Transition Metal Chemistry of Cyclopropenes and Cyclopropanes

Chem. Rev. 2007, 107, 3117−3179

3117

Transition Metal Chemistry of Cyclopropenes and Cyclopropanes Michael Rubin,*,† Marina Rubina,† and Vladimir Gevorgyan*,‡ Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, and Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607 Received October 10, 2006

Contents 1. Introduction 1.1. Cyclopropenes 1.2. Methylenecyclopropanes 1.3. Vinylcyclopropanes 1.4. Cyclopropanes 2. Reactions of Cyclopropenes 2.1. Addition Reactions 2.1.1. Carbometalation Reactions 2.1.2. Hydrometalation Reactions 2.1.3. Dimetalation Reactions 2.1.4. Addition of Carbon- and Nitrogen-Based Pronucleophiles 2.1.5. Hydrogenation Reactions 2.1.6. Hydroformylation Reactions 2.1.7. Pauson−Khand Reaction 2.1.8. Dipolar [2 + 3] Cycloaddition 2.2. Formal Substitution Reactions 2.2.1. Cyclopropenyl Moiety as the Nucleophilic Component in Cross-Coupling Reactions 2.2.2. Cyclopropenyl Moiety as the Electrophilic Component in Cross-Coupling Reactions 2.2.3. Heck-Type Arylation 2.2.4. Tsuji−Trost Reaction 2.3. Isomerization and Cycloisomerization Reactions 2.3.1. Carbonylative Cycloisomerizations of Vinylcyclopropenes 2.3.2. Cycloisomerization of 3-Acyl- and 3-Alkoxycarbonylcyclopropenes into Furans 2.3.3. Cycloisomerization of Cyclopropenyl Imines into Pyrroloheterocycles 2.4. Metathesis Reactions 2.4.1. Ring-Opening Metathesis Polymerization 2.4.2. Ring-Opening Cross Metathesis of Cyclopropenone Acetals 2.5. Stoichiometric Reactions Leading to Isolable Organometallic Complexes 2.5.1. η2-Cyclopropenylmetal Complexes 2.5.2. Transformation of Cyclopropenes into Vinylcarbene Metal Complexes 2.5.3. Rearrangement of Metallabenzvalenes into Metallabenzenes

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* To whom correspondence should be addressed. M.R.: phone, +1(785) 864-5071; fax, +1(785) 864-5396; e-mail, [email protected]. V.G.: phone, +1(312) 355-3579; fax, +1(312) 355-0836; e-mail: [email protected]. † University of Kansas. ‡ University of Illinois at Chicago.

2.5.4. Reactions of Vinylcyclopropenes 2.5.5. Metallacyclization Reactions 2.5.6. Miscellaneous Stoichiometric Reactions 3. Reactions of Methylenecyclopropanes 3.1. Addition Reactions 3.1.1. Hydrometalation Reactions 3.1.2. Dimetalation Reactions 3.1.3. Hydroamination and Hydroxylation Reactions 3.1.4. Addition of Carbon-Based Pronucleophiles 3.2. Cycloaddition Reactions 3.2.1. [2 + 2 + 1] Cycloaddition (Pauson−Khand Reaction) 3.2.2. [2 + 2 + 2] Cycloaddition 3.2.3. Dipolar [2 + 3] Cycloaddition 3.2.4. [3 + 2] and [3 + 2 + 2] Cycloadditions 3.2.5. [4 + 1] Cycloaddition 3.2.6. Cascade Reactions Involving Carbopalladation of the Double Bond of Methylenecyclopropane 3.3. Isomerization and Cycloisomerization Reactions 3.3.1. Rearrangement of Methylenecyclopropanes into Cyclobutenes 3.3.2. Cycloisomerization of Acyl-Substituted Methylenecyclopropanes 3.4. Polymerization Reactions 4. Reactions of Vinyl-, Allenyl-, and Alkynylcyclopropanes 4.1. Addition Reactions Accompanied by Ring Opening 4.1.1. Addition Reactions Leading to Acyclic Products 4.1.2. Addition/Cycloisomerization Reactions 4.2. Cycloaddition Reactions 4.2.1. Intramolecular [5 + 2] Cycloaddition with Alkynes and Alkenes 4.2.2. Intermolecular [5 + 2] Cycloaddition with Alkynes and Allenes 4.2.3. Multicomponent Reactions Involving [5 + 2] Cycloaddition 4.2.4. Miscellaneous Cycloaddition Reactions 4.3. Cycloisomerization Reactions 4.3.1. Cycloisomerization into Cyclobutanes 4.3.2. Cycloisomerization into Cyclopentenes 4.4. Metathesis Reactions 5. Reactions of Other Cyclopropanes 5.1. Cross-Coupling Reactions

10.1021/cr050988l CCC: $65.00 © 2007 American Chemical Society Published on Web 07/11/2007

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Kumada−Corriu Cross-Coupling 3167 Negishi Cross-Coupling 3168 Stille Cross-Coupling 3169 Suzuki−Miyaura Cross-Coupling 3170 Oxidative Homocoupling of 3172 Cyclopropylmetal Species 5.2. Miscellaneous Reactions 3172 3172 5.2.1. C−H Activation Reactions 5.2.2. Rearrangement of Acylcyclopropanes into 3173 Dihydrofurans 5.2.3. Cycloaddition of Nitrones to 3173 Cyclopropanes 5.2.4. [3 + 2] Cycloaddition of Activated 3174 Cyclopropanes to Enones 6. Conclusion 3174 7. Abbreviations 3174 8. Acknowledgments 3175 9. References 3175

Rubin et al.

5.1.1. 5.1.2. 5.1.3. 5.1.4. 5.1.5.

Multum in parVo1

Marina Rubina was born in Syktyvkar, Russia. She received her B.Sc. from Syktyvkar State University in 1996. She spent 4 years (1995−1999) at the Moscow State University, first as an undergraduate researcher and then as a graduate student. Marina received her Ph.D. from the University of Illinois at Chicago in 2004, where she was working under the supervision of Prof. Gevorgyan. She is currently a Postdoctoral Fellow at the University of Kansas.

1. Introduction Three-membered carbocycles are extremely important versatile building blocks for organic chemistry. Their unique structural and electronic properties give rise to an array of very interesting, characteristic transformations. Indeed, the chemistry of small rings is now enjoying a renaissance, which was unimaginable before. Until slightly over a decade ago, transition metal-assisted transformations of small rings were mostly limited to the synthesis of stoichiometric organometallic complexes. Today, transition metal-catalyzed chemistry of three-membered carbocycles is a quickly developing area which is the primary focus of many research groups around the world. This review highlights recent advances in the transition metal-catalyzed chemistry of cyclopropenes, methylenecyclopropanes, vinylcyclopropanes, and cyclopropanes. Unavoidably, there may be some overlap with existing

Michael Rubin was born in Ekaterinburg, Russia. He received his B.Sc. in 1994 and his Ph.D. in 1998 from the Moscow State University. He was a Visiting Researcher at the University of Wales in 1996 and at ICMO, Universite de Paris-Sud in 1997. In 1999−2005 he was working in Prof. Gevorgyan’s group, first as a postdoctoral researcher and then as a Research Assistant Professor. Currently he is an Assistant Professor at the University of Kansas, Department of Chemistry, and the NSF Center for Environmentally Beneficial Catalysis. His research interests include the development of novel synthetic methodologies and investigation of reaction mechanisms. Another area of his interest concerns the development of catalytic processes in supercritical fluids and expanded liquid phases.

Vladimir Gevorgyan was born in Krasnodar, Russia, in 1956. He received his B.Sc. from Kuban State University in 1978 and his Ph.D. from the Latvian Institute of Organic Synthesis in 1984, where he was promoted to Group Leader in 1986. He spent 2 years (1992−1994) at Tohoku University in Sendai, Japan, the first as a JSPS Postdoctoral Fellow and the second as a Ciba-Geigy International Postdoctoral Fellow. In the following year (1995) he worked as a Visiting Professor at CNR, Bologna, Italy. He returned to Tohoku University in 1996 as an Assistant Professor and was promoted to Associate Professor in 1997. In 1999 he moved to the University of Illinois at Chicago as an Associate Professor. He was promoted to the rank of Full Professor in 2003. Prof. Gevorgyan’s current research interests cover four main areas. The first is concerned with development of highly selective Pd-catalyzed benzannulation reactions. The second area of interest focuses on development of novel transition metal-catalyzed methods for the synthesis of heterocyclic and naturally occurring compounds. The third area of interest covers the development of selective Lewis acid-catalyzed bond formation and cleavage reactions. The fourth deals with the chemistry of strained ring systems.

reviews covering related topics, in which case, references are provided in the corresponding sections. Our goal, however, is to provide the reader with a contemporary overview, primarily from the mechanistic standpoint, of recent developments in the area of transition metal-catalyzed chemistry of three-membered carbocycles.

1.1. Cyclopropenes Cyclopropenes possess significant strain,2 which makes these species great energy reservoirs and defines their unusually high reactivity.3 Clever reaction design allows for

Transition Metal Chemistry of Cyclopropenes

Chemical Reviews, 2007, Vol. 107, No. 7 3119

Scheme 1

utilization of this energy, giving rise to novel transformations, which are unknown for normal olefins, allenes, and alkynes. The conformationally rigid scaffold of the cyclopropene represents an ideal model for mechanistic investigations and design of novel stereoselective transformations. The increased π-density of its double bond makes cyclopropene a very attractive substrate for π-philic transition metals. This opens avenues for extremely rich coordination chemistry, for different types of rearrangements, as well as for addition and cycloaddition reactions. For decades, cyclopropenes were synthesized mostly from available cyclopropane precursors via elimination reactions. This chemistry was previously comprehensively reviewed by Baird.4,5 In addition to these classical synthetic methods, novel, efficient protocols involving enantioselective cyclopropenation of alkynes by Doyle,6 Davies,7 and Corey8 have emerged. Furthermore, expedient approaches toward chiral cyclopropenes via diastereomeric resolution and parallel kinetic resolution strategies were disclosed by Fox.9 Taken together with efficient, preparative, multigram scale protocols developed by Gevorgyan10 and Nakamura,11 these methods dramatically expanded the arsenal of available diversely substituted cyclopropenyl synthons. The most abundant type of reactions, which have lately received a lot of attention, involve transition metal-catalyzed addition of various entities across the double bond of cyclopropene, which can proceed both with and without ring opening (Scheme 1). These include the following: carbo-, hydro-, and dimetalation reactions (a-c), addition of carbon-, nitrogen- and oxygen-based pronucleophiles (d, e), catalytic

hydrogenation and hydroformylation reactions (f, g), the Pauson-Khand reaction (h), and [2 + 3] cycloadditions (i). Another important type of transformation involves formal substitution reactions, which proceed with preservation of the small cycle and the strained double bond. Examples of these substitution reactions include cross-coupling reactions, in which cyclopropene can serve as both the nucleophilic (j) and the electrophilic (k) component, the Heck reaction (l), electrophilic arylation (m), and the Tsuji-Trost reaction (n). Similarly to all cyclic olefins, cyclopropenes can undergo a ring-opening metathesis reaction (o). Various types of cycloisomerizations (p) as well as formation of stoichiometric complexes with transition metals (q) are two other very important types of transformations characteristic of cyclopropenes. It should be noted that the chemistry of specific classes of cyclopropenes, such as cycloproparenes,12 triafulvenes,13 and their heteroatom analogues,14,15 will not be addressed in this review.

1.2. Methylenecyclopropanes Methylenecyclopropane (MCP) is the smallest carbocycle with an exo-methylene moiety.16 The rigidity and symmetry of this molecule confer its orbital symmetry,17 which, in turn, is responsible for the unique reactivity of MCPs. Arguably, the chemistry of MCPs18 is the most rapidly developing among all small ring compounds. Research in this field is driven by numerous groups, led by de Meijere,19 Yamamoto,20 and Lautens,21 to name a few.


Rubin et al.

Scheme 2

There are two main characteristic reactivity patterns of MCPs with respect to the transition metal-catalyzed reactions (Scheme 2). The first is the great aptitude of cyclopropylmethyl metal species (A), produced upon carbometalation of the exo-methylene double bond of MCP, toward β-carbon elimination, which ultimately leads to homoallylic compounds (a-d). Alternatively, analogous transformations proceeding via A without ring cleavage produce cyclopropylmethyl derivatives (a, b) or spiro-cycloadducts (e-g). The second reactivity pattern arises from the ability of MCPs to produce reactive trimethylenemethane (TMM) complexes (B), or metallacyclobutane species (C, D), capable of undergoing various cycloaddition reactions (h). MCPs also readily undergo cycloisomerization (j) and polymerization reactions (k) in the presence of transition metal complexes. In this review, the main emphasis is placed on the most recent advances in the transition metal-catalyzed chemistry of MCPs. The earlier developments in this field were comprehensively covered in excellent reviews by Binger,22 Donaldson,23 Lautens,24 and Yamamoto.20

1.3. Vinylcyclopropanes Vinylcyclopropane (VCP) is another very versatile strained cyclic synthon, which is best compared to 1,3-butadiene, owing to the pronounced tendency of the cyclopropyl Walshtype “banana-shaped” HOMO to form conjugation with π-orbitals of the double bond. Theoretical computations,25

photoelectron spectroscopy,26 and electron diffraction analysis27 suggest the σ-bond connecting the cyclopropyl and the vinyl group in VCP has an increased double-bond character by 13-15% and, thus, is significantly shorter than a normal σ-bond. The chemistry of VCPs is very rich and has been extensively developed by several research groups, including Wender,28 Trost,29 de Meijere,30 and others. First, VCPs readily produce two different π-allylmetal intermediates E and F (Scheme 3). Reactions proceeding via intermediate E give rise to various substitution reactions accompanied by ring cleavage (a). Another important class of transformations involving VCPs is the transition metal-catalyzed nucleophilic substitution, or Tsuji-Trost reaction (d), proceeding via η31,1-dimethyleneallylpalladium species (F). The cycloaddition chemistry of VCPs (b, c), particularly [5 + 2] cycloaddition reactions and related cascade transformations, has been significantly elaborated in the past decade. Transition metalmediated transformations of VCPs were previously reviewed.31,32 Finally, VCPs can undergo cycloisomerization (e)33,34 and cross-metathesis reactions (f). In this review we primarily focus on recent developments in the chemistry of VCPs, with emphasis placed on characteristic transition metal-catalyzed transformations, which set them apart from alkenes and “nonconjugated” cyclopropanes. The related chemistry of allenyl- and alkynylcyclopropanes is also briefly discussed. The Tsuji-Trost reaction (d) was recently comprehensively reviewed by Salau¨n35 and, therefore, is not covered herein.



