of Diazomethane in a DualChannel Microreactor. Angew. Chem., Int. Ed. 2011, 50, 5952−5955. (23) Mastronardi, F.; Gutmann, B.; Kappe, C. O. Continuous Flow Generation and Reactions of Anhydrous Diazomethane Using a Teflon AF-2400 Tube-in-Tube Reactor. Org. Lett. 2013, 15, 5590− 5593. (24) Polyzos, A.; O'Brien, M.; Petersen, T. P.; Baxendale, I. R.; Ley, S. V. The Continuous-Flow Synthesis of Carboxylic Acids using CO2 in a Tube-In-Tube Gas Permeable Membrane Reactor. Angew. Chem., Int. Ed. 2011, 50, 1190−1193. (25) Pinho, V. D.; Gutmann, B.; Miranda, L. S. M.; de Souza, R. O. M. A.; Kappe, C. O. Continuous Flow Synthesis of α-Halo Ketones: Essential Building Blocks of Antiretroviral Agents. J. Org. Chem. 2014, 79, 1555−1562. (26) Note that, as the diazomethane is being made and consumed in a continuous process, its concentration in the reactor at any one time remains very low. (27) Martin, L. J.; Marzinzik, A. L.; Ley, S. V.; Baxendale, I. R. Safe and Reliable Synthesis of Diazoketones and Quinoxalines in a Continuous Flow Reactor. Org. Lett. 2011, 13, 320−323. (28) Bray, P. A.; Sokas, R. K. Delayed Respiratory Fatality From Trimethylsilyldiazomethane: What Do Workers Need to Know About Potentially Hazardous Exposures? J. Occup. Environ. Med. 2015, 57, e15−e16. (29) Pace, V.; Verniest, G.; Sinisterra, J.-V.; Alcántara, A. R.; De Kimpe, N. Improved Arndt−Eistert Synthesis of α-Diazoketones Requiring Minimal Diazomethane in the Presence of Calcium Oxide as Acid Scavenger. J. Org. Chem. 2010, 75, 5760−5763. (30) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Choi, H.-S.; Fong, K. C.; He, Y.; Yoon, W. H. New Synthetic Technology for the Synthesis of Hindered α-Diazoketones via Acyl Mesylates. Org. Lett. 1999, 1, 883−886. (31) Cuevas-Yañez, E.; García, M. A.; de la Mora, M. A.; Muchowski, J. M.; Cruz-Almanza, R. Novel Synthesis of α-Diazoketones from Acyloxyphosphonium Aalts and Diazomethane. Tetrahedron Lett. 2003, 44, 4815−4817. (32) Siciliano, C.; De Marco, R.; Guidi, L. E.; Spinella, M.; Liguori, A. A One-Pot Procedure for the Preparation of N-9-Fluorenylmethyloxycarbonyl-α-amino Diazoketones from α-Amino Acids. J. Org. Chem. 2012, 77, 10575−10582. (33) Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. An Improved Method for the Synthesis of α-Diazo Ketones. J. Org. Chem. 1990, 55, 1959−1964.

N-phthaloyl-tert-leucinate ribonucleic acid room temperature structure−activity relationship spiro phosphoric acid trialkylsilyl tert-butyldiphenylsilyl tert-butylbenzenesulfonyl prolinate tert-butyldimethylsilyl N-(tetrachlorobenzophthaloyl)-tert-leucinate 5,10,15,20-tetrakis(2,6-dichlorophenyl)21H,23H-porphine trifluoroacetic acid trifluoroacetate 1,1,1-trifluoroacetylacetonate trifluoroethanol trifluoroacetamide N-(tetrafluorobenzophthaloyl)-tert-leucinate tetrahydrofuran tube-in-tube trimethylsilyl 2-(trimethylsilyl)ethyl tolyl triphenylacetate triphenylmethyl 4-tolylsulfonyl 5,10,15,20-tetra-p-tolyl-21H,23H-porphine 2,2′-bis(bis(3,5-xylyl)phosphino)-1,1′-binaphthyl

REFERENCES (1) Ye, T.; McKervey, M. A. Organic Synthesis with α-Diazo Carbonyl Compounds. Chem. Rev. 1994, 94, 1091−1160. (2) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds; John Wiley & Sons: New York, 1998. (3) Doyle, M. P.; Forbes, D. C. Recent Advances in Asymmetric Catalytic Metal Carbene Transformations. Chem. Rev. 1998, 98, 911− 936. (4) Zhang, Z.; Wang, J. Recent Studies on the Reactions of αDiazocarbonyl Compounds. Tetrahedron 2008, 64, 6577−6605. (5) Wee, A. G. H. Rhodium(II)-Catalyzed Reaction of Diazocompounds in the Service of Organic Synthesis of Natural and NonNatural Products. Curr. Org. Synth. 2006, 3, 499−555. (6) Zhao, X.; Zhang, Y.; Wang, J. Recent Developments in CopperCatalyzed Reactions of Diazo Compounds. Chem. Commun. 2012, 48, 10162−10173. (7) Zhou, C.-Y.; Huang, J.-S.; Che, C.-M. Ruthenium-PorphyrinCatalyzed Carbenoid Transfer Reactions. Synlett 2010, 2010, 2681− 2700. (8) For an earlier review, see: Maas, G. New Syntheses of Diazo Compounds. Angew. Chem., Int. Ed. 2009, 48, 8186−8195. (9) Diazomethane [MAK Value Documentation, 1999]. The MAKCollection for Occupational Health and Safety; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2002. (10) Proctor, L. D.; Warr, A. J. Development of a Continuous Process for the Industrial Generation of Diazomethane. Org. Process Res. Dev. 2002, 6, 884−892. (11) National Institute for Occupational Safety and Health. Diazomethane, May 1994. http://www.cdc.gov/niosh/idlh/334883. html (accessed August 14, 2015). (12) Archibald, T. G.; Huang, D.-s.; Pratton, M. H.; Barnard, J. C. Large-Scale Batch Process for Diazomethane Manufacture. US5817778A, 1998; Chem. Abstr. 1998, 129, 262006. (13) Archibald, T. G.; Barnard, J. C.; Reese, H. F. Continuous Process for Diazomethane from an N-Methyl-N-nitrosoamine and 10060


Chemical Reviews

Review

to Aldehydes: Asymmetric Synthesis of 1,2-Diols. J. Am. Chem. Soc. 2012, 134, 2075−2084. (55) Jiang, N.; Qu, Z.; Wang, J. 1,2-Aryl and 1,2-Hydride Migration in Transition Metal Complex Catalyzed Diazo Decomposition: A Novel Approach to α-Aryl-β-enamino Esters. Org. Lett. 2001, 3, 2989− 2992. (56) Zhao, Y.; Jiang, N.; Wang, J. An Efficient Synthesis of α-Aryl β(N-Tosyl)amino Phosphonate Derivatives from α-Diazophosphonate. Tetrahedron Lett. 2003, 44, 8339−8342. (57) Zhao, Y.; Ma, Z.; Zhang, X.; Zou, Y.; Jin, X.; Wang, J. A Highly Stereoselective Addition of the Anion Derived from α-Diazoacetamide to Aromatic N-Tosylimines. Angew. Chem., Int. Ed. 2004, 43, 5977− 5980. (58) Zhao, Y.; Wang, J. Nucleophilic Addition to CO and CN Bonds by Nucleophiles Containing a Diazo Group. Synlett 2005, 2886−2892. (59) Zhao, Y.; Jiang, N.; Chen, S.; Peng, C.; Zhang, X.; Zou, Y.; Zhang, S.; Wang, J. Concise and Diastereoselective Approach to synand anti-N-Tosyl-α-hydroxy β-Amino Acid Derivatives. Tetrahedron 2005, 61, 6546−6552. (60) Uraguchi, D.; Sorimachi, K.; Terada, M. Organocatalytic Asymmetric Direct Alkylation of α-Diazoester via C−H Bond Cleavage. J. Am. Chem. Soc. 2005, 127, 9360−9361. (61) Chen, S.; Zhao, Y.; Wang, J. Preparation of Cyclic N-tertButylsulfonyl Enamines by Rh(II)-Mediated Ring Expansion of αDiazoesters. Synthesis 2006, 2006, 1705−1710. (62) Hashimoto, T.; Maruoka, K. Design of Axially Chiral Dicarboxylic Acid for Asymmetric Mannich Reaction of Arylaldehyde N-Boc Imines and Diazo Compounds. J. Am. Chem. Soc. 2007, 129, 10054−10055. (63) Cuevas-Yañ ez, E.; Muchowski, J. M.; Cruz-Almanza, R. Metalation of α-Diazocarbonyl Compounds Using Grignard Reagents. A Convenient Synthesis of α-Diazo-β-ketoesters and Mixed Esters of α-Diazomalonate. Tetrahedron Lett. 2004, 45, 2417−2419. (64) Saraireh, I. A. M. Synthesis and Characterization of Chiral di(NProtected-α-amino)diazo-β-diketones from α-Diazoketones and Imidazolides Derived from Amino Acids. Tetrahedron Lett. 2012, 53, 2023−2025. (65) Lancou, A.; Haroun, H.; Kundu, U. K.; Legros, F.; Zimmermann, N.; Mathé-Allainmat, M.; Lebreton, J.; Dujardin, G.; Gaulon-Nourry, C.; Gosselin, P. α-Triethylsilyl-α-diazoacetone in Double Cross-Aldolisation: Convenient Acetone Equivalent toward 5Hydroxy-1,3-diketones. Tetrahedron 2012, 68, 9652−9657. (66) Kaupang, Å.; Bonge-Hansen, T. α-Bromodiazoacetamides − a New Class of Diazo Compounds for Catalyst-Free, Ambient Temperature Intramolecular C−H Insertion Reactions. Beilstein J. Org. Chem. 2013, 9, 1407−1413. (67) Schnaars, C.; Hennum, M.; Bonge-Hansen, T. Nucleophilic Halogenations of Diazo Compounds, a Complementary Principle for the Synthesis of Halodiazo Compounds: Experimental and Theoretical Studies. J. Org. Chem. 2013, 78, 7488−7497. (68) Bonge, H. T.; Hansen, T. Computational Study of Cyclopropanation Reactions with Halodiazoacetates. J. Org. Chem. 2010, 75, 2309−2320. (69) Peng, C.; Cheng, J.; Wang, J. Palladium-Catalyzed CrossCoupling of Aryl or Vinyl Iodides with Ethyl Diazoacetate. J. Am. Chem. Soc. 2007, 129, 8708−8709. (70) Aller, E.; Molina, P.; Lorenzo, Á . N-Isocyanotriphenyliminophosphorane; a Convenient Reagent for the Conversion of Acyl Chlorides into α-Diazoketones. Synlett 2000, 526−528. (71) Pinho, V. D.; Burtoloso, A. C. B. Preparation of α,β-Unsaturated Diazoketones Employing a Horner−Wadsworth−Emmons Reagent. J. Org. Chem. 2011, 76, 289−292. (72) Rosset, I. G.; Burtoloso, A. C. B. Preparation of Z-α,βUnsaturated Diazoketones from Aldehydes. Application in the Construction of Substituted Dihydropyridin-3-ones. J. Org. Chem. 2013, 78, 9464−9470.

(34) Abad, A.; Agulló, C.; Cuñat, A. C.; de Alfonso Marzal, I.; Navarro, I.; Gris, A. A Unified Synthetic Approach to Trachylobane-, Beyerane-, Atisane- and Kaurane-Type Diterpenes. Tetrahedron 2006, 62, 3266−3283. (35) Arthuis, M.; Beaud, R.; Gandon, V.; Roulland, E. CounteranionDirected Catalysis in the Tsuji−Trost Reaction: Stereocontrolled Access to 2,5-Disubstituted 3-Hydroxy-Tetrahydrofurans. Angew. Chem., Int. Ed. 2012, 51, 10510−10514. (36) Shibuya, G. M.; Enquist, J. A.; Stoltz, B. M. Enantioselective Synthesis of the 5−6−7 Carbocyclic Core of the Gagunin Diterpenoids. Org. Lett. 2013, 15, 3480−3483. (37) Taber, D. F.; Sheth, R. B.; Joshi, P. V. Simple Preparation of αDiazo Esters. J. Org. Chem. 2005, 70, 2851−2854. (38) Goddard-Borger, E. D.; Stick, R. V. An Efficient, Inexpensive, and Shelf-Stable Diazotransfer Reagent: Imidazole-1-sulfonyl Azide Hydrochloride. Org. Lett. 2007, 9, 3797−3800. (39) Fischer, N.; Goddard-Borger, E. D.; Greiner, R.; Klapötke, T. M.; Skelton, B. W.; Stierstorfer, J. Sensitivities of Some Imidazole-1sulfonyl Azide Salts. J. Org. Chem. 2012, 77, 1760−1764. (40) Ye, H.; Liu, R.; Li, D.; Liu, Y.; Yuan, H.; Guo, W.; Zhou, L.; Cao, X.; Tian, H.; Shen, J.; Wang, P. G.; et al. A Safe and Facile Route to Imidazole-1-sulfonyl Azide as a Diazotransfer Reagent. Org. Lett. 2013, 15, 18−21. (41) Katritzky, A. R.; El Khatib, M.; Bol’shakov, O.; Khelashvili, L.; Steel, P. J. Benzotriazol-1-yl-sulfonyl Azide for Diazotransfer and Preparation of Azidoacylbenzotriazoles. J. Org. Chem. 2010, 75, 6532− 6539. (42) Katritsky, A. R.; El Khatib, M. Chemical Safety: Benzotriazole-1sulfonyl Azide. Chem. Eng. News 2012, 90 (2), 4. (43) Chiara, J. L.; Suárez, J. R. Synthesis of α-Diazo Carbonyl Compounds with the Shelf-Stable Diazo Transfer Reagent Nonafluorobutanesulfonyl Azide. Adv. Synth. Catal. 2011, 353, 575−579. (44) Muthyala, M. K.; Choudhary, S.; Kumar, A. Synthesis of Ionic Liquid-Supported Sulfonyl Azide and Its Application in Diazotransfer Reaction. J. Org. Chem. 2012, 77, 8787−8791. (45) Kitamura, M.; Yano, M.; Tashiro, N.; Miyagawa, S.; Sando, M.; Okauchi, T. Direct Synthesis of Organic Azides from Primary Amines with 2-Azido-1,3-dimethylimidazolinium Hexafluorophosphate. Eur. J. Org. Chem. 2011, 2011, 458−462. (46) Kitamura, M.; Tashiro, N.; Takamoto, Y.; Okauchi, T. Direct Synthesis of Acyl Azides from Carboxylic Acids Using 2-Azido-1,3dimethylimidazolinium Chloride. Chem. Lett. 2010, 39, 732−733. (47) Kitamura, M.; Kato, S.; Yano, M.; Tashiro, N.; Shiratake, Y.; Sando, M.; Okauchi, T. A Reagent for Safe and Efficient DiazoTransfer to Primary Amines: 2-Azido-1,3-dimethylimidazolinium Hexafluorophosphate. Org. Biomol. Chem. 2014, 12, 4397−4406. (48) Jiang, N.; Wang, J. DBU-Promoted Condensation of Acyldiazomethanes to Aldehydes and Imines Under Catalytic Conditions. Tetrahedron Lett. 2002, 43, 1285−1287. (49) Erhunmwunse, M. O.; Steel, P. G. A Simple One-Pot Preparation of Diazoacetoacetate Derivatives from Aldehydes. J. Org. Chem. 2008, 73, 8675−8677. (50) Li, P.; Majireck, M. M.; Korboukh, I.; Weinreb, S. M. A Mild, Efficient Method for the Oxidation of α-Diazo-β-hydroxyesters to αDiazo-β-ketoesters. Tetrahedron Lett. 2008, 49, 3162−3164. (51) Yao, W.; Wang, J. Direct Catalytic Asymmetric Aldol-Type Reaction of Aldehydes with Ethyl Diazoacetate. Org. Lett. 2003, 5, 1527−1530. (52) Hasegawa, K.; Arai, S.; Nishida, A. Synthesis of α-Diazo-βhydroxyesters through a One-Pot Protocol by Phase-Transfer Catalysis: Application to Enantioselective Aldol-Type Reaction and Diastereoselective Synthesis of α-Amino-β-hydroxyester Derivatives. Tetrahedron 2006, 62, 1390−1401. (53) Trost, B. M.; Malhotra, S.; Fried, B. A. Magnesium-Catalyzed Asymmetric Direct Aldol Addition of Ethyl Diazoacetate to Aromatic, Aliphatic, and α,β-Unsaturated Aldehydes. J. Am. Chem. Soc. 2009, 131, 1674−1675. (54) Trost, B. M.; Malhotra, S.; Koschker, P.; Ellerbrock, P. Development of the Enantioselective Addition of Ethyl Diazoacetate 10061


Chemical Reviews

Review

(92) Visser, P.; Zuhse, R.; Wong, M. W.; Wentrup, C. Reactivity of Carbenes and Ketenes in Low-Temperature Matrices. Carbene CO Trapping, Wolff Rearrangement, and Ketene−Pyridine Ylide (Zwitterion) Observation. J. Am. Chem. Soc. 1996, 118, 12598−16202. (93) Burdzinski, G.; Zhang, Y.; Wang, J.; Platz, M. S. Concerted Wolff Rearrangement in Two Simple Acyclic Diazocarbonyl Compounds. J. Phys. Chem. A 2010, 114, 13065−13068. (94) Burdzinski, G.; Rehault, J.; Wang, J.; Platz, M. S. A Study of the Photochemistry of Diazo Meldrum’s Acid by Ultrafast Time-Resolved Spectroscopies. J. Phys. Chem. A 2008, 112, 10108−10112. (95) Wang, J.; Burdzinski, G.; Kubicki, J.; Gustafson, T. L.; Platz, M. S. Ultrafast Carbene-Carbene Isomerization. J. Am. Chem. Soc. 2008, 130, 5418−5419. (96) Wang, Y.; Yuzawa, T.; Hamaguchi, H.-o.; Toscano, J. P. TimeResolved IR Studies of 2-Naphthyl(carbomethoxy)carbene: Reactivity and Direct Experimental Estimate of the Singlet/Triplet Energy Gap. J. Am. Chem. Soc. 1999, 121, 2875−2882. (97) Chiang, Y.; Kresge, A. J.; Popik, V. V. Scavenging of Intermediates Formed in Photolysis of α-Diazocarbonyl Compounds and Hydroxycyclopropenones. Implication on the Mechanism of the Photo-Wolff Reaction. J. Am. Chem. Soc. 1999, 121, 5930−5932. (98) Wang, Y.; Toscano, J. P. Time-Resolved IR Studies of 4-Diazo3-isochromanone: Direct Kinetic Evidence for a Non-Carbene Route to Ketene. J. Am. Chem. Soc. 2000, 122, 4512−4513. (99) Vaske, Y. S. M.; Mahoney, M. E.; Konopelski, J. P.; Rogow, D. L.; McDonald, W. J. Enantiomerically Pure trans-β-Lactams from αAmino Acids via Compact Fluorescent Light (CFL) Continuous-Flow Photolysis. J. Am. Chem. Soc. 2010, 132, 11379−11385. (100) Koch, K.; Podlech, J. Exceptionally Simple Homologation of Protected α- to β-Amino Acids in the Presence of Silica Gel. Synth. Commun. 2005, 35, 2789−2794. (101) Sudrik, S. G.; Maddanimath, T.; Chaki, N. K.; Chavan, S. P.; Chavan, S. P.; Sonawane, H. R.; Vijayamohanan, K. Evidence for the Involvement of Silver Nanoclusters during the Wolff Rearrangement of α-Diazoketones. Org. Lett. 2003, 5, 2355−2358. (102) Sudrik, S. G.; Sharma, J.; Chavan, V. B.; Chaki, N. K.; Sonawane, H. R.; Vijayamohanan, K. P. Wolff Rearrangement of αDiazoketones Using in Situ Generated Silver Nanoclusters as Electron Mediators. Org. Lett. 2006, 8, 1089−1092. (103) Ovalles, S. R.; Hansen, J. H.; Davies, H. M. L. Thermally Induced Cycloadditions of Donor/Acceptor Carbenes. Org. Lett. 2011, 13, 4284−4287. (104) Neupane, P.; Li, X.; Jung, J. H.; Lee, Y. R.; Kim, S. H. Efficient One-Pot Synthesis of Cyclic β-Enaminoamides by Thermal Wolff Rearrangement of Cyclic 2-Diazo-1,3-dicarbonyls and Conversion to Uracil Derivatives. Tetrahedron 2012, 68, 2496−2508. (105) Zrig, S.; Andrioletti, B.; Rose, E.; Colin, J. Improved Synthesis of 2,2′-dimethoxy-1,1′-Binaphthyl-3,3′-Diacetic Acid Derivatives. Tetrahedron Lett. 2005, 46, 1103−1105. (106) Dyer, J.; Jockusch, S.; Balsanek, V.; Sames, D.; Turro, N. TwoPhoton Induced Uncaging of a Reactive Intermediate. Multiphoton in Situ Detection of a Potentially Valuable Label for Biological Applications. J. Org. Chem. 2005, 70, 2143−2147. (107) Dussault, P. H.; Xu, C. Curtius Rearrangement and Wolff Homologation of Functionalized Peroxides. Tetrahedron Lett. 2004, 45, 7455−7457. (108) Cantel, S.; Martinez, J.; Fehrentz, J.-A. Synthesis of Chiral αAmino-diazoketones on Solid Support: An Access to β-Homologated Amino Acid Derivatives. Synlett 2004, 2791−2793. (109) Zhang, W.; Romo, D. Transformation of Fused Bicyclic and Tricyclic β-Lactones to Fused γ-Lactones and 3(2H)-Furanones via Ring Expansions and O−H Insertions. J. Org. Chem. 2007, 72, 8939− 8942. (110) Seki, H.; Georg, G. I. Synthesis of Amino Acid Derived Enaminones via Wolff Rearrangement Using Vinylogous Amides as Carbon Nucleophiles. J. Am. Chem. Soc. 2010, 132, 15512−15513. (111) Seki, H.; Georg, G. I. Three-Component Synthesis of Cyclic Enaminones via Ketene Cyclization. Org. Lett. 2011, 13, 2147−2149.

(73) Pinho, V. D.; Burtoloso, A. C. B. Total Synthesis of (−)-Indolizidine 167B via an Unusual Wolff Rearrangement from an α,β-Unsaturated Diazoketone. Tetrahedron Lett. 2012, 53, 876−878. (74) Shi, W. F.; Ma, M.; Wang, J. B. An efficient and Mild Preparation of Vinyl Diazo Carbonyl Compounds. Chin. Chem. Lett. 2004, 15, 911−914. (75) Rianelli, R. d. S.; da Silva, F. d. C.; de Souza, M. C. B. V.; Ferreira, V. F. Mild Procedure for Preparing Vinyldiazoacetic Acid Esters of Carbohydrate Acetonides. Lett. Org. Chem. 2006, 3, 73−77. (76) Barluenga, J.; Lonzi, G.; Riesgo, L.; Tomás, M.; López, L. A. Direct Access to β-Oxodiazo Compounds by Copper(II)-Catalyzed Oxidative Rearrangement of Stabilized Vinyl Diazo Derivatives. J. Am. Chem. Soc. 2011, 133, 18138−18141. (77) Dawande, S. G.; Kanchupalli, V.; Kalepu, J.; Chennamsetti, H.; Lad, B. S.; Katukojvala, S. Rhodium Enalcarbenoids: Direct Synthesis of Indoles by Rhodium(II)-Catalyzed [4 + 2] Benzannulation of Pyrroles. Angew. Chem., Int. Ed. 2014, 53, 4076−4080. (78) Jadhav, A. M.; Pagar, V. V.; Liu, R.-S. Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds. Angew. Chem., Int. Ed. 2012, 51, 11809−11813. (79) Qian, Y.; Shanahan, C. S.; Doyle, M. P. Templated Carbene Metathesis Reactions from the Modular Assembly of Enol-Diazo Compounds and Propargyl Acetates. Eur. J. Org. Chem. 2013, 2013, 6032−6037. (80) Truong, P.; Shanahan, C. S.; Doyle, M. P. Divergent Stereocontrol of Acid Catalyzed Intramolecular Aldol Reactions of 2,3,7-Triketoesters: Synthesis of Highly Functionalized Cyclopentanones. Org. Lett. 2012, 14, 3608−3611. (81) Liu, Y.; Zhang, Y.; Jee, N.; Doyle, M. P. Construction of Highly Functionalized Diazoacetoacetates via Catalytic Mukaiyama−Michael Reactions. Org. Lett. 2008, 10, 1605−1608. (82) Xu, X.; Zavalij, P. Y.; Doyle, M. P. Synthesis of Tetrahydropyridazines by a Metal−Carbene-Directed Enantioselective Vinylogous N−H Insertion/Lewis Acid-Catalyzed Diastereoselective Mannich Addition. Angew. Chem., Int. Ed. 2012, 51, 9829−9833. (83) Doyle, M. P.; Kundu, K.; Russell, A. E. Catalytic Addition Methods for the Synthesis of Functionalized Diazoacetoacetates and Application to the Construction of Highly Substituted Cyclobutanones. Org. Lett. 2005, 7, 5171−5174. (84) Xu, X.; Ratnikov, M. O.; Zavalij, P. Y.; Doyle, M. P. Multifunctionalized 3-Hydroxypyrroles in a Three-Step, One-Pot Cascade Process from Methyl 3-TBSO-2-diazo-3-butenoate and Nitrones. Org. Lett. 2011, 13, 6122−6125. (85) Kundu, K.; Doyle, M. P. Constructing Chiral Diazoacetoacetates by Enantioselective Catalytic Mukaiyama Aldol Reactions. Tetrahedron: Asymmetry 2006, 17, 574−577. (86) Davies, H. M. L.; Stafford, D. G.; Hansen, T. Catalytic Asymmetric Synthesis of Diarylacetates and 4,4-Diarylbutanoates. A Formal Asymmetric Synthesis of (+)-Sertraline. Org. Lett. 1999, 1, 233−236. (87) Davies, H. M. L.; Hu, B. Highly Stereoselective [3 + 2] Annulations by Cyclopropanation of Vinyl Ethers with Rhodium(II)Stabilized Vinylcarbenoids Followed by a Formally Forbidden 1,3Sigmatropic Rearrangement. J. Org. Chem. 1992, 57, 3186−3190. (88) Buske, G. R. Chemical Safety: Benzotriazole-1-sulfonyl Azide. Chem. Eng. News 2012, 90 (15), 4−5. (89) Kirmse, W. 100 Years of the Wolff Rearrangement. Eur. J. Org. Chem. 2002, 2002, 2193−2256. (90) For a comprehensive account of the chemistry of ketenes, including their early history and methods of synthesis, see: Tidwell, T. T. The First Century of Ketenes (1905−2005): The Birth of a Versatile Family of Reactive Intermediates. Angew. Chem., Int. Ed. 2005, 44, 5778−5785. (91) For a more recent review by Tidwell of ketenes as reactive intermediates, in particular their intermolecular cycloaddition reactions, see: Allen, A. D.; Tidwell, T. T. Ketenes and Other Cumulenes as Reactive Intermediates. Chem. Rev. 2013, 113, 7287− 7342. 10062