Scheme 3

Scheme 4

1.4. Cyclopropanes A few classes of transition metal-catalyzed reactions involving cyclopropane-containing substrates, in which the cyclopropyl group demonstrated a unique reactivity pattern, are summarized in this section (Scheme 4). These include cross-coupling reactions (a, b), C-H activation (c), rearrangements of acylcyclopropanes into dihydrofurans (d), and cycloaddition reactions (e). Cross-coupling reactions represent the most developed area, with the main contributors in this field being Deng,36 Charette,37 Pietruszka,38 and others. A large body of literature on transition metal-catalyzed transformations of cyclopropanes, in which the cyclopropyl group does not undergo any chemical transformation and simply serves as an alkyl substituent, is not discussed here.

2. Reactions of Cyclopropenes 2.1. Addition Reactions 2.1.1. Carbometalation Reactions In contrast to moderately selective and rather substratespecific noncatalytic additions of various entities to cyclopropenes,39 analogous transition metal-catalyzed transformations appeared to be significantly more general with regard to both cyclopropene substrates and addition reagents. Employment of catalysts also allowed for controlling and fine-tuning of the diastereo- and enantioselectivity of the reactions and for significant improvement of the yields. Thus, Nakamura first demonstrated that the use of an iron catalyst facilitated carbomagnesation of cyclopropenone acetals and enabled addition of a wide range of Grignard reagents, including aryl- and alkenylmagnesium halides, which did not react in the absence of catalyst (Scheme 5).40

Scheme 5

Scheme 6

Nakamura has also shown catalytic asymmetric carbozincation of cyclopropenone acetals in the presence of an iron catalyst and chiral phosphine ligands (Scheme 6).40 Interestingly, addition of TMEDA was necessary for achieving high enantioselectivities, as, in the absence of this additive, racemic products were obtained. Later, Fox developed directed carbomagnesation of cyclopropenylcarbinol MOM ethers 1 in the presence of Cu catalyst (Scheme 7).41 Alkyl and vinyl Grignard reagents worked well in this reaction, generally providing very good syn-selectivity. Trapping the cyclopropylmagnesium intermediate with different electrophiles allowed for easy installation of various functional groups in the three-membered ring. Remarkably, unprotected cyclopropenylcarbinols 2 appeared to be much more reactive than ethers, affording tetra- and pentasubstituted cyclopropanes 3 in good yields and with improved syn-selectivity, and allowing for efficient

3122 Chemical Reviews, 2007, Vol. 107, No. 7 Scheme 7

Scheme 8

Rubin et al. Scheme 10

Scheme 11

Scheme 12

Scheme 9 Scheme 13

carbometalation even with benzyl- and alkynylmagnesium halides (Scheme 8).41 Very recently, Fox reported a significant extension of this methodology, in which the highly diastereo- and enantioselective carbomagnesation of cyclopropenylcarbinols was achieved in the presence of N-methylprolinol as a chiral additive (Scheme 9).42 Serendipitously, it was discovered that reproducibly high enantioselectivities can only be achieved when methoxide ions are present in the reaction mixture. Grignard reagents other than MeMgCl also provided excellent diastereoselectivity; however, they allowed for moderate enantioselectivity only. It was also noted that Cu catalyst is not required for carbomagnesation of 1,2-unsubstituted cyclopropenylcarbinols 4, as the latter are more reactive than the corresponding 1-alkyl-substituted substrates (Scheme 9).42 This highly stereoselective transformation permits rapid access to nonracemic tri- and tetrasubstituted hydroxymethylcyclopropanes 5 with relative stereochemistry complementary to that normally obtained in the enantioselective cyclopropanation reaction.43

2.1.2. Hydrometalation Reactions Gevorgyan reported highly efficient palladium-catalyzed hydrostannation of cyclopropenes to produce tri-, tetra-, and pentasubstituted cyclopropylstannanes in very good yields (Scheme 10).44 In contrast to the radical-initiated transselective hydrostannation,45 this reaction proceeded highly cis-selectively and with excellent facial selectivity controlled

by steric factors. In all cases, single diastereomers of cyclopropylstannanes 6 were obtained, except for cyclopropenes bearing alkoxymethyl substituents, which exhibited a notable directing effect, affording cis-cyclopropylstannanes 6a,b as major products (Scheme 10).44 Later, this approach was used by Corey for the synthesis of optically active cyclopropylstannane 8 from enantiomerically enriched 1,3disubstituted cyclopropene 7 (Scheme 11).8 Gevorgyan also disclosed catalytic asymmetric hydrostannation of 3,3-disubstituted cyclopropenes 9 in the presence of the Rh(I) complex bearing a chiral diamide-based phosphine ligand 10 (Scheme 12).46 Good yields, high degrees of diastereo- and enantioselectivity, and excellent functional group compatibility are the clear advantages of this approach. Besides its great practical value as a direct route to synthetically useful cyclopropyltin building blocks,47 this reaction is also conceptually important, as it represents the first example of transition metal-catalyzed asymmetric hydrostannation of a carbon-carbon double bond.46 It was also found that hydrosilylation of cyclopropene 11 with trichlorosilane proceeds smoothly from the less hindered face in the presence of [(π-allyl)PdCl]2 and a bulky electronrich ligand, tris(2,6-dimethoxyphenyl)phosphine (TDMPP). Exhaustive alkylation of 12 with MeLi afforded corresponding cyclopropyltrimethylsilane 13 in good overall yield (Scheme 13).57 Efficient hydrosilylation and hydrogermylation with triorganylmetal hydrides proceed in the presence

Transition Metal Chemistry of Cyclopropenes Scheme 14

Chemical Reviews, 2007, Vol. 107, No. 7 3123 Scheme 17

Scheme 18 Scheme 15

Scheme 19

of catalytic amounts of PtCl2, affording cyclopropylsilanes 14 and cyclopropylgermanes 15 in good to excellent yields. Steric factors efficiently govern the facial selectivity of this reaction (Scheme 14).48 It was further shown by Gevorgyan that the rhodiumcatalyzed asymmetric hydroboration of 3,3-disubstituted cyclopropenes 9 affords cis-cyclopropylboronates 16 with virtually perfect diastereoselectivity and very high enantioselectivity (Scheme 15).49 In contrast to the sterically controlled hydrostannation reactions, the enantio- and diastereoselectivities of the hydroboration were controlled by the directing effect of an ester or alkoxymethyl substituent.

2.1.3. Dimetalation Reactions Gevorgyan demonstrated a highly diastereoselective Pdcatalyzed silastannation and distannation of cyclopropenes (Scheme 16).44 It was found that employment of tert-isooctyl isocyanide50,51 in combination with palladium acetate effected facile addition of the bimetallic species to 3,3-disubstituted cyclopropenes,44 whereas the use of arylisocyanide ligand allowed for smooth dimetalation of 1,3-disubstituted and 1,3,3-trisubstituted cyclopropanes.48 Analogously to the Pdcatalyzed hydrostannation reaction (Scheme 10), the facial selectivity of the dimetalation was entirely controlled by steric factors (Scheme 16).44 Remarkably, silastannation of cyclopropenes substituted at C-1 proceeded highly regioselectively with the stannyl moiety adding to the most hindered position. Scheme 16

Pd catalyst. Thus, Chisholm demonstrated that 3,3-disubstituted cyclopropenes react with aliphatic acetylenes to give alkynylcyclopropanes (Scheme 18).56 These mild and neutral conditions permitted employment of functional groups such as aldehydes, carboxylic acids, and alcohols, which are incompatible with basic organometallic reagents. However, in the reaction with unsymmetrical cyclopropenes, only moderate facial selectivity was achieved (Scheme 18).56 It was also shown that activated tetrasubstituted cyclopropene 20, possessing an ester functionality at C-1, undergoes regioselective syn-addition of aryl alkynes to form pentasubstituted cyclopropane 21 (Scheme 19).57 Yamamoto investigated the palladium-catalyzed addition of carbon- and nitrogen-based pronucleophiles to 3,3dihexylcyclopropene. The reaction occurred at elevated temperatures and was accompanied by ring opening, leading to olefin 25 (Scheme 20).58 The proposed mechanistic rationale involved oxidative addition of Pd(0) species into the proximal C-C bond of cyclopropene to give palladacyclobutene intermediate 22. The latter, after pallada-ene reaction with a pronucleophile, afforded π-allylpalladium species 24 (Scheme 20). An alternative suggested pathway involved hydropalladation of the strained cyclopropene double bond, followed by thermally induced isomerization of σ-cyclopropylpalladium species 23 into the π-allylpalladium complex 24. Reductive elimination from the latter produced allylic products 25 in moderate to good yields (Scheme 20).58

2.1.5. Hydrogenation Reactions 2.1.4. Addition of Carbon- and Nitrogen-Based Pronucleophiles Similarly to alkynes52,53 and allenes,54,55 which undergo reductive cross-coupling with terminal alkynes to produce conjugated enynes 17, 18, and 19 (Scheme 17), cyclopropenes can undergo addition of acetylenes in the presence of

Cyclopropenes undergo facile hydrogenation in the presence of heterogeneous Pd catalysts. Employment of a Pd/ CaCO3 catalyst combination proved very efficient,59 whereas use of Pd on carbon60,61 was shown to trigger rapid ring opening of the resulting cyclopropane. Addition of dihydrogen to the double bond of cyclopropene occurs from the less hindered face; therefore, high facial selectivity can be achieved for substrates with a substantially different steric


Rubin et al.

Scheme 20

Scheme 21

2.1.6. Hydroformylation Reactions

Scheme 22

Stoichiometric hydroformylation of cyclopropenes by HMn(CO)5 or HCo(CO)5 to produce cyclopropylcarboxaldehyde 29 was shown by Orchin (Scheme 23).63,64 Initially obtained low yields of 29 (37-39%) were significantly improved by carrying out the reaction in detergent medium, which suppressed overreduction.65 Orchin proposed a radical pathway for this transformation to account for the formation of the reduced side product 30. Later, Noyori investigated analogous hydroformylation in supercritical CO266 and suggested that a nonradical pathway is the more likely mechanism for this reaction.

2.1.7. Pauson−Khand Reaction

Scheme 23

environment of the faces. Thus, highly diastereoselective Pd/ CaCO3-catalyzed hydrogenation of optically active cyclopropene 26 was achieved by Corey en route to (9R,10S)dihydrosterculic acid (27) (Scheme 21).8 A single example of the highly efficient catalytic enantioselective hydrogenation of prochiral cyclopropene was shown by Kawamura.62 This transformation was catalyzed by a Rh(I) complex bearing a ruthenocene-based chiral diphosphine ligand 28 and was limited to tetrasubstituted cyclopropenes bearing a carboxylic group at the double bond (Scheme 22). Scheme 24

The first attempts to engage cyclopropenes in the PausonKhand reaction (PKR) were made by Nefedov and Smit (Scheme 24).67 It was found that treatment of trisubstituted cyclopropene 31 with dicobalthexacarbonyl complex 32 in hexane resulted in homocyclocarbonylation of two cyclopropenes to give cyclopentanone 34 as a major product. However, desired cyclopentenone 33 was obtained in good yield upon heating the reactants on dry silica gel. Small amounts of phenol 35, a product of ring expansion of 33, were produced under either conditions.67 Employment of 3,3dimethylcyclopropene 36 in this reaction predominantly led to tricyclic homocyclocarbonylation product 37 due to the extremely high reactivity of 1,2-unsubstituted cyclopropenes. Later, Witulski demonstrated that, in contrast to other olefins, which required ambient or elevated temperatures, 3,3-diethylcyclopropene (38) underwent the PKR with Nalkynylamide in the presence of N-oxide at temperatures as low as -30 °C, providing, however, only a moderate yield of the cycloaddition product 39 (Scheme 25).68


Scheme 26


cally enriched substrates (Scheme 28).71 The reaction proceeded readily in the presence of sulfide and N-oxide promoters in a highly diastereoselective manner, to give a single isomer of cyclopentenone 44. 1,3-Disubstituted cyclopropene (R1 ) H, R2 ) n-hexyl) appeared to be much less efficient, providing a poor yield of the corresponding cyclopentenone (22%). Remarkably, in contrast to the endoselectivity reported by Nefedov,67 formation of exo-adducts was observed in this case, as unambiguously confirmed by X-ray studies.71

2.1.8. Dipolar [2 + 3] Cycloaddition

Scheme 27

Scheme 28

Cyclopropenes are very efficient dipolarophiles and are well-known for their ability to readily undergo [2 + 3] cycloadditions with various dipolar entities.39 These reactions usually proceed at ambient temperature or upon thermal activation and do not require a transition metal catalyst. Recently, Molchanov demonstrated that cyclopropenes 9 and 47 undergo cycloaddition reaction with carbonyl ylides 46, generated in situ from diazocompounds 45 in the presence of Rh2(OAc)4 (Scheme 29).72 The reaction proceeds stereoselectively to give adducts 48 and 49 with exo-configuration, which was rationalized in terms of steric factors. It was also found that the electronic properties of the substituent at C-3 play an important role in controlling the reactivity of cyclopropenes toward cycloaddition. Thus, while cyclopropenes possessing an H, Alk, or Ar substituent at C-3 generally reacted readily, providing good yields of adducts 48 and 49, cycloaddition of the substrates bearing electronwithdrawing groups, such as CO2Me or CN, was much less efficient (Scheme 29).

2.2. Formal Substitution Reactions It was also shown by Pericas and Riera that the chemoselectivity of the PKR of cyclopropene depends on the size of the substituent at the acetylene (Scheme 26).69 Thus, employment of bulky tert-butyl- or triphenylsilylalkynes suppressed insertion of a second molecule of cyclopropene, providing cycloaddition product 40 exclusively in a very high yield, whereas phenylacetylene and 1-octyne afforded mixtures of bi- and tricyclic ketones 40 and 41. de Meijere also demonstrated an example of the intramolecular Pauson-Khand reaction of alkyne-tethered cyclopropene 42, producing tricyclic enone 43, albeit in low yield (Scheme 27).70 Recently, Fox reported an efficient protocol for the PKR of 1,2,3-trisubstituted cyclopropenes, including enantiomeriScheme 29

2.2.1. Cyclopropenyl Moiety as the Nucleophilic Component in Cross-Coupling Reactions Treatment of cyclopropenyl halides with zinc powder or direct lithiation of the cyclopropene double bond followed by transmetalation with zinc chloride affords cyclopropenylzinc reagents, which undergo facile cross-coupling in the presence of Pd or Cu catalysts (Scheme 30). Thus, Nakamura demonstrated that the Negishi cross-coupling reaction of vinyl and aryl iodides with cyclopropenylzinc species 50, derived from cyclopropenonacetal, produced, after hydrolysis, the corresponding cyclopropenones 51 in very high yields (Scheme 31).73,74 Likewise, tetrasubstituted cyclopropenes 53 could be obtained via efficient Negishi cross-coupling of cyclopropenylzinc reagent 52, as shown


Scheme 31

Rubin et al.

transmetalation and electrophile trapping, to give functionalized tri- and tetrasubstituted cyclopropenes in good yields. Furthermore, cyclopropenylcarboxylic acid 56, bearing a terminal alkynyl group, underwent lithiation/transmetalation and subsequent cross-coupling at both sp2- and sp-carbon sites, to produce bis-arylated product 57 (Scheme 33).76 While the Negishi coupling protocol proved very efficient for functionalization of the cyclopropene double bond, the Stille cross-coupling reaction of bis-stannylcyclopropenes 58 provided good yields with select electrophiles only (Scheme 34).77 A twofold cross-coupling of phenyl iodide with distannane 59 afforded diphenylcyclopropene 60 in moderate yield (Scheme 34). Scheme 34

2.2.2. Cyclopropenyl Moiety as the Electrophilic Component in Cross-Coupling Reactions Scheme 32

by de Meijere. Choi has also found that 2-chloro-3,3difluorocyclopropenylzinc iodide (54) efficiently undergoes cross-coupling with acyl and alkyl halides in the presence of Cu catalyst (Scheme 31).75 The latter method, however, suffers from poor availability of parent cyclopropenyliodides. This very efficient metalation approach, though, is not applicable to cyclopropenes possessing an ester functionality due to rapid ring opening of such substrates in the presence of a strong base (Scheme 32).76 A viable alternative to the base-sensitive alkoxycarbonylcyclopropenes was suggested by Fox, who demonstrated that carboxylic acid derivatives can be used instead of esters in a one-pot deprotonation/transmetalation/cross-coupling reaction (Scheme 33).76 It was shown that bis-anion 55 has increased stability toward ring opening, allowing for efficient Scheme 33

In addition to serving as good precursors for nucleophilic cyclopropenylzinc reagent 54 in the Negishi cross-coupling reaction (Scheme 31), 3,3-difluorocyclopropenyliodides 61 also proved very efficient as electrophilic counterparts in the Heck cross-coupling reaction with activated olefins.78 The otherwise unstable 1-iodocyclopropenes79 were sufficiently stabilized in this case by two fluoro substituents, allowing for good yields of vinylcyclopropenes 62, most of which were obtained as single E-stereoisomers (Scheme 35).78 Furthermore, treatment of 61 with methyl fluorosulfonyldifluoroacetate in the presence of copper catalyst produced trifluoromethylated cyclopropenes 63 in good yields (Scheme 35).78 Recently, a new application of cyclopropenyl iodides as electrophilic components in Sonogashira cross-coupling was reported by Chen.80 Although this reaction did not proceed under standard conditions for Sonogashira reaction, its modification employing stoichiometric silver carbonate proved successful, providing the corresponding 1-alkynylcyclopropenes 64 in fair to good yields (Scheme 36).80



2.2.3. Heck-Type Arylation An efficient method for the direct Heck-type arylation of cyclopropenes proceeding with preservation of the threemembered ring was recently reported by Gevorgyan (Scheme 37).81 Very mild conditions of this reaction allow for easy installation of aryl and hetaryl substituents in ester-containing cyclopropenes, which are incompatible with other protocols involving deprotonation by strong bases (Vide supra). Application of this methodology to nonracemic substrates provided direct access to optically active tetrasubstituted cyclopropenes 65,81 unavailable via asymmetric cyclopropenation methods (Scheme 37).6,7 Mechanistic studies strongly supported an electrophilic pathway as the most probable route for this transformation (Scheme 38).81

Scheme 36

2.2.4. Tsuji−Trost Reaction

Scheme 37

A single example of the palladium-catalyzed allylic alkylation reaction involving cyclopropenes was demonstrated by de Meijere (Scheme 39).70 It was found that π-allylpalladium intermediate 68 generated from various primary and secondary cyclopropenylmethyl esters 66 in the presence of different palladium catalysts underwent selective alkylation at the R-position to produce cyclopropenylmethyl derivatives 67. No allylic transposition or ring-opened products were detected in all these reactions. In contrast, the tertiary cyclopropenylisopropyl acetate 69 produced a mixture of regioisomeric products 70 and 71 (Scheme 40).70

2.3. Isomerization and Cycloisomerization Reactions 2.3.1. Carbonylative Cycloisomerizations of Vinylcyclopropenes The ability of vinyl- and arylcyclopropenes to efficiently produce metallacyclobutene species (section 2.5.4) has been studied by several research groups in conjunction with the Scheme 38

Scheme 39

Scheme 40


Rubin et al.

Scheme 41

Scheme 42

Do¨tz benzannulation reaction.82 It was proposed that arylcyclopropene 73, in combination with metal carbonyl complexes of Cr, Mo, and W, can serve as a convenient alternative for the traditional Do¨tz approach utilizing stoichiometric Fisher carbene complexes 72 and alkyne reactants, thereby opening the possibility for the development of a truly catalytic process (Scheme 41).83 Indeed, initial experiments by Semmelhack and coworkers83 demonstrated that arylcyclopropenes undergo smooth carbonylative cycloisomerization into naphthols in the presence of substoichiometric and even catalytic amounts of Cr and Mo carbonyl complexes (Scheme 42). In some cases, however, the reaction was complicated by the formation of indene side products. Interestingly, the regioselectivity with respect to the relative orientation of R1 and R2 groups in the reaction with arylcyclopropenes was opposite to that observed in the corresponding reaction between the Fisher carbene complex and alkyne. Thus, while naphthol 76 was obtained as a major product in the latter case, the regioisomeric 75 formed predominantly or exclusively upon cycloisomerization of 74.83 Likewise, it was shown that vinylcyclopropenes undergo Do¨tz benzannulation in the presence of Mo(CO)683 and [RhCl(CO)2]284 to produce phenols; however, in both cases, the chemoselectivity of this reaction suffered from the formation of cyclopentadiene side products. Rhodium complex [RhCl(CO)2]2 was also used in the cycloisomerization of cyclopropenyl ketones and esters into pyrones and furans by Liebeskind.84 Generally, the reaction with cyclopropenylcarboxylates afforded pyrone products only, with regioselectivity controlled by the size of the R2 and R3 groups and favoring the formation of pyrones with a smaller substituent in the R-position to the carbonyl group. Cyclopropenylketones displayed a strong tendency toward formation of furans, which, however, could be suppressed by increasing CO pressure. To account for the formation of different chemo- and regioisomers, Liebeskind proposed the following mechanistic rationale (Scheme 43).84 Initially, electrophilic attack of a precoordinated Rh(CO)2Cl complex on the double bond of cyclopropene 77 affords the best stabilized tertiary cyclopropyl cation 78. Subsequent ring expansion provides metallocyclobutene 79, which exists in equilibrium with its regioisomer 80, occurring via a cycloreversion-cycloaddition pathway. This equilibrium is sig-

Scheme 43

nificantly shifted to the left when R3 ) H, since the 1,3disubstituted metallocyclobutene species is more stable than its 1,2-disubstituted analogue. Both 79 and 80 either rapidly cycloisomerize into furans 81 and 82 or undergo CO insertion, ultimately producing the corresponding pyrone products 83 and 84, respectively (Scheme 43).84

2.3.2. Cycloisomerization of 3-Acyl- and 3-Alkoxycarbonylcyclopropenes into Furans The first example of transition metal-catalyzed cycloisomerization of cyclopropene into furan was reported by Nefedov.85 He investigated the possibility of generating a vinylcarbenoid species by the ring opening of 2-alkylcyclopropenecarboxylates 85 in the presence of CuCl. The generated carbenoid was trapped by norbornadiene (nbd) to produce vinylcyclopropane adduct 86 in good yield. Attempts to trap the reactive species with other alkenes failed, leading instead to the formation of 2-alkoxyfurans 87 (Scheme 44). Based on these results, it was proposed that the rearrangement of cyclopropenes into furans occurs via a carbenoid intermediate. Later, Davies observed partial or complete rearrangement of cyclopropenes into furans during the Rh(II)-catalyzed cyclopropenation of terminal alkynes with carbenoids derived Scheme 44


from diazoesters and diazoketones (Scheme 45).86 It was found that prolonged exposure of cyclopropene 88 to Rh(II) acetate caused sluggish cycloisomerization of the cyclopropenation product into 2,3,5-trisubstituted furan 90. Interestingly, the ring cleavage in this case took place at the most substituted single bond of the cyclopropene, in contrast to Nefedov’s reaction, in which scission occurred at the least substituted single bond (Scheme 44). The mechanistic rationale provided by Davies involved heterolytic bond cleavage to give zwitterionic intermediate 89, in which the vinylic cation is stabilized by an adjacent phenyl group. Although this reaction proceeded much more slowly in the absence of rhodium, the exact role of the metal in the ring cleavage remained unclear. It was also shown that addition of copper triflate or tetrafluoroborate triggered very quick isomerization of cyclopropene 88 into the same furan 90, which, once formed, rapidly decomposed under these reaction conditions (Scheme 45).86 A few other groups also documented formation of furans as side products in the cyclopropenation reactions catalyzed by Rh(II) carboxylate complexes.87,88 Evidence for the carbenoid nature of the cyclopropene to furan rearrangement was also obtained by Mu¨ller and Doyle, who found that cycloisomerization of cyclopropenylcarboxylate 91 catalyzed by Rh2pfb4 produced cyclopentylideneacetate 93 as a major Scheme 46

Scheme 47


product along with traces of furan 95.87,89 It was proposed that the two different products arise from the two stereoisomeric rhodium vinylcarbene species E-92 and Z-92, formed upon the ring opening of cyclopropene 91. The E-isomer, with the ester group oriented away from the rhodium center, is unable to cycloisomerize into furan; however, it can undergo C-H insertion at the tethered methoxyalkyl group to produce cyclopentylidene 93. The minor Z-isomer, despite having the same possibility for C-H insertion, rather undergoes rapid electrocyclic cyclization into 94, which after reductive elimination of Rh provides furan 95 (Scheme 46).89 Further evidence in support of the vinylcarbenoid mechanism of the transition metal-catalyzed acylcyclopropeneto-furan rearrangement was obtained by Padwa.88 It was reported that furan 98, generated from cyclopropene 96 and Rh(II) acetate, rapidly underwent a second intermolecular [2 + 1] cycloaddition with vinylcarbenoid 97 to produce unstable oxabicyclohexene 99, which after facile Cope rearrangement afforded oxabicyclic compound 100 as a major product (Scheme 47).88 It was eventually discovered that carrying out the reaction between an alkyne and a diazocarbonyl compound in the presence of Rh or Cu catalyst at elevated temperatures allows for direct access to furans in a single step without isolation or even observation of cyclopropene intermediates.90 This method quickly became very popular as a convenient and general approach to diversely substituted furans,91 and it has often been referred to as Rh-catalyzed [2 + 3] dipolar cycloaddition. Alternative points of view on the mechanism of this transformation have been disclosed. Thus, Hoye suggested that formation of the furan may proceed via an independent route, which does not involve the cyclopropanation step.92 Specifically, it was proposed that cyclization of Rh(II)-carbenoid 101 into furan 107 can occur via rhodacyclobutene 102, which is more likely to be directly produced from the zwitterionic intermediate 104, rather than


Rubin et al.