Chemical Reviews

Review

Rearrangement of 3-(Thieno-2-yl)-3-oxo-2-diazopropanoates. Org. Lett. 2002, 4, 873−876. (131) Lawlor, M. D.; Lee, T. W.; Danheiser, R. L. RhodiumCatalyzed Rearrangement of α-Diazo Thiol Esters to Thio-Substituted Ketenes. Application in the Synthesis of Cyclobutanones, Cyclobutenones, and β-Lactams. J. Org. Chem. 2000, 65, 4375−4384. (132) Hixson, S. S.; Hixson, S. H. Photochemistry of S-Methyl Diazothioacetate. J. Org. Chem. 1972, 37, 1279−1280. (133) Georgian, V.; Boyer, S. K.; Edwards, B. Photochemistry of αDiazo Thioesters: Migratory Aptitude of Sulfur vs. Oxygen in the Photochemical Wolff Rearrangement. J. Org. Chem. 1980, 45, 1686− 1688. (134) Jones, J.; Kresge, A. J. Flash Photolytic Generation and Reactivity of Phenyl(methylthio)ketene in Aqueous Solution. J. Org. Chem. 1992, 57, 6467−6469. (135) Podlech, J.; Linder, M. R. Cycloadditions of Ketenes Generated in the Wolff Rearrangement. Stereoselective Synthesis of Aminoalkyl-Substituted β-Lactams from α-Amino Acids. J. Org. Chem. 1997, 62, 5873−5883. (136) Linder, M. R.; Podlech, J. Synthesis of Peptidomimetics Containing a β-Lactam Moiety Using Peptidic Diazoketones and Imines in a Staudinger Reaction. Org. Lett. 1999, 1, 869−871. (137) Linder, M. R.; Podlech, J. Synthesis of β-Lactams from Diazoketones and Imines: The Use of Microwave Irradiation. Org. Lett. 2001, 3, 1849−1851. (138) Sarpong, R.; Su, J. T.; Stoltz, B. M. The Development of a Facile Tandem Wolff/Cope Rearrangement for the Synthesis of Fused Carbocyclic Skeletons. J. Am. Chem. Soc. 2003, 125, 13624−13625. (139) Wiberg, K. B.; Snoonian, J. R.; Lahti, P. M. Ring Contraction of a Two-Carbon Bridged Spiropentane. Tetrahedron Lett. 1996, 37, 8285−8288. (140) Wiberg, K. B.; Snoonian, J. R. Ring Expansion and Contraction of a Two-Carbon Bridged Spiropentane. J. Org. Chem. 1998, 63, 1390−1401. (141) Blair, P. A.; Chang, S.-J.; Shechter, H. Photolytic, Thermal, Addition, and Cycloaddition Reactions of 2-Diazo-5,6- and −3,8disubstituted Acenaphthenones. J. Org. Chem. 2004, 69, 7123−7133. (142) McMahon, R. J.; Chapman, O. L.; Hayes, R. A.; Hess, T. C.; Krimmer, H. P. Mechanistic Studies on the Wolff Rearrangement: The Chemistry and Spectroscopy of Some α-Keto Carbenes. J. Am. Chem. Soc. 1985, 107, 7597−7606. (143) Conti, P.; Kozikowski, A. P. New Synthesis of 2Aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I (ABHxD-I), a Potent Metabotropic Receptor Agonist. Tetrahedron Lett. 2000, 41, 4053−4056. (144) Snyder, S. A.; Corey, E. J. Concise Total Syntheses of Palominol, Dolabellatrienone, β-Araneosene, and Isoedunol via an Enantioselective Diels−Alder Macrobicyclization. J. Am. Chem. Soc. 2006, 128, 740−742. (145) Zhang, L.; Koreeda, M. Total Synthesis of (+)-Acanthodoral by the Use of a Pd-Catalyzed Metal-ene Reaction and a Nonreductive 5-exo-Acyl Radical Cyclization. Org. Lett. 2004, 6, 537−540. (146) Mascitti, V.; Corey, E. J. Total Synthesis of (±)-Pentacycloanammoxic Acid. J. Am. Chem. Soc. 2004, 126, 15664−15665. (147) Mascitti, V.; Corey, E. J. Enantioselective Synthesis of Pentacycloanammoxic Acid. J. Am. Chem. Soc. 2006, 128, 3118−3119. (148) Feldman, K. S.; Nuriye, A. Y. Extending Pummerer Reaction Chemistry: Application to the Assembly of the Pentacyclic Core of Dibromopalau’amine. Org. Lett. 2010, 12, 4532−4535. (149) Köpke, T.; Pink, M.; Zaleski, J. M. Expansion by Contraction: Diversifying the Photochemical Reactivity Scope of Diazo-oxochlorins toward Development of in Situ Alkylating Agents. J. Am. Chem. Soc. 2008, 130, 15864−15871. (150) Karpov, G. V.; Popik, V. V. Triggering of the Bergman Cyclization by Photochemical Ring Contraction. Facile Cycloaromatization of Benzannulated Cyclodeca-3,7-diene-1,5-diynes. J. Am. Chem. Soc. 2007, 129, 3792−3793. (151) Gómez, M.; Paneque, M.; Poveda, M. L.; Alvarez, E. Transition Metal Migration upon Attempting the Wolff Rearrangement of an

(112) Wu, J.; Chen, W.; Hu, M.; Zou, H.; Yu, Y. Synthesis of Polysubstituted 5-Aminooxazoles from α- Diazocarbonyl Esters and αIsocyanoacetamides. Org. Lett. 2010, 12, 616−618. (113) Brückmann, R.; Schneider, K.; Maas, G. Wolff Rearrangement of (1-Diazo-2-oxoalkyl)silanes. Tetrahedron 1989, 45, 5517−5530. (114) Bucher, S. M.; Brückmann, R.; Maas, G. Aryl Trialkylsilyl Ketenes: Acid-Catalyzed Synthesis from 1-Aryl-2-diazo-2-trialkylsilylethanones and Their Conversion into 3-Silyl-1-silyloxyallenes. Eur. J. Org. Chem. 2008, 2008, 4426−4433. (115) Austin, W. F.; Zhang, Y.; Danheiser, R. L. Reactions of (Trialkylsilyl)vinylketenes with Lithium Ynolates: A New Benzannulation Strategy. Org. Lett. 2005, 7, 3905−3908. (116) Austin, W. F.; Zhang, Y.; Danheiser, R. L. A Benzannulation Strategy for the Synthesis of Phenols and Heteroaromatic Compounds Based on the Reaction of (Trialkylsilyl)vinylketenes with Lithium Ynolates. Tetrahedron 2008, 64, 915−925. (117) Marsden, S. P.; Pang, W.-K. Efficient, General Synthesis of Silylketenes via an Unusual Rhodium Mediated Wolff Rearrangement. Chem. Commun. 1999, 1199−1200. (118) Dalton, A. M.; Zhang, Y.; Davie, C. P.; Danheiser, R. L. Synthesis of 2-Indanones via [4 + 1] Annulation Reactions of (Trialkylsilyl)arylketenes. Org. Lett. 2002, 4, 2465−2468. (119) Willumstad, T. P.; Haze, O.; Mak, X. Y.; Lam, T. Y.; Wang, Y.P.; Danheiser, R. L. Batch and Flow Photochemical Benzannulations Based on the Reaction of Ynamides and Diazo Ketones. Application to the Synthesis of Polycyclic Aromatic and Heteroaromatic Compounds. J. Org. Chem. 2013, 78, 11450−11469. (120) Chen, Z.-B.; Hong, D.; Wang, Y.-G. A Cascade Approach to Pyridines from 2-Azido-2,4-dienoates and α-Diazocarbonyl Compounds. J. Org. Chem. 2009, 74, 903−905. (121) Yang, Y.-Y.; Shou, W.-G.; Chen, Z.-B.; Hong, D.; Wang, Y.-G. A Tandem Approach to Isoquinolines from 2-Azido-3-arylacrylates and α-Diazocarbonyl Compounds. J. Org. Chem. 2008, 73, 3928− 3930. (122) Presset, M.; Coquerel, Y.; Rodriguez, J. Microwave-Assisted Domino and Multicomponent Reactions with Cyclic Acylketenes: Expeditious Syntheses of Oxazinones and Oxazindiones. Org. Lett. 2009, 11, 5706−5709. (123) Presset, M.; Coquerel, Y.; Rodriguez, J. Periselectivity Switch of Acylketenes in Cycloadditions with 1-Azadienes: MicrowaveAssisted Diastereoselective Domino Three-Component Synthesis of α-Spiro-δ-lactams. Org. Lett. 2010, 12, 4212−4215. (124) Presset, M.; Mohanan, K.; Hamann, M.; Coquerel, Y.; Rodriguez, J. 1,3-Dipolar Cycloaddition of Hydrazones with α-Oxoketenes: A Three-Component Stereoselective Entry to Pyrazolidinones and an Original Class of Spirooxindoles. Org. Lett. 2011, 13, 4124−4127. (125) Lucas, N. C. d.; Andraos, J.; Netto-Ferreira, J. C.; Scaiano, J. C. Laser Flash Photolysis Study of the Reactivity of α-Ketenylbenzocyclobutenone with Water and Alcohols. Tetrahedron Lett. 1995, 36, 677−680. (126) Gerstenberger, B. S.; Lin, J.; Mimieux, Y. S.; Brown, L. E.; Oliver, A. G.; Konopelski, J. P. Structural Characterization of an Enantiomerically Pure Amino Acid Imidazolide and Direct Formation of the β-Lactam Nucleus from an α-Amino Acid. Org. Lett. 2008, 10, 369−372. (127) Dong, C.; Mo, F.; Wang, J. Highly Diastereoselective Addition of the Lithium Enolate of α-Diazoacetoacetate to N-Sulfinyl Imines: Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines. J. Org. Chem. 2008, 73, 1971−1974. (128) Islami, M. R.; Allen, A. D.; Vukovic, S.; Tidwell, T. T. NPyrrolylketene: A Nonconjugated Heteroarylketene. Org. Lett. 2011, 13, 494−497. (129) Yong, K.; Salim, M.; Capretta, A. Intramolecular Carbenoid Insertions: Reactions of α-Diazo Ketones Derived from Furanyl-, Thienyl-, (Benzofuranyl)-, and (Benzothienyl)acetic Acids with Rhodium(II) Acetate. J. Org. Chem. 1998, 63, 9828−9833. (130) Lee, D. J.; Kim, K.; Park, Y. J. Novel Synthesis of 5,6-Dihydro4H-thieno[3,2-b]pyrrol-5-ones via the Rhodium(II)-Mediated Wolff 10063


Chemical Reviews

Review

Ir(III) Five-Membered Metallacycle. J. Am. Chem. Soc. 2007, 129, 6092−6093. (152) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Stereoselective Cyclopropanation Reactions. Chem. Rev. 2003, 103, 977−1050. (153) Pellissier, H. Recent Developments in Asymmetric Cyclopropanation. Tetrahedron 2008, 64, 7041−7095. (154) Nicolas, I.; Le Maux, P.; Simonneaux, G. Asymmetric Catalytic Cyclopropanation Reactions in Water. Coord. Chem. Rev. 2008, 252, 727−735. (155) Maas, G. Ruthenium-Catalysed Carbenoid Cyclopropanation Reactions with Diazo Compounds. Chem. Soc. Rev. 2004, 33, 183−190. (156) Yu, M.; Pagenkopf, B. L. Recent Advances in Donor−Acceptor (DA) Cyclopropanes. Tetrahedron 2005, 61, 321−347. (157) Majumdar, K. C.; Chattopadhyay, S. K. Heterocycles in Natural Product Synthesis; John Wiley & Sons: Weinheim, Germany, 2011. (158) Tang, P.; Qin, Y. Recent Applications of Cyclopropane-Based Strategies to Natural Product Synthesis. Synthesis 2012, 44, 2969− 2984. (159) Chen, D. Y. K.; Pouwer, R. H.; Richard, J.-A. Recent Advances in the Total Synthesis of Cyclopropane-Containing Natural Products. Chem. Soc. Rev. 2012, 41, 4631−4642. (160) Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, R. Asymmetric Induction in Carbenoid Reaction by Means of a Dissymmetric Copper Chelate. Tetrahedron Lett. 1966, 7, 5239−5244. (161) Aratani, T. Catalytic Asymmetric Synthesis of Cyclopropanecarboxylic Acids: An Application of Chiral Copper Carbenoid Reaction. Pure Appl. Chem. 1985, 57, 1839−1844. (162) Lowenthal, R. E.; Abiko, A.; Masamune, S. Asymmetric Catalytic Cyclopropanation of Olefins: Bis-Oxazoline Copper Complexes. Tetrahedron Lett. 1990, 31, 6005−6008. (163) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. Bis(oxazolines) as Chiral Ligands in Metal-Catalyzed Asymmetric Reactions. Catalytic, Asymmetric Cyclopropanation of Olefins. J. Am. Chem. Soc. 1991, 113, 726−728. (164) Fritschi, H.; Leutenegger, U.; Pfaltz, A. Chiral CopperSemicorrin Complexes as Enantioselective Catalysts for the Cyclopropanation of Olefins by Diazo Compounds. Angew. Chem., Int. Ed. Engl. 1986, 25, 1005−1006. (165) Müller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. C2-Symmetric 4,4′,5,5′-Tetrahydrobi(oxazoles) and 4,4′,5,5′-Tetrahydro-2,2′methylenebis[oxazoles] as Chiral Ligands for Enantioselective Catalysis Preliminary Communication. Helv. Chim. Acta 1991, 74, 232−240. (166) Fritschi, H.; Leutenegger, U.; Siegmann, K.; Pfaltz, A.; Keller, W.; Kratky, C. Semicorrin Metal Complexes as Enantioselective Catalysts. Part 1. Synthesis of Chiral Semicorrin Ligands and General Concepts. Helv. Chim. Acta 1988, 71, 1541−1552. (167) McManus, H. A.; Guiry, P. J. Recent Developments in the Application of Oxazoline-Containing Ligands in Asymmetric Catalysis. Chem. Rev. 2004, 104, 4151−4202. (168) Hargaden, G. C.; Guiry, P. J. Recent Applications of OxazolineContaining Ligands in Asymmetric Catalysis. Chem. Rev. 2009, 109, 2505−2550. (169) Desimoni, G.; Faita, G.; Jørgensen, K. A. Update 1 of: C2Symmetric Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis. Chem. Rev. 2011, 111, PR284−PR437. (170) Itagaki, M.; Masumoto, K.; Suenobu, K.; Yamamoto, Y. Studies of Copper−Bisoxazoline-Catalyzed Asymmetric Cyclopropanation of 2,5-Dimethyl-2,4-hexadiene. Org. Process Res. Dev. 2006, 10, 245−250. (171) Itagaki, M.; Masumoto, K.; Yamamoto, Y. Asymmetric Cyclopropanation of 2,5-Dimethyl-2,4-hexadiene by Copper Catalysts Bearing New Bisoxazoline Ligands. J. Org. Chem. 2005, 70, 3292− 3295. (172) Mazet, C.; Köhler, V.; Pfaltz, A. Chiral Boron-Bridged Bisoxazolines: Readily Available Anionic Ligands for Asymmetric Catalysis. Angew. Chem., Int. Ed. 2005, 44, 4888−4891.

(173) Irmak, M.; Groschner, A.; Boysen, M. M. K. GlucoBox Liganda New Carbohydrate-Based Bis(oxazoline) Ligand. Synthesis and First Application. Chem. Commun. 2007, 177−179. (174) Xu, Z.-H.; Zhu, S.-N.; Sun, X.-L.; Tang, Y.; Dai, L.-X. Sidearm Effects in the Enantioselective Cyclopropanation of Alkenes with Aryldiazoacetates Catalyzed by Trisoxazoline/Cu(I). Chem. Commun. 2007, 1960−1962. (175) Chen, S.; Rong, C.; Feng, P.; Li, S.; Shi, Y. Stereoselective Construction of the Tetracyclic Core of Cryptotrione. Org. Biomol. Chem. 2012, 10, 5518−5520. (176) Harrar, K.; Reiser, O. Enantioselective Synthesis of (−)-Paeonilide. Chem. Commun. 2012, 48, 3457−3459. (177) Zaragoza Dorwald, F. Metal Carbenes in Organic Synthesis; Wiley-VCH: Weinheim, Germany, 1999. (178) Wang, H. B.; Guptill, D. M.; Varela-Alvarez, A.; Musaev, D. G.; Davies, H. M. L. Rhodium-Catalyzed Enantioselective Cyclopropanation of Electron-Deficient Alkenes. Chem. Sci. 2013, 4, 2844−2850. (179) Lian, Y.; Miller, L. C.; Born, S.; Sarpong, R.; Davies, H. M. L. Catalyst-Controlled Formal [4 + 3] Cycloaddition Applied to the Total Synthesis of (+)-Barekoxide and (−)-Barekol. J. Am. Chem. Soc. 2010, 132, 12422−12425. (180) Charette, A. B.; Wurz, R. Progress towards Asymmetric Intermolecular and Intramolecular Cyclopropanations Using α-Nitroα-diazo Carbonyl Substrates. J. Mol. Catal. A: Chem. 2003, 196, 83− 91. (181) Lin, W.; Charette, A. B. Rhodium-Catalysed Asymmetric Intramolecular of Substituted Allylic Cyanodiazoacetates. Adv. Synth. Catal. 2005, 347, 1547−1552. (182) Marcoux, D.; Charette, A. B. trans-Directing Ability of Amide Groups in Cyclopropanation: Application to the Asymmetric Cyclopropanation of Alkenes with Diazo Reagents Bearing Two Carboxy Groups. Angew. Chem., Int. Ed. 2008, 47, 10155−10158. (183) Marcoux, D.; Goudreau, S. R.; Charette, A. B. trans-Directing Ability of the Amide Group: Enabling the Enantiocontrol in the Synthesis of 1,1-Dicarboxy Cyclopropanes. Reaction Development, Scope, and Synthetic Applications. J. Org. Chem. 2009, 74, 8939−8955. (184) Lindsay, V. N. G.; Lin, W.; Charette, A. B. Experimental Evidence for the All-Up Reactive Conformation of Chiral Rhodium(II) Carboxylate Catalysts: Enantioselective Synthesis of cis-Cyclopropane α-Amino Acids. J. Am. Chem. Soc. 2009, 131, 16383−16385. (185) Marcoux, D.; Azzi, S.; Charette, A. B. TfNH2 as Achiral Hydrogen-Bond Donor Additive to Enhance the Selectivity of a Transition Metal Catalyzed Reaction. Highly Enantio- and Diastereoselective Rhodium-Catalyzed Cyclopropanation of Alkenes Using αCyano Diazoacetamide. J. Am. Chem. Soc. 2009, 131, 6970−6972. (186) Vanier, S. F.; Larouche, G.; Wurz, R. P.; Charette, A. B. Formal Synthesis of Belactosin A and Hormaomycin via a Diastereoselective Intramolecular Cyclopropanation of an α-Nitro Diazoester. Org. Lett. 2010, 12, 672−675. (187) Lindsay, V. N. G.; Nicolas, C.; Charette, A. B. Asymmetric Rh(II)-Catalyzed Cyclopropanation of Alkenes with Diacceptor Diazo Compounds: p-Methoxyphenyl Ketone as a General Stereoselectivity Controlling Group. J. Am. Chem. Soc. 2011, 133, 8972−8981. (188) Lindsay, V. N. G.; Fiset, D.; Gritsch, P. J.; Azzi, S.; Charette, A. B. Stereoselective Rh2(S-IBAZ)4-Catalyzed Cyclopropanation of Alkenes, Alkynes, and Allenes: Asymmetric Synthesis of Diacceptor Cyclopropylphosphonates and Alkylidenecyclopropanes. J. Am. Chem. Soc. 2013, 135, 1463−1470. (189) Lindsay, V. N. G.; Charette, A. B. Design and Synthesis of Chiral Heteroleptic Rhodium(II) Carboxylate Catalysts: Experimental Investigation of Halogen Bond Rigidification Effects in Asymmetric Cyclopropanation. ACS Catal. 2012, 2, 1221−1225. (190) Doyle, M. P.; Davies, S. B.; Hu, W. Optimization of Enantiocontrol in cis-Selective Cyclopropanation Reactions Catalyzed by Dirhodium(II) Tetrakis[alkyl 2-oxaazetidine-4(S)-carboxylates]. Chem. Commun. 2000, 867−868. (191) Hu, W.; Timmons, D. J.; Doyle, M. P. In Search of High Stereocontrol for the Construction of cis-Disubstituted Cyclopropane Compounds. Total Synthesis of a Cyclopropane-Configured Urea10064


Chemical Reviews

Review

PETT Analogue That Is a HIV-1 Reverse Transcriptase Inhibitor. Org. Lett. 2002, 4, 901−904. (192) Rosenberg, M. L.; Krivokapic, A.; Tilset, M. Highly cisSelective Cyclopropanations with Ethyl Diazoacetate Using a Novel Rh(I) Catalyst with a Chelating N-Heterocyclic Iminocarbene Ligand. Org. Lett. 2009, 11, 547−550. (193) Rosenberg, M. L.; Langseth, E.; Krivokapic, A.; Gupta, N. S.; Tilset, M. Investigation of Ligand Steric Effects on a Highly cisSelective Rh(I) Cyclopropanation Catalyst. New J. Chem. 2011, 35, 2306−2313. (194) Rosenberg, M. L.; Vlašaná, K.; Gupta, N. S.; Wragg, D.; Tilset, M. Highly cis-Selective Rh(I)-Catalyzed Cyclopropanation Reactions. J. Org. Chem. 2011, 76, 2465−2470. (195) Pellissier, H.; Clavier, H. Enantioselective Cobalt-Catalyzed Transformations. Chem. Rev. 2014, 114, 2775−2823. (196) Nishiyama, H.; Park, S. B.; Haga, M.; Aoki, K.; Itoh, K. Ruthenium(II)Cl2-Bis(oxazolinyl)bipyridine Complex. Its Structure and Reactivity. Chem. Lett. 1994, 1111−1114. (197) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K. New Chiral Ruthenium Bis(oxazolinyl)pyridine Catalyst. Efficient Asymmetric Cyclopropanation of Olefins with Diazoacetates. J. Am. Chem. Soc. 1994, 116, 2223−2224. (198) Simpson, J. H.; Godfrey, J.; Fox, R.; Kotnis, A.; Kacsur, D.; Hamm, J.; Totelben, M.; Rosso, V.; Mueller, R.; Delaney, E.; et al. A Pilot-Scale Synthesis of (1R)-trans-2-(2,3-Dihydro-4-benzofuranyl)cyclopropanecarboxylic acid: A Practical Application of Asymmetric Cyclopropanation Using a Styrene as a Limiting Reagent. Tetrahedron: Asymmetry 2003, 14, 3569−3574. (199) Nishiyama, H.; Itoh, Y.; Sugawara, Y.; Matsumoto, H.; Aoki, K.; Itoh, K. Chiral Ruthenium(II)−Bis(2-oxazolin-2-yl)pyridine Complexes. Asymmetric Catalytic Cyclopropanation of Olefins and Diazoacetates. Bull. Chem. Soc. Jpn. 1995, 68, 1247−1262. (200) Che, C.-M.; Huang, J.-S.; Lee, F.-W.; Li, Y.; Lai, T.-S.; Kwong, H.-L.; Teng, P.-F.; Lee, W.-S.; Lo, W.-C.; Peng, S.-M.; et al. Asymmetric Inter- and Intramolecular Cyclopropanation of Alkenes Catalyzed by Chiral Ruthenium Porphyrins. Synthesis and Crystal Structure of a Chiral Metalloporphyrin Carbene Complex. J. Am. Chem. Soc. 2001, 123, 4119−4129. (201) Miller, J. A.; Gross, B. A.; Zhuravel, M. A.; Jin, W.; Nguyen, S. T. Axial Ligand effects: Utilization of Chiral Sulfoxide Additives for the Induction of Asymmetry in (Salen)ruthenium(II) Olefin Cyclopropanation Catalysts. Angew. Chem., Int. Ed. 2005, 44, 3885−3889. (202) Li, G.-Y.; Zhang, J.; Chan, P. W. H.; Xu, Z.-J.; Zhu, N.; Che, C.-M. Enantioselective Intramolecular Cyclopropanation of cis-Alkenes by Chiral Ruthenium(II) Schiff Base Catalysts and Crystal Structures of (Schiff base)ruthenium Complexes Containing Carbene, PPh3, and CO Ligands. Organometallics 2006, 25, 1676−1688. (203) Uchida, T.; Katsuki, T. α-Diazoacetates as Carbene Precursors: Metallosalen-Catalyzed Asymmetric Cyclopropanation. Synthesis 2006, 2006, 1715−1723. (204) Gill, C. S.; Venkatasubbaiah, K.; Jones, C. W. Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-Pyridine Catalysts for the Asymmetric Cyclopropanation of Olefins. Adv. Synth. Catal. 2009, 351, 1344−1354. (205) Chanthamath, S.; Phomkeona, K.; Shibatomi, K.; Iwasa, S. Highly Stereoselective Ru(II)-Pheox Catalyzed Asymmetric Cyclopropanation of Terminal Olefins with Succinimidyl Diazoacetate. Chem. Commun. 2012, 48, 7750−7752. (206) Chanthamath, S.; Nguyen, D. T.; Shibatomi, K.; Iwasa, S. Highly Enantioselective Synthesis of Cyclopropylamine Derivatives via Ru(II)-Pheox-Catalyzed Direct Asymmetric Cyclopropanation of Vinylcarbamates. Org. Lett. 2013, 15, 772−775. (207) Chanthamath, S.; Takaki, S.; Shibatomi, K.; Iwasa, S. Highly Stereoselective Cyclopropanation of α,β-Unsaturated Carbonyl Compounds with Methyl (Diazoacetoxy)acetate Catalyzed by a Chiral Ruthenium(II) Complex. Angew. Chem., Int. Ed. 2013, 52, 5818−5821. (208) Intrieri, D.; Caselli, A.; Gallo, E. Cyclopropanation Reactions Mediated by Group 9 Metal Porphyrin Complexes. Eur. J. Inorg. Chem. 2011, 2011, 5071−5081.