Scheme 48

Scheme 49

Scheme 50

via the oxidative addition of Rh into the C-C bond of the highly strained and unstable bicyclic cyclopropene species 103. Rhodacyclobutene 102 via σ-bond metathesis affords vinylcarbenoid 105, which, upon electrocyclic cyclization into 106 and reductive elimination, provides furan 107 (Scheme 48).92 Experimental data obtained by Padwa supported the viability of the strained bicyclic cyclopropene intermediate of type 103 (Scheme 48) and suggested that the vinylcarbenoid species (105) is indeed being produced upon the ring opening of the former.93 By taking advantage of the facile addition of alcohols across the cyclopropene double bond, he succeeded trapping the strained cyclic species 109 obtained under conditions typical for intramolecular cycloisomerization of diazocarbonyl compounds into furans (Scheme 49). The only product isolated in high yield corresponded to structure 110. No signs of product 112 arising from the insertion of vinylcarbene 111 into the neighboring OH group were detected, which would be

unavoidable if the direct transformation of 108 to 111 took place.93 The viability of the spirocyclopropene intermediate 114 in the cycloaddition of dione 113 to phenylacetylene, catalyzed by various chiral Rh(II) complexes, was discussed by Mu¨ller (Scheme 50).94 He rationalized that the observed lack of enantioinduction might be taken as evidence of the intermediacy of 114. Indeed, since both possible isomers of 114 are meso-compounds, thermal rearrangement of the latter into furan 116 should produce a racemate, while the route via direct formation of Rh(II)-carbenoid 115 should provide enantiomerically enriched furan 116. On the other hand, it was previously demonstrated that the rearrangement of achiral cyclopropenecarboxylates in the presence of optically active Rh(II) complexes may also proceed enantioselectively.95 Therefore, the absence of enantiomeric induction in the described example (Scheme 50) cannot be taken as unambiguous evidence for the involvement of cyclopropene intermediate 114 and could be simply a result



Scheme 51

Scheme 52

Scheme 53

of inefficacy of the chiral catalyst in this particular transformation.94 The analogous transformation of unsymmetrical diazodiones appeared to be unselective, providing mixtures of two regiosiomeric furans.96,97 This reaction was employed in the expeditious synthesis of isodictamnine from diazoquinolinedione 117 by Pirrung (Scheme 51).97 The Rh(II)-catalyzed carbenoid transfer/cycloisomerization/intramolecular Diels-Alder cycloaddition cascade was employed by Padwa in the stereoselective synthesis of complex polycyclic scaffolds (Scheme 52).98,99 Thus, intramolecular cycloaddition of the Rh-carbenoid generated from diazocompound 118 via cyclopropene intermediate 119 produced bicyclic furan 120. The latter underwent intramolecular [4 + 2] cycloaddition with the tethered dienophile affording polycyclic ketal 121, which, in turn, rearranged into the more stable tautomer 122, possessing all the

necessary connectivity and relative stereochemistry of strychnine.99 It was also shown by Padwa that Rh(I) complexes are capable of catalyzing the ring expansion of 3-acylcyclopropenes to furans, however, with complementary regioselectivity, providing 2,5-disubsituted furans 125 instead of 2,4disubsituted products, which are normally observed in the Rh(II)-catalyzed reactions operating via carbenoid intermediates (Scheme 47).88 It was proposed that this transformation can proceed via the metallocyclobutene species 124, which can potentially be directly produced from the oxidative addition of rhodium into the C1-C3 bond of cyclopropene 123 (Scheme 53).88 Alternatively, 124 can arise from the cycloreversion-cycloaddition pathway similar to that previously proposed by Liebeskind for the carbonylative cycloisomerization of cyclopropenyl ketones and esters into


Rubin et al.

Scheme 54

Scheme 55

pyrones (section 2.3.1).84 However, in contrast to Liebeskind’s transformation, which was carried out under CO pressure and produced mixtures of regioisomeric furans as side products, Padwa’s reaction afforded 2,5-disubstituted furans exclusively. An alternative point of view on the mechanism of acylcyclopropene ring expansion was recently disclosed by Ma.100 He has demonstrated that the regioselectivity of this cycloisomerization can be effectively controlled through the employment of different transition metal catalysts. Thus, reaction of cyclopropene 126 in the presence of CuI produced 2,3,4-trisubstituted furan 134, while the PdCl2-catalyzed transformation afforded 2,3,5-trisubstituted furan 130. The dramatic difference in the reactivity was explained in terms of the opposite regioselectivity of halometalation in the two different catalytic cycles (Scheme 54).100 Accordingly, in the PdCl2-catalyzed process (cycle A), chloropalladation of 126 produces σ-cyclopropylpalladium species 127, in which the Pd atom resides at the least substituted carbon atom. Subsequent β-carbon elimination affords palladium enolate 128, which in turn undergoes endo-oxapalladation, providing dihydrofuran species 129. β-Dechloropalladation from the latter produces furan 130 (Scheme 54).100 In the coppercatalyzed reaction (cycle B), iodocupration proceeds with the opposite regiochemistry, providing cyclopropyl cuprate 131, with the metal attached to the most substituted carbon atom. The final steps are analogous to those shown in cycle A, involving formation of copper enolate 132 followed by the ring closure to give the dihydrofuryl copper species 133, which ultimately produces regioisomeric furan 134 (Scheme 54).100 While the reasons for the proposed reversal of the halometalation regiochemistry are unclear, this mechanistic

rationale is intriguing. Besides, the synthetic usefulness of this cycloisomerization methodology is undoubtful, as it offers the possibility to efficiently control the regiochemistry of the product.

2.3.3. Cycloisomerization of Cyclopropenyl Imines into Pyrroloheterocycles Recently Gevorgyan developed a novel iminocyclopropene to pyrrole rearrangement, which represents an aza-analogue of acylcyclopropene to furan cycloisomerization reaction, described in section 2.3.2.101 It was found that catalytic amounts of Rh(I) efficiently produced 1,3,5-trisubstituted indolizines 136, presumably via the rhodium vinylcarbenoid species 135 (Scheme 55). Remarkably, complementary regiochemistry of the cyclopropene ring cleavage was observed when the reaction was carried out in the presence of Cu(I) catalysts. In this case, 2,3,5-trisubstituted indolizines 137 were obtained in excellent yields (Scheme 55).101 Extension of this cycloisomerization methodology to other heterocyclic systems proved successful: under the same reaction conditions, oxazolylcyclopropene 138 was smoothly converted into pyrrolooxazole 139 (Scheme 56).101 Scheme 56


Scheme 58

Scheme 59

2.4. Metathesis Reactions Due to significant exothermicity accompanying cleavage of strained rings, ring-opening metathesis (ROM) of cyclopropenes may appear as a very facile and readily occurring transformation. However, as with any reaction sensitive to steric factors, the success of ROM involving cyclopropenes is highly dependent on the substitution pattern of the substrate, and ROM can be significantly suppressed by the presence of very large substituents at C-3.102 A few known successful examples of metathesis reactions involving cyclopropenes are described below. It is believed, however, that the full potential of this powerful transformation of cyclopropenes is yet to be discovered.

2.4.1. Ring-Opening Metathesis Polymerization A single example of living ring-opening metathesis polymerization (ROMP) of cyclopropenes was recently reported by Schrock (Scheme 57).103 3,3-Disubstituted cyclopropenes 141 in the presence of Mo initiators 140 produced corresponding polymers in very high yields. Proton NMR spectra of 142 confirmed >99% trans double bonds in the products. Carbon NMR spectra suggested, however, that the polymers were not highly tactic. Several diblock and triblock copolymers consisting of cyclopropenes 141, dicarbomethoxynorbornadiene, and methyltetracyclododecene were also prepared and characterized.103

2.4.2. Ring-Opening Cross Metathesis of Cyclopropenone Acetals Efficient ring-opening cross metathesis of cyclopropenone acetal 143 with terminal alkenes and dienes in the presence Scheme 60


of the first-generation Grubbs catalyst was demonstrated by Parrain and Santelli (Scheme 58).104 The reaction appeared to be very sensitive to steric factors and proceeded selectively with a monosubstituted double bond, leaving a disubstituted olefin moiety intact. Furthermore, no products were observed in the reactions with sterically encumbered monosubstituted alkenes, such as vinyltrimethylsilane, 3,3-dimethylbutene, and methallyltrimethylsilane. Very high E-selectivity was obtained in the reactions with styrene and allylsilanes, whereas linear alkenes and dienes provided somewhat lower E/Z ratios. Interestingly, an attempt to engage 1,6-diene 144, bearing a primary alkene moiety with a substituted allylic position, in the cross metathesis with 143 afforded no desired triene; protected divinyl ketone 145 and the ring closing metathesis product 146 were formed instead (Scheme 59). The same primary alkene fragment in compound 148 was successfully involved in cross metathesis with cyclopropenone acetal 147 in the presence of the second-generation Grubbs catalyst (Scheme 60).105 After subsequent deprotection, divinyl ketone 149 was obtained in 63% yield as a 3:2 mixture of E- and Z-isomers. In the perspective of the total synthesis of bistramide A, in which this transformation was used as one of the key steps, this rather poor stereoselectivity was inconsequential, since the resulting olefin moiety was reduced later in the course of the synthesis.

2.5. Stoichiometric Reactions Leading to Isolable Organometallic Complexes The highly strained double bond of cyclopropene makes it an excellent ligand for various π-philic transition metals. Strong donation of electron density from the π-orbitals of cyclopropene to the hybrid spd-orbital of the transition metal, as well as significant d-π* back-donation, weakens the double bond of cyclopropene, releasing the strain and leading to thermodynamically favorable, yet reactive, metallabicyclobutane species. The organometallic chemistry of η2complexes of cyclopropenes is very rich, including transformations with ring expansion106 to produce alkylidene species, metallabenzenes, and cyclopentadienyl complexes, and reactions with preservation of the ring involving migratory insertion of cyclopropene into a metal-carbon bond, to afford various metallacyclic frameworks.

2.5.1. η2-Cyclopropenylmetal Complexes Generally, η2-complexes of cyclopropenes with transition metals are unstable and have been characterized only as reactive intermediates in oxidative dimerization and oligomerization reactions. However, employment of sterically hindered cyclopropenes allowed for isolable η2-complexes of Ni(0), which were characterized by NMR.107 Thus, Schindler demonstrated that reaction of cyclopropene 150 with [(bipy)Ni(COD)] afforded isolable η2-complex 151, the structure of which was confirmed by X-ray analysis (Scheme 61).108 Similarly, crystalline η2-cyclopropene complexes of


Rubin et al.

Scheme 61

Scheme 62

Scheme 63

Scheme 64

Ir (152),109 Pt (153, 154),110 and Mo (155)111 were prepared (Scheme 61). Butenschon reported preparation of an isolable η2-cyclopropene Co(I) complex 157 by reduction of Co(II) complex 156.112 Upon heating, the former produced η4-isoprene complex 160 (Scheme 62). It was proposed that at elevated temperatures complex 157 undergoes migratory insertion of cobalt into the C-C bond of cyclopropene to afford cobaltacyclobutene 158.113 Formation of metallacyclobutenes from cyclopropenes is typical for a number of transition metals; this transformation was proposed in many catalytic addition reactions with ring opening (see section 2.3). The reactivity of metallacyclobutenes strongly depends on their structures. Thus, complex 158, possessing six equivalent β-hydrogen atoms, readily undergoes β-hydride elimination to form Co(III) hydrido complex 159, which after reductive elimination produces 160 (Scheme 62). When β-hydride elimination is impossible, as in cobaltacyclobutene 161 obtained from 3,3-dimethoxycyclopropene, such complexes can be isolated (Scheme 63).113 However, hemiacetal 162, obtained by Lewis acid-catalyzed hydrolytic cleavage of 161, underwent β-hydride elimination from oxygen, producing η2acrylate complex 163.113

Scheme 65

2.5.2. Transformation of Cyclopropenes into Vinylcarbene Metal Complexes The lack of β-hydrogen atoms in a metallacyclobutene complex opens up the possibility for an entirely different

reactivity pattern. Thus, complex 164, prepared from 3,3diphenylcyclopropene, underwent σ-bond metathesis to afford Co(I) vinylcarbene complex 165 (Scheme 64).112 A similar transformation was described by Grubbs for η2cyclopropene complexes of tungsten 167 and 168 (Scheme 65). Obtained via ligand exchange with phosphite complexes 166, these yellow compounds were stable at room temperature but readily transformed into orange vinylcarbene complexes 169-171 at 80 °C (Scheme 65).114 Likewise, vinylcarbene complexes of Ti(II),115 Zr(II) (172),116 Re(V) (173),117 Ta (174),118 and Os (175)119 were prepared by transition metal-mediated ring opening of cyclopropenes


(Scheme 66). Grubbs showed that vinylcarbene complexes of Ru(II) (176),120,121 the generation I catalysts for olefin metathesis and ring-opening metathesis polymerization reactions, can be smoothly obtained from 3,3-diphenylcyclopropene and Ru(II) precursors.120

2.5.3. Rearrangement of Metallabenzvalenes into Metallabenzenes Another type of η2-cyclopropene complexes, metallabenzvalenes (178, 179) are rare examples of highly strained but isolable metallabicyclobutane species. These unusually stable compounds can be obtained via the reaction of cyclopropenylvinyllithium species 177 and Vaska’s type complexes of Ir(I) and Rh(I) (Scheme 67).122,123 Metallabenzvalenes represent valence isomers of metallabenzenes (180, 181) into which they rearrange in solution at elevated temperatures (Scheme 67). Reaction of Vaska’s complex with lithiated vinylcyclopropene 182, bearing two electronically different substituents (alkyl and aryl) at the strained double bond, afforded 2-aryl iridabenzene 183 predominantly, accompanied by small amounts of isomeric 3-aryl iridabenzene 187 (Scheme 68).124 The exact mechanism of this valence isomerization is still unclear. Concerted path A (Scheme 68) was supported by Scheme 67

Scheme 68


computational studies;124,125 however, it fails to explain preferential formation of 183. An alternative rationale presumes reversible reductive elimination/migratory insertion of η2-cyclopropene ligand to form σ-vinyl complex 184.126 Although never detected in the reaction with Ir(I), a related complex with Pt(II) was isolated and characterized by X-ray crystallography.127 From 184, one possibility (path B) entails regioselective insertion of iridium into the more polarized C-C σ-bond of cyclopropene to afford intermediate Dewar iridabenzene 185, which collapses to iridabenzene 183 via rapid valence isomerization (path B, Scheme 68).126-128 In the nonconcerted mechanism (path C), nucleophilic attack of the cyclopropene double bond at the electron-deficient Ir center of 184 to produce benzylic cyclopropyl cation 186 was proposed.124 Skeletal rearrangement of the latter, however, would lead to the minor isomer 187, which was observed in trace amounts (Scheme 68). Iridabenzenes 183 undergo facile rearrangement into iridacenes 189. The mechanism of this reaction, which proceeds slowly at 50-60 °C, involves migratory insertion of carbene into the Ir-C bond to form coordinatively unsaturated η1-cyclopentadienyl species 188, which after loss of PPh3 affords thermodynamically more stable η5-cyclopentadienyliridium complex 189 (Scheme 69).124,129 Similarly, metallabenzenes and metallacenes of Pt127,130 and Os131 were obtained by reaction of corresponding transition metal complexes with σ-vinyl-η2-cyclopropene ligands.

2.5.4. Reactions of Vinylcyclopropenes Of all the transition metal-mediated chemistry of cyclopropenes, reactions involving vinylcyclopropenes 190 are perhaps the most studied and, arguably, the most interesting transformations (Scheme 70).132 Migratory insertion of the metal into the σ-bond of precoordinated vinylcyclopropene (191) produces metallacyclobutene 192, which upon reversible β-carbon elimination leads to η2-alkyne vinylcarbene species 193. Metallacyclobutene 192 can also be represented as metallacyclopropane 194, which helps rationalize the diverse skeletal transformations of these compounds occurring upon reductive elimination of the metal, as shown in Scheme 70. Thus, elimination of bonds cd affords vinylcyclopropene complex 191, whereas elimination of bonds Scheme 70


Rubin et al.

Scheme 71

Scheme 72

ac produces metalla[3.1.0]bicyclohexene 195. Analogously, the reaction involving cleavage of bonds ad and bc gives η2-cyclopentadiene complex 197 and metallacyclohexadiene 196, respectively. Finally, elimination of bonds bd leads to metalla[2.2.0]bicyclohexene 198. All these routes were confirmed by reactions of 2H- and 13C-labeled vinylcyclopropenes with [Ir(PMe3)2(acac)].132,133 Metallacyclobutenes of type 192 and metallacyclohexadienes of type 196 were observed as intermediates in transition metal-promoted ring-opening reactions of vinylcyclopropenes into η5-cyclopentadienyl ligands. Thus, Donovan demonstrated that cyclopropene 199 reacted with [Rh(C2H4)2Cl]2 to produce rhodacyclobutene dimer 200,134 the indenyl derivative of which (201) underwent spontaneous ring closure to η4-cyclopentadiene complex 202.135 The latter, in turn, underwent facile oxidation into sterically encumbered rhodacenium species 203 (Scheme 71).136 Dimer 200, upon prolonged storage in a solution of CH2Cl2 at room temperature, underwent a similar ring closure to afford 204, which was isolated as η5-cyclopentadienyl derivative 205 (Scheme 71).137 In similar transformations reported by Rheingold and Hughes, vinylcyclopropene 206 reacted with Scheme 73

[Rh(PMe3)2Cl]2 to give rhodacyclobutene 207, which existed in rapid equilibrium with rhodacyclohexadiene 208, as determined by variable temperature NMR studies. It was proposed that, upon heating, 207 undergoes cyclization into η4-cyclopentadiene complex 209, which, after loss of one phosphine ligand, experienced endo-H migration to the metal to afford η5-cyclopentadienylrhodium hydride complex 210 (Scheme 72).138 A similar transformation into rhodium hydride complex 211 proceeded much more easily when [Rh(PPri3)2Cl]2 was employed; however, no intermediates were observed in this case (Scheme 72).138 Hughes proposed an alternative mechanistic route for the Rh-mediated ring expansion of vinylcyclopropenes into rhodacyclohexadienes. According to this rationale, initial electrophilic attack of Rh onto the vinyl double bond in 212 produces zwitterionic complex 213, bearing a cyclopropenylmethylcarbocation fragment. The latter undergoes Demjanov-type ring expansion to form cyclobutenyl cation 214 (Scheme 73). Most likely, nucleophilic attack of anionic Rh at the less sterically hindered site a produces rhoda[2.2.0]Scheme 74

bicyclohexene species 215, whereas less probable attack at the more hindered site b would give rise to isomeric complex 216. Both species 215 and 216, equivalents of 198 described above (Scheme 70), can experience isomerization into



Scheme 75

Scheme 76

rhodacyclohexadienes 217 and 218, respectively. Upon chloride abstraction, both isomers 217 and 218 would afford cationic η5-cyclopentadienyl complex 219.139 Analogous rearrangement of vinylcyclopropenes upon chloropalladation was also observed by Breslow, who isolated and characterized the resulting palladium complexes 220, bearing η3(chloromethyl)cyclobutenyl ligands (Scheme 74).140 In another related transformation, vinylcyclopropene 206 reacted with various cyclopentadienyl complexes of Ru(II) to afford ruthenocenes 221 (Scheme 75).141,142 It was demonstrated that this reaction proceeds via η2-cyclopentadiene intermediate of type 197142 rather than via a metallacyclohexadiene species of type 196 (Scheme 70). It was also shown that 206, upon treatment with Fe2(CO)9, underwent carbonylative ring expansion to produce η4-cyclohexadienone complex 222.142,143 Analogous catalytic transformations mechanistically related to the Do¨tz benzannulation reaction82 of vinylcyclopropenes in the presence of various metal carbonyl complexes leading to phenols are discussed in section 2.3.1.

2.5.5. Metallacyclization Reactions Cyclopropenes readily undergo [2π + 2π] cycloaddition reactions to afford trans-tricyclo[3.1.0.02,4]hexanes in the Scheme 77

presence of various transition metals, such as Ni,144 Pd,145,146 and Cu.147 The mechanism of this reaction involves consecutive formation of η2-cyclopropene complexes 224 and 225 through coordination of one and two cyclopropene ligands 223, respectively. Subsequent metallacyclization, analogous to the well-known metallacylization of alkynes to metallacyclopentadienes,148 gives tricyclic metallacyclopentane species 226 (Scheme 76). Ligand exchange, followed by reductive elimination, produces tricyclic dimer 227 and regenerates the catalytically active η2-cyclopropene species 224 (Scheme 76). Tricyclic species 226 with Pd,149 Ni,150 or Ti115 are reasonably stable and can be isolated. Thus, Hashmi reported reaction of cyclopropene 228 with palladium affording a mixture of enantiomeric trans-palladacycles 229 and 230. The latter, upon treatment with (+)-DIOP, were converted to separable diastereomeric complexes 231 and 232 (Scheme 77).151 An alternative approach to optically active palladacycles involved metallacyclization of cyclopropene 233 bearing two (S)-lactate auxiliaries. C2-symmetric compound 234 was obtained as a major product in a mixture with small amounts of other diastereomers (Scheme 78).152 Scheme 78

The tricylic complex of type 226 (Scheme 76), obtained from 1,2-unsubstituted cyclopropenes, is much more reactive and undergoes oligomerization with excess cyclopropene or other olefins present in the mixture to produce polycylic metallacycloheptane species 235 (Scheme 79). The latter can undergo reductive elimination to afford cyclohexane 236.153 Alternatively, a reaction run under CO pressure produces seven-membered cyclic ketones 237 (Scheme 79).154 Furthermore, two consecutive carbometalations via intermediate metallacyclononane species 238155 can lead to



Scheme 83

Scheme 80 Scheme 84

Scheme 81

Scheme 85

tetrameric eight-membered cycle 239 (Scheme 79).146,156 This transformation was reported by Risse, who showed that a (η3-allyl)Pd(Cp) complex reacts with 2 equiv of PhMe2P and excess cyclopropene 240 to produce nine-membered palladacycle 241, which is stable at low temperatures. Interestingly, upon warming above 0 °C, this compound undergoes spontaneous reductive elimination to afford syndiotactic cyclic tetramer 242.157 Alternatively, low-temperature reduction of 241 afforded syndiotactic linear tetramer 243 (Scheme 80).158 Pfeffer reported that cyclopropenes can undergo migratory insertion in C,N-cyclopalladated benzylamine derivative 244 (Scheme 81).159 It was shown that, depending on the cyclopropene structure, this reaction proceeds with or without ring opening, producing a π-allylpalladium species (245) or a cyclopropylpalladium complex (246), respectively.

Dihalocyclopropene 251 subjected to reaction with anionic η6-aryl chromium complex 252 produced chromium(0) cyclopropenylidene species 253, as demonstrated by Schubert (Scheme 83).161 Furthermore, tetrahalocyclopropene 254, when treated with excess K[CpFe(CO)2], afforded the product of triple substitution, cyclopropenylium salt 255 (Scheme 84).162 Analogously, exhaustive substitution of halogen atoms in the trichlorocyclopropenylium salt 256 by other anionic transition metal carbonyl species provided complex 257. Similarly to other cyclopropenylium salts, η1-cyclopropylium complexes of transition metals are susceptible to nucleophilic attack. Thus, Bartmann demonstrated that addition of various nucleophiles occurs selectively at the β-position of complex 258, due to the strong directing effect of the metal, affording σ-cyclopropenyl complexes 259a-c in good yields (Scheme 85).163

2.5.6. Miscellaneous Stoichiometric Reactions 3-Halocyclopropenes readily undergo allylic substitution when treated with anionic transition metal complexes. Thus, Berke reported reaction of cyclopropene 247 with Na[Re(CO)5], affording σ-cyclopropenyl complex 248 in good yield (Scheme 82).160 Upon irradiation, the latter was converted into η3-cyclopropenyl complex 249, which existed in equilibrium with rhenacyclobutadiene 250 (Scheme 82).160 3,3-

3. Reactions of Methylenecyclopropanes 3.1. Addition Reactions 3.1.1. Hydrometalation Reactions The general mechanism of the transition metal-catalyzed hydrosilylation of methylenecyclopropanes is summarized



Scheme 89

Scheme 87

Scheme 90

in Scheme 86. Oxidative addition of catalyst into the H-Si bond to give metal hydride species 260 is followed by hydrometalation of the double bond of MCP to form alkylmetal complex 261. Next, two alternative pathways, A and B, lead to the formation of a cyclopropylmethylsilane 262 or to a ring-opening product 263, respectively. Path A involves direct formation of a C-Si bond upon reductive elimination of metal, whereas path B presumes initial β-carbon elimination to produce homoallylmetal species 263, which, after reductive elimination, affords homoallylsilanes 264 (Scheme 86). Both paths A and B concurrently operate in platinum-catalyzed hydrosilylation, while Rh-catalyzed reactions proceed selectively via path B. Thus, treatment of unsubstituted MCP with excess methyldichlorosilane in the presence of H2PtCl6 catalyst afforded a mixture of (cyclopropylmethyl)silane 265 and 1,4-bis-silyl butane 266.164 While the former product is obtained via pathway A, the latter is produced via initial formation of 4-silyl-1-butene according to path B followed by a second hydrosilylation of the resulting olefin (Scheme 87). Platinum-catalyzed hydrosilylation of MCPs possessing substituents in the ring was shown to be very substrate selective.165 Thus, 2,2-diphenylsubstituted MCP 267 underwent this reaction with complete preservation of the threemembered ring (via pathway A), whereas employment of an alkyl analogue resulted in partial ring opening, affording mixtures of (cyclopropylmethyl)silanes 268 and isomeric olefins 269. Furthermore, hydrosilylation of monosubstituted MCPs provided ring-opened products exclusively. The latter are formed via pathway B with selective cleavage of a less substituted cyclopropyl bond (Scheme 88).165 On the other hand, Beletskaya demonstrated that Rh(I)catalyzed hydrosilylation of methylenecyclopropanes 270 always proceeds with cleavage of the cyclopropane ring, according to path B, to produce homoallyl silanes 271 as mixtures of E- and Z-isomers (Scheme 89).166 The cyclopropyl-substituted analogues 272 can undergo twofold and even threefold hydrosilylation with excess hydrosilane via the same pathway B, with consecutive opening of all cyclopropyl rings to give 273 and 274. Interestingly, hydrosilylation of dicyclopropyl-substituted MCP 272 in the presence of [RhCl(C4H6)]2 catalyst afforded MCP 274 as a

major product, formation of which cannot be explained by the above-mentioned mechanism and presumably proceeds via direct insertion of the metal into the proximal bond of the cyclopropyl substituent (Scheme 90).20,166 Similarly to the hydrosilylation reaction, Pd(PPh3)4catalyzed hydrostannation of MCPs proceeds with ring opening via path B (Scheme 86) to produce homoallystannane 275 (Scheme 91).167 The analogous reaction performed under heterogeneous conditions in the presence of Pd(OH)2/C afforded a mixture of homoallylstannane 275 and distannane 276, resulting from further hydrostannation of product 275. It was also shown that carrying out hydrostannation in the presence of excess HSnBu3 enables selective formation of 276 in good yields (Scheme 91).167

3.1.2. Dimetalation Reactions de Meijere demonstrated that palladium-catalyzed dimetalation of MCPs can proceed with or without ring opening. Thus, intermolecular disilylation of bicyclopropylidene 277 catalyzed by Pd(OAc)2 in the presence of tert-isooctylisocyanide ligand proceeded smoothly, affording the corresponding bicyclopropyl disilanes 278 in high yields (Scheme 92).51 However, the analogous reaction of 277 with 2 equiv of silastannane produced bicyclopropyldistannane 279 and hexamethyldisilane, presumably due to palladium-catalyzed disproportionation of silastannane (Scheme 93).51,168 Disilylation of 277 by FMe2SiSiMe2F occurs with ring cleavage via silapalladation/β-carbon elimination. The double bond in product 280 is much less strained than that in the parent bicyclopropylidene 277, and thus, it does not undergo


Rubin et al.