(209) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. Highly Enantioselective Cyclopropanation with Co(II)-Salen Complexes: Control of cis- and trans-Selectivity by Rational Ligand-Design. Adv. Synth. Catal. 2001, 343, 79−88. (210) Katsuki, T. Chiral Metallosalen Complexes: Structures and Catalyst Tuning for Asymmetric Epoxidation and Cyclopropanation. Adv. Synth. Catal. 2002, 344, 131−147. (211) Ito, Y. N.; Katsuki, T. Asymmetric Catalysis of New Generation Chiral Metallosalen Complexes. Bull. Chem. Soc. Jpn. 1999, 72, 603−619. (212) Chen, Y.; Fields, K. B.; Zhang, X. P. Bromoporphyrins as Versatile Synthons for Modular Construction of Chiral Porphyrins: Cobalt-Catalyzed Highly Enantioselective and Diastereoselective Cyclopropanation. J. Am. Chem. Soc. 2004, 126, 14718−14719. (213) Huang, L.; Chen, Y.; Gao, G.-Y.; Zhang, X. P. Diastereoselective and Enantioselective Cyclopropanation of Alkenes Catalyzed by Cobalt Porphyrins. J. Org. Chem. 2003, 68, 8179−8184. (214) Chen, Y.; Zhang, X. P. Trans Effect on Cobalt Porphyrin Catalyzed Asymmetric Cyclopropanation. Synthesis 2006, 2006, 1697− 1700. (215) Chen, Y.; Zhang, X. P. Asymmetric Cyclopropanation of Styrenes Catalyzed by Metal Complexes of D2-Symmetrical Chiral Porphyrin: Superiority of Cobalt over Iron. J. Org. Chem. 2007, 72, 5931−5934. (216) Doyle, M. P. Exceptional Selectivity in Cyclopropanation Reactions Catalyzed by Chiral Cobalt(II)−Porphyrin Catalysts. Angew. Chem., Int. Ed. 2009, 48, 850−852. (217) Chen, Y.; Ruppel, J. V.; Zhang, X. P. Cobalt-Catalyzed Asymmetric Cyclopropanation of Electron-Deficient Olefins. J. Am. Chem. Soc. 2007, 129, 12074−12075. (218) Anding, B. J.; Ellern, A.; Woo, L. K. Olefin Cyclopropanation Catalyzed by Iridium(III) Porphyrin Complexes. Organometallics 2012, 31, 3628−3635. (219) Nicolas, I.; Roisnel, T.; Maux, P. L.; Simonneaux, G. Asymmetric Intermolecular Cyclopropanation of Alkenes by Diazoketones Catalyzed by Halterman Iron Porphyrins. Tetrahedron Lett. 2009, 50, 5149−5151. (220) Cao, Z.-Y.; Wang, X.; Tan, C.; Zhao, X.-L.; Zhou, J.; Ding, K. Highly Stereoselective Olefin Cyclopropanation of Diazooxindoles Catalyzed by a C2-Symmetric Spiroketal Bisphosphine/Au(I) Complex. J. Am. Chem. Soc. 2013, 135, 8197−8200. (221) Cao, Z.-Y.; Zhou, F.; Yu, Y.-H.; Zhou, J. A Highly Diastereoand Enantioselective Hg(II)-Catalyzed Cyclopropanation of Diazooxindoles and Alkenes. Org. Lett. 2013, 15, 42−45. (222) Padwa, A.; Krumpe, K. E. Application of Intramolecular Carbenoid Reactions in Organic Synthesis. Tetrahedron 1992, 48, 5385−5453. (223) Xu, Z.-J.; Fang, R.; Zhao, C.; Huang, J.-S.; Li, G.-Y.; Zhu, N.; Che, C.-M. cis-β-Bis(carbonyl) Ruthenium−Salen Complexes: X-ray Crystal Structures and Remarkable Catalytic Properties toward Asymmetric Intramolecular Alkene Cyclopropanation. J. Am. Chem. Soc. 2009, 131, 4405−4417. (224) Zhang, J.-L.; Liu, Y.-L.; Che, C.-M. Chiral Ruthenium Porphyrin Encapsulated in Ordered Mesoporous Molecular Sieves (MCM-41 and MCM-48) as Catalysts for Asymmetric Alkene Epoxidation and Cyclopropanation. Chem. Commun. 2002, 2906− 2907. (225) Ho, C.-M.; Zhang, J.-L.; Zhou, C.-Y.; Chan, O.-Y.; Yan, J. J.; Zhang, F.-Y.; Huang, J.-S.; Che, C.-M. A Water-Soluble Ruthenium Glycosylated Porphyrin Catalyst for Carbenoid Transfer Reactions in Aqueous Media with Applications in Bioconjugation Reactions. J. Am. Chem. Soc. 2010, 132, 1886−1894. (226) Xu, X.; Lu, H.; Ruppel, J. V.; Cui, X.; Lopez de Mesa, S.; Wojtas, L.; Zhang, X. P. Highly Asymmetric Intramolecular Cyclopropanation of Acceptor-Substituted Diazoacetates by Co(II)-Based Metalloradical Catalysis: Iterative Approach for Development of NewGeneration Catalysts. J. Am. Chem. Soc. 2011, 133, 15292−15295. 10065


Chemical Reviews

Review

propanation of Diazoacetates Catalyzed by Chiral CuI and RhII Compounds. Angew. Chem., Int. Ed. Engl. 1996, 35, 1334−1336. (248) Weathers, T. M., Jr.; Wang, Y.; Doyle, M. P. Polyether Macrocycles from Intramolecular Cyclopropanation and Ylide Formation. Effect of Catalyst and Coordination. J. Org. Chem. 2006, 71, 8183−8189. (249) Doyle, M. P.; Hu, W.; Chapman, B.; Marnett, A. B.; Peterson, C. S.; Vitale, J. P.; Stanley, S. A. Enantiocontrolled Macrocycle Formation by Catalytic Intramolecular Cyclopropanation. J. Am. Chem. Soc. 2000, 122, 5718−5728. (250) Doyle, M. P. Perspective on Dirhodium Carboxamidates as Catalysts. J. Org. Chem. 2006, 71, 9253−9260. (251) Doyle, M. P.; Davies, S. B.; Hu, W. Dirhodium(II) Tetrakis[methyl 2-oxaazetidine-4-carboxylate]: A Chiral Dirhodium(II) Carboxamidate of Exceptional Reactivity and Selectivity. Org. Lett. 2000, 2, 1145−1147. (252) Davies, H. M. L.; Doan, B. D. Enantioselective Synthesis of Fused Cycloheptadienes by a Tandem Intramolecular Cyclopropanation/Cope Rearrangement Sequence. J. Org. Chem. 1999, 64, 8501− 8508. (253) Taber, D. F.; Sheth, R. B.; Tian, W. Synthesis of (+)-Coronafacic Acid. J. Org. Chem. 2009, 74, 2433−2437. (254) Rubin, M.; Rubina, M.; Gevorgyan, V. Recent Advances in Cyclopropene Chemistry. Synthesis 2006, 2006, 1221−1245. (255) Marek, I.; Simaan, S.; Masarwa, A. Enantiomerically Enriched Cyclopropene Derivatives: Versatile Building Blocks in Asymmetric Synthesis. Angew. Chem., Int. Ed. 2007, 46, 7364−7376. (256) Doyle, M. P.; Protopopova, M.; Muller, P.; Ene, D.; Shapiro, E. A. Effective Uses of Dirhodium(II) Tetrakis[methyl 2-oxopyrrolidine5(R or S)-carboxylate] for Highly Enantioselective Intermolecular Cyclopropenation Reactions. J. Am. Chem. Soc. 1994, 116, 8492−8498. (257) Davies, H. M. L.; Lee, G. H. Dirhodium(II) Tetra(N(dodecylbenzenesulfonyl)prolinate) Catalyzed Enantioselective Cyclopropenation of Alkynes. Org. Lett. 2004, 6, 1233−1236. (258) Goto, T.; Takeda, K.; Shimada, N.; Nambu, H.; Anada, M.; Shiro, M.; Ando, K.; Hashimoto, S. Highly Enantioselective Cyclopropenation Reaction of 1-Alkynes with α-Alkyl-α-Diazoesters Catalyzed by Dirhodium(II) Carboxylates. Angew. Chem., Int. Ed. 2011, 50, 6803−6808. (259) Briones, J. F.; Davies, H. M. L. Rh2(S-PTAD)4-Catalyzed Asymmetric Cyclopropenation of Aryl Alkynes. Tetrahedron 2011, 67, 4313−4317. (260) Boruta, D. T.; Dmitrenko, O.; Yap, G. P. A.; Fox, J. M. Rh2(SPTTL)3TPAa Mixed-Ligand Dirhodium(II) Catalyst for Enantioselective Reactions of α-Alkyl-α-diazoesters. Chem. Sci. 2012, 3, 1589− 1593. (261) Briones, J. F.; Hansen, J.; Hardcastle, K. I.; Autschbach, J.; Davies, H. M. L. Highly Enantioselective Rh2(S-DOSP)4-Catalyzed Cyclopropenation of Alkynes with Styryldiazoacetates. J. Am. Chem. Soc. 2010, 132, 17211−17215. (262) Diaz-Requejo, M. M.; Mairena, M. A.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Perez, P. J. A Family of Highly Active Copper(I)-Homoscorpionate Catalysts for the Alkyne Cyclopropenation Reaction. Chem. Commun. 2001, 1804−1805. (263) Park, E. J.; Kim, S. H.; Chang, S. Copper-Catalyzed Reaction of α-Aryldiazoesters with Terminal Alkynes: A Formal [3 + 2] Cycloaddition Route Leading to Indene Derivatives. J. Am. Chem. Soc. 2008, 130, 17268−17269. (264) Zhou, L.; Ma, J.; Zhang, Y.; Wang, J. Copper-Catalyzed Cascade Coupling/Cyclization of Terminal Alkynes with Diazoacetates: A Straightforward Route for Trisubstituted Furans. Tetrahedron Lett. 2011, 52, 5484−5487. (265) Cui, X.; Xu, X.; Lu, H.; Zhu, S.; Wojtas, L.; Zhang, X. P. Enantioselective Cyclopropenation of Alkynes with Acceptor/Acceptor-Substituted Diazo Reagents via Co(II)-Based Metalloradical Catalysis. J. Am. Chem. Soc. 2011, 133, 3304−3307. (266) Uehara, M.; Suematsu, H.; Yasutomi, Y.; Katsuki, T. Enantioenriched Synthesis of Cyclopropenes with a Quaternary

(227) Uchida, T.; Saha, B.; Katsuki, T. Co(II)−Salen-Catalyzed Asymmetric Intramolecular Cyclopropanation. Tetrahedron Lett. 2001, 42, 2521−2524. (228) Honma, M.; Nakada, M. Enantioselective Intramolecular Cyclopropanation of α-Diazo-β-keto Sulfones: Asymmetric Synthesis of Bicyclo[4.1.0]heptanes and Tricyclo[4.4.0.0]decenes. Tetrahedron Lett. 2003, 44, 9007−9011. (229) Honma, M.; Sawada, T.; Fujisawa, Y.; Utsugi, M.; Watanabe, H.; Umino, A.; Matsumura, T.; Hagihara, T.; Takano, M.; Nakada, M. Asymmetric Catalysis on the Intramolecular Cyclopropanation of αDiazo-β-keto Sulfones. J. Am. Chem. Soc. 2003, 125, 2860−2861. (230) Sawada, T.; Nakada, M. Asymmetric Catalysis of Intramolecular Cyclopropanation of 5-Aryl-1-diazo-1-mesitylsulfonyl-5hexen-2-ones. Adv. Synth. Catal. 2005, 347, 1527−1532. (231) Takeda, H.; Nakada, M. Studies on the Structure− Enantioselectivity Relationships in the Catalytic Asymmetric Intramolecular Cyclopropanation Reaction of α-Diazo-β-keto Sulfones Possessing a Methyl-Substituted Phenyl Group. Tetrahedron: Asymmetry 2006, 17, 2896−2906. (232) Ida, R.; Nakada, M. Highly Enantioselective Preparation of Tricyclo[4.4.0.05,7]decene Derivatives via Catalytic Asymmetric Intramolecular Cyclopropanation Reactions of α-Diazo-β-keto Esters. Tetrahedron Lett. 2007, 48, 4855−4859. (233) Sawada, T.; Nakada, M. Preparation of New Chiral Bisoxazoline Ligands for the Catalytic Asymmetric Intramolecular Cyclopropanation of α-Diazo-β-keto Phenyl Sulfone to Afford a Useful Bicyclo[3.1.0]hexane Derivative. Tetrahedron: Asymmetry 2012, 23, 350−356. (234) Takeda, H.; Honma, M.; Ida, R.; Sawada, T.; Nakada, M. Catalytic Asymmetric Intramolecular Cyclopropanation of 2-Diazo-3oxo-6-heptenoic Acid Esters. Synlett 2007, 2007, 579−582. (235) Miyamoto, H.; Iwamoto, M.; Nakada, M. A New Asymmetric Total Synthesis of Enantiopure (−)-Malyngolide. Heterocycles 2005, 66, 61−68. (236) Takeda, H.; Watanabe, H.; Nakada, M. Asymmetric Total Synthesis of Enantiopure (−)-Methyl Jasmonate via Catalytic Asymmetric Intramolecular Cyclopropanation of α-Diazo-β-keto Sulfone. Tetrahedron 2006, 62, 8054−8063. (237) Honma, M.; Nakada, M. Enantioselective Total Synthesis of (+)-Digitoxigenin. Tetrahedron Lett. 2007, 48, 1541−1544. (238) Watanabe, H.; Nakada, M. Synthetic Studies on (−)-Scabronine A. Tetrahedron Lett. 2008, 49, 1518−1522. (239) Hirai, S.; Nakada, M. An Enantioselective Approach to (−)-Platencin via Catalytic Asymmetric Intramolecular Cyclopropanation. Tetrahedron Lett. 2010, 51, 5076−5079. (240) Abe, M.; Saito, A.; Nakada, M. Synthetic Studies on Nemorosone via Enantioselective Intramolecular Cyclopropanation. Tetrahedron Lett. 2010, 51, 1298−1302. (241) Uwamori, M.; Saito, A.; Nakada, M. Stereoselective Total Synthesis of Nemorosone. J. Org. Chem. 2012, 77, 5098−5107. (242) Sawada, T.; Nakada, M. Enantioselective Total Synthesis of (+)-Colletoic Acid via Catalytic Asymmetric Intramolecular Cyclopropanation of an α-Diazo-β-keto Diphenylphosphine Oxide. Org. Lett. 2013, 15, 1004−1007. (243) Uwamori, M.; Nakada, M. Stereoselective Total Synthesis of (±)-Hyperforin via Intramolecular Cyclopropanation. Tetrahedron Lett. 2013, 54, 2022−2025. (244) Uwamori, M.; Nakada, M. Stereoselective Total Synthesis of Garsubellin A. J. Antibiot. 2013, 66, 141−145. (245) Honma, M.; Takeda, H.; Takano, M.; Nakada, M. Development of Catalytic Asymmetric Intramolecular Cyclopropanation of αDiazo-β-Keto Sulfones and Applications to Natural Product Synthesis. Synlett 2009, 2009, 1695−1712. (246) Yang, J.; Song, H.; Xiao, X.; Wang, J.; Qin, Y. Biomimetic Approach to Perophoramidine and Communesin via an Intramolecular Cyclopropanation Reaction. Org. Lett. 2006, 8, 2187−2190. (247) Doyle, M. P.; Peterson, C. S.; Parker, D. L., Jr. Formation of Macrocyclic Lactones by Enantioselective Intramolecular Cyclo10066


Chemical Reviews

Review

Stereocenter, Versatile Building Blocks. J. Am. Chem. Soc. 2011, 133, 170−171. (267) Briones, J. F.; Davies, H. M. L. Silver Triflate-Catalyzed Cyclopropenation of Internal Alkynes with Donor-/Acceptor-Substituted Diazo Compounds. Org. Lett. 2011, 13, 3984−3987. (268) Briones, J. F.; Davies, H. M. L. Gold(I)-Catalyzed Asymmetric Cyclopropenation of Internal Alkynes. J. Am. Chem. Soc. 2012, 134, 11916−11919. (269) Padwa, A.; Weingarten, M. D. Cascade Processes of Metallo Carbenoids. Chem. Rev. 1996, 96, 223−270. (270) Doyle, M. P.; Ene, D. G.; Peterson, C. S.; Lynch, V. Macrocyclic Cyclopropenes by Highly Enantioselective Intramolecular Addition of Metal Carbenes to Alkynes. Angew. Chem., Int. Ed. 1999, 38, 700−702. (271) McNamara, O. A.; Maguire, A. R. The NorcaradieneCycloheptatriene Equilibrium. Tetrahedron 2011, 67, 9−40. (272) Reisman, S. E.; Nani, R. R.; Levin, S. Buchner and Beyond: Arene Cyclopropanation as Applied to Natural Product Total Synthesis. Synlett 2011, 2011, 2437−2442. (273) Anciaux, A. J.; Demonceau, A.; Hubert, A. J.; Noels, A. F.; Petiniot, N.; Teyssié, P. Catalytic Control of Reactions of Dipoles and Carbenes; an Easy and Efficient Synthesis of Cycloheptatrienes from Aromatic Compounds by an Extension of Buchner’s Reaction. J. Chem. Soc., Chem. Commun. 1980, 765−766. (274) McKervey, M. A.; Tuladhar, S. M.; Twohig, M. F. Efficient Synthesis of Bicyclo[5.3.0]decatrienones and of 2-Tetralones via Rhodium(II) Acetate-Catalysed Cyclisation of α-Diazoketones Derived from 3-Arylpropionic acids. J. Chem. Soc., Chem. Commun. 1984, 129−130. (275) Vogel, E.; Wiedemann, W.; Roth, H. D.; Eimer, J.; Gunther, H. Ein Beitrag zum Norcaradien- Cycloheptatrien-Strukturproblem. Justus Liebigs Ann. Chem. 1972, 759, 1−36. (276) Roth, W. R.; Klarner, F. G.; Siepert, G.; Lennartz, H. W. Hydrierwärmen, IV. Zur Frage der Homoaromatizität von Norcaradien und Cycloheptatrien. Chem. Ber. 1992, 125, 217−224. (277) Ciganek, E. 7,7-Dicyanonorcaradienes. J. Am. Chem. Soc. 1965, 87, 652−653. (278) Ciganek, E. The Direct Observation of a NorcaradieneCyclohepatriene Equilibrium. J. Am. Chem. Soc. 1965, 87, 1149−1150. (279) Ciganek, E. The Cycloheptatriene-Norcaradiene System. I. 7,7Dicyanonorcaradienes. Preparation and Structure Proof. J. Am. Chem. Soc. 1967, 89, 1454−1458. (280) Reich, H. J.; Ciganek, E.; Roberts, J. D. Nuclear Magnetic Resonance Spectroscopy. Kinetics of a 7,7-Dicyanonorcaradiene Valence Tautomerism. J. Am. Chem. Soc. 1970, 92, 5166−5169. (281) Ciganek, E. Cycloheptatriene-Norcaradiene System. III. Dependence of the Ground-State Enthalpy Difference on Substituents in the 7 Position. J. Am. Chem. Soc. 1971, 93, 2207−2215. (282) Garst, M. E.; Roberts, V. A. Synthesis of 3- and 4(Carbethoxy)-2,4,6-cycloheptatrien-1-one. J. Org. Chem. 1982, 47, 2188−2190. (283) Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Tuladhar, S. M.; Twohig, M. F. The Intramolecular Buchner Reaction of Aryl Diazoketones. Substituent Effects and Scope in Synthesis. J. Chem. Soc., Perkin Trans. 1 1990, 1047−1054. (284) Mbuvi, H. M.; Woo, L. K. Addition of Carbenes Derived from Aryldiazoacetates to Arenes Using Chloro(tetraphenylporphyrinato)iron as Catalyst. J. Porphyrins Phthalocyanines 2009, 13, 136−152. (285) Lovely, C. J.; Browning, R. G.; Badarinarayana, V.; Dias, H. V. R. A Silver-Catalyzed Büchner Reaction. Tetrahedron Lett. 2005, 46, 2453−2455. (286) Anciaux, A. J.; Demonceau, A.; Noels, A. F.; Hubert, A. J.; Warin, R.; Teyssié, P. Transition-Metal-Catalyzed Reactions of Diazo Compounds. 2. Addition to Aromatic Molecules: Catalysis of Buchner’s Synthesis of Cycloheptatrienes. J. Org. Chem. 1981, 46, 873−876. (287) Wyatt, E. E.; Galloway, W. R. J. D.; Spring, D. R. Regioselectivity in Thermal Rhodium(II)-Catalysed Buchner-Type

Reactions of Substituted Aryl Halides: Studies toward the Synthesis of Halide-Substituted Cycloheptatrienes. Synlett 2011, 2011, 1449−1453. (288) Bestmann, H. J.; Moll, C.; Bingel, C. Reaction of C60 with αDiazoketones: Methano- and Dihydrofuranofullerenes. Synlett 1996, 1996, 729−730. (289) Nakamura, Y.; Inamura, K. I.; Oomuro, R.; Laurenco, R.; Tidwell, T. T.; Nishimura, J. Formation of Fulleroids as Major Products and Application of Solid State Reaction in the Functionalization of [60]Fullerene by Aromatic Diazoketones. Org. Biomol. Chem. 2005, 3, 3032−3038. (290) Isaacs, L.; Wehrsig, A.; Diederich, F. Improved Purification of C60 and Formation of σ- and π-Homoaromatic Methano-Bridged Fullerenes by Reaction with Alkyl Diazoacetates. Helv. Chim. Acta 1993, 76, 1231−1250. (291) Isaacs, L.; Diederich, F. Structures and Chemistry of Methanofullerenes: A Versatile Route into N-[(Methanofullerene)carbonyl]-Substituted Amino Acids. Helv. Chim. Acta 1993, 76, 2454− 2464. (292) Diederich, F.; Isaacs, L.; Philp, D. Valence Isomerism and Rearrangements in Methanofullerenes. J. Chem. Soc., Perkin Trans. 2 1994, 391−394. (293) Skiebe, A.; Hirsch, A. A Facile Method for the Synthesis of Amino Acid and Amido Derivatives of C60. J. Chem. Soc., Chem. Commun. 1994, 335−336. (294) Roberti, M.; Natalini, B.; Andrisano, V.; Seraglia, R.; Gioiello, A.; Pellicciari, R. Thermal and Catalytic Reactions of Ethyl Diazopyruvate with [60]Fullerene. Tetrahedron 2010, 66, 7329−7332. (295) Tuktarov, A. R.; Khuzin, A. A.; Popod’ko, N. R.; Dzhemilev, U. M. Cycloaddition of Diazothioates to [60]Fullerene. Tetrahedron Lett. 2012, 53, 3123−3125. (296) Yamada, M.; Akasaka, T.; Nagase, S. Carbene Additions to Fullerenes. Chem. Rev. 2013, 113, 7209−7264. (297) Sonaware, H. R.; Bellur, S. N.; Sudrick, S. G. Applications of Chemoselective Rhodium-Carbenoid Reaction with the Aromatic Nucleus. Ind. J. Chem., Sect. B 1992, 31, 606−607. (298) Costantino, A.; Linstrumelle, G.; Julia, S. Products Formed by Treating 1-Diazo-4-phenylbutan-2-one with Copper Powder. Synthesis of Tricyclo[5.3.0.01,6]decan-8-one. Bull. Soc. Chim. Fr. 1970, 907−912. (299) Cordi, A. A.; Lacoste, J. M.; Hennig, P. A Reinvestigation of the Intramolecular Buchner Reaction of 1-Diazo-4-phenylbutan-2-ones Leading to 2-Tetralones. J. Chem. Soc., Perkin Trans. 1 1993, 3−4. (300) Manitto, P.; Monti, D.; Zanzola, S.; Speranza, G. A Reinvestigation of the Rh2(OAc)4-Catalysed Decomposition of 1Diazo-4-(2-methoxyphenyl)alkan-2-ones: Evidence for Ionic ‘RingWalk’ Rearrangement in Norcaradiene Derivatives. Chem. Commun. 1999, 543−544. (301) Maguire, A. R.; O'Leary, P.; Harrington, F.; Lawrence, S. E.; Blake, A. J. Dynamic Equilibria in the Products of Intramolecular Buchner Additions of Diazoketones to Aryl Rings Bearing Methoxy Substituents. J. Org. Chem. 2001, 66, 7166−7177. (302) Maguire, A. R.; Buckley, N. R.; O'Leary, P.; Ferguson, G. Excellent Stereocontrol in Intramolecular Buchner Cyclisations and Subsequent Cycloadditions; Stereospecific Construction of Polycyclic Systems. Chem. Commun. 1996, 2595−2596. (303) McNamara, O. A.; Buckley, N. R.; O'Leary, P.; Harrington, F.; Kelly, N.; O'Keeffe, S.; Stack, A.; O'Neill, S.; Lawrence, S. E.; Slattery, C. N.; et al. Catalyst and Substituent Effects on the Rhodium(II)Catalysed Intramolecular Buchner Reaction. Tetrahedron 2014, 70, 6870−6878. (304) McDowell, P. A.; Foley, D. A.; O’Leary, P.; Ford, A.; Maguire, A. R. Asymmetric Synthesis of cis-7-Methoxycalamenene via the Intramolecular Buchner Reaction of an α-Diazoketone. J. Org. Chem. 2012, 77, 2035−2040. (305) Merlic, C. A.; Zechman, A. L.; Miller, M. M. Reactivity of (η6Arene)tricarbonylchromium Complexes with Carbenoids: Arene Activation or Protection? J. Am. Chem. Soc. 2001, 123, 11101−11102. (306) Levin, S.; Nani, R. R.; Reisman, S. E. Rapid Assembly of the Salvileucalin B Norcaradiene Core. Org. Lett. 2010, 12, 780−783. 10067