Scheme 91

Scheme 92

second-fold disilylation. Similarly, products of silaboration, silastannation, and silacyanation were obtained in moderate to good yields (Scheme 93).51 Furthermore, under the same conditions, both tethered disilane derivatives 281 and 283 underwent intramolecular disilylation on their bicyclopropylidene moieties to form silabicyclic products 282 and 284, respectively (Scheme 94).51 Suginome169 and de Meijere51 demonstrated that the key migratory insertion step in the transition metal-catalyzed silaboration reaction of MCPs is highly substrate dependent. Thus, bicyclopropylidene 277 afforded vinylsilane 285, Scheme 93

Scheme 94

resulting from migratory insertion into the Si-Pd bond, whereas benzylidenecyclopropane 286 produced vinylboronate 287, indicative of a borapalladation mechanism (Scheme 95). The selectivity of the β-carbon elimination step was also investigated (Scheme 96).169 It was found that both palladium- and platinum-catalyzed silaboration reactions of ester 288 afforded mixtures of stereoisomeric vinylboronates 290 with the Z-isomer being a major product. In contrast, silaboration of disubstituted MCP 291 appeared to be more sensitive to the catalyst’s nature, favoring formation of the E-vinylboronate 292 in the presence of palladium catalyst, and the Z-isomer 293 in the platinum-catalyzed reaction (Scheme 96).169 Remarkably, it was shown that silaboration of cycloalkylidenecyclopropanes can follow two distinct pathways by complementary use of palladium and platinum catalysts



Scheme 95

Scheme 96

Scheme 97

(Scheme 97).169 Thus, reaction of 294 with silaboronate 289 in the presence of a platinum complex provided vinylboronate 295 exclusively via cleavage of the proximal C-C bond, while the analogous palladium-catalyzed reaction afforded allylboronate 296 via insertion into the distal C-C bond (Scheme 97).169

3.1.3. Hydroamination and Hydroxylation Reactions Palladium-catalyzed intermolecular hydroamination of methylenecyclopropane was investigated by Yamamoto.170 It was shown that the reaction of MCP 297 with a variety of secondary amines produces allylamines 298 as a major Scheme 98

product (Scheme 98).170,171 However, when phthalimide was employed in this reaction, compound 299, with reverse regiochemistry of addition, was obtained as a sole product (Scheme 98).171 Likewise, lactams, oxazolidinones, and ureas 300 serve as good nitrogen pronucleophiles, affording Scheme 99


Rubin et al.

Scheme 100

Scheme 101

allylamines 301 in high yields (Scheme 99).172 Similar selectivity in the reactions of methylenecyclopropanes with sulfonamides was also observed by Shi.173 Intramolecular hydroamination of benzylidenecyclopropanes 302 possessing an ortho-amino group allowed for the efficient preparation of tetrahydroquinolines 303 (Scheme 99).172 The proposed mechanism for the palladium-catalyzed hydroamination of MCPs begins with oxidative addition of Pd(0) species to the N-H bond of the nitrogen pronucleophile to give Pd(II) hydride species 304. The latter undergoes hydropalladation across the CdC bond of MCP with regioselectivity opposite to that observed in the hydrometalation reaction (path B, Scheme 86) to afford cyclopropylpalladium complex 309 (Scheme 100, path A).170,171 Subsequent cleavage of the distal CsC bond produces π-allylpalladium species 310, which upon reductive eliminaScheme 102

tion affords allylamine 311 (Scheme 100). To account for the formation of the regioisomeric hydroamination product 308 obtained in the reaction with phthalimide, reversed regioselectivity of hydropalladation was proposed. The resulting cyclopropylmethyl palladium species 305 would provide, after β-carbon elimination, homoallylpalladium complex 306. Migration of palladium via reversible β-hydride elimination/hydropalladation would lead to a more stable π-allylpalladium species 307, which ultimately would provide allylamine 308 (Scheme 100, path B).170,171 Yamamoto also investigated addition of various alcohols to MCPs in the presence of catalytic amounts of palladium complexes.174 Different Pd(0) and Pd(II) complexes enabled transformation of 312 into a mixture of allylic ether 313 and butadiene 314. The best optimized conditions involving Pd(PPh3)4/o-Tol3P combination allowed for clean hydroxylation with only trace amounts of 314 detected (Scheme 101).174 The proposed mechanism for this transformation (Scheme 102, path A) is similar to the hydroamination mechanism described above (Scheme 100, path A). Concurrent formation of side products 314 was believed to proceed via deprotonation of species 315, leading to trimethylenemethane (TMM) complex 316. The latter, upon rearrangement into isomeric 317 followed by reprotonation, provides



Scheme 104 Scheme 107

Scheme 105

Scheme 108

π-allylpalladium species 318, which undergoes β-hydride elimination to afford butadiene 319 (Scheme 102, path B). Yamamoto further showed that hydration of MCPs catalyzed by copper(II) triflate also proceeds with ring cleavage, producing homoallyl alcohols 320 (Scheme 103).175 It was found that high yields can be achieved only in the presence of an optimal amount of water (2 equiv), as an excess deactivates the catalyst. Eisen demonstrated that, in contrast to late transition metals, titanium(IV)-catalyzed intermolecular hydroamination of methylenecyclopropanes produces regioisomeric imines in good to excellent yield (Scheme 104).176 It was proposed that this reaction is catalyzed by imidotitanium species 325 produced upon reaction of octahedral titanium complex 324 with a primary amine (Scheme 105). 1,2-Insertion of 325 into the double bond of MCP 321 affords azatitanacyclobutane complex 326, which can undergo skeletal rearrangement via two different pathways to produce five-membered cyclic complexes 327 and 329. Rearrangement involving cleavage of a more substituted proximal bond of cyclopropane (pathway A) in 326 would lead to intermediate 327, in which titanium is attached to a secondary benzylic carbon. Alternatively, path B presumes cleavage of a less substituted proximal bond and formation of intermediate 329, with titanium attached to a primary carbon. Protolytic cleavage of the Ti-C bond in complexes 327 and 329 with another molecule of amine leads to bis-amido complexes 328 and 330, respectively. The latter, upon 1,2-elimination, regenerate the catalytically active imidotitanium species 325 and, after tautomerization, produce imines 322 and 323 (Scheme 105).176 Overall, formation of a more stable species 327 vs 329 makes pathway A favorable, leading to linear imine 322 as a major product.

3.1.4. Addition of Carbon-Based Pronucleophiles Various heteroaromatic compounds, such as furans, thiophenes, pyrroles, and thiazoles, can be efficiently allylated by reaction with methylenecyclopropanes in the presence of palladium catalyst (Scheme 106).177,178 Two alternative mechanistic pathways were proposed for this transformation (paths A and B, Scheme 107). Path A commences with C-H activation of the heterocyclic substrate by Pd(0) complex to form palladium(II) hydride species 332, which undergoes hydropalladation of the methylenecyclopropane double bond, providing cyclopropylpalladium complex 333. The final steps are similar to those proposed for hydroamination and hydroxylation of MCPs (section 3.1.3), including cleavage of the distal bond in 333 to give π-allylpalladium species 334, and reductive elimination to afford product 335 (Scheme 107).178 According to path B, the same π-allylpalladium species 334 can be produced via oxidative addition of Pd(0) into the distal bond of 336, followed by the palladaene reaction between palladacyclobutane 337 and the C-H bond of heterocyclic compound 331 (Scheme 107).178 Palladium-catalyzed hydrocarbonation of MCPs proceeds smoothly with C-H pronucleophiles, such as malonates, malononitriles, and β-ketoesters.179 Interestingly, simple methyl ketones 338 also add to methylenecyclopropanes 270 with ring opening, affording homoallyl ketones 339 (Scheme 108).180 Mechanistically, this transformation resembles hydrocarbonation of MCP by heterocyclic pronucleophiles (Scheme 107). Pathways involving hydropalladation of MCP


with palladium enolate (340) and an ene-reaction between methyl ketone and palladacyclobutane (342) have been proposed to lead to π-allylpalladium enolate 341, which upon reductive elimination affords product 339 in moderate to good yields (Scheme 108).180

3.2. Cycloaddition Reactions 3.2.1. [2 + 2 + 1] Cycloaddition (Pauson−Khand Reaction) The first example of a stoichiometric Pauson-Khand reaction (PKR) on MCP was demonstrated by Smit (Scheme 109).181 Excess 343 reacted with dicobalthexacarbonyl complexes of various alkynes adsorbed on a porous solid support (silica, alumina, or zeolites), providing cyclized cyclopentenones 344 and 345 in fair to good yields. The regioselectivity of this reaction was found to be strongly dependent on the nature of acetylene. Thus, cyclopentenones 344 were obtained as major products with complexes of terminal alkynes (343, R2 ) H), whereas Co-complexed internal alkynes gave predominantly isomeric cyclopentenones 345. Interestingly, the analogous reaction in homogeneous conditions led to extensive polymerization and poor yields of cyclization products.181 Later, Witulski demonstrated that the PKR between cobalt complex of ynamine 346 and MCP in the presence of trimethylamine N-oxide afforded cyclopentenone 347 in high yield (Scheme 109).68,182 Scheme 110

Scheme 111

Rubin et al.

The intramolecular PKR involving MCP was demonstrated by Salau¨n and de Meijere. The strained tri- and even tetrasubstituted double bonds of 348 reacted smoothly, providing tricyclic products 349 in moderate to high yields. In contrast, nonstrained olefin 350 did not undergo cyclization under these reaction conditions (Scheme 110).183 Only a few examples exist in the literature on the preparation of optically active cyclopentenones via the Pauson-Khand reaction of MCPs. Thus, intramolecular cyclization of nonracemic methylenecyclopropane 351 proceeded smoothly at -78 °C, producing cyclopentenone 352 with high diastereoselectivity (Scheme 111).184 When carried out at room temperature, this reaction afforded a mixture of diastereomeric products 352. The diastereoselectivity in the cyclization of ketal 353 depended on the chiral auxiliary employed, gradually increasing when more sterically encumbered substrates were used (Scheme 111).185 Motherwell observed an unusual rearrangement accompanying an intramolecular PKR of MCP 354. When the reaction was carried out at room temperature, traces of expected cyclopentenone 355 were formed, accompanied by large amounts of rearranged product 356. Interestingly, none of the carbon atoms from the alkyne moiety was incorporated in the cyclopentenone ring of 356. The reaction at elevated temperatures led to exclusive formation of rearranged cyclopentenone 356 (Scheme 112).186 To rationalize the formation of 356, it was suggested that the normal Pauson-Khand intermediate 357 undergoes protolytic cleavage of the cobalt cage cluster with eventual protons to form cationic π-allylcobalt species 358, which cyclizes into 359 and, after deprotonation, produces dimetallacycle 360. The latter rearranges into the more stable cage cluster 361, responsible for the formation of product 356 (Scheme 112).186

3.2.2. [2 + 2 + 2] Cycloaddition Malacria and de Meijere described a cobalt-mediated intramolecular [2 + 2 + 2] cycloaddition of MCP- and bicyclopropylidene-tethered enediynes 362 to provide cobaltcomplexed polycyclic dienes 363. It was found that the presence of an electron-withdrawing substituent at the



Scheme 112

Scheme 113

Scheme 114

cyclopropyl ring cleavage via three different routes, involving oxidative addition of the transition metal into the proximal (A) or distal (B) C-C bond or the formation of a metalcomplexed TMM intermediate (C) (Scheme 115). Intermolecular [3 + 2] cycloadditions were developed by Noyori,189 Binger,190 and Trost,191 and intramolecular versions were investigated by Lautens,21 Motherwell,192 and Nakamura.193 Transition metal-catalyzed [3 + 2] cycloaddition reactions of MCPs with various unsaturated compounds, including alkenes,194-196 alkynes,21,193 carbon dioxide,197 and ketenimines,198 were developed, evolving over the years into a powerful tool for the construction of five-membered carboand heterocycles. These reactions were highlighted in several excellent reviews,20,22,199 and therefore only the latest progress in this area will be discussed herein. Scheme 116

acetylenic terminus of precursor 362 was essential for successful cyclization (Scheme 113).187