Chemical Reviews

Review

of Metal-Carbene-Induced Zwitterionic Intermediates. Angew. Chem., Int. Ed. 2014, 53, 13098−13101. (325) Zheng, C.; You, S.-L. Recent Development of Direct Asymmetric Functionalization of Inert C−H Bonds. RSC Adv. 2014, 4, 6173−6214. (326) Tayama, E.; Yanaki, T.; Iwamoto, H.; Hasegawa, E. Copper(II) Triflate Catalyzed Intermolecular Aromatic Substitution of N,NDisubstituted Anilines with Diazo Esters. Eur. J. Org. Chem. 2010, 2010, 6719−6721. (327) Fructos, M. R.; Belderrain, T. R.; de Frémont, P.; Scott, N. M.; Nolan, S. P.; Díaz-Requejo, M. M.; Pérez, P. J. A Gold Catalyst for Carbene-Transfer Reactions from Ethyl Diazoacetate. Angew. Chem., Int. Ed. 2005, 44, 5284−5288. (328) Rivilla, I.; Gómez-Emeterio, B. P.; Fructos, M. R.; DíazRequejo, M. M.; Pérez, P. J. Exclusive Aromatic vs Aliphatic C−H Bond Functionalization by Carbene Insertion with Gold-Based Catalysts. Organometallics 2011, 30, 2855−2860. (329) Xie, J.; Pan, C.; Abdukader, A.; Zhu, C. Gold-Catalyzed C(sp3)−H Bond Functionalization. Chem. Soc. Rev. 2014, 43, 5245− 5256. (330) Yu, Z.; Ma, B.; Chen, M.; Wu, H.-H.; Liu, L.; Zhang, J. Highly Site-Selective Direct C−H Bond Functionalization of Phenols with αAryl-α-diazoacetates and Diazooxindoles via Gold Catalysis. J. Am. Chem. Soc. 2014, 136, 6904−6907. (331) Yu, X.; Yu, S.; Xiao, J.; Wan, B.; Li, X. Rhodium(III)-Catalyzed Azacycle-Directed Intermolecular Insertion of Arene C−H Bonds into α-Diazocarbonyl Compounds. J. Org. Chem. 2013, 78, 5444−5452. (332) Lian, Y.; Davies, H. M. L. Rhodium-Catalyzed [3 + 2] Annulation of Indoles. J. Am. Chem. Soc. 2010, 132, 440−441. (333) DeAngelis, A.; Shurtleff, V. W.; Dmitrenko, O.; Fox, J. M. Rhodium(II)-Catalyzed Enantioselective C−H Functionalization of Indoles. J. Am. Chem. Soc. 2011, 133, 1650−1653. (334) Watanabe, N.; Ohtake, Y.; Hashimoto, S.-i.; Shiro, M.; Ikegami, S. Asymmetric Creation of Quaternary Carbon Centers by Enantiotopically Selective Aromatic C−H Insertion Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 1995, 36, 1491− 1494. (335) Doyle, M. P.; Shanklin, M. S.; Pho, H. Q.; Mahapatro, S. N. Rhodium(II) Acetate and Nafion-H Catalyzed Decomposition of NAryldiazoamides. Efficient Synthesis of 2(3H)-Indolinones. J. Org. Chem. 1988, 53, 1017−1022. (336) Wee, A. G. H.; Liu, B.; Zhang, L. Dirhodium Tetraacetate Catalyzed Carbon−Hydrogen Insertion Reaction in N-Substituted αCarbomethoxy-α-diazoacetanilides and Structural Analogs. Substituent and Conformational Effects. J. Org. Chem. 1992, 57, 4404−4414. (337) Wang, H.-L.; Li, Z.; Wang, G.-W.; Yang, S.-D. Silver Catalyzed Intramolecular Cyclization for Synthesis of 3-Alkylideneoxindoles via C−H Functionalization. Chem. Commun. 2011, 47, 11336−11338. (338) Chan, W.-W.; Kwong, T.-L.; Yu, W.-Y. Ruthenium-Catalyzed Intramolecular Cyclization of Diazo-β-ketoanilides for the Synthesis of 3-Alkylideneoxindoles. Org. Biomol. Chem. 2012, 10, 3749−3755. (339) Mo, S.; Yang, Z.; Xu, J. Aqueous Copper Nitrate Catalyzed Synthesis of 3-Alkylideneoxindoles from α-Diazo-β-ketoanilides. Eur. J. Org. Chem. 2014, 2014, 3923−3929. (340) Hashimoto, T.; Yamamoto, K.; Maruoka, K. Catalytic Enantioselective Intramolecular Cyclization of N-Aryl Diazoamides Using a Titanium−BINOLate Complex. Chem. Commun. 2014, 50, 3220−3223. (341) Moody, C. J.; Doyle, K. J.; Elliott, M. C.; Mowlem, T. J. Synthesis of Heterocyclic Natural Products: Model Studies towards Diazonamide A. Pure Appl. Chem. 1994, 66, 2107−2110. (342) Yang, Z.; Xu, J. Synthesis of Benzo-γ-sultams via the RhCatalyzed Aromatic C−H Functionalization of Diazosulfonamides. Chem. Commun. 2014, 50, 3616−3618. (343) Collomb, D.; Chantegrel, B.; Deshayes, C. Chemoselectivity in the Rhodium(II) Acetate Catalysed Decomposition of α-Diazo-β-ketoγ,δ-alkenyl-δ-aryl Compounds: Aromatic C−H Insertion Reaction or Wolff Rearrangement-Electrocyclization. Tetrahedron 1996, 52, 10455−10472.

(307) Levin, S.; Nani, R. R.; Reisman, S. E. Enantioselective Total Synthesis of (+)-Salvileucalin B. J. Am. Chem. Soc. 2011, 133, 774− 776. (308) Nani, R. R.; Reisman, S. E. α-Diazo-β-ketonitriles: Uniquely Reactive Substrates for Arene and Alkene Cyclopropanation. J. Am. Chem. Soc. 2013, 135, 7304−7311. (309) Kane, J. L.; Shea, K. M.; Crombie, A. L.; Danheiser, R. L. A Ring Expansion−Annulation Strategy for the Synthesis of Substituted Azulenes. Preparation and Suzuki Coupling Reactions of 1-Azulenyl Triflates. Org. Lett. 2001, 3, 1081−1084. (310) Crombie, A. L.; Kane, J. L.; Shea, K. M.; Danheiser, R. L. Ring Expansion-Annulation Strategy for the Synthesis of Substituted Azulenes and Oligoazulenes. 2. Synthesis of Azulenyl Halides, Sulfonates, and Azulenylmetal Compounds and Their Application in Transition-Metal-Mediated Coupling Reactions. J. Org. Chem. 2004, 69, 8652−8667. (311) Sugimura, T.; Sato, Y.; Im, C. Y.; Okuyama, T. Asymmetric Synthesis of Deoxypolypropionate Units via Stereoselective Hydrogenation of Optically Active Cycloheptatriene. Org. Lett. 2004, 6, 4439−4442. (312) Sugimura, T.; Im, C. Y.; Sato, Y.; Okuyama, T. Stereoselective Hydrogenation of Conjugate Diene Directed by Hydroxy Group and Asymmetric Synthesis of Deoxypolypropionate Units. Tetrahedron 2007, 63, 4027−4038. (313) Kennedy, M.; McKervey, M. A. Pseudoguaianolides from Intramolecular Cycloadditions of Aryl Diazoketones: Synthesis of (±)-Confertin and an Approach to the Synthesis of (±)-Damsin. J. Chem. Soc., Perkin Trans. 1 1991, 2565−2574. (314) Foley, D. A.; O'Leary, P.; Buckley, N. R.; Lawrence, S. E.; Maguire, A. R. Synthetic Approaches to the Daucane Sesquiterpene Derivatives Employing the Intramolecular Buchner Cyclisation of αDiazoketones. Tetrahedron 2013, 69, 1778−1794. (315) King, G. R.; Mander, L. N.; Monck, N. J. T.; Morris, J. C.; Zhang, H. A New and Efficient Strategy for the Total Synthesis of Polycyclic Diterpenoids: The Preparation of Gibberellins (±)-GA103 and (±)-GA73. J. Am. Chem. Soc. 1997, 119, 3828−3829. (316) Frey, B.; Wells, A. P.; Rogers, D. H.; Mander, L. N. Synthesis of the Unusual Diterpenoid Tropones Hainanolidol and Harringtonolide. J. Am. Chem. Soc. 1998, 120, 1914−1915. (317) Zhang, H.; Appels, D. C.; Hockless, D. C. R.; Mander, L. N. A New Approach to the Total Synthesis of the Unusual Diterpenoid Tropone, Harringtonolide. Tetrahedron Lett. 1998, 39, 6577−6580. (318) Padwa, A.; Austin, D. J.; Hornbuckle, S. F.; Semones, M. A.; Doyle, M. P.; Protopopova, M. N. Control of Chemoselectivity in Catalytic Carbenoid Reactions. Dirhodium(II) Ligand Effects on Relative Reactivities. J. Am. Chem. Soc. 1992, 114, 1874−1876. (319) Doyle, M. P.; Ene, D. G.; Forbes, D. C.; Pillow, T. H. Chemoselectivity and Enantiocontrol in Catalytic Intramolecular Metal Carbene Reactions of Diazo Acetates Linked to Reactive Functional Groups by Naphthalene-1,8-dimethanol. Chem. Commun. 1999, 1691−1692. (320) Padwa, A.; Austin, D. J.; Price, A. T.; Semones, M. A.; Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A. Ligand Effects on Dirhodium(II) Carbene Reactivities. Highly Effective Switching between Competitive Carbenoid Transformations. J. Am. Chem. Soc. 1993, 115, 8669−8680. (321) O’Keeffe, S.; Harrington, F.; Maguire, A. R. Enantioselective Intramolecular Büchner Reaction of α-Diazoketones. Synlett 2007, 2007, 2367−2370. (322) O’Neill, S.; O’Keeffe, S.; Harrington, F.; Maguire, A. R. Enhancement of Enantioselection in the Copper-Catalysed Intramolecular Buchner Reaction by Variation of the Counterion. Synlett 2009, 2009, 2312−2314. (323) Slattery, C. N.; Clarke, L.-A.; O'Neill, S.; Ring, A.; Ford, A.; Maguire, A. R. Investigation of Additive Effects in Enantioselective Copper-Catalysed C−H Insertion and Aromatic Addition Reactions of α-Diazocarbonyl Compounds. Synlett 2012, 23, 765−767. (324) Jia, S.; Xing, D.; Zhang, D.; Hu, W. Catalytic Asymmetric Functionalization of Aromatic C−H Bonds by Electrophilic Trapping 10068


Chemical Reviews

Review

(344) Ma, B.; Chen, F.-L.; Xu, X.-Y.; Zhang, Y.-N.; Hu, L.-H. α-Diazo β-Keto Ester as Precursor to Aromatic C−H Insertion and Wolff Rearrangement with Different Directing Groups. Adv. Synth. Catal. 2014, 356, 416−420. (345) Zhang, X.; Lei, M.; Zhang, Y.-N.; Hu, L.-H. Rh-Catalyzed Intramolecular Aromatic C−H Insertion of α-Diazo β-ketoesters: Synthesis of 4-Carbonyl Chroman Derivatives. Tetrahedron 2014, 70, 3400−3406. (346) Park, C. P.; Nagle, A.; Yoon, C. H.; Chen, C.; Jung, K. W. Formal Aromatic C−H Insertion for Stereoselective Isoquinolinone Synthesis and Studies on Mechanistic Insights into the C−C Bond Formation. J. Org. Chem. 2009, 74, 6231−6236. (347) Etkin, N.; Babu, S. D.; Fooks, C. J.; Durst, T. Preparation of 3Acetyl-2-Hydroxyindoles via Rhodium Carbenoid Aromatic CarbonHydrogen Insertion. J. Org. Chem. 1990, 55, 1093−1096. (348) Watanabe, N.; Ogawa, T.; Ohtake, Y.; Ikegami, S.; Hashimoto, S.-i. Dirhodium(II) Tetrakis[N-phthaloyl-(S)-tert-leucinate]: A Notable Catalyst for Enantiotopically Selective Aromatic Substitution Reactions of α-Diazocarbonyl Compounds. Synlett 1996, 1996, 85−86. (349) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. C−H Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals. Angew. Chem., Int. Ed. 2012, 51, 8960−9009. (350) Tambar, U. K.; Ebner, D. C.; Stoltz, B. M. A Convergent and Enantioselective Synthesis of (+)-Amurensinine via Selective C−H and C−C Bond Insertion Reactions. J. Am. Chem. Soc. 2006, 128, 11752−11753. (351) Qiu, H.; Li, M.; Jiang, L.-Q.; Lv, F.-P.; Zan, L.; Zhai, C.-W.; Doyle, M. P.; Hu, W.-H. Highly Enantioselective Trapping of Zwitterionic Intermediates by Imines. Nat. Chem. 2012, 4, 733−738. (352) Slattery, C. N.; Ford, A.; Maguire, A. R. Catalytic Asymmetric C−H Insertion Reactions of α-Diazocarbonyl Compounds. Tetrahedron 2010, 66, 6681−6705. (353) Davies, H. M. L.; Antoulinakis, E. G. Recent Progress in Asymmetric Intermolecular C−H Activation by Rhodium Carbenoid Intermediates. J. Organomet. Chem. 2001, 617−618, 47−55. (354) Forbes, D. C.; McMills, M. C. Catalytic Asymmetric Metal Carbene Transformations. Curr. Org. Chem. 2001, 5, 1091−1105. (355) Davies, H. M. L. Catalytic Asymmetric C−H Activation of sp3 Hybridized C−H Bonds by Means of Carbenoid C−H Insertions: Applications in Organic Synthesis. J. Mol. Catal. A: Chem. 2002, 189, 125−135. (356) Davies, H. M. L.; Nikolai, J. Catalytic and Enantioselective Allylic C−H Activation with Donor−Acceptor-Substituted Carbenoids. Org. Biomol. Chem. 2005, 3, 4176−4187. (357) Gois, P. M. P.; Afonso, C. A. M. Stereo- and Regiocontrol in the Formation of Lactams by Rhodium-Carbenoid C−H Insertion of α-Diazoacetamides. Eur. J. Org. Chem. 2004, 2004, 3773−3788. (358) Davies, H. M. L.; Beckwith, R. E. J. Catalytic Enantioselective C−H Activation by Means of Metal-Carbenoid-Induced C−H Insertion. Chem. Rev. 2003, 103, 2861−2904. (359) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Catalytic Carbene Insertion into C−H Bonds. Chem. Rev. 2010, 110, 704−724. (360) Davies, H. M. L.; Loe, Ø. Intermolecular C−H Insertions of Donor/Acceptor-Substituted Rhodium Carbenoids: A Practical Solution for Catalytic Enantioselective C−H Activation. Synthesis 2004, 2004, 2595−2608. (361) Davies, H. M. L.; Morton, D. Guiding Principles for Site Selective and Stereoselective Intermolecular C−H Functionalization by Donor/Acceptor Rhodium Carbenes. Chem. Soc. Rev. 2011, 40, 1857−1869. (362) Doyle, M. P.; Ratnikov, M.; Liu, Y. Intramolecular Catalytic Asymmetric Carbon-Hydrogen Insertion Reactions. Synthetic Advantages in Total Synthesis in Comparison with Alternative Approaches. Org. Biomol. Chem. 2011, 9, 4007−4016. (363) Davies, H. M. L.; Dick, A. R. Functionalization of Carbon− Hydrogen Bonds through Transition Metal Carbenoid Insertion. Top. Curr. Chem. 2010, 292, 303−345.

(364) Taber, D. F.; Petty, E. H. General Route to Highly Functionalized Cyclopentane Derivatives by Intramolecular C−H Insertion. J. Org. Chem. 1982, 47, 4808−4809. (365) Taber, D. F.; Ruckle, R. E. Cyclopentane Construction by Dirhodium Tetraacetate-Mediated Intramolecular C−H Insertion: Steric and Electronic Effects. J. Am. Chem. Soc. 1986, 108, 7686−7693. (366) Taber, D. F.; Ruckle, R. E. Diastereoselection in RhodiumMediated Intramolecular C−H Insertion: Preparation of a trans-3,4 Dialkyl Cyclopentane. Tetrahedron Lett. 1985, 26, 3059−3062. (367) Taber, D. F.; Raman, K. Enantioselective Carbocyclization: A Facile Route to Chiral Cyclopentanes. J. Am. Chem. Soc. 1983, 105, 5935−5937. (368) Taber, D. F.; Raman, K.; Gaul, M. D. Enantioselective Ring Construction: Synthesis of (+)-Estrone Methyl Ether. J. Org. Chem. 1987, 52, 28−34. (369) Taber, D. F.; You, K. K.; Rheingold, A. L. Predicting the Diastereoselectivity of Rh-Mediated Intramolecular C−H Insertion. J. Am. Chem. Soc. 1996, 118, 547−556. (370) Taber, D. F.; You, K. K. Highly Diastereoselective Cyclopentane Construction: Enantioselective Synthesis of the Dendrobatid Alkaloid 251F. J. Am. Chem. Soc. 1995, 117, 5757−5762. (371) Wenkert, E.; Davis, L. L.; Mylari, B. L.; Solomon, M. F.; Da Silva, R. R.; Shulman, S.; Warnet, R. J.; Ceccherelli, P.; Curini, M.; Pellicciari, R. Cyclopentanone Synthesis by Intramolecular Carbon− Hydrogen Insertion of Diazo Ketones. A Diterpene-to-Steroid Skeleton Conversion. J. Org. Chem. 1982, 47, 3242−3247. (372) Taber, D. F.; Petty, E. H.; Raman, K. Enantioselective Ring Construction: Synthesis of (+)-α-Cuparenone. J. Am. Chem. Soc. 1985, 107, 196−199. (373) Taber, D. F.; Herr, R. J.; Pack, S. K.; Geremia, J. M. A Convenient Method for the Preparation of (Z)-α,β-Unsaturated Carbonyl Compounds. J. Org. Chem. 1996, 61, 2908−2910. (374) Jung, Y. C.; Yoon, C. H.; Turos, E.; Yoo, K. S.; Jung, K. W. Total Syntheses of (−)-α-Kainic Acid and (+)-α-Allokainic Acid via Stereoselective C−H Insertion and Efficient 3,4-Stereocontrol. J. Org. Chem. 2007, 72, 10114−10122. (375) Bequette, J. P.; Jungong, C. S.; Novikov, A. V. Enantioselective Synthesis of Bakuchiol Using Diazosulfonate C−H Insertion to Install the Quaternary Center. Tetrahedron Lett. 2009, 50, 6963−6964. (376) Taber, D. F.; Nelson, C. G. Aliphatic C−H to C−C Conversion: Synthesis of (−)-Cameroonan-7α-ol. J. Org. Chem. 2011, 76, 1874−1882. (377) Taber, D. F.; Paquette, C. M.; Gu, P.; Tian, W. Cyclohexanones by Rh-Mediated Intramolecular C−H Insertion. J. Org. Chem. 2013, 78, 9772−9780. (378) Hinman, A.; Du Bois, J. A Stereoselective Synthesis of (−)-Tetrodotoxin. J. Am. Chem. Soc. 2003, 125, 11510−11511. (379) Nicolaou, K. C.; Stepan, A. F.; Lister, T.; Li, A.; Montero, A.; Tria, G. S.; Turner, C. I.; Tang, Y.; Wang, J.; Denton, R. M.; et al. Design, Synthesis, and Biological Evaluation of Platensimycin Analogues with Varying Degrees of Molecular Complexity. J. Am. Chem. Soc. 2008, 130, 13110−13119. (380) Hashimoto, S.-i.; Watanabe, N.; Ikegami, S. Enantioselecitve Intramolecular C−H Insertion of α-Diazo-β-keto Esters Catalyzed by Homochiral Rhodium(II) Carboxylates. Tetrahedron Lett. 1990, 31, 5173−5174. (381) Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Roos, G. H. P. Asymmetric Synthesis in Carbon−Carbon Bond Forming Reactions of α-Diazoketones Catalysed by Homochiral Rhodium(II) Carboxylates. J. Chem. Soc., Chem. Commun. 1990, 361−362. (382) Hashimoto, S.-i.; Watanabe, N.; Sato, T.; Shiro, M.; Ikegami, S. Enhancement of Enantioselectivity in Intramolecular C−H Insertion Reactions of α-Diazo-β-keto Esters Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 1993, 34, 5109−5112. (383) Hashimoto, S.-I.; Watanabe, N.; Ikegami, S. Enantioselective Intramolecular C−H Insertion Reactions. Synlett 1994, 1994, 353− 355. (384) Estevan, F.; Herbst, K.; Lahuerta, P.; Barberis, M.; PerezPrieto, J. Chiral Dirhodium(II) Catalysts with Orthometalated Aryl 10069


Chemical Reviews

Review

Phosphine Ligands: Synthesis and Application for Enantioselective C− H Insertion of α-Diazo Ketones. Organometallics 2001, 20, 950−957. (385) Minami, K.; Saito, H.; Tsutsui, H.; Nambu, H.; Anada, M.; Hashimoto, S.-i. Highly Enantio- and Diastereoselective Construction of 1,2-Disubstituted Cyclopentane Compounds by Dirhodium(II) Tetrakis[N-phthaloyl-(S)-tert-leucinate]-Catalyzed C−H Insertion Reactions of α-Diazo Esters. Adv. Synth. Catal. 2005, 347, 1483−1487. (386) Takeda, K.; Oohara, T.; Anada, M.; Nambu, H.; Hashimoto, S. A Polymer-Supported Chiral Dirhodium(II) Complex: Highly Durable and Recyclable Catalyst for Asymmetric Intramolecular C−H Insertion Reactions. Angew. Chem., Int. Ed. 2010, 49, 6979−6983. (387) Doyle, M. P.; Van Oeveren, A.; Westrum, L. J.; Protopopova, M. N.; Clayton, T. W. Asymmetric Synthesis of Lactones with High Enantioselectivity by Intramolecular Carbon-Hydrogen Insertion Reactions of Alkyl Diazoacetates Catalyzed by Chiral Rhodium(II) Carboxamides. J. Am. Chem. Soc. 1991, 113, 8982−8984. (388) Bode, J. W.; Doyle, M. P.; Protopopova, M. N.; Zhou, Q.-L. Intramolecular Regioselective Insertion into Unactivated Prochiral Carbon−Hydrogen Bonds with Diazoacetates of Primary Alcohols Catalyzed by Chiral Dirhodium(II) Carboxamidates. Highly Enantioselective Total Synthesis of Natural Lignan Lactones. J. Org. Chem. 1996, 61, 9146−9155. (389) Wee, A. G. H. A Facile Synthesis of (−)- and (+)-GeissmanWaiss Lactone via Intramolecular Rh(II)-Carbenoid Mediated C−H Insertion Reaction: Synthesis of (1R,7R,8R)-Turneforcidine. Tetrahedron Lett. 2000, 41, 9025−9029. (390) Doyle, M. P.; Hu, W.; Valenzuela, M. V. Total Synthesis of (S)(+)-Imperanene. Effective Use of Regio- and Enantioselective Intramolecular Carbon−Hydrogen Insertion Reactions Catalyzed by Chiral Dirhodium(II) Carboxamidates. J. Org. Chem. 2002, 67, 2954− 2959. (391) Doyle, M. P.; Zhou, Q.-L.; Raab, C. E.; Roos, G. H. P. Improved Enantioselection for Chiral Dirhodium(II) CarboxamideCatalysed Carbon-Hydrogen Insertion Reactions of Tertiary Alkyl Diazoacetates. Tetrahedron Lett. 1995, 36, 4745−4748. (392) Müller, P.; Polleux, P. Enantioselective Formation of Bicyclic Lactones by Rhodium-Catalyzed Intramolecular CH-Insertion reactions. Helv. Chim. Acta 1994, 77, 645−654. (393) Doyle, M. P.; Dyatkin, A. B.; Roos, G. H. P.; Canas, F.; Pierson, D. A.; van Basten, A.; Müller, P.; Polleux, P. Diastereocontrol for Highly Enantioselective Carbon−Hydrogen Insertion Reactions of Cycloalkyl Diazoacetates. J. Am. Chem. Soc. 1994, 116, 4507−4508. (394) Doyle, M. P.; May, E. J. Enantioselective β-Lactone Formation for Phenyldiazoacetates. Synlett 2001, 2001, 967−969. (395) Doyle, M. P.; Davies, S. B.; May, E. J. High Selectivity from Configurational Match/Mismatch in Carbon−Hydrogen Insertion Reactions of Steroidal Diazoacetates Catalyzed by Chiral Dirhodium(II) Carboxamidates. J. Org. Chem. 2001, 66, 8112−8119. (396) McKervey, M. A.; Ye, T. Asymmetric Synthesis of Substituted Chromanones. J. Chem. Soc., Chem. Commun. 1992, 823−824. (397) Saito, H.; Oishi, H.; Kitagaki, S.; Nakamura, S.; Anada, M.; Hashimoto, S. Enantio- and Diastereoselective Synthesis of cis-2-Aryl3-methoxycarbonyl-2,3-dihydrobenzofurans via the Rh(II)-Catalyzed C−H Insertion Process. Org. Lett. 2002, 4, 3887−3890. (398) Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. A New Chiral Rh(II) Catalyst for Enantioselective [2 + 1]Cycloaddition. Mechanistic Implications and Applications. J. Am. Chem. Soc. 2004, 126, 8916−8918. (399) Davies, H. M. L.; Grazini, M. V. A.; Aouad, E. Asymmetric Intramolecular C−H Insertions of Aryldiazoacetates. Org. Lett. 2001, 3, 1475−1477. (400) Reddy, R. P.; Lee, G. H.; Davies, H. M. L. Dirhodium Tetracarboxylate Derived from Adamantylglycine as a Chiral Catalyst for Carbenoid Reactions. Org. Lett. 2006, 8, 3437−3440. (401) Natori, Y.; Tsutsui, H.; Sato, N.; Nakamura, S.; Nambu, H.; Shiro, M.; Hashimoto, S. Asymmetric Synthesis of Neolignans (−)-epiConocarpan and (+)-Conocarpan via Rh(II)-Catalyzed C−H Insertion Process and Revision of the Absolute Configuration of (−)-epi-Conocarpan. J. Org. Chem. 2009, 74, 4418−4421.