3.2.3. Dipolar [2 + 3] Cycloaddition Dipolar cycloadditions of MCPs are scarce and employ the MCP unit as a two-carbon component. Thus, carbonyl ylide 365 generated by Rh(II)-catalyzed decomposition of diazodione 364 underwent dipolar cycloaddition with a double bond of MCP 270 (Scheme 114), providing mixtures of spirocyclopropanated products 366 and 367 in poor to moderate yields and variable regio- and stereoselectivities.188

3.2.4. [3 + 2] and [3 + 2 + 2] Cycloadditions Nickel- and palladium-catalyzed cycloadditions involving an MCP unit as a three-carbon component proceed with Scheme 115

Yamamoto reported palladium-catalyzed cycloaddition of MCPs with aldehydes200 and imines,201 providing easy access to 3-methylene derivatives of tetrahydrofuran (368) and pyrrolidine (369), respectively. These reactions, however, proceeded with poor diastereoselectivity, leading to almost equimolar mixtures of diastereomeric products (Scheme 116).200,201 It was also found that MCPs substituted in the ring did not react with aldehydes under these conditions.200


Scheme 118

The mechanistic rationale proposed by Yamamoto (Scheme 117) involved oxidative addition of Pd(0) species into the distal bond of MCP and subsequent [3 + 2] cycloaddition, according to path B (Scheme 115). It should be mentioned, however, that formation of the same product 370 could also be envisioned via route C, involving a Pd-TMM complex (Scheme 115). This pathway would also explain formation of regioisomeric product 371, observed in the reaction between MCP 372 and sterically hindered imines (Scheme 117).201 Likewise, the palladium-catalyzed [3 + 2] cycloaddition of MCPs to 1,2-diazines 373 produced the corresponding Scheme 119

Scheme 120

Rubin et al.

cycloadducts 374 via activation of the distal bond of 270. Subsequent isomerization of 374 followed by aromatization proceeded smoothly under the reaction conditions, leading to pyrrolopyridazines 375 in moderate to good yields (Scheme 118).202 Kaufmann reported the Ni-catalyzed [3 + 2] cycloaddition of MCP 376 with alkenylboronates 377. It was found that the reaction proceeded sluggishly with unsubstituted vinylboronate 377 (R ) H), but introduction of an electronwithdrawing substituent allowed for the dramatic increase of reactivity leading to very high yields of cyclopentylboronates 378 (Scheme 119).203 Alkynes undergo facile intramolecular Ni- or Pd-catalyzed [3 + 2] cycloaddition with MCPs via the TMM intermediate 382 (Scheme 120), which is usually generated either from alkyne-tethered MCPs 379, with an exo-methylene double bond,21-193 or from the isomeric precursors 380 and 381, with an internal olefin moiety (Scheme 120).204 The corresponding cyclization products 383 and 384 were obtained in high yields. Interestingly, the same transformation can be performed in the presence of the first-generation Grubbs catalyst (Scheme 120).205 Although the mechanism of this transformation is not clear, it is believed to be different from the mechanism proposed for the Pd-catalyzed reaction. Some experimental data support the hypothesis that the cycloaddition reaction is being promoted by a non-carbenoid ruthenium species generated under the reaction conditions.205 Saito reported the Ni-catalyzed intermolecular [3 + 2 + 2] cocyclization of ethyl cyclopropylideneacetate and cyclopropylideneacetone 385 with bulky terminal alkynes to produce cycloheptadienes 386 (Scheme 121). The presence of an electron-deficient substituent at the MCP was crucial for the success of this cyclization, as all attempts to engage alkylidenecyclopropanes in this transformation failed.206 The proposed mechanistic rationale involves formation of the nickelacyclopentadiene species 387 from two alkyne molecules and subsequent carbonickelation of the proximal σ-bond of MCP (388) to produce metallacyclooctadiene intermediate 390. Alternatively, nickelacycle 390 can be obtained via carbonickelation of the CdC bond in 385 to give cyclopropylnickel species 389, followed by β-carbon



Scheme 121

Scheme 122

produced next as a result of β-hydride elimination from 399 (Scheme 124). From this point, the reaction can potentially follow two different pathways. The first route is closely related to the classical Heck reaction pathway, which in the case of MCP proceeds with cleavage of the strained cycle (Scheme 124). According to this route (path A), a Heck reaction product 404 is produced via dissociation of palladium. An alternative route presumes reversible hydropalladation of 400 leading to π-allyl palladium species 401, which, in the presence of nucleophilic reagents, can follow the Tsuji-Trost reaction pathway, affording products of allylic substitution 402 and 403 (path B, Scheme 124). Scheme 124

elimination. The latter, after reductive elimination, furnishes the cyclization product 386 and restores the catalytic Ni(0) species (Scheme 122).206

3.2.5. [4 + 1] Cycloaddition A formal [4 + 1] cycloaddition of Fisher carbenes 392 and MCPs 391 was reported by de Meijere. The reaction proceeded in wet methanol, providing cyclopentenones 393 in fair to reasonable yields and variable diastereoselectivities (Scheme 123).207 This reaction is believed to proceed via initial [2 + 2] cycloaddition to give chromacyclobutane 394, followed by ring expansion into chromacyclopentane 395. Migratory insertion of CO into 395 and subsequent reductive elimination of chromium provides cyclopentenone 396, which then isomerizes into a more stable conjugate ketone 393 (Scheme 123).207

3.2.6. Cascade Reactions Involving Carbopalladation of the Double Bond of Methylenecyclopropane The general mechanism for the Pd-catalyzed arylation reaction involving MCP is summarized in Scheme 124. First, oxidative addition of the Pd(0) species into an organyl halide produces organylpalladium complex 397, which undergoes carbopalladation of the CdC bond of MCP to form cyclopropylmethylpalladium 398, which, in turn, experiences facile β-carbon elimination, leading to the homoallylpalladium species 399. An η2-complex of butadiene 400 is Scheme 123

One of the first examples of cascade transformations involving vinylation or arylation of an MCP terminated by trapping with a nucleophile was reported by Gore.208 In this protocol, methylenecyclopropane reacted with bromopropene and sodium malonate in the presence of catalytic amounts of Pd(dba)2 and dppe to produce a regioisomeric mixture of dienes 405 and 406 in 55% overall yield (Scheme 125).208 The intramolecular version of this reaction between PhI and MCP 407 tethered to a stabilized anion in the presence of a Pd(0) catalyst afforded predominantly cyclopropyl-substituted cyclopentane 408, along with small amounts of ring-opened product 409.209 While catalytic cycle B described above (Scheme 124) can account for the formation of olefin 409, an alternative route leading to the major product 408 did not involve either β-carbon elimination or a π-allylpalladium intermediate.209 Instead, it was suggested that cyclopropylmethylpalladium species 411, formed upon carbopalladation of MCP 407 with 410, undergoes intramolecular nucleophilic attack on palladium rather than β-carbon elimination, leading


Rubin et al.

Scheme 125

Scheme 126

obtained exclusively (Scheme 128).211 Reaction of 277 with O’Donnel’s nucleophilic glycine equivalent 418 (Z1 ) CO2Et, Z2 ) NCPh2) allows for synthesis of MCP derivatives of R-amino acids, although with rather low diastereoselectivity (dr 3:1).211 Furthermore, primary and nonhindered secondary amines can be efficiently employed as N-nucleophiles in this reaction, providing allylamines 420, generally Scheme 128

to palladacyclohexane 412. The latter, after reductive elimination, provides cyclized product 408 (Scheme 126).209 The palladium-catalyzed Heck-type reaction of MCPs leading to conjugated dienes (path A, Scheme 124) was reported by de Meijere. Intermolecular coupling of bicyclopropylidene (277) with iodobenzene afforded diene 413, which is not isolable, due to low stability, but can efficiently be trapped as Diels-Alder adduct 414 (Scheme 127).210 Likewise, cross-coupling of 277 with vinyl iodide produced unstable cross-conjugated triene 415, which was trapped in situ at room temperature with dimethylmaleate to give monoadduct 416. It was found that addition of the second equivalent of the dienophile is possible at elevated temperature to afford bis-adduct 417 as a mixture of diastereomers (Scheme 127).210 This chemistry was later adapted for combinatorial applications; three-, four-, and five-component couplings involving the Heck reaction/Diels-Alder cycloaddition cascade were implemented.194 Bicyclopropylidene 277 also reacts with iodobenzene in the presence of malonic ester derivatives 418 as carbon nucleophiles via a π-allylpalladium intermediate (catalytic cycle B, Scheme 124). In this case, products of nucleophilic attack at the less sterically hindered allylic terminus 419 are Scheme 127

in very high yield. Remarkably, no twofold substitution was observed, which is a common side process in the palladiumcatalyzed Tsuji-Trost reaction with primary amines (Scheme 128).211 When vinyl iodide was used as electrophilic component in this reaction, nucleophilic attack by amine produced diene 421, which can be used in the one-pot [4 + 2] cycloaddition with suitable dienophiles, affording spirobicyclic and spirotricyclic products 422 in fair to good yields (Scheme 129).212 Grigg reported a four-component palladium-catalyzed cascade transformation involving carbonylative intramolecular arylation reaction of bicyclopropylidene 277 (Scheme 130).213 Two equivalents of carbon monoxide were incorporated in the final spirocyclic diketone 423, which was obtained in good yield along with traces of lactone 424. The



Scheme 129

Scheme 130

Scheme 131

mechanistic rationale for the formation of isomeric products 423 and 424 is summarized in Scheme 131. Initially, oxidative addition of the Pd(0) species into the Ar-I bond, followed by migratory insertion of CO, produces acylpalladium complex 425. The latter undergoes carbopalladation of the bicyclopropylidene double bond to give bicyclopropylpalladium species 426, which upon β-carbon elimination provides homoallylpalladium complex 427. Subsequent migratory insertion of a second CO molecule gives acylpalladium species 428a or its rotamer 428b. Next, 5-endotrig cyclization of 428a into 429, followed by intramolecular nucleophilic attack of the heteroatom on palladium, produces palladacycle 430, which, after reductive elimination, affords the major product, spirodiketone 423 (Scheme 131). Alternatively, intramolecular Michael addition of the heteroatom

moiety on the cyclopropylideneketone double bond in 428b would produce enolate 431, intramolecular nucleophilic attack of which on palladium would give oxapalladacycle 432. The latter, after reductive elimination, would furnish side product 424 (Scheme 131).213 de Meijere has further shown that, despite only a minor difference in the substitution pattern, 2-bromo-1,6-dienes 433a and 433b exhibit dramatically different reactivity in the Pd-catalyzed cascade Heck cross-coupling/[4 + 2] cycloaddition reaction. Thus, diene 433a produced exodimethylenecyclopentane 434, which was trapped as DielsAlder adduct 435 with methyl acrylate. At the same time, 6-Me analogue 433b produced triene 436 under similar reaction conditions (Scheme 132).214 It was suggested that, in both cases, oxidative addition of Pd(0) species into 433,


Rubin et al.

Scheme 132

Scheme 133

leading to alkenylpalladium complex 437, takes place and that, when R ) H, the addition is followed by 5-exo-trig cyclization, affording cyclopropylpalladium complex 438. The latter, after β-hydride elimination, produces diene 434 (Scheme 133). The reaction followed a different pathway when methyl-substituted complex 433b (R ) Me) was employed, as the β-hydride elimination step is either impossible or highly unfavorable. Thus, 6-endo-trig cyclization of 433b produces cyclohexylpalladium species 439, which, after β-carbon elimination, provides σ-alkylpalladium complex 440. Subsequent β-hydride elimination produces [3]-dendralene 436 in good yield (Scheme 133).214 Another cascade transformation involving bicyclopropylidene shown by de Meijere features 5-exo-dig cyclization of bromoenyne 441 into vinylpalladium species 442. The latter, upon intermolecular carbopalladation with bicyclopropylidene, gives bicyclopropylpalladium 443. Subsequent β-carbon elimination followed by reductive elimination produces conjugated tetraene 444 (Scheme 134).215 When the reaction was performed in acetonitrile at 80 °C, tetraenes 444 were isolated in fair to good yields (Scheme 135). In contrast, carrying out the reaction in DMF afforded tricyclic products 445, resulting from 6e-electrocyclic ring closure of 444. It was also shown that tetraene 444 can be quantitatively converted into 445 upon heating at 130 °C

Scheme 134

(Scheme 135). Likewise, conjugated enyne 446 produced the corresponding pentaene 447, which, under the reaction conditions, underwent two consecutive pericyclic ring closures, providing tetracyclic product 448, albeit in low yield (Scheme 135).215



Scheme 135

3.3. Isomerization and Cycloisomerization Reactions 3.3.1. Rearrangement of Methylenecyclopropanes into Cyclobutenes An efficient synthesis of cyclobutenes via transition metalcatalyzed rearrangement of MCPs was recently independently developed by Fu¨rstner216 and Shi.217 It was demonstrated that, in the presence of catalytic amounts of Pd(II)217 or Pt(II)216 complexes, MCPs 449 were converted into cyclobutenes 450 in high yields (Scheme 136). In both cases, a clean 1,2-deuterium shift with >97% D incorporation into the cyclobutene product 450-d was observed (Scheme 136).216,217 The mechanistic rationale proposed by Fu¨rstner involves electrophilic addition of the platinum catalyst to the double bond of 449 to generate cyclopropylmethyl cation 451, followed by Demjanov rearrangement,18 providing zwitterionic cyclobutyl species 452, which can also be drawn as carbenoid platinum complex 453. Subsequent 1,2-hydride shift provides isomeric tertiary cyclobutyl cation 454, which affords cyclobutene 450 after elimination of metal (Scheme 137).216 Shi suggested an alternative mechanism, according to which the palladium-catalyzed transformation begins with halopalladation of MCP 449 with PdBr2, formed in situ upon the reaction between Pd(OAc)2 and CuBr2. The resulting cyclopropylpalladium species 455 undergoes β-hydride elimination with the formation of a η2-Pd(II) hydride complex