(402) Kurosawa, W.; Kan, T.; Fukuyama, T. Stereocontrolled Total Synthesis of (−)-Ephedradine A (Orantine). J. Am. Chem. Soc. 2003, 125, 8112−8113. (403) Koizumi, Y.; Kobayashi, H.; Wakimoto, T.; Furuta, T.; Fukuyama, T.; Kan, T. Total Synthesis of (−)-Serotobenine. J. Am. Chem. Soc. 2008, 130, 16854−16855. (404) Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Daniel, K. L. Enantiocontrol and Regiocontrol in Lactam Syntheses by Intramolecular Carbon-Hydrogen Insertion Reactions of Diazoacetamides Catalyzed by Chiral Rhodium(II) Carboxamides. Tetrahedron Lett. 1992, 33, 7819−7822. (405) Doyle, M. P.; Oon, S.-M.; van der Heide, F. R.; Brown, C. B. βLactam Formation via Rhodium(II) Catalyzed Carbon-Hydrogen Insertion Reactions of α-Diazo Amides. Bioorg. Med. Chem. Lett. 1993, 3, 2409−2414. (406) McCarthy, N.; McKervey, M. A.; Ye, T.; McCann, M.; Murphy, E.; Doyle, M. P. A New Rhodium(II) Phosphate Catalyst for Diazocarbonyl Reactions Including Asymmetric Synthesis. Tetrahedron Lett. 1992, 33, 5983−5986. (407) Watanabe, N.; Anada, M.; Hashimoto, S.-i.; Ikegami, S. Enantioselective Intramolecular C−H Insertion Reactions of N-AlkylN-tert-Butyl-α-Methoxycarbonyl-α-Diazoacetamides Catalyzed by Dirhodium(II) Carboxylates: Catalytic, Asymmetric Construction of 2-Azetidinones. Synlett 1994, 1994, 1031−1034. (408) Zakrzewska, M. E.; Cal, P. M. S. D.; Candeias, N. R.; BogelŁukasik, R.; Afonso, C. A. M.; Ponte, M. N.; Gois, P. M. P. Intramolecular C−H Insertion Catalyzed by Dirhodium(II) Complexes Using CO2 as the Reaction Media. Green Chem. Lett. Rev. 2012, 5, 211−240. (409) Anada, M.; Hashimoto, S.-i. Enantioselective Intramolecular C−H Insertion Route to a Key Intermediate for the Synthesis of Trinem Antibiotics. Tetrahedron Lett. 1998, 39, 9063−9066. (410) Anada, M.; Watanabe, N. Highly Enantioselective Construction of Key Azetidin-2-ones for the Synthesis of Carbapenem Antibiotics via Intramolecular C−H Insertion Reactions of αMethoxycarbonyl-α-diazoacetamides Catalysed by Chiral Dirhodium(II) Carboxylates. Chem. Commun. 1998, 1517−1518. (411) Anada, M.; Mita, O.; Watanabe, H.; Kitagaki, S.; Hashimoto, S. Catalytic Enantioselective Synthesis of the Phosphodiesterase Type IV Inhibitor (R)-(−)-Rolipram via Intramolecular C−H Insertion Process. Synlett 1999, 1999, 1775−1777. (412) Wee, A. G. H.; Duncan, S. C.; Fan, G.-j. Intramolecular Asymmetric C−H Insertion of N-Arylalkyl, N-bis(trimethylsilyl)methyldiazoamides Mediated by Chiral Rhodium(II) Catalysts. Synthesis of (R)-β-Benzyl-γ-aminobutyric Acid. Tetrahedron: Asymmetry 2006, 17, 297−307. (413) Wee, A. G. H.; Duncan, S. C. The Rhodium(II)-Catalyzed Reaction of N-Bis(trimethylsilylmethyl)diazoamides: Steric, Electronic and Conformational Effects. Tetrahedron Lett. 2002, 43, 6173−6176. (414) Doyle, M. P.; Hu, W.; Wee, A. G. H.; Wang, Z.; Duncan, S. C. Influences of Catalyst Configuration and Catalyst Loading on Selectivities in Reactions of Diazoacetamides. Barrier to Equilibrium between Diastereomeric Conformations. Org. Lett. 2003, 5, 407−410. (415) Wee, A. G. H.; Duncan, S. C. The Bis(trimethylsilyl)methyl Group as an Effective N-Protecting Group and Site-Selective Control Element in Rhodium(II)-Catalyzed Reaction of Diazoamides. J. Org. Chem. 2005, 70, 8372−8380. (416) Lim, H.-J.; Sulikowski, G. A. Enantioselective Synthesis of a 1,2-Disubstituted Mitosene by a Copper-Catalyzed Intramolecular Carbon−Hydrogen Insertion Reaction of a Diazo Ester. J. Org. Chem. 1995, 60, 2326−2327. (417) Flynn, C. J.; Elcoate, C. J.; Lawrence, S. E.; Maguire, A. R. Highly Enantioselective Intramolecular Copper Catalyzed C−H Insertion Reactions of α-Diazosulfones. J. Am. Chem. Soc. 2010, 132, 1184−1185. (418) Slattery, C. N.; Maguire, A. R. Asymmetric Copper-Catalysed Intramolecular C−H Insertion Reactions of α-Diazo-β-keto Sulfones. Org. Biomol. Chem. 2011, 9, 667−669. 10070


Chemical Reviews

Review

(419) Clarke, L. A.; Ring, A.; Ford, A.; Sinha, A. S.; Lawrence, S. E.; Maguire, A. R. Enantioselective Copper Catalysed C−H Insertion Reaction of 2-Sulfonyl-2-diazoacetamides to Form γ-Lactams. Org. Biomol. Chem. 2014, 12, 7612−7628. (420) Demonceau, A.; Noels, A. F.; Hubert, A. J.; Teyssié, P. Transition-Metal-Catalysed Reactions of Diazoesters. J. Chem. Soc., Chem. Commun. 1981, 688−689. (421) Callot, H. J.; Metz, F. Homologation of n-Alkanes Using Diazoesters and Rhodium(III) Porphyrins. Enhanced Attack on Primary C−H Bonds. Tetrahedron Lett. 1982, 23, 4321−4324. (422) Demonceau, A.; Noels, A. F.; Hubert, A. J.; Teyssie, P. Transition Metal-Catalyzed Reactions of Diazo Esters. Insertion into Carbon−Hydrogen Bonds of Paraffins Catalyzed by Bulky Rhodium(II) Carboxylates: Enhanced Attack on Primary Carbon−Hydrogen Bonds. Bull. Soc. Chim. Belg. 1984, 93, 945−948. (423) Callot, H. J.; Metz, F. Selective Two-Carbon Methyl Group Homologation Using Diazo Esters and Rhodium(III) Porphyrins. Nouv. J. Chim. 1985, 9, 167−171. (424) Davies, H. M. L.; Hansen, T. Asymmetric Intermolecular Carbenoid C−H Insertions Catalyzed by Rhodium(II) (S)-N-(pDodecylphenyl)sulfonylprolinate. J. Am. Chem. Soc. 1997, 119, 9075− 9076. (425) Davies, H. M. L.; Beckwith, R. E. J.; Antoulinakis, E. G.; Jin, Q. New Strategic Reactions for Organic Synthesis: Catalytic Asymmetric C−H Activation α to Oxygen as a Surrogate to the Aldol Reaction. J. Org. Chem. 2003, 68, 6126−6132. (426) Davies, H. M. L.; Antoulinakis, E. G. Asymmetric Catalytic C− H Activation Applied to the Synthesis of Syn-Aldol Products. Org. Lett. 2000, 2, 4153−4156. (427) Davies, H. M. L.; Antoulinakis, E. G.; Hansen, T. Catalytic Asymmetric Synthesis of Syn-Aldol Products from Intermolecular C− H Insertions between Allyl Silyl Ethers and Methyl Aryldiazoacetates. Org. Lett. 1999, 1, 383−386. (428) Davies, H. M. L.; Ren, P.; Jin, Q. Catalytic Asymmetric Allylic C−H Activation as a Surrogate of the Asymmetric Claisen Rearrangement. Org. Lett. 2001, 3, 3587−3590. (429) Davies, H. M. L.; Venkataramani, C.; Hansen, T.; Hopper, D. W. New Strategic Reactions for Organic Synthesis: Catalytic Asymmetric C−H Activation α to Nitrogen as a Surrogate for the Mannich Reaction. J. Am. Chem. Soc. 2003, 125, 6462−6468. (430) Davies, H. M. L.; Ren, P. Catalytic Asymmetric C−H Activation of Silyl Enol Ethers as an Equivalent of an Asymmetric Michael Reaction. J. Am. Chem. Soc. 2001, 123, 2070−2071. (431) Davies, H. M. L.; Yang, J.; Nikolai, J. Asymmetric C−H Insertion of Rh(II) Stabilized Carbenoids into Acetals: A C−H Activation Protocol as a Claisen Condensation Equivalent. J. Organomet. Chem. 2005, 690, 6111−6124. (432) Davies, H. M. L.; Venkataramani, C. Catalytic Enantioselective Synthesis of β2-Amino Acids. Angew. Chem., Int. Ed. 2002, 41, 2197− 2199. (433) Davies, H. M. L.; Yang, J. Influence of a β-Alkoxy Substituent on the C−H Activation Chemistry of Alkyl Ethers. Adv. Synth. Catal. 2003, 345, 1133−1138. (434) Davies, H. M. L.; Jin, Q. Intermolecular C−H Activation at Benzylic Positions: Synthesis of (+)-Imperanene and (−)-α-Conidendrin. Tetrahedron: Asymmetry 2003, 14, 941−949. (435) Nadeau, E.; Li, Z.; Morton, D.; Davies, H. M. L. Rhodium Carbenoid Induced Intermolecular C−H Functionalization at Tertiary C−H Bonds. Synlett 2009, 2009, 151−154. (436) Davies, H. M. L.; Gregg, T. M. Asymmetric Synthesis of (+)-Indatraline Using Rhodium-Catalyzed C−H Activation. Tetrahedron Lett. 2002, 43, 4951−4953. (437) Davies, H. M. L.; Ni, A. Enantioselective Synthesis of β-Amino Esters and its Application to the Synthesis of the Enantiomers of the Antidepressant Venlafaxine. Chem. Commun. 2006, 3110−3112. (438) Davies, H. M. L.; Walji, A. M.; Townsend, R. J. Catalytic Asymmetric C−H Activation by Methyl Thiophen-3-yldiazoacetate Applied to the Synthesis of (+)-Cetiedil. Tetrahedron Lett. 2002, 43, 4981−4983.

(439) Davies, H. M. L.; Hansen, T.; Hopper, D. W.; Panaro, S. A. Highly Regio-, Diastereo-, and Enantioselective C−H Insertions of Methyl Aryldiazoacetates into Cyclic N-Boc-Protected Amines. Asymmetric Synthesis of Novel C2-Symmetric Amines and threoMethylphenidate. J. Am. Chem. Soc. 1999, 121, 6509−6510. (440) Manning, J. R.; Sexton, T.; Childers, S. R.; Davies, H. M. L. 1Naphthyl and 4-Indolyl Arylalkylamines as Selective Monoamine Reuptake Inhibitors. Bioorg. Med. Chem. Lett. 2009, 19, 58−61. (441) Davies, H. M. L.; Dai, X.; Long, M. S. Combined C−H Activation/Cope Rearrangement as a Strategic Reaction in Organic Synthesis: Total Synthesis of (−)-Colombiasin A and (−)-Elisapterosin B. J. Am. Chem. Soc. 2006, 128, 2485−2490. (442) Davies, H. M. L.; Dai, X. Application of the Combined C−H Activation/Cope Rearrangement as a Key Step in the Total Syntheses of the Assigned Structure of (+)-Elisabethadione and a (+)-pBenzoquinone Natural Product. Tetrahedron 2006, 62, 10477−10484. (443) Davies, H. M. L.; Walji, A. M. Direct Synthesis of (+)-Erogorgiaene through a Kinetic Enantiodifferentiating Step. Angew. Chem., Int. Ed. 2005, 44, 1733−1735. (444) Lian, Y.; Davies, H. M. L. Combined C−H Functionalization/ Cope Rearrangement with Vinyl Ethers as a Surrogate for the Vinylogous Mukaiyama Aldol Reaction. J. Am. Chem. Soc. 2011, 133, 11940−11943. (445) Bykowski, D.; Wu, K.-H.; Doyle, M. P. Vinyldiazolactone as a Vinylcarbene Precursor: Highly Selective C−H Insertion and Cyclopropanation Reactions. J. Am. Chem. Soc. 2006, 128, 16038− 16039. (446) Davies, H. M. L.; Hedley, S. J.; Bohall, B. R. Asymmetric Intermolecular C−H Functionalization of Benzyl Silyl Ethers Mediated by Chiral Auxiliary-Based Aryldiazoacetates and Chiral Dirhodium Catalysts. J. Org. Chem. 2005, 70, 10737−10742. (447) Biffis, A.; Braga, M.; Cadamuro, S.; Tubaro, C.; Basato, M. A Fluorous Chiral Dirhodium(II) Complex as a Recyclable Asymmetric Catalyst. Org. Lett. 2005, 7, 1841−1844. (448) Fraile, J. M.; Garcia, J. I.; Mayoral, J. A.; Roldan, M. Simple and Efficient Heterogeneous Copper Catalysts for Enantioselective C−H Carbene Insertion. Org. Lett. 2007, 9, 731−733. (449) Fraile, J. M.; Lopez-Ram-de-Viu, P.; Mayoral, J. A.; Roldan, M.; Santafe-Valero, J. Enantioselective C−H Carbene Insertions with Homogeneous and Immobilized Copper Complexes. Org. Biomol. Chem. 2011, 9, 6075−6081. (450) Fraile, J. M.; Mayoral, J. A.; Ravasio, N.; Roldán, M.; Sordelli, L.; Zaccheria, F. Heterogeneous Catalysts for Carbene Insertion Reactions. J. Catal. 2011, 281, 273−278. (451) Suematsu, H.; Katsuki, T. Iridium(III) Catalyzed Diastereoand Enantioselective C−H Bond Functionalization. J. Am. Chem. Soc. 2009, 131, 14218−14219. (452) Wang, J.-C.; Xu, Z.-J.; Guo, Z.; Deng, Q.-H.; Zhou, C.-Y.; Wan, X.-L.; Che, C.-M. Highly Enantioselective Intermolecular Carbene Insertion to C−H and Si−H Bonds Catalyzed by a Chiral Iridium(III) Complex of a D4-Symmetric Halterman Porphyrin Ligand. Chem. Commun. 2012, 48, 4299−4301. (453) Very recently Wang and co-workers have extended the range of X−Y insertion processes to include catalyzed insertion into C−C single bonds. So far this rare C−C bond cleavage process has only been exemplified for benzocyclobutenols with diazoesters: Xia, Y.; Liu, Z.; Liu, Z.; Ge, R.; Ye, F.; Hossain, M.; Zhang, Y.; Wang, J. Formal Carbene Insertion into C−C Bond: Rh(I)-Catalyzed Reaction of Benzocyclobutenols with Diazoesters. J. Am. Chem. Soc. 2014, 136, 3013−3015. (454) Dumitrescu, L.; Azzouzi-Zriba, K.; Bonnet-Delpon, D.; Crousse, B. Nonmetal Catalyzed Insertion Reactions of Diazocarbonyls to Acid Derivatives in Fluorinated Alcohols. Org. Lett. 2011, 13, 692−695. (455) Aviv, I.; Gross, Z. Iron Porphyrins Catalyze the Synthesis of Non-Protected Amino Acid Esters from Ammonia and Diazoacetates. Chem. Commun. 2006, 4477−4479. 10071


Chemical Reviews

Review

(456) Zhang, X.; Sui, Z. Application of Carbenoid N−H Insertion in the Synthesis of the Tricyclic 1,4-Dihydropyrazines. Tetrahedron Lett. 2006, 47, 5953−5955. (457) Livant, P.; Jie, Y.; Wang, X. Solvent Effects in a Carbenoid N− H Insertion Route to Triarylamines via 2-Diazo-1,3-cyclohexanedione. Tetrahedron Lett. 2005, 46, 2113−2116. (458) Chanthamath, S.; Thongjareun, S.; Shibatomi, K.; Iwasa, S. Ru(II)-Pheox Catalyzed N−H Insertion Reaction of Diazoacetamides: Synthesis of N-Substituted α-Aminoamides. Tetrahedron Lett. 2012, 53, 4862−4865. (459) Hansen, S. R.; Spangler, J. E.; Hansen, J. H.; Davies, H. M. L. Metal-Free N−H Insertions of Donor/Acceptor Carbenes. Org. Lett. 2012, 14, 4626−4629. (460) So, S. S.; Mattson, A. E. Urea Activation of α-Nitrodiazoesters: An Organocatalytic Approach to N−H Insertion Reactions. J. Am. Chem. Soc. 2012, 134, 8798−8801. (461) Auvil, T. J.; So, S. S.; Mattson, A. E. Arylation of Diazoesters by a Transient N−H Insertion Organocascade. Angew. Chem., Int. Ed. 2013, 52, 11317−11320. (462) Saito, H.; Morita, D.; Uchiyama, T.; Miyake, M.; Miyairi, S. Cinchona Alkaloids Induce Asymmetry in the Insertion Reaction of Thermally Generated Carbenes into N−H Bonds. Tetrahedron Lett. 2012, 53, 6662−6664. (463) Xu, B.; Zhu, S.-F.; Xie, X.-L.; Shen, J.-J.; Zhou, Q.-L. Asymmetric N−H Insertion Reaction Cooperatively Catalyzed by Rhodium and Chiral Spiro Phosphoric Acids. Angew. Chem., Int. Ed. 2011, 50, 11483−11486. (464) Peng, C.; Cheng, J.; Wang, J. Sequential Copper(I)-Catalyzed Reaction of Amines with o-Acetylenyl-Substituted Phenyldiazoacetates. Adv. Synth. Catal. 2008, 350, 2359−2364. (465) Pavlyuk, O.; Teller, H.; McMills, M. C. An Efficient Synthesis of Nitrogen-Containing Heterocycles via a Tandem Carbenoid N−H Insertion/Ring-Closing Metathesis Sequence. Tetrahedron Lett. 2009, 50, 2716−2718. (466) Honey, M. A.; Blake, A. J.; Campbell, I. B.; Judkins, B. D.; Moody, C. J. One-Pot Synthesis of N-Methylindoles from NMethylanilines and of Benzofurans from Phenols Using TransitionMetal Carbene X−H Insertion Reactions. Tetrahedron 2009, 65, 8995−9001. (467) Shi, B.; Lewis, W.; Campbell, I. B.; Moody, C. J. A Concise Route to Pyridines from Hydrazides by Metal Carbene N−H Insertion, 1,2,4-Triazine Formation, and Diels−Alder Reaction. Org. Lett. 2009, 11, 3686−3688. (468) Wang, Y.; Zhu, Y.; Chen, Z.; Mi, A.; Hu, W.; Doyle, M. P. A Novel Three-Component Reaction Catalyzed by Dirhodium(II) Acetate: Decomposition of Phenyldiazoacetate with Arylamine and Imine for Highly Diastereoselective Synthesis of 1,2-Diamines. Org. Lett. 2003, 5, 3923−3926. (469) Huang, H.; Wang, Y.; Chen, Z.; Hu, W. Rhodium-Catalyzed, Three-Component Reaction of Diazo Compounds with Amines and Azodicarboxylates. Adv. Synth. Catal. 2005, 347, 531−534. (470) Ma, X.; Jiang, J.; Lv, S.; Yao, W.; Yang, Y.; Liu, S.; Xia, F.; Hu, W. An Ylide Transformation of Rhodium(I) Carbene: Enantioselective Three-Component Reaction through Trapping of Rhodium(I)Associated Ammonium Ylides by β-Nitroacrylates. Angew. Chem., Int. Ed. 2014, 53, 13136−13139. (471) Hong, D.; Zhu, Y.; Li, Y.; Lin, X.; Lu, P.; Wang, Y. ThreeComponent Synthesis of Polysubstituted Pyrroles from α-Diazoketones, Nitroalkenes, and Amines. Org. Lett. 2011, 13, 4668−4671. (472) Wang, C.; Xing, D.; Wang, D.; Wu, X.; Hu, W. Synthesis of 3Amino-3-hydroxymethyloxindoles and 3-Hydroxy-3-hydroxymethyloxindoles by Rh2(OAc)4-Catalyzed Three-Component Reactions of 3Diazooxindoles with Formaldehyde and Anilines or Water. J. Org. Chem. 2014, 79, 3908−3916. (473) Aviv, I.; Gross, Z. Iron(III) Corroles and Porphyrins as Superior Catalysts for the Reactions of Diazoacetates with Nitrogenor Sulfur-Containing Nucleophilic Substrates: Synthetic Uses and Mechanistic Insights. Chem. - Eur. J. 2008, 14, 3995−4005.

(474) Baumann, L. K.; Mbuvi, H. M.; Du, G.; Woo, L. K. Iron Porphyrin Catalyzed N−H Insertion Reactions with Ethyl Diazoacetate. Organometallics 2007, 26, 3995−4002. (475) Tishinov, K.; Schmidt, K.; Häussinger, D.; Gillingham, D. G. Structure-Selective Catalytic Alkylation of DNA and RNA. Angew. Chem., Int. Ed. 2012, 51, 12000−12004. (476) Antos, J. M.; McFarland, J. M.; Iavarone, A. T.; Francis, M. B. Chemoselective Tryptophan Labeling with Rhodium Carbenoids at Mild pH. J. Am. Chem. Soc. 2009, 131, 6301−6308. (477) Bagley, M. C.; Buck, R. T.; Hind, S. L.; Moody, C. J. Synthesis of Functionalised Oxazoles and Bis-Oxazoles. J. Chem. Soc., Perkin Trans. 1 1998, 591−600. (478) Davies, J. R.; Kane, P. D.; Moody, C. J. N−H Insertion Reactions of Rhodium Carbenoids. Part 5: A Convenient Route to 1,3Azoles. Tetrahedron 2004, 60, 3967−3977. (479) Moody, C. J.; Bagley, M. C. Total Synthesis of (+)-Nostocyclamide. J. Chem. Soc., Perkin Trans. 1 1998, 601−608. (480) Bagley, M. C.; Bashford, K. E.; Hesketh, C. L.; Moody, C. J. Total Synthesis of the Thiopeptide Promothiocin A. J. Am. Chem. Soc. 2000, 122, 3301−3313. (481) Davies, J. R.; Kane, P. D.; Moody, C. J. The Diazo Route to Diazonamide A. Studies on the Indole Bis-oxazole Fragment. J. Org. Chem. 2005, 70, 7305−7316. (482) Shi, B.; Blake, A. J.; Lewis, W.; Campbell, I. B.; Judkins, B. D.; Moody, C. J. Rhodium Carbene Routes to Oxazoles and Thiazoles. Catalyst Effects in the Synthesis of Oxazole and Thiazole Carboxylates, Phosphonates, and Sulfones. J. Org. Chem. 2010, 75, 152−161. (483) Davies, J. R.; Kane, P. D.; Moody, C. J.; Slawin, A. M. Z. Control of Competing N−H Insertion and Wolff Rearrangement in Dirhodium(II)-Catalyzed Reactions of 3-Indolyl Diazoketoesters. Synthesis of a Potential Precursor to the Marine 5-(3-Indolyl)oxazole Martefragin A. J. Org. Chem. 2005, 70, 5840−5851. (484) Bentley, D. J.; Moody, C. J. Asymmetric Synthesis of the Central Tryptophan Residue of Stephanotic Acid. Org. Biomol. Chem. 2004, 2, 3545−3547. (485) Buck, R. T.; Clarke, P. A.; Coe, D. M.; Drysdale, M. J.; Ferris, L.; Haigh, D.; Moody, C. J.; Pearson, N. D.; Swann, E. The Carbenoid Approach to Peptide Synthesis. Chem. - Eur. J. 2000, 6, 2160−2167. (486) Muthusamy, S.; Srinivasan, P. Facile Chemoselective Rhodium Carbenoid N−H Insertion Reactions: Synthesis of 3-Arylamino- or 3Heteroarylpiperidin-2-ones. Tetrahedron Lett. 2005, 46, 1063−1066. (487) Clapham, B.; Spanka, C.; Janda, K. D. Solid-Phase Rhodium Carbenoid Reactions: An N−H Insertion Route to a Diverse Series of Oxazoles. Org. Lett. 2001, 3, 2173−2176. (488) Matsushita, H.; Lee, S.-H.; Yoshida, K.; Clapham, B.; Koch, G.; Zimmermann, J.; Janda, K. D. N−H Insertion Reactions of Boc-Amino Acid Amides: Solution- and Solid-Phase Synthesis of Pyrazinones and Pyrazines. Org. Lett. 2004, 6, 4627−4629. (489) Lee, S.-H.; Yoshida, K.; Matsushita, H.; Clapham, B.; Koch, G.; Zimmermann, J.; Janda, K. D. N−H Insertion Reactions of Primary Ureas: The Synthesis of Highly Substituted Imidazolones and Imidazoles from Diazocarbonyls. J. Org. Chem. 2004, 69, 8829−8835. (490) Lee, S.-H.; Clapham, B.; Koch, G.; Zimmermann, J.; Janda, K. D. Rhodium Carbenoid N−H Insertion Reactions of Primary Ureas: Solution and Solid-Phase Synthesis of Imidazolones. Org. Lett. 2003, 5, 511−514. (491) Wang, Y.; Zhu, S. Convenient Synthesis of Polyfunctionalized β-Fluoropyrroles from Rhodium(II)-Catalyzed Intramolecular N−H Insertion Reactions. Org. Lett. 2003, 5, 745−748. (492) Vyavahare, V. P.; Chattopadhyay, S.; Puranik, V. G.; Dhavale, D. D. Rh(II)-Catalyzed Intramolecular N-H Insertion of D-GlucoseDerived δ-Amino α-Diazo β-Ketoester: Synthesis of Pyrrolidine Iminosugars. Synlett 2007, 2007, 559−562. (493) Wang, J.; Hou, Y.; Wu, P. Intramolecular N−H Insertion of αDiazocarbonyls Catalyzed by Cu(acac)2: An Efficient Route to Derivatives of 3-Oxoazetidines, 3-Oxopyrrolidines and 3-Oxopiperidines. J. Chem. Soc., Perkin Trans. 1 1999, 2277−2280. (494) Davis, F. A.; Wu, Y.; Xu, H.; Zhang, J. Asymmetric Synthesis of Cis-5-Substituted Pyrrolidine 2-Phosphonates Using Metal Carbenoid 10072


Chemical Reviews

Review

NH Insertion and δ-Amino β-Ketophosphonates. Org. Lett. 2004, 6, 4523−4525. (495) Garcia, C. F.; McKervey, M. A.; Ye, T. Asymmetric Catalysis of Intramolecular N−H Insertion Reactions of α-Diazocarbonyls. Chem. Commun. 1996, 1465−1466. (496) For a brief summary up to 2007, see: Moody, C. J. Enantioselective Insertion of Metal Carbenes into N−H Bonds: A Potentially Versatile Route to Chiral Amine Derivatives. Angew. Chem., Int. Ed. 2007, 46, 9148−9150. (497) Liu, B.; Zhu, S.-F.; Zhang, W.; Chen, C.; Zhou, Q.-L. Highly Enantioselective Insertion of Carbenoids into N−H Bonds Catalyzed by Copper Complexes of Chiral Spiro Bisoxazolines. J. Am. Chem. Soc. 2007, 129, 5834−5835. (498) Zhu, S.-F.; Xu, B.; Wang, G.-P.; Zhou, Q.-L. Well-Defined Binuclear Chiral Spiro Copper Catalysts for Enantioselective N−H Insertion. J. Am. Chem. Soc. 2012, 134, 436−442. (499) Zhu, S.-F.; Zhou, Q.-L. Transition-Metal-Catalyzed Enantioselective Heteroatom−Hydrogen Bond Insertion Reactions. Acc. Chem. Res. 2012, 45, 1365−1377. (500) Lee, E. C.; Fu, G. C. Copper-Catalyzed Asymmetric N−H Insertion Reactions: Couplings of Diazo Compounds with Carbamates to Generate α-Amino Acids. J. Am. Chem. Soc. 2007, 129, 12066− 12067. (501) Xue, J.; Luk, H. L.; Platz, M. S. Direct Observation of a Carbene-Alcohol Ylide. J. Am. Chem. Soc. 2011, 133, 1763−1765. (502) Busch-Petersen, J.; Corey, E. J. A Rhodium(II) Catalytic Approach to the Synthesis of Ethers of a Minor Component in a Tautomeric Set. Org. Lett. 2000, 2, 1641−1643. (503) Radha Krishna, P.; Prapurna, Y. L.; Alivelu, M. InCl3 Catalyzed Carbene Insertion into O−H bonds: Efficient Synthesis of Ethers. Tetrahedron Lett. 2011, 52, 3460−3462. (504) Austeri, M.; Rix, D.; Zeghida, W.; Lacour, J. r. m. CpRuCatalyzed O−H Insertion and Condensation Reactions of αDiazocarbonyl Compounds. Org. Lett. 2011, 13, 1394−1397. (505) Miller, D. J.; Moody, C. J. Synthetic Applications of the O−H Insertion Reactions of Carbenes and Carbenoids Derived from Diazocarbonyl and Related Diazo Compounds. Tetrahedron 1995, 51, 10811−10843. (506) Debarge, S.; Balzarini, J.; Maguire, A. R. Design and Synthesis of α-Carboxy Phosphononucleosides. J. Org. Chem. 2011, 76, 105− 126. (507) Hladezuk, I.; Chastagner, V.; Collins, S. G.; Plunkett, S. J.; Ford, A.; Debarge, S.; Maguire, A. R. Development of O−H Insertion for the Attachment of Phosphonates to Nucleosides; Synthesis of αCarboxy Phosphononucleosides. Tetrahedron 2012, 68, 1894−1909. (508) Peddibhotla, S.; Dang, Y.; Liu, J. O.; Romo, D. Simultaneous Arming and Structure/Activity Studies of Natural Products Employing O−H Insertions: An Expedient and Versatile Strategy for Natural Products-Based Chemical Genetics. J. Am. Chem. Soc. 2007, 129, 12222−12231. (509) Maier, T. C.; Fu, G. C. Catalytic Enantioselective O−H Insertion Reactions. J. Am. Chem. Soc. 2006, 128, 4594−4595. (510) Zhu, S.-F.; Cai, Y.; Mao, H.-X.; Xie, J.-H.; Zhou, Q.-L. Enantioselective Iron-Catalysed O−H Bond Insertions. Nat. Chem. 2010, 2, 546−551. (511) Saito, H.; Iwai, R.; Uchiyama, T.; Miyake, M.; Miyairi, S. Chiral Induction by Cinchona Alkaloids in the Rhodium(II)-Catalyzed O−H Insertion Reaction. Chem. Pharm. Bull. 2010, 58, 872−874. (512) Gong, J.; Lin, G.; Sun, W.; Li, C.-C.; Yang, Z. Total Synthesis of (±) Maoecrystal V. J. Am. Chem. Soc. 2010, 132, 16745−16746. (513) Zhu, S.-F.; Song, X.-G.; Li, Y.; Cai, Y.; Zhou, Q.-L. Enantioselective Copper-Catalyzed Intramolecular O−H Insertion: An Efficient Approach to Chiral 2-Carboxy Cyclic Ethers. J. Am. Chem. Soc. 2010, 132, 16374−16376. (514) Chen, C.; Zhu, S.-F.; Liu, B.; Wang, L.-X.; Zhou, Q.-L. Highly Enantioselective Insertion of Carbenoids into O−H Bonds of Phenols: An Efficient Approach to Chiral α-Aryloxycarboxylic Esters. J. Am. Chem. Soc. 2007, 129, 12616−12617.

(515) Osako, T.; Panichakul, D.; Uozumi, Y. Enantioselective Carbenoid Insertion into Phenolic O−H Bonds with a Chiral Copper(I) Imidazoindolephosphine Complex. Org. Lett. 2012, 14, 194−197. (516) Xie, X.-L.; Zhu, S.-F.; Guo, J.-X.; Cai, Y.; Zhou, Q.-L. Enantioselective Palladium-Catalyzed Insertion of α-Aryl-α-diazoacetates into the O−H Bonds of Phenols. Angew. Chem., Int. Ed. 2014, 53, 2978−2981. (517) Song, X.-G.; Zhu, S.-F.; Xie, X.-L.; Zhou, Q.-L. Enantioselective Copper-Catalyzed Intramolecular Phenolic O−H Bond Insertion: Synthesis of Chiral 2-Carboxy Dihydrobenzofurans, Dihydrobenzopyrans, and Tetrahydrobenzooxepines. Angew. Chem., Int. Ed. 2013, 52, 2555−2558. (518) Huang, H.; Guo, X.; Hu, W. Efficient Trapping of Oxonium Ylides with Imines: A Highly Diastereoselective Three-Component Reaction for the Synthesis of β-Amino-α-hydroxyesters with Quaternary Stereocenters. Angew. Chem., Int. Ed. 2007, 46, 1337− 1339. (519) Guo, X.; Hu, W. Novel Multicomponent Reactions via Trapping of Protic Onium Ylides with Electrophiles. Acc. Chem. Res. 2013, 46, 2427−2440. (520) Qian, Y.; Xu, X.; Jiang, L.; Prajapati, D.; Hu, W. A Strategy to Synthesize Taxol Side Chain and (−)-epi Cytoxazone via Chiral Brønsted Acid-Rh2(OAc)4 Co-catalyzed Enantioselective ThreeComponent Reactions. J. Org. Chem. 2010, 75, 7483−7486. (521) Lu, C.-D.; Liu, H.; Chen, Z.-Y.; Hu, W.-H.; Mi, A.-Q. ThreeComponent Reaction of Aryl Diazoacetates, Alcohols, and Aldehydes (or Imines): Evidence of Alcoholic Oxonium Ylide Intermediates. Org. Lett. 2005, 7, 83−86. (522) Zhang, X.; Huang, H.; Guo, X.; Guan, X.; Yang, L.; Hu, W. Catalytic Enantioselective Trapping of an Alcoholic Oxonium Ylide with Aldehydes: RhII/ZrIV-Co-Catalyzed Three-Component Reactions of Aryl Diazoacetates, Benzyl Alcohol, and Aldehydes. Angew. Chem., Int. Ed. 2008, 47, 6647−6649. (523) Guo, X.; Huang, H.; Yang, L.; Hu, W. Trapping of Oxonium Ylide with Isatins: Efficient and Stereoselective Construction of Adjacent Quaternary Carbon Centers. Org. Lett. 2007, 9, 4721−4723. (524) Alcaide, B.; Almendros, P.; Aragoncillo, C.; Callejo, R.; Ruiz, M. P.; Torres, M. R. Rhodium-Catalyzed Synthesis of 3-Hydroxy-βlactams via Oxonium Ylide Generation: Three-Component Reaction between Azetidine-2,3-diones, Ethyl Diazoacetate, and Alcohols. J. Org. Chem. 2009, 74, 8421−8424. (525) Zhu, Y.; Zhai, C.; Yang, L.; Hu, W. Copper(II)-Catalyzed Highly Diastereoselective Three-Component Reactions of Aryl Diazoacetates with Alcohols and Chalcones: An Easy Access to Furan Derivatives. Chem. Commun. 2010, 46, 2865−2867. (526) Han, X.; Jiang, L.; Tang, M.; Hu, W. Diastereoselective ThreeComponent Reactions of Aryldiazoacetates with Alcohols/Water and Alkynals: Application to Substituted Enelactones. Org. Biomol. Chem. 2011, 9, 3839−3843. (527) Guo, Z.; Cai, M.; Jiang, J.; Yang, L.; Hu, W. Rh2(OAc)4-AgOTf Cooperative Catalysis in Cyclization/Three-Component Reactions for Concise Synthesis of 1,2-Dihydroisoquinolines. Org. Lett. 2010, 12, 652−655. (528) Urabe, F.; Miyamoto, S.; Takahashi, K.; Ishihara, J.; Hatakeyama, S. Formal [4 + 1]-Cycloaddition of Homopropargyl Alcohols to Diazo Dicarbonyl Compounds Giving Substituted Tetrahydrofurans. Org. Lett. 2014, 16, 1004−1007. (529) Xu, X.; Han, X.; Yang, L.; Hu, W. Highly Diastereoselective Synthesis of Fully Substituted Tetrahydrofurans by a One-Pot Cascade Reaction of Aryldiazoacetates with Allyl Alcohols. Chem. - Eur. J. 2009, 15, 12604−12607. (530) Fisher, T. J.; Mattson, A. E. Synthesis of α-Peroxyesters via Organocatalyzed O−H Insertion of Hydroperoxides and Aryl Diazoesters. Org. Lett. 2014, 16, 5316−5319. (531) Dakin, L. A.; Schaus, S. E.; Jacobsen, E. N.; Panek, J. S. Carbenoid Insertions into the Silicon-Hydrogen Bond Catalyzed by Chiral Copper(I) schiff base complexes. Tetrahedron Lett. 1998, 39, 8947−8950. 10073


Chemical Reviews

Review

(532) Davies, H. M. L.; Hansen, T.; Rutberg, J.; Bruzinski, P. R. Rhodium(II) (S)-N-(Arylsulfonyl)prolinate Catalyzed Asymmetric Insertions of Vinyl- and Phenylcarbenoids into the Si−H Bond. Tetrahedron Lett. 1997, 38, 1741−1744. (533) Ge, M.; Corey, E. J. A Method for the Catalytic Enantioselective Synthesis of 6-Silylated 2-Cyclohexenones. Tetrahedron Lett. 2006, 47, 2319−2321. (534) Zhang, Y.-Z.; Zhu, S.-F.; Wang, L.-X.; Zhou, Q.-L. CopperCatalyzed Highly Enantioselective Carbenoid Insertion into Si−H Bonds. Angew. Chem., Int. Ed. 2008, 47, 8496−8498. (535) Zhang, Y.-Z.; Zhu, S.-F.; Cai, Y.; Mao, H.-X.; Zhou, Q.-L. Copper-Catalyzed Enantioselective Carbenoid Insertion into S−H Bonds. Chem. Commun. 2009, 5362−5364. (536) Osipov, S. N.; Lange, T.; Tsouker, P.; Spengler, J.; Hennig, L.; Koksch, B.; Berger, S.; El-Kousy, S. M.; Burger, K. Hexafluoroacetone as a Protecting and Activating Reagent: Synthesis of New Types of Fluoro-Substituted α-Amino, α-Hydroxy and α-Mercapto Acids. Synthesis 2004, 2004, 1821−1829. (537) Tao, J.; Tran, R.; Murphy, G. K. Dihaloiodoarenes: α,αDihalogenation of Phenylacetate Derivatives. J. Am. Chem. Soc. 2013, 135, 16312−16315. (538) Pasceri, R.; Bartrum, H. E.; Hayes, C. J.; Moody, C. J. Nucleophilic Fluorination of β-Ketoester Derivatives with HBF4. Chem. Commun. 2012, 48, 12077−12079. (539) Padwa, A.; Hornbuckle, S. F. Ylide Formation from the Reaction of Carbenes and Carbenoids with Heteroatom Lone Pairs. Chem. Rev. 1991, 91, 263−309. (540) Nozaki, H.; Takaya, H.; Noyori, R. Reaction of Carbethoxycarbene with 2-Phenyloxirane and 2-Phenyloxetane. Tetrahedron 1966, 22, 3393−3401. (541) Ando, W.; Kondo, S.; Nakayama, K.; Ichibori, K.; Kohoda, H.; Yamato, H.; Imai, I.; Nakaido, S.; Migita, T. Decomposition of Dimethyl Diazomalonate in Allyl Compounds Containing Heteroatoms. J. Am. Chem. Soc. 1972, 94, 3870−3876. (542) Friedrich, K.; Jansen, U.; Kirmse, W. Oxygen Ylides - I.: Reactions of Carbenes with Oxetane. Tetrahedron Lett. 1985, 26, 193− 196. (543) Nozaki, H.; Takaya, H.; Noyori, R. The Reaction of Ethyl Diazoacetate with Styrene Oxide. Tetrahedron Lett. 1965, 6, 2563− 2567. (544) Clark, J. S. Diastereoselective Synthesis of 2,5-Dialkyl Tetrahydrofuran-3-ones by a Copper-Catalysed Tandem Carbenoid Insertion and Ylide Rearrangement Reaction. Tetrahedron Lett. 1992, 33, 6193−6196. (545) Clark, J. S.; Whitlock, G. A. A Short Synthesis of (±)-Decarestrictine L. Tetrahedron Lett. 1994, 35, 6381−6382. (546) Clark, J. S.; Fessard, T. C.; Wilson, C. A Concise and Stereoselective Synthesis of the A-Ring Fragment of the Gambieric Acids. Org. Lett. 2004, 6, 1773−1776. (547) Marmsäter, F. P.; West, F. G. Iterative Approach to Polycyclic Ethers Based on Stereoselective Oxonium Ylide [2,3]-Shifts. J. Am. Chem. Soc. 2001, 123, 5144−5145. (548) Kumaraswamy, G.; Sadaiah, K.; Ramakrishna, D. S.; Police, N.; Sridhar, B.; Bharatam, J. Highly Enantioselective Carbon-Carbon Bond Formation by Cu-Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement: Application to the Syntheses of Seven-Membered Oxacycles and Six-Membered Carbocycles. Chem. Commun. 2008, 5324−5326. (549) Pirrung, M. C.; Werner, J. A. Intramolecular Generation and [2,3]-Sigmatropic Rearrangement of Oxonium Ylides. J. Am. Chem. Soc. 1986, 108, 6060−6062. (550) Roskamp, E. J.; Johnson, C. R. Generation and Rearrangements of Oxonium Ylides. J. Am. Chem. Soc. 1986, 108, 6062−6063. (551) Pirrung, M. C.; Brown, W. L.; Rege, S.; Laughton, P. Total Synthesis of (+)-Griseofulvin. J. Am. Chem. Soc. 1991, 113, 8561− 8562. (552) Doyle, M. P.; Bagheri, V.; Harn, N. K. Facile Catalytic Methods for Intermolecular Generation of Allylic Oxonium Ylides and Their Stereoselective [2,3]- Sigmatropic Rearrangement. Tetrahedron Lett. 1988, 29, 5119−5122.

(553) Yakura, T.; Matsui, K.; Matsuzaka, K.; Yamashita, M. Stereoselective Synthesis of 5-Substituted 2-Allyl-3-oxotetrahydrofuran-2-carboxylates Using Rhodium(II)-Catalyzed Oxonium Ylide Formation−[2,3] Shift. Heterocycles 2009, 79, 353−358. (554) Yakura, T.; Ozono, A.; Matsui, K.; Yamashita, M.; Fujiwara, T. Application of a Stereoselective Rhodium(II)-Catalyzed Oxonium Ylide Formation−[2,3]-Sigmatropic Rearrangement of an α-Diazo-βketo Ester to the Synthesis of 2-epi-Cinatrin C1 Dimethyl Ester. Synlett 2013, 24, 65−68. (555) Pierson, N.; Fernández-García, C.; McKervey, M. A. Catalytic Asymmetric Oxonium Ylide - [2,3] Sigmatropic Rearrangement with Diazocarbonyl Compounds: First Use of C2-Symmetry in Rh(II) Carboxylates. Tetrahedron Lett. 1997, 38, 4705−4708. (556) Kitagaki, S.; Yanamoto, Y.; Tsutsui, H.; Anada, M.; Nakajima, M.; Hashimoto, S. Enantioselective [2,3]-Sigmatropic and [1,2]Stevens Rearrangements via Intramolecular Formation of Allylic Oxonium Ylides Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 2001, 42, 6361−6364. (557) Hodgson, D. M.; Petroliagi, M. Rh(II)-Binaphthol Phosphate Catalysts in the Enantioselective Intramolecular Oxonium Ylide Formation−[3,2] Sigmatropic Rearrangement of α-Diazo-β-ketoesters. Tetrahedron: Asymmetry 2001, 12, 877−881. (558) Shimada, N.; Nakamura, S.; Anada, M.; Shiro, M.; Hashimoto, S. Enantioselective Construction of a 2,8-Dioxabicyclo[3.2.1]octane Ring System via [2,3]-Sigmatropic Rearrangement of Oxonium Ylide Using Chiral Dirhodium(II) Carboxylates. Chem. Lett. 2009, 38, 488− 489. (559) Ye, T.; Garcia, C. F.; McKervey, M. A. Chemoselectivity and Stereoselectivity of Cyclisation of α-Diazocarbonyls Leading to Oxygen and Sulfur Heterocycles Catalysed by Chiral Rhodium and Copper Catalysts. J. Chem. Soc., Perkin Trans. 1 1995, 1373−1379. (560) Clark, J. S.; Krowiak, S. A.; Street, L. J. Synthesis of Cyclic Ethers from Copper Carbenoids by Formation and Rearrangement of Oxonium Ylides. Tetrahedron Lett. 1993, 34, 4385−4388. (561) West, F. G.; Naidu, B. N.; Tester, R. W. Profound Catalyst Effects in the Generation and Reactivity of Carbenoid-Derived Cyclic Ylides. J. Org. Chem. 1994, 59, 6892−6894. (562) Li, Z.; Davies, H. M. L. Enantioselective C−C Bond Formation by Rhodium-Catalyzed Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement between Donor/Acceptor Carbenoids and Allylic Alcohols. J. Am. Chem. Soc. 2010, 132, 396−401. (563) Li, Z.; Boyarskikh, V.; Hansen, J. H.; Autschbach, J.; Musaev, D. G.; Davies, H. M. L. Scope and Mechanistic Analysis of the Enantioselective Synthesis of Allenes by Rhodium-Catalyzed Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement between Donor/ Acceptor Carbenoids and Propargylic Alcohols. J. Am. Chem. Soc. 2012, 134, 15497−15504. (564) Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. Homogeneous Catalysis in the Decomposition of Diazo Compounds by Copper Chelates: Asymmetric Carbenoid Reactions. Tetrahedron 1968, 24, 3655−3669. (565) Ito, K.; Yoshitake, M.; Katsuki, T. Chiral Bipyrindine and Biquinoline ligands: Their Asymmetric Synthesis and Application to the Synthesis of trans-Whisky Lactone. Tetrahedron 1996, 52, 3905− 3920. (566) Doyle, M. P.; Ene, D. G.; Forbes, D. C.; Tedrow, J. S. Highly Enantioselective Oxonium Ylide Formation and Stevens Rearrangement Catalyzed by Chiral Dirhodium(II) Carboxamidates. Tetrahedron Lett. 1997, 38, 4367−4370. (567) Brogan, J. B.; Bauer, C. B.; Rogers, R. D.; Zercher, C. K. Selectivity in the Rearrangements of Oxonium Ylides. Tetrahedron Lett. 1996, 37, 5053−5056. (568) Gillespie, R. J.; Murray-Rust, J.; Murray-Rust, P.; Porter, A. E. A. Rhodium(II)-Catalysed Addition of Dimethyl Diazomalonate to Thiophen: A Simple Synthesis of Thiophenium Bismethoxycarbonylmethylides and Crystal and Molecular Structure of the Unsubstituted Methylide. J. Chem. Soc., Chem. Commun. 1978, 83−84. (569) Tamura, Y.; Mukai, C.; Nakajima, N.; Ikeda, M.; Kido, M. Synthesis, Stereochemistry, and Rearrangement of Thioxanthen-10-io10074


Chemical Reviews

Review

(bismethoxycarbonyl)methanides and Their 9-Alkyl Derivatives. J. Chem. Soc., Perkin Trans. 1 1981, 212−217. (570) Moody, C. J.; Slawin, A. M. Z.; Taylor, R. J.; Williams, D. J. Rhodium Carbenoid Mediated Cyclisations. Synthesis and X-ray Structures of Cyclic Sulphoxonium Ylides. Tetrahedron Lett. 1988, 29, 6009−6012. (571) Moody, C. J.; Taylor, R. J. Rhodium Carbenoid Mediated Cyclisations. Part 6. Synthesis of Cyclic Sulphoxonium ylides. Tetrahedron 1990, 46, 6525−6544. (572) Shi, G.; Xu, Y.; Xu, M. Carbenoid Entry into Trifluoromethylated Molecules: Preparation of Functionalized CF3-Containing γ,δUnsaturated Carboxylic Esters by Rhodium-Catalyzed Reaction of Ethyl 3,3,3-Trifluoro-2-diazo-propionate with Allylic Sulfides and Their Further Facile Conversion to Trifluoromethylated Conjugated Dienoic Esters. Tetrahedron 1991, 47, 1629−1648. (573) Liao, M.; Peng, L.; Wang, J. Rh(II)-Catalyzed Sommelet− Hauser Rearrangement. Org. Lett. 2008, 10, 693−696. (574) Li, Y.; Shi, Y.; Huang, Z.; Wu, X.; Xu, P.; Wang, J.; Zhang, Y. Catalytic Thia-Sommelet−Hauser Rearrangement: Application to the Synthesis of Oxindoles. Org. Lett. 2011, 13, 1210−1213. (575) Nishibayashi, Y.; Ohe, K.; Uemura, S. The First Example of Enantioselective Carbenoid Addition to Organochalcogen Atoms: Application to [2,3]Sigmatropic Rearrangement of Allylic Chalcogen Ylides. J. Chem. Soc., Chem. Commun. 1995, 1245−1246. (576) Fukuda, T.; Katsuki, T. Co(III)-Salen Catalyzed Carbenoid Reaction: Stereoselective [2,3]Sigmatropic Rearrangement of S-Ylides Derived from Allyl Aryl Sulfides. Tetrahedron Lett. 1997, 38, 3435− 3438. (577) McMillen, D. W.; Varga, N.; Reed, B. A.; King, C. Asymmetric Copper-Catalyzed [2,3]-Sigmatropic Rearrangements of Alkyl- and Aryl-Substituted Allyl Sulfides. J. Org. Chem. 2000, 65, 2532−2536. (578) Zhang, X.; Ma, M.; Wang, J. Catalytic Asymmetric [2,3] Sigmatropic Rearrangement of Sulfur Ylides Generated from Carbenoids and Propargyl Sulfides. Tetrahedron: Asymmetry 2003, 14, 891−895. (579) Liao, M.; Wang, J. Highly Efficient [2,3]-Sigmatropic Rearrangement of Sulfur Ylide Derived from Rh(II) Carbene and Sulfides in Water. Green Chem. 2007, 9, 184−188. (580) Ma, M.; Peng, L.; Li, C.; Zhang, X.; Wang, J. Highly Stereoselective [2,3]-Sigmatropic Rearrangement of Sulfur Ylide Generated through Cu(I) Carbene and Sulfides. J. Am. Chem. Soc. 2005, 127, 15016−15017. (581) Kametani, T.; Yukawa, H.; Honda, T. Stereoselective Synthesis of Pyrrolizidine Alkaloids, (+)-Heliotridine and (+)-Retronecine, by Means of an Intermolecular Carbenoid Displacement Reaction. J. Chem. Soc., Chem. Commun. 1988, 685−687. (582) Kametani, T.; Yukawa, H.; Honda, T. Stereocontrolled Synthesis of Necine Bases, (+)-Heliotridine and (+)-Retronecine. J. Chem. Soc., Perkin Trans. 1 1990, 571−577. (583) Kametani, T.; Yukawa, H.; Honda, T. A Novel Synthesis of Pyrrolizidine Alkaloids by Means of an Intramolecular Carbenoid Displacement (ICD) Reaction. J. Chem. Soc., Perkin Trans. 1 1988, 833−837. (584) Kametani, T.; Yukawa, H.; Honda, T. Synthesis of Pyrrolizidine Alkaloids, (±)-Trachelanthamidine, (±)-Isoretronecanol, and (±)-Supinidine, by Means of an Intramolecular Carbenoid Displacement (ICD) Reaction. J. Chem. Soc., Chem. Commun. 1986, 651−652. (585) Kametani, T.; Kawamura, K.; Tsubuki, M.; Honda, T. Synthesis of an Aromatic Sesquiterpene, (±)-Cuparene, via Construction of a Quaternary Carbon Centre by an Intramolecular Carbenoid Displacement Reaction. J. Chem. Soc., Chem. Commun. 1985, 1324−1325. (586) Kametani, T.; Kawamura, K.; Tsubuki, M.; Honda, T. Synthesis of Aromatic Sesquiterpenes, (±)-Cuparene and (±)-Laurene by Means of an Intramolecular Carbenoid Displacement (ICD) Reaction. J. Chem. Soc., Perkin Trans. 1 1988, 193−199.