456. Next, reversible hydropalladation produces cyclopropylmethylpalladium species 457, which after R-elimination of bromide affords carbenoid species 458. The latter in turn undergoes ring expansion into cyclobutene 450 (Scheme 138).217 However, involvement of the η2-palladium hydride intermediate 456, which is highly susceptible to D/H scrambling with eventual proton sources,219 especially in the presence of acetate ligands,55,220 contradicts the virtually clean 1,2-deuterium migration observed in this reaction. Thus, it is likely that the palladium-catalyzed cycloisomerization may also proceed via a mechanism analogous to that depicted in Scheme 137. The synthetic potential of these two methodologies is very high, as they allow for efficient conversion of the readily available MCPs into important four-membered cyclic building blocks, synthetic approaches toward which have thus far been very limited. Scheme 138

Scheme 136

Scheme 137

3.3.2. Cycloisomerization of Acyl-Substituted Methylenecyclopropanes Ma reported that acyl-substituted MCPs 459 undergo smooth cycloisomerization into 4H-pyrans 460 in the presence of catalytic amounts of Pd(II).221 Interestingly, in the presence of NaI in refluxing acetone, the same palladium catalyst triggered a different cycloisomerization, affording alkylidenedihydrofurans 461, which after prolonged heating isomerized into furans 462 (Scheme 139).221 It was also shown that MCP 463, possessing a tetrasubstituted double bond, gave 2H-pyran 464 under these reaction conditions (Scheme 139).


Rubin et al.

Scheme 139

Scheme 140

A plausible mechanistic rationale for these unusual cycloisomerizations is summarized in Scheme 140. It was proposed that the palladium catalyst coordinates to the exomethylene double bond of 459, making it more electrophilic, thereby triggering intramolecular cyclization to produce cyclopropyl oxocarbenium intermediate 465. The latter, in turn, undergoes ring expansion to produce homoallyl cation 466, which collapses to give homoallyl chloride 467. An alternative route to species 467 is believed to involve chloropalladation of 459, followed by subsequent β-carbon elimination to give palladium enolate species 468 and intramolecular 6-endo-trig oxopalladation of the vinyl chloride moiety in 468 (Scheme 140).221 Next, dihydropyranylpalladium species 467 undergoes isomerization via reversible β-hydride elimination/hydropalladation, the regiochemistry of which depends on the nature of substituent R4. When R4 ) H or D, a new double bond is formed to produce a more thermodynamically favorable enol ether 470. The latter in turn affords species 471, which experiences β-chloride elimination, affording 4H-pyran 460. In the reaction of deuterated compound 459 (R4 ) D), ca. 75% deuterium incorporation into product 460 was observed (Scheme 140).221 When R4 ) Alk, the only possible pathway for β-hydride elimination affords conjugated diene 469, which upon hydropalladation and β-chloride elimination produces 2H-pyran 464 (Scheme 140).221

Scheme 141

In contrast to the Pd(II)-catalyzed cycloisomerization of 459 (Scheme 139), the reaction of acyl-substituted MCPs in the presence of Pd(0) complexes produced only small amounts of dihydrofuran 461, while its regioisomer 472 was formed as a major product (Scheme 141).221 Both 472 and 461 isomerized into the corresponding furans upon treatment with HCl. It was proposed that oxidative addition of Pd(0) species into the distal C-C bond of 459 is responsible for the observed reversal of the regiochemistry (Scheme 142). The resulting palladacyclobutane 474 rearranges into palladium enolate complex 475, which via η3-η1-equilibrium produces cyclopalladated complexes 476 and 477. Subsequent reductive elimination affords the corresponding exoalkylidene dihydrofurans 461 and 472.221



Scheme 142

3.4. Polymerization Reactions Palladium-catalyzed co- and terpolymerization of MCP with CO proceeded with partial ring opening to afford polyketones 478 containing both cyclic and ring-opened exomethylene units in the chain (Scheme 143).222 Scheme 143

to afford regulated polyketone 483 with cyclohexane rings incorporated in the polymer chain (Scheme 145).224 It was shown that the cis/trans stereoselectivity of the 1,2-cyclohexyl units as well as the tacticity of the polyketone is strongly dependent on the palladium ligands and the solvent used. The observed partial epimerization of one of the centers leading to the formation of a thermodynamically more favorable trans-isomer was rationalized via the reversible β-hydride elimination of palladium during polymer growth.225 Scheme 145

In contrast, it was demonstrated that copolymerization of the aryl-substituted MCP 479 with CO in the presence of PdCl(Me)(bpy) and NaBARF affords polyketones 480 composed of ring-opened structural units exclusively.223 Kinetic and isotope-labeling studies suggest that the mechanism of this reaction involves initial CO insertion into the Pd-alkyl bond of the growing polymer, subsequent migratory insertion of the double bond of cyclic monomer 479 into the Pd-acyl bond, and then β-alkyl elimination with cleavage of either a proximal or a distal bond of the cyclopropane ring in 481, which produces two repeating units A and B, respectively, with the molar content ratio of A to B of 1.6:1 (Scheme 144).223 Analogously, ring-opening copolymerization of 7-methylenebicyclo[4.1.0]heptane 482 with CO in the presence of palladium diamine complexes and NaBARF proceeds readily Scheme 144

Osakada demonstrated that Co- and Ni-catalyzed polymerization of aryl- or ester-substituted methylenecyclopropanes 484 can proceed with preservation of the three-membered ring to produce a well-regulated polymer 485 with head-totail linkage of the monomer units (Scheme 146).226,227 It was shown that the molecular weight of the polymer increases with the introduction of electron-withdrawing substituents in the aryl ring of the monomer. Cobalt catalyst 487 in combination with modified methylaluminoxane (MMAO) enables alternating copolymerization of methylenecyclopropane with ethylene to cleanly produce regulated copolymer 486, consisting of two alternating monomer units with no homopolymers or random copolymer units detected by NMR analysis.226 Employment of 2-methyl-2-phenyl-1-methylenecyclopropane as an additive to suppress ethylene homopolymerization was found to be necessary to obtain the regulated copolymer structure. Scheme 146


Rubin et al.

Scheme 147

Scheme 148

4. Reactions of Vinyl-, Allenyl-, and Alkynylcyclopropanes

Scheme 149

4.1. Addition Reactions Accompanied by Ring Opening 4.1.1. Addition Reactions Leading to Acyclic Products Ring opening of VCP in the presence of Pd(II) complexes was first demonstrated in stoichiometric chloropalladation and carbopalladation reactions producing various isolable dimeric π-allylpalladium species of type 489 and 492 (Scheme 147).32 Two mechanistic pathways were proposed to account for the formation of the regioisomeric products observed in the reactions with different Pd(II) sources. Thus, reactions involving palladium(II) chloride were believed to proceed via electrophilic addition of Pd(II) to the double bond of VCP to form cyclopropylmethylcation species 488. The latter, upon nucleophilic attack at the cyclopropyl group, would afford dimeric η3-complex 489 (Scheme 147, path A). Alternatively, reactions with alkylpalladium complexes would proceed via initial carbopalladation of the double bond of VCP to produce cyclopropylmethylpalladium species 490, which via β-carbon elimination would give an open-chain alkylpalladium intermediate 491. Subsequent reversible β-hydride elimination/hydropalladation would produce the regioisomeric dimeric complex 492 (Scheme 147, path B).32 Vinylcyclopropanes possessing activating electronwithdrawing groups undergo addition of nucleophiles accompanied by ring opening in the presence of Pd(0) complexes (Scheme 148).32,228 The mechanism of this reaction can be rationalized via SN2′-type nucleophilic attack of palladium at the vinyl group in 493, leading to ring opening of the cyclopropane. Subsequent protonolysis of the resulting anion 495 gives π-allylpalladium species 496, which, upon nucleophilic substitution at the π-allylpalladium

moiety, produces olefin 494 (Scheme 148). When this reaction was performed in the presence of catalytic amounts of pronucleophile, the latter served as an initiator of palladium-catalyzed anionic ring-opening polymerization of vinylcyclopropanes.229 According to the proposed mechanistic rationale, nucleophilic attack of the stabilized carbanionic terminus of the growing chain at π-allylpalladium species 495 led to polymer elongation (Scheme 149). On the other hand, Pd(0)-catalyzed reductive ring cleavage of VCP by formic acid produces regioisomeric olefins 497 (Scheme 150).230 While this reaction essentially follows the above-discussed mechanism (Scheme 148),32nucleophilic attack of the hydride species occurs at the metal center rather than at the η3-ligand, leading to overall inversion of configuration, as confirmed by the reaction on bicyclic VCP 498.230 Lautens reported that this transformation also proceeds efficiently with substrates possessing only one activating electron-withdrawing group (Scheme 151).231 Furthermore, it was shown that activated VCPs readily produce E-allylboronic acids in the presence of tetrahydroxydiboron and the palladium pincer complex 500 bearing two selenium donor atoms (Scheme 152).232 Although the mechanism of this reaction was not detailed, it was proposed that it proceeds via the formation of palladium-boron species 501 and does not involve any π-allylpalladium intermediates.232 A plausible mechanism for this reaction may involve borapalladation of the double bond of 493 with 501, followed



Scheme 150

Scheme 151

Scheme 154

Scheme 152

Scheme 153

by β-carbon elimination to give an alkylpalladium species of type 491 (path B in Scheme 147). The latter, upon reaction with HCl, regenerates catalyst 500 and produces allyboronic acid, which is converted in situ into a more stable potassium trifluoroborate derivative 499. Notably, this reaction did not proceed in the presence of Pd(0) complexes, such as Pd2(dba)3 or Pd(PPh3)4.232 Substrate-controlled highly regioselective reductive ring opening of either proximal bonds a or b of VCPs catalyzed by palladium on carbon was shown by Barrett (Scheme 153).60 Thus, selective cleavage of bond a leading to branched alkanes 502 was observed with iso-alkyl- and cycloalkylsubstituted VCPs, whereas aryl- and vinylsubstituted substrates provided linear products 503 exclusively via scission of bond b. Interestingly, the double bond of VCPs was also reduced under these conditions, and cleavage of the three-membered ring did not occur in the absence of the double bond in the substrate. The observed switch of the regioselectivity in the case of aryl- and alkenylsubstituted VCPs was believed to be a result of the strong catalyst chelation to the π-bonds of the substrate, which directs insertion of palladium into the more substituted bond b.60 Suginome and Ito showed that vinylcyclopropanes undergo regio- and stereoselective silaboration in the presence of Ni

catalyst to produce (ω-borylalkyl)-substituted allylsilanes 504 (Scheme 154).280 The very high E-selectivity was explained in terms of the preferential s-trans-conformation of VCP during the migratory insertion of the cyclopropyl group into the Ni-B bond in 505 (cycle A). Formation of a side product, cyclopentene 506 (section 4.3.2), was observed in some cases, which presumably resulted from the competing direct reaction of VCP with Ni(0) species (cycle B).280

4.1.2. Addition/Cycloisomerization Reactions A hydrosilylation-initiated cycloisomerization of 1,6enynes 507 to produce alkenylcyclopentanes 508 was reported by Widenhoefer.233 This reaction is catalyzed by cationic palladium(II) phenanthroline complex 514, generated from 509 in the presence of sodium tetraarylborate additive (Scheme 155). Silapalladation of the terminal olefin moiety of 507 with 514 produces cationic σ-alkylpalladium species 511, which undergoes 5-exo-trig carbopalladation to furnish cyclopropylmethyl palladium complex 512. The latter, upon facile β-carbon elimination, affords homoallyl palladium 513, which after hydride transfer converts to product 508 (Scheme 156). A single example of this transformation, performed in the presence of chiral Pd complex 510 (Scheme 155), demonstrated enantiomeric induction of 73%.233 Shair reported that rhodium-catalyzed intramolecular hydroacylation of VCP 515 proceeds with cyclopropyl ring opening to produce cyclooctenones 516 along with traces of cyclopropylcyclopentanones 517 (Scheme 157).234 The mechanism of this transformation involves oxidative addition of Rh(I) species into the C-H bond of aldehyde 515


Rubin et al.

Scheme 155

Scheme 156

Scheme 159


Scheme 158

followed by 6-endo-trig hydrorhodation to produce rhodacyclohexanone 518. Subsequent β-carbon elimination affords rhodacyclononenone 519, which after reductive elimination gives cyclooctenone 516 (Scheme 158). Reductive elimination occurring prior to ring expansion from 518 produces cyclopentanone side product 517 (Scheme 158).234

4.2. Cycloaddition Reactions 4.2.1. Intramolecular [5 + 2] Cycloaddition with Alkynes and Alkenes Rh(I)-catalyzed intramolecular [5 + 2] cycloaddition of vinylcyclopropanes (VCPs) to alkynes was first demonstrated

by Wender in 1995.235 Featured as a formal homologue of the Diels-Alder [4 + 2] cycloaddition, this transformation has opened up an easy access to diverse seven-membered ring