(587) Mortimer, A. J. P.; Aliev, A. E.; Tocher, D. A.; Porter, M. J. Synthesis of the Tagetitoxin Core via Photo-Stevens Rearrangement. Org. Lett. 2008, 10, 5477−5480. (588) Price Mortimer, A. J.; Plet, J. R. H.; Obasanjo, O. A.; Kaltsoyannis, N.; Porter, M. J. Inter- and Intramolecular Reactions of 1-Deoxy-1-thio-1,6-anhydrosugars with α-Diazoesters: Synthesis of the Tagetitoxin Core by Photochemical Ylide Rearrangement. Org. Biomol. Chem. 2012, 10, 8616−8627. (589) Qu, J.-P.; Xu, Z.-H.; Zhou, J.; Cao, C.-L.; Sun, X.-L.; Dai, L.-X.; Tang, Y. Ligand-Accelerated Asymmetric [1,2]-Stevens Rearrangment of Sulfur Ylides via Decomposition of Diazomalonates Catalyzed by Chiral Bisoxazoline/Copper Complex. Adv. Synth. Catal. 2009, 351, 308−312. (590) Felthouse, T. R. The Chemistry, Structure, and Metal-Metal Bonding in Compounds of Rhodium(II). Prog. Inorg. Chem. 1982, 29, 73−166. (591) Doyle, M. P.; Tamblyn, W. H.; Bagheri, V. Highly Effective Catalytic Methods for Ylide Generation from Diazo Compounds. Mechanism of the Rhodium- and Copper-Catalyzed Reactions with Allylic Compounds. J. Org. Chem. 1981, 46, 5094−5102. (592) Roberts, E.; Sançon, J. P.; Sweeney, J. B.; Workman, J. A. First Efficient and General Copper-Catalyzed [2,3]-Rearrangement of Tetrahydropyridinium Ylids. Org. Lett. 2003, 5, 4775−4777. (593) Clark, J. S.; Hodgson, P. B.; Goldsmith, M. D.; Street, L. J. Rearrangement of Ammonium Ylides Produced by Intramolecular Reaction of Catalytically Generated Metal Carbenoids. Part 1. Synthesis of Cyclic Amines. J. Chem. Soc., Perkin Trans. 1 2001, 0, 3312−3324. (594) Clark, J. S.; Hodgson, P. B.; Goldsmith, M. D.; Blake, A. J.; Cooke, P. A.; Street, L. J. Rearrangement of Ammonium Ylides Produced by Intramolecular Reaction of Catalytically Generated Metal Carbenoids. Part 2. Stereoselective Synthesis of Bicyclic Amines. J. Chem. Soc., Perkin Trans. 1 2001, 0, 3325−3337. (595) Clark, J. S.; Middleton, M. D. Synthesis of Novel α-Substituted and α,α-Disubstituted Amino Acids by Rearrangement of Ammonium Ylides Generated from Metal Carbenoids. Org. Lett. 2002, 4, 765−768. (596) Clark, J. S.; Hodgson, P. B. An Enantioselective Synthesis of the CE Ring System of the Alkaloids Manzamine A, E and F, and Ircinal A. Tetrahedron Lett. 1995, 36, 2519−2522. (597) Roberts, E.; Sançon, J. P.; Sweeney, J. B. A New Class of Ammonium Ylid for [2,3]-Sigmatropic Rearrangement Reactions: eneendo-Spiro Ylids. Org. Lett. 2005, 7, 2075−2078. (598) West, F. G.; Glaeske, K. W.; Naidu, B. N. One-Step Synthesis of Tertiary α-Amino Ketones and α-Amino Esters From Amines and Diazocarbonyl Compounds. Synthesis 1993, 1993, 977−980. (599) West, F. G.; Naidu, B. N. New Route to Substituted Piperidines via the Stevens [1,2]-Shift of Ammonium Ylides. J. Am. Chem. Soc. 1993, 115, 1177−1178. (600) West, F. G.; Naidu, B. N. Applications of Stevens [1,2]-Shifts of Cyclic Ammonium Ylides. A Route to Morpholin-2-ones. J. Org. Chem. 1994, 59, 6051−6056. (601) West, F. G.; Naidu, B. N. Piperidines via Ammonium Ylide [1,2]-Shifts: A Concise, Enantioselective Route to (−)-Epilupinine from Proline Ester. J. Am. Chem. Soc. 1994, 116, 8420−8421. (602) Naidu, B. N.; West, F. G. A Short, Enantioselective Synthesis of (−)-Epilupinine from Proline via a Spirocyclic Ammonium Ylide. Tetrahedron 1997, 53, 16565−16574. (603) Beall, L. S.; Padwa, A. An Approach to the Cephalotaxine Ring Skeleton Using an Ammonium Ylide/Stevens [1, 2]-Rearrangement. Tetrahedron Lett. 1998, 39, 4159−4162. (604) Padwa, A.; Beall, L. S.; Eidell, C. K.; Worsencroft, K. J. An Approach toward Isoindolobenzazepines Using the Ammonium Ylide/ Stevens [1,2]-Rearrangement Sequence. J. Org. Chem. 2001, 66, 2414−2421. (605) Mucedda, M.; Muroni, D.; Saba, A.; Manassero, C. Concise Diastereospecific Pyrrolo[1,2-a][1,4]benzodiazepinone Synthesis. Tetrahedron 2007, 63, 12232−12238. (606) Guo, X.; Yue, Y.; Hu, G.; Zhou, J.; Zhao, Y.; Yang, L.; Hu, W. Trapping of an Ammonium Ylide with Activated Ketones: Synthesis of 10075


Chemical Reviews

Review

β-Hydroxy-α-Amino Esters with Adjacent Quaternary Stereocenters. Synlett 2009, 2009, 2109−2114. (607) Zhu, Y.; Zhai, C.; Yang, L.; Hu, W. Highly Regioselective, Three-Component Reactions of Diazoacetates with Anilines and β,γUnsaturated α-Keto Esters: 1,2-Addition versus 1,4-Addition. Eur. J. Org. Chem. 2011, 2011, 1113−1124. (608) Wang, Y.; Chen, Z.; Mi, A.; Hu, W. Novel C−C Bond Formation through Addition of Ammonium Ylides to Arylaldehydes: A Facile Approach to β-Aryl-β-hydroxy α-Amino Acid Frameworks. Chem. Commun. 2004, 2486−2487. (609) Lu, C.-D.; Liu, H.; Chen, Z.-Y.; Hu, W.-H.; Mi, A.-Q. The Rhodium Catalyzed Three-Component Reaction of Diazoacetates, Titanium(IV) Alkoxides and Aldehydes. Chem. Commun. 2005, 2624− 2626. (610) Yue, Y.; Guo, X.; Chen, Z.; Yang, L.; Hu, W. Copper(I) Hexafluorophosphate: A Dual Functional Catalyst for ThreeComponent Reactions of Methyl Phenyldiazoacetate with Alcohols and Aldehydes or α-Ketoesters. Tetrahedron Lett. 2008, 49, 6862− 6865. (611) Hodgson, D. M.; Labande, A. H.; Muthusamy, S. Cycloadditions of Carbonyl Ylides Derived from Diazocarbonyl Compounds. Organic Reactions; John Wiley & Sons, Inc.: Hoboken, NJ, 2013; Vol. 80, pp 133−496. (612) Padwa, A. Intramolecular Cycloaddition of Carbonyl Ylides as a Strategy for Natural Product Synthesis. Tetrahedron 2011, 67, 8057− 8072. (613) Anaç, O.; Güngör, F. Ş. Electrocyclization Reactions of Vinyl, Styryl, and Butadienyl Conjugated Carbonyl/Azomethine Ylides. Tetrahedron 2010, 66, 5931−5953. (614) France, S.; Phun, L. H. Enantio- and Diastereoselective Rh(II)Catalyzed 1,3-Dipolar Cycloadditions of Carbonyl Ylides and Their Recent Applications in Complex Molecule Synthesis. Curr. Org. Synth. 2010, 7, 332−347. (615) Padwa, A. Domino Reactions of Rhodium(II) Carbenoids for Alkaloid Synthesis. Chem. Soc. Rev. 2009, 38, 3072−3081. (616) Wang, J. Synthetic Reactions of MC and MN Bonds: Ylide Formation, Rearrangement, and 1,3-Dipolar Cycloaddition. In Comprehensive Organometallic Chemistry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier: Oxford, U.K., 2007; Vol. 11, pp 151−178. (617) Padwa, A. The interaction of Rhodium Carbenoids with Carbonyl Compounds as a Method for the Synthesis of Tetrahydrofurans. J. Organomet. Chem. 2005, 690, 5533−5540. (618) Padwa, A. Catalytic Decomposition of Diazo Compounds as a Method for Generating Carbonyl-Ylide Dipoles. Helv. Chim. Acta 2005, 88, 1357−1374. (619) Khlebnikov, A. F.; Novikov, M. S.; Kostikov, R. R. Iminium Ylides from Carbenes and Carbenoids: Generation and Synthetic Applications. Russ. Chem. Rev. 2005, 74, 171−192. (620) Mehta, G.; Muthusamy, S. Tandem Cyclization−Cycloaddition Reactions of Rhodium Generated Carbenoids from α-Diazo Carbonyl Compounds. Tetrahedron 2002, 58, 9477−9504. (621) Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A. Catalytic Enantioselective Rearrangements and Cycloadditions Involving Ylides from Diazo Compounds. Chem. Soc. Rev. 2001, 30, 50−61. (622) Doyle, M. P.; Hu, W.; Timmons, D. J. Epoxides and Aziridines from Diazoacetates via Ylide Intermediates. Org. Lett. 2001, 3, 933− 935. (623) Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.; Vasbinder, M. M.; Xavier, K. R. Stereocontrol in Intermolecular Dirhodium(II)-Catalyzed Carbonyl Ylide Formation and Reactions. Dioxolanes and Dihydrofurans. J. Org. Chem. 1997, 62, 7210−7215. (624) Russell, A. E.; Brekan, J.; Gronenberg, L.; Doyle, M. P. Divergence of Carbonyl Ylide Reactions as a Function of Diazocarbonyl Compound and Aldehyde Substituent: Dioxolanes, Dioxolenes, and Epoxides. J. Org. Chem. 2004, 69, 5269−5274. (625) Jiang, B.; Zhang, X.; Luo, Z. High Diastereoselectivity in Intermolecular Carbonyl Ylide Cycloaddition with Aryl Aldehyde Using Methyl Diazo(trifluoromethyl)acetate. Org. Lett. 2002, 4, 2453− 2455.

(626) Lu, C.-D.; Chen, Z.-Y.; Liu, H.; Hu, W.-H.; Mi, A.-Q. Highly Chemoselective 2,4,5-Triaryl-1,3-dioxolane Formation from Intermolecular 1,3-Dipolar Addition of Carbonyl Ylide with Aryl Aldehydes. Org. Lett. 2004, 6, 3071−3074. (627) Muthusamy, S.; Ramkumar, R.; Mishra, A. K. Chemo- and Diastereoselective Synthesis of Spiro-Dioxolanes from Intermolecular Carbonyl Ylide Cycloaddition with Aryl Aldehyde. Tetrahedron Lett. 2011, 52, 148−150. (628) Skaggs, A. J.; Lin, E. Y.; Jamison, T. F. Cobalt ClusterContaining Carbonyl Ylides for Catalytic, Three-Component Assembly of Oxygen Heterocycles. Org. Lett. 2002, 4, 2277−2280. (629) Nair, V.; Mathai, S.; Nair, S. M.; Rath, N. P. A Facile ThreeComponent Reaction of Dicarbomethoxycarbene, Aldehydes and oQuinones: Synthesis of Novel Spiro-Dioxolanes. Tetrahedron Lett. 2003, 44, 8407−8409. (630) Nair, V.; Mathai, S.; Varma, R. L. The Three-Component Reaction of Dicarbomethoxycarbene, Aldehydes, and β-Nitrostyrenes: A Stereoselective Synthesis of Substituted Tetrahydrofurans. J. Org. Chem. 2004, 69, 1413−1414. (631) Lu, C.-D.; Chen, Z.-Y.; Liu, H.; Hu, W.-H.; Mi, A.-Q.; Doyle, M. P. A Facile Three-Component One-Pot Synthesis of Structurally Constrained Tetrahydrofurans That Are t-RNA Synthetase Inhibitor Analogues. J. Org. Chem. 2004, 69, 4856−4859. (632) Qiu, L.; Guo, X.; Zhou, J.; Liu, S.; Yang, L.; Wu, X.; Hu, W. A Stereoselective Synthesis of Fully Substituted Tetrahydrofurans through 1,3-Dipolar Cycloaddition with Cinnamaldehydes: An Easy Access to Chroman Derivatives. RSC Adv. 2013, 3, 20065−20070. (633) Zhu, S.; Chen, L.; Wang, C.; Liang, R.; Wang, X.; Ren, Y.; Jiang, H. A Practical System to Synthesize the Multiple-Substituted 2,5-Dihydrofuran by the Intermolecular Dipolar Cycloaddition Reactions Involving Acceptor/Acceptor-Substituted Diazo Reagents. Tetrahedron 2011, 67, 5507−5515. (634) DeAngelis, A.; Panne, P.; Yap, G. P. A.; Fox, J. M. RhCatalyzed Formation of Dioxolanes from α-Alkyl Diazoesters: Diastereoselective Cycloadditions of Carbonyl Ylides with Selectivity over β-Hydride Elimination. J. Org. Chem. 2008, 73, 1435−1439. (635) DeAngelis, A.; Taylor, M. T.; Fox, J. M. Unusually Reactive and Selective Carbonyl Ylides for Three-Component Cycloaddition Reactions. J. Am. Chem. Soc. 2009, 131, 1101−1105. (636) Hashimoto, Y.; Itoh, K.; Kakehi, A.; Shiro, M.; Suga, H. Diastereoselective Synthesis of Tetrahydrofurans by Lewis Acid Catalyzed Intermolecular Carbenoid−Carbonyl Reaction−Cycloaddition Sequences: Unusual Diastereoselectivity of Lewis Acid Catalyzed Cycloadditions. J. Org. Chem. 2013, 78, 6182−6195. (637) Torssell, S.; Kienle, M.; Somfai, P. 1,3-Dipolar Cycloadditions of Carbonyl Ylides to Aldimines: A Three-Component Approach to syn-α-Hydroxy-β-amino Esters. Angew. Chem., Int. Ed. 2005, 44, 3096−3099. (638) Torssell, S.; Somfai, P. 1,3-Dipolar Cycloadditions of Carbonyl Ylides to Aldimines: Scope, Limitations and Asymmetric Cycloadditions. Adv. Synth. Catal. 2006, 348, 2421−2430. (639) Rajasekaran, T.; Karthik, G.; Sridhar, B.; Subba Reddy, B. V. Dual Behavior of Isatin-Based Cyclic Ketimines with Dicarbomethoxy Carbene: Expedient Synthesis of Highly Functionalized Spirooxindolyl Oxazolidines and Pyrrolines. Org. Lett. 2013, 15, 1512−1515. (640) Suga, H.; Ishida, H.; Ibata, T. Stereocontrol of Metal-Catalyzed Cycloaddition of Carbonyl Ylide with N-Substituted Maleimide. Tetrahedron Lett. 1998, 39, 3165−3166. (641) Suga, H.; Kakehi, A.; Ito, S.; Inoue, K.; Ishida, H.; Ibata, T. Stereocontrol in Rare Earth Metal Triflate-Catalyzed 1,3-Dipolar Cycloaddition Reaction of 2-Benzopyrylium-4-olate with Aldehydes. Org. Lett. 2000, 2, 3145−3148. (642) Suga, H.; Inoue, K.; Inoue, S.; Kakehi, A. Highly Enantioselective 1,3-Dipolar Cycloaddition Reactions of 2-Benzopyrylium-4-olate Catalyzed by Chiral Lewis Acids. J. Am. Chem. Soc. 2002, 124, 14836−14837. (643) Suga, H.; Inoue, K.; Inoue, S.; Kakehi, A.; Shiro, M. Chiral 2,6Bis(oxazolinyl)pyridine−Rare Earth Metal Complexes as Catalysts for 10076


Chemical Reviews

Review

and (5 S)-Phenyloxazin-2,3-dione. Tetrahedron Lett. 1997, 38, 3107− 3110. (660) Drew, M. G. B.; Fengler-Veith, M.; Harwood, L. M.; Jahans, A. W. Highly Selective Chirally Templated Isomünchnone Cycloadditions of Achiral Aldehydes: Synthesis of an Enantiopure α,βDihydroxyacid. Tetrahedron Lett. 1997, 38, 4521−4524. (661) Gan, Y.; Harwood, L. M.; Richards, S. C.; Smith, I. E. D.; Vinader, V. Cycloadditions of Chiral Carbonyl Ylides with Imine Dipolarophiles as a Route to Enantiomerically Pure α-Amino-βhydroxy Acids. Tetrahedron: Asymmetry 2009, 20, 723−725. (662) Padwa, A.; Prein, M. π-Facial Diastereoselection in [3 + 2]Cycloadditions of Isomünchnone Dipoles. J. Org. Chem. 1997, 62, 6842−6854. (663) Padwa, A.; Prein, M. Acyclic Stereocontrol in [3 + 2]Cycloadditions of Amino Acid-Derived Isomünchnone Dipoles. Tetrahedron 1998, 54, 6957−6976. (664) Straub, C. S.; Padwa, A. Synthesis of the Angiotensin Converting Enzyme Inhibitor (−)-A58365A via an Cycloaddition Reaction. Org. Lett. 1999, 1, 83−86. (665) Padwa, A.; Sheehan, S. M.; Straub, C. S. An IsomünchnoneBased Method for the Synthesis of Highly Substituted 2(1H)Pyridones. J. Org. Chem. 1999, 64, 8648−8659. (666) Sheehan, S. M.; Padwa, A. New Synthetic Route to 2Pyridones and Its Application toward the Synthesis of (±)-Ipalbidine. J. Org. Chem. 1997, 62, 438−439. (667) Harris, J. M.; Padwa, A. A New β-Carbolinone Synthesis Using a Rh(II)-Promoted [3 + 2]-Cycloaddition and Pd(0) Cross-Coupling/ Heck Cyclization Chemistry. Org. Lett. 2003, 5, 4195−4197. (668) Mmutlane, E. M.; Harris, J. M.; Padwa, A. 1,3-Dipolar Cycloaddition Chemistry for the Preparation of Novel IndolizinoneBased Compounds. J. Org. Chem. 2005, 70, 8055−8063. (669) Padwa, A.; Hasegawa, T.; Liu, B.; Zhang, Z. Rhodium(II)Catalyzed Cyclization of Amido Diazo Carbonyl Compounds. J. Org. Chem. 2000, 65, 7124−7133. (670) Padwa, A.; Zhang, Z. J.; Zhi, L. Cyclization−Cycloaddition Cascade of Rhodium Carbenoids Using Different Carbonyl Groups. Highlighting the Position of Interaction. J. Org. Chem. 2000, 65, 5223−5232. (671) Padwa, A.; Curtis, E. A. Generation of Carbonyl Ylide Dipoles from the Rh(II)-Catalyzed Cyclization of α-Diazo-β-keto-1,5-diesters. ARKIVOC 2001, 2001, 51−60. (672) Curtis, E. A.; Worsencroft, K. J.; Padwa, A. Cyclization of Rhodium Carbenoids Using Ester and Amido Carbonyl Groups. Tetrahedron Lett. 1997, 38, 3319−3322. (673) Padwa, A.; Snyder, J. P.; Curtis, E. A.; Sheehan, S. M.; Worsencroft, K. J.; Kappe, C. O. Rhodium(II)-Catalyzed Equilibration of Push-Pull Carbonyl and Ammonium Ylides. A Computationally Based Understanding of the Reaction Pathway. J. Am. Chem. Soc. 2000, 122, 8155−8167. (674) Weingarten, M. D.; Prein, M.; Price, A. T.; Snyder, J. P.; Padwa, A. Theoretical Insights Regarding the Cycloaddition Behavior of Push−Pull Stabilized Carbonyl Ylides. J. Org. Chem. 1997, 62, 2001−2010. (675) Savinov, S. N.; Austin, D. J. The Diastereoselective Cycloaddition of Vinyl Ethers with Isomünchnones. Chem. Commun. 1999, 1813−1814. (676) Savinov, S. N.; Austin, D. J. Modular Evolution of a Chiral Auxiliary for the 1,3-Dipolar Cycloaddition of Isomünchnones with Vinyl Ethers. Org. Lett. 2002, 4, 1415−1418. (677) Savinov, S. N.; Austin, D. J. Diastereofacial Solid Phase Synthesis and Self-Promoted Cleavage of a [2.2.1] Bicyclic Diversity Scaffold. Org. Lett. 2002, 4, 1419−1422. (678) Hodgson, D. M.; Brückl, T.; Glen, R.; Labande, A. H.; Selden, D. A.; Dossetter, A. G.; Redgrave, A. J. Catalytic Enantioselective Intermolecular Cycloadditions of 2-Diazo-3,6-diketoester-Derived Carbonyl Ylides with Alkene Dipolarophiles. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 5450−5454. (679) Hodgson, D. M.; Labande, A. H.; Glen, R.; Redgrave, A. J. Catalytic Enantioselective Intermolecular Cycloadditions of a 2-Diazo-

Highly Enantioselective 1,3-Dipolar Cycloaddition Reactions of 2Benzopyrylium-4-olates. J. Org. Chem. 2005, 70, 47−56. (644) Suga, H.; Suzuki, T.; Inoue, K.; Kakehi, A. Asymmetric Cycloaddition Reactions between 2-Benzopyrylium-4-olates and 3-(2Alkenoyl)-2-oxazolidinones in the Presence of 2,6-Bis(oxazolinyl)pyridine-Lanthanoid Complexes. Tetrahedron 2006, 62, 9218−9225. (645) Suga, H.; Ishimoto, D.; Higuchi, S.; Ohtsuka, M.; Arikawa, T.; Tsuchida, T.; Kakehi, A.; Baba, T. Dipole-LUMO/DipolarophileHOMO Controlled Asymmetric Cycloadditions of Carbonyl Ylides Catalyzed by Chiral Lewis Acids. Org. Lett. 2007, 9, 4359−4362. (646) Suga, H.; Higuchi, S.; Ohtsuka, M.; Ishimoto, D.; Arikawa, T.; Hashimoto, Y.; Misawa, S.; Tsuchida, T.; Kakehi, A.; Baba, T. Inverse Electron Demand Asymmetric Cycloadditions of Cyclic Carbonyl Ylides Catalyzed by Chiral Lewis AcidsScope and Limitations of Diazo and Olefinic Substrates. Tetrahedron 2010, 66, 3070−3089. (647) Suga, H.; Ebiura, Y.; Fukushima, K.; Kakehi, A.; Baba, T. Efficient Catalytic Effects of Lewis Acids in the 1,3-Dipolar Cycloaddition Reactions of Carbonyl Ylides with Imines. J. Org. Chem. 2005, 70, 10782−10791. (648) García Ruano, J. L.; Fraile, A.; Martín, M. R.; Núñez, A. First Asymmetric Cycloaddition of Carbonyl Ylides to Vinyl Sulfoxides and Furan-2(5H)-ones. J. Org. Chem. 2006, 71, 6536−6541. (649) Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Ganguly, B.; Suresh, E.; Dastidar, P. Tandem Cyclization−Cycloaddition Behavior of Rhodium Carbenoids with Carbonyl Compounds: Stereoselective Studies on the Construction of Novel Epoxy-Bridged Tetrahydropyranone Frameworks. J. Org. Chem. 2002, 67, 8019−8033. (650) Muthusamy, S.; Krishnamurthi, J.; Nethaji, M. Highly Regio-, Chemo- and Diastereoselective Synthesis of Oxa-Bridged Spirocycles: A Novel Observation of Reverse Selectivity. Chem. Commun. 2005, 3862−3864. (651) Zhou, C.-Y.; Yu, W.-Y.; Che, C.-M. Ruthenium(II) Porphyrin Catalyzed Tandem Carbonyl Ylide Formation and 1,3-Dipolar Cycloaddition Reactions of α-Diazo Ketones. Org. Lett. 2002, 4, 3235−3238. (652) Zhou, C.-Y.; Chan, P. W. H.; Yu, W.-Y.; Che, C.-M. Study of Substrate Dependence on the Diastereoselectivity of the Ruthenium(II) Porphyrin Catalyzed Tandem Formation and 1,3-Dipolar Cycloaddition Reactions of Carbonyl Ylides. Synthesis 2003, 2003, 1403−1412. (653) Rout, L.; Harned, A. M. Allene Carboxylates as Dipolarophiles in Rh-Catalyzed Carbonyl Ylide Cycloadditions. Chem. - Eur. J. 2009, 15, 12926−12928. (654) Molchanov, A. P.; Diev, V. V.; Kopf, J.; Kostikov, R. R. First Example of 1,3-Dipolar Cycloaddition of Carbonyl Ylides to Cyclopropenes. Russ. J. Org. Chem. 2004, 40, 431−433. (655) Diev, V. V.; Kostikov, R. R.; Gleiter, R.; Molchanov, A. P. Cyclopropenes in the 1,3-Dipolar Cycloaddition with Carbonyl Ylides: Experimental and Theoretical Evidence for the Enhancement of σWithdrawal in 3-Substituted-Cyclopropenes. J. Org. Chem. 2006, 71, 4066−4077. (656) Molchanov, A. P.; Diev, V. V.; Magull, J.; Vidović, D.; Kozhushkov, S. I.; de Meijere, A.; Kostikov, R. R. Carbonyl Ylide Cycloadditions to C,C-Double Bonds of Methylenecyclopropanes. Eur. J. Org. Chem. 2005, 2005, 593−599. (657) Rodier, F.; Rajzmann, M.; Parrain, J.-L.; Chouraqui, G.; Commeiras, L. Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium-Catalyzed [3 + 2] Cycloaddition Reaction: Experimental and Theoretical Studies. Chem. - Eur. J. 2013, 19, 2467−2477. (658) Angell, R.; Fengler-Veith, M.; Finch, H.; Harwood, L. M.; Tucker, T. T. Cycloadditions of 1,3-Oxazolium-4-olates (Isomünchnones) by Rhodium(II)-Induced Decomposition of α-Diazocarbonyl Derivatives of (5R)- and (5S)-Phenyloxazin-3-one as a Chiral Template. Tetrahedron Lett. 1997, 38, 4517−4520. (659) Angell, R.; Drew, M. G. B.; Fengler-Veith, M.; Finch, H.; Harwood, L. M.; Jahans, A. W.; Tucker, T. T. Novel Chiral Templates for 1,3-Oxazolium-4-olate (Isomünchnone) Cycloadditions: (5 R)10077


Chemical Reviews

Review

3,6-diketoester-Derived Carbonyl Ylide with Alkyne and Strained Alkene Dipolarophiles. Tetrahedron: Asymmetry 2003, 14, 921−924. (680) Hodgson, D. M.; Labande, A. H.; Pierard, F. Y. T. M. Extended Scope of Dirhodium(II)-Catalysed Enantioselective Intramolecular 1,3-Dipolar Cycloadditions of Carbonyl Ylides with Alkene and Alkyne Dipolarophiles. Synlett 2003, 34, 59−62. (681) Hodgson, D. M.; Glen, R.; Redgrave, A. J. [3 + 2] Cycloaddition Reactions of Arylacetylenes with Carbonyl Ylides Derived from 1-Aryl-1-diazohexane-2,5-diones. Tetrahedron Lett. 2002, 43, 3927−3930. (682) Hodgson, D. M.; Avery, T. D.; Donohue, A. C. Concise, Stereoselective Syntheses of cis-Nemorensic Acid and 4-Hydroxy-cisnemorensic Acid via Tandem Carbonyl Ylide Formation−Cycloaddition. Org. Lett. 2002, 4, 1809−1811. (683) Hodgson, D. M.; Le Strat, F.; Avery, T. D.; Donohue, A. C.; Brückl, T. Stereocontrolled Syntheses of the Nemorensic Acids Using 6-Diazoheptane-2,5-dione in Carbonyl Ylide Cycloadditions. J. Org. Chem. 2004, 69, 8796−8803. (684) Hodgson, D. M.; Le Strat, F. Use of Allene in 1,3-Dipolar Addition to a Carbonyl Ylide: Syntheses of 3-Hydroxy-cis-Nemorensic Acid and Nemorensic acid. Chem. Commun. 2004, 822−823. (685) Kitagaki, S.; Anada, M.; Kataoka, O.; Matsuno, K.; Umeda, C.; Watanabe, N.; Hashimoto, S.-i. Enantiocontrol in Tandem Carbonyl Ylide Formation and Intermolecular 1,3-Dipolar Cycloaddition of αDiazo Ketones Mediated by Chiral Dirhodium(II) Carboxylate Catalyst. J. Am. Chem. Soc. 1999, 121, 1417−1418. (686) Kitagaki, S.; Yasugahira, M.; Anada, M.; Nakajima, M.; Hashimoto, S. Enantioselective Intermolecular 1,3-Dipolar Cycloaddition via Ester-Derived Carbonyl Ylide Formation Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 2000, 41, 5931− 5935. (687) Tsutsui, H.; Shimada, N.; Abe, T.; Anada, M.; Nakajima, M.; Nakamura, S.; Nambu, H.; Hashimoto, S. Catalytic Enantioselective Tandem Carbonyl Ylide Formation/1,3-Dipolar Cycloaddition Reactions of α-Diazo Ketones with Aromatic Aldehydes using Dirhodium(II) Tetrakis[N-benzene-fused-phthaloyl-(S)-valinate]. Adv. Synth. Catal. 2007, 349, 521−526. (688) Kurosaki, Y.; Shimada, N.; Anada, M.; Nambu, H.; Hashimoto, S. Catalytic Asymmetric Construction of the exo-7-Aryl-6,8dioxabicyclo[3.2.1]octane Framework of Psoracorylifols B and C Using a Carbonyl Ylide Cycloaddition Strategy. Bull. Korean Chem. Soc. 2010, 31, 694−696. (689) Shimada, N.; Anada, M.; Nakamura, S.; Nambu, H.; Tsutsui, H.; Hashimoto, S. Catalytic Enantioselective Intermolecular Cycloaddition of 2-Diazo-3,6-diketoester-Derived Carbonyl Ylides with Alkynes and Styrenes Using Chiral Dirhodium(II) Carboxylates. Org. Lett. 2008, 10, 3603−3606. (690) Shimada, N.; Oohara, T.; Krishnamurthi, J.; Nambu, H.; Hashimoto, S. Catalytic Enantioselective Intermolecular Cycloaddition of Diazodiketoester-Derived Carbonyl Ylides with Indoles Using Chiral Dirhodium(II) Carboxylates. Org. Lett. 2011, 13, 6284−6287. (691) Takeda, K.; Oohara, T.; Shimada, N.; Nambu, H.; Hashimoto, S. Continuous Flow System with a Polymer-Supported Dirhodium(II) Catalyst: Application to Enantioselective Carbonyl Ylide Cycloaddition Reactions. Chem. - Eur. J. 2011, 17, 13992−13998. (692) Krishnamurthi, J.; Nambu, H.; Takeda, K.; Anada, M.; Yamano, A.; Hashimoto, S. Enantioselective Cycloaddition of Carbonyl Ylides with Arylallenes Using Rh2(S-TCPTTL)4. Org. Biomol. Chem. 2013, 11, 5374−5382. (693) Hodgson, D. M.; Stupple, P. A.; Johnstone, C. Catalytic Enantioselective Tandem Carbonyl Ylide Formation-Cycloaddition. Tetrahedron Lett. 1997, 38, 6471−6472. (694) Hodgson, D. M.; Stupple, P. A.; Johnstone, C. Efficient RhII Binaphthol Phosphate Catalysts for Enantioselective Intramolecular Tandem Carbonyl Ylide Formation-Cycloaddition of α-Diazo-β-keto Esters. Chem. Commun. 1999, 2185−2186. (695) Hodgson, D. M.; Stupple, P. A.; Pierard, F. Y. T. M.; Labande, A. H.; Johnstone, C. Development of Dirhodium(II)-Catalyzed

Generation and Enantioselective 1,3-Dipolar Cycloaddition of Carbonyl Ylides. Chem. - Eur. J. 2001, 7, 4465−4476. (696) Hodgson, D. M.; Selden, D. A.; Dossetter, A. G. Synthesis and Evaluation of 4,4′,6,6′-Tetrasubstituted Binaphtholphosphate Dirhodium(II) Complexes as Catalysts in Enantioselective Carbonyl Ylide Formation−Cycloaddition Reactions. Tetrahedron: Asymmetry 2003, 14, 3841−3849. (697) Hodgson, D. M.; Labande, A. H.; Pierard, F. Y. T. M.; Expósito Castro, M. Á . The Scope of Catalytic Enantioselective Tandem Carbonyl Ylide Formation−Intramolecular [3 + 2] Cycloadditions. J. Org. Chem. 2003, 68, 6153−6159. (698) Hodgson, D. M.; Glen, R.; Grant, G. H.; Redgrave, A. J. Catalytic Enantioselective [3 + 2]-Cycloadditions of DiazoketoneDerived Aryl-Substituted Carbonyl Ylides. J. Org. Chem. 2003, 68, 581−586. (699) Hodgson, D. M.; Glen, R.; Redgrave, A. J. Catalytic Enantioselective Tandem Carbonyl Ylide FormationIntramolecular Cycloaddition with Unsaturated α-Diazo-β,ε-diketo sulfones. Tetrahedron: Asymmetry 2009, 20, 754−757. (700) Hodgson, D. M.; Angrish, D.; Labande, A. H. One-Pot CrossMetathesis/Tandem Carbonyl Ylide Formation-Intramolecular Cycloaddition of an Unsaturated 2-Diazo-3,6-diketoester. Chem. Commun. 2006, 627−628. (701) Hodgson, D. M.; Angrish, D. Oxapolycycles from One-Pot Cross-Metathesis/Carbonyl Ylide Formation-Intramolecular Cycloaddition of α-Diazo-β-keto Esters. Adv. Synth. Catal. 2006, 348, 2509− 2514. (702) Zhang, X.; Ko, R. Y. Y.; Li, S.; Miao, R.; Chiu, P. Allenes as Dipolarophiles in the Intramolecular Carbene Cyclization-Cycloaddition Cascade Reaction. Synlett 2006, 2006, 1197−1200. (703) Shi, B.; Merten, S.; Wong, D. K. Y.; Chu, J. C. K.; Liu, L. L.; Lam, S. K.; Jäger, A.; Wong, W.-T.; Chiu, P.; Metz, P. The RhodiumCatalyzed Carbene Cyclization Cycloaddition Cascade Reaction of Vinylsulfonates. Adv. Synth. Catal. 2009, 351, 3128−3132. (704) Brodney, M. A.; Padwa, A. Generation and Trapping of NAcyliminium Ions Derived from Isomünchnone Cycloadducts. A Versatile Route to Functionalized Heterocycles. J. Org. Chem. 1999, 64, 556−565. (705) Padwa, A.; Brodney, M. A.; Marino, J. P.; Osterhout, M. H.; Price, A. T. Tandem Dipolar Cycloaddition−Mannich Cyclization as an Approach to Tricyclic Nitrogen Heterocycles. J. Org. Chem. 1997, 62, 67−77. (706) Padwa, A.; Austin, D. J.; Price, A. T.; Weingarten, M. D. Studies on the Intramolecular Cycloaddition Reaction of Isomünchnones Derived from N-Alkenyl Substituted Diazoimides. Tetrahedron 1996, 52, 3247−3260. (707) Padwa, A.; Hertzog, D. L.; Nadler, W. R. Intramolecular Cycloaddition of Isomunchnone Dipoles to Heteroaromatic πSystems. J. Org. Chem. 1994, 59, 7072−7084. (708) England, D. B.; Eagan, J. M.; Merey, G.; Anac, O.; Padwa, A. The Rhodium(II) Carbenoid Cyclization−Cycloaddition Cascade of α-Diazo Dihydroindolinones for the Synthesis of Novel Azapolycyclic Ring Systems. Tetrahedron 2008, 64, 988−1001. (709) Mejía-Oneto, J. M.; Padwa, A. Ligand Effects in the Rh(II) Catalyzed Reaction of α-Diazo Ketoamides. Tetrahedron Lett. 2004, 45, 9115−9118. (710) Mejía-Oneto, J. M.; Padwa, A. Intramolecular [3 + 2]Cycloaddition Reaction of Push−Pull Dipoles Across Heteroaromatic π-Systems. Org. Lett. 2004, 6, 3241−3244. (711) Padwa, A.; Lynch, S. M.; Mejía-Oneto, J. M.; Zhang, H. Cycloaddition Chemistry of 2-Vinyl-Substituted Indoles and Related Heteroaromatic Systems. J. Org. Chem. 2005, 70, 2206−2218. (712) Hong, X.; Mejía-Oneto, J. M.; France, S.; Padwa, A. Rhodium Carbenoid Induced Cycloadditions of Diazo Ketoimides Across Indolyl π-Bonds. Synlett 2007, 2007, 775−779. (713) Padwa, A.; Kissell, W. S.; Eidell, C. K. Cyclization− Cycloaddition Cascades for the Construction of Azapolycyclic ring Systems. Can. J. Chem. 2001, 79, 1681−1693. 10078


Chemical Reviews

Review

(714) Kissel, W. S.; Padwa, A. A Push-Pull Carbonyl Ylide Cycloaddition Approach Directed toward Lycorine. Tetrahedron Lett. 1999, 40, 4003−4006. (715) Johnson, T.; Cheshire, D. R.; Stocks, M. J.; Thurston, V. T. A Carbonyl Ylide Approach to Substituted Furans. Synlett 2001, 646− 648. (716) Padwa, A.; Price, A. T. Tandem Cyclization-Cycloaddition Reaction of Rhodium Carbenoids as an Approach to the Aspidosperma Alkaloids. J. Org. Chem. 1995, 60, 6258−6259. (717) Padwa, A.; Price, A. T. Synthesis of the Pentacyclic Skeleton of the Aspidosperma Alkaloids Using Rhodium Carbenoids as Reactive Intermediates. J. Org. Chem. 1998, 63, 556−565. (718) Hong, X.; France, S.; Mejía-Oneto, J. M.; Padwa, A. Cycloaddition Protocol for the Assembly of the Hexacyclic Framework Associated with the Kopsifoline Alkaloids. Org. Lett. 2006, 8, 5141− 5144. (719) Hong, X.; France, S.; Padwa, A. A Dipolar Cycloaddition Approach toward the Kopsifoline Alkaloid Framework. Tetrahedron 2007, 63, 5962−5976. (720) Marino, J. P.; Osterhout, M. H.; Padwa, A. An Approach to Lysergic Acid Utilizing an Intramolecular Isomünchnone Cycloaddition Pathway. J. Org. Chem. 1995, 60, 2704−2713. (721) Li, H.; Cheng, B.; Boonnak, N.; Padwa, A. An Approach toward the Alkaloid (±)-Mersicarpine Using a Rhodium(II) Carbenoid Cyclization−Cycloaddition Cascade of an α-Diazo Dihydroindolinone. Tetrahedron 2011, 67, 9829−9836. (722) Padwa, A.; Precedo, L.; Semones, M. A. Model Studies Directed toward the Total Synthesis of (±)-Ribasine. A Tandem Cyclization−Cycloaddition Route Leading to the Core Skeleton. J. Org. Chem. 1999, 64, 4079−4088. (723) Padwa, A.; Boonsombat, J.; Rashatasakhon, P.; Willis, J. Efficient Construction of the Oxatricyclo[6.3.1.00,0]dodecane Core of Komaroviquinone Using a Cyclization/Cycloaddition Cascade of a Rhodium Carbenoid Intermediate. Org. Lett. 2005, 7, 3725−3727. (724) Padwa, A.; Chughtai, M. J.; Boonsombat, J.; Rashatasakhon, P. A Rh(II)-Catalyzed Cycloaddition Approach toward the Synthesis of Komaroviquinone. Tetrahedron 2008, 64, 4758−4767. (725) Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. An Approach toward the Illudin Family of Sesquiterpenes Using the Tandem Cyclization−Cycloaddition Reaction of Rhodium Carbenoids. J. Org. Chem. 1997, 62, 1317−1325. (726) Padwa, A.; Sandanayaka, V. P.; Curtis, E. A. Synthetic Studies toward Illudins and Ptaquilosin. A Highly Convergent Approach via the Dipolar Cycloaddition of Carbonyl Ylides. J. Am. Chem. Soc. 1994, 116, 2667−2668. (727) Padwa, A.; Brodney, M. A.; Marino, J. P.; Sheehan, S. M. Utilization of the Intramolecular Cycloaddition−Cationic π-Cyclization of an Isomü n chnone Derivative for the Synthesis of (±)-Lycopodine. J. Org. Chem. 1997, 62, 78−87. (728) Padwa, A.; Harring, S. R.; Semones, M. A. Cycloaddition Reaction of Mesoionic Betaines as an Approach toward Trialkylindoline Alkaloids. J. Org. Chem. 1998, 63, 44−54. (729) England, D. B.; Padwa, A. Synthesis of (±)-3H-Epivincamine via a Rh(II)-Triggered Cyclization/Cycloaddition Cascade. Org. Lett. 2007, 9, 3249−3252. (730) England, D. B.; Padwa, A. General Access to the Vinca and Tacaman Alkaloids Using a Rh(II)-Catalyzed Cyclization/Cycloaddition Cascade. J. Org. Chem. 2008, 73, 2792−2802. (731) Mejía-Oneto, J. M.; Padwa, A. Application of the Rh(II) Cyclization/Cycloaddition Cascade for the Total Synthesis of (±)-Aspidophytine. Org. Lett. 2006, 8, 3275−3278. (732) Mejía-Oneto, J. M.; Padwa, A. Total Synthesis of the Alkaloid (±)-Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry. Helv. Chim. Acta 2008, 91, 285−302. (733) Dauben, W. G.; Dinges, J.; Smith, T. C. A Convergent Approach toward the Tigliane Ring System. J. Org. Chem. 1993, 58, 7635−7637.

(734) McMills, M. C.; Zhuang, L.; Wright, D. L.; Watt, W. A Carbonyl-Ylide Approach to the Tigliane Diterpenes. Tetrahedron Lett. 1994, 35, 8311−8314. (735) Kinder, F. R.; Bair, K. W. Total Synthesis of (±)-Illudin M. J. Org. Chem. 1994, 59, 6965−6967. (736) Baldwin, J. E.; Mayweg, A. V. W.; Neumann, K.; Pritchard, G. J. Studies toward the Biomimetic Synthesis of Tropolone Natural Products via a Hetero Diels−Alder Reaction. Org. Lett. 1999, 1, 1933− 1935. (737) Wood, J. L.; Thompson, B. D.; Yusuff, N.; Pflum, D. A.; Matthäus, M. S. P. Total Synthesis of (±)-Epoxysorbicillinol. J. Am. Chem. Soc. 2001, 123, 2097−2098. (738) Kataoka, O.; Kitagaki, S.; Watanabe, N.; Kobayashi, J.-i.; Nakamura, S.-i.; Shiro, M.; Hashimoto, S.-i. Toward the SecondGeneration Synthesis of Zaragozic Acids: Construction of the 2,8Dioxabicyclo[3.2.1]octane Core System via Tandem Carbonyl Ylide Formation and 1,3-Dipolar Cycloaddition Sequence. Tetrahedron Lett. 1998, 39, 2371−2374. (739) Nakamura, S.; Hirata, Y.; Kurosaki, T.; Anada, M.; Kataoka, O.; Kitagaki, S.; Hashimoto, S. Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C by a Carbonyl Ylide Cycloaddition Strategy. Angew. Chem., Int. Ed. 2003, 42, 5351−5355. (740) Hirata, Y.; Nakamura, S.; Watanabe, N.; Kataoka, O.; Kurosaki, T.; Anada, M.; Kitagaki, S.; Shiro, M.; Hashimoto, S. Total Syntheses of Zaragozic Acids A and C by a Carbonyl Ylide Cycloaddition Strategy. Chem. - Eur. J. 2006, 12, 8898−8925. (741) Nakamura, S. Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C. Chem. Pharm. Bull. 2005, 53, 1−10. (742) Nakamura, S.; Sugano, Y.; Kikuchi, F.; Hashimoto, S. Total Synthesis and Absolute Stereochemistry of Polygalolides A and B. Angew. Chem., Int. Ed. 2006, 45, 6532−6535. (743) Sugano, Y.; Kikuchi, F.; Toita, A.; Nakamura, S.; Hashimoto, S. Total Syntheses of (+)-Polygalolide A and (+)-Polygalolide B: Elucidation of the Absolute Stereochemistry and Biogenetic Implications. Chem. - Eur. J. 2012, 18, 9682−9690. (744) Hodgson, D. M.; Bailey, J. M.; Harrison, T. A CycloadditionRearrangement Approach to the Squalestatins. Tetrahedron Lett. 1996, 37, 4623−4626. (745) Hodgson, D. M.; Bailey, J. M.; Villalonga-Barber, C.; Drew, M. G. B.; Harrison, T. Selectivity in the Cycloadditions of Carbonyl Ylides with Glyoxylates: An Approach to the Zaragozic Acids-Squalestatins. J. Chem. Soc., Perkin Trans. 1 2000, 3432−3443. (746) Hodgson, D. M.; Villalonga-Barber, C.; Goodman, J. M.; Pellegrinet, S. C. Synthetic and Computational Studies on the Tricarboxylate Core of 6,7-Dideoxysqualestatin H5 Involving a Carbonyl Ylide Cycloaddition-Rearrangement. Org. Biomol. Chem. 2010, 8, 3975−3984. (747) Koyama, H.; Ball, R. G.; Berger, G. D. A Novel Synthetic Approach toward the Zaragozic Acids Core Structure. Tetrahedron Lett. 1994, 35, 9185−9188. (748) Graening, T.; Bette, V.; Neudörfl, J.; Lex, J.; Schmalz, H.-G. Total Synthesis of (−)-Colchicine via a Rh-Triggered Cycloaddition Cascade. Org. Lett. 2005, 7, 4317−4320. (749) Termath, A. O.; Ritter, S.; König, M.; Kranz, D. P.; Neudörfl, J.-M.; Prokop, A.; Schmalz, H.-G. Synthesis of Oxa-B-Ring Analogs of Colchicine through Rh-Catalyzed Intramolecular [5 + 2] Cycloaddition. Eur. J. Org. Chem. 2012, 2012, 4501−4507. (750) Navickas, V.; Ushakov, D. B.; Maier, M. E.; Ströbele, M.; Meyer, H. J. Synthesis of the Guaianolide Ring System via Cycloaddition of a Bicyclic Carbonyl Ylide with Allyl Propiolate. Org. Lett. 2010, 12, 3418−3421. (751) Kim, C. H.; Jang, K. P.; Choi, S. Y.; Chung, Y. K.; Lee, E. A Carbonyl Ylide Cycloaddition Approach to Platensimycin. Angew. Chem., Int. Ed. 2008, 47, 4009−4011. (752) Jang, K. P.; Kim, C. H.; Na, S. W.; Kim, H.; Kang, H.; Lee, E. Isoplatensimycin: Synthesis and Biological Evaluation. Bioorg. Med. Chem. Lett. 2009, 19, 4601−4602. (753) Jang, K. P.; Kim, C. H.; Na, S. W.; Jang, D. S.; Kim, H.; Kang, H.; Lee, E. 7-Phenylplatensimycin and 11-Methyl-7-phenylplatensi10079


Chemical Reviews

Review

mycin: More Potent Analogs of Platensimycin. Bioorg. Med. Chem. Lett. 2010, 20, 2156−2158. (754) Raolji, G. B.; Garçon, S.; Greene, A. E.; Kanazawa, A. A Modular Approach to Oxoindolizino Quinolines: Efficient Synthesis of Mappicine Ketone (Nothapodytine B). Angew. Chem., Int. Ed. 2003, 42, 5059−5061. (755) Anderson, R. J.; Raolji, G. B.; Kanazawa, A.; Greene, A. E. A Novel, Expeditious Synthesis of Racemic Camptothecin. Org. Lett. 2005, 7, 2989−2991. (756) Grillet, F.; Baumlová, B.; Prévost, G.; Constant, J.-F.; Chaumeron, S.; Bigg, D. C. H.; Greene, A. E.; Kanazawa, A. Synthesis and Bioevaluation of 22-Hydroxyacuminatine Analogs. Bioorg. Med. Chem. Lett. 2008, 18, 2143−2146. (757) Tang, C.-J.; Babjak, M.; Anderson, R. J.; Greene, A. E.; Kanazawa, A. Novel, Efficient Total Synthesis of Natural 20(S)Camptothecin. Org. Biomol. Chem. 2006, 4, 3757−3759. (758) Babjak, M.; Kanazawa, A.; Anderson, R. J.; Greene, A. E. Concise Synthesis of 22-Hydroxyacuminatine, Cytotoxic Camptothecinoid from Camptotheca acuminata, by Pyridone Benzannulation. Org. Biomol. Chem. 2006, 4, 407−409. (759) Kanazawa, A.; Muniz, M. N.; Baumlová, B.; Ljungdahl, N.; Greene, A. E. New Route to Natural Camptothecin through Isomünchnone Cycloaddition. Synlett 2008, 2008, 2275−2278. (760) Grillet, F.; Sabot, C.; Anderson, R.; Babjak, M.; Greene, A. E.; Kanazawa, A. Intramolecular Isomünchnone Cycloaddition Approach to the Antitumor Agent Camptothecin. Tetrahedron 2011, 67, 2579− 2584. (761) Lam, S. K.; Chiu, P. Asymmetric Total Synthesis of (−)-Indicol by a Carbene Cyclization−Cycloaddition Cascade Strategy. Chem. - Eur. J. 2007, 13, 9589−9599. (762) Rodier, F.; Parrain, J.-L.; Chouraqui, G.; Commeiras, L. First Studies Directed towards the Diastereoselective Synthesis of the BCD Tricyclic Core of Brownin F. Org. Biomol. Chem. 2013, 11, 4178− 4185. (763) Geng, Z.; Chen, B.; Chiu, P. Total Synthesis of Pseudolaric Acid A. Angew. Chem., Int. Ed. 2006, 45, 6197−6201. (764) Chiu, P. Application of the Carbene Cyclization-Cycloaddition Cascade in Total Synthesis. Pure Appl. Chem. 2005, 77, 1183−1189. (765) Chen, B.; Ko, R. Y. Y.; Yuen, M. S. M.; Cheng, K.-F.; Chiu, P. A Tandem Metal Carbene Cyclization−Cycloaddition Approach to the Pseudolaric Acids. J. Org. Chem. 2003, 68, 4195−4205. (766) Chiu, P.; Chen, B.; Cheng, K. F. A Rhodium Carbene Cyclization−Cycloaddition Cascade Strategy toward the Pseudolaric Acids. Org. Lett. 2001, 3, 1721−1724. (767) Shimada, N.; Hanari, T.; Kurosaki, Y.; Takeda, K.; Anada, M.; Nambu, H.; Shiro, M.; Hashimoto, S. Catalytic Asymmetric Synthesis of the endo-6-Aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one Natural Product from Ligusticum chuanxing via 1,3-Dipolar Cycloaddition of a FormylDerived Carbonyl Ylide Using Rh2(S-TCPTTL)4. J. Org. Chem. 2010, 75, 6039−6042. (768) Shimada, N.; Hanari, T.; Kurosaki, Y.; Anada, M.; Nambu, H.; Hashimoto, S. Catalytic Asymmetric Synthesis of Descurainin via 1,3Dipolar Cycloaddition of a Carbonyl Ylide Using Rh2(R-TCPTTL)4. Tetrahedron Lett. 2010, 51, 6572−6575. (769) Nambu, H.; Hikime, M.; Krishnamurthi, J.; Kamiya, M.; Shimada, N.; Hashimoto, S. Asymmetric Approach to the Pentacyclic Skeleton of Aspidosperma Alkaloids via Enantioselective Intramolecular 1,3-Dipolar Cycloaddition of Carbonyl Ylides Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 2009, 50, 3675−3678. (770) Suga, H.; Hashimoto, Y.; Yasumura, S.; Takezawa, R.; Itoh, K.; Kakehi, A. Chiral Lewis Acid Catalyzed Asymmetric Cycloadditions of Carbonyl Ylides Generated from Diazoimide Derivatives and Their Synthetic Applications to Indolizidine Alkaloids. J. Org. Chem. 2013, 78, 10840−10852.

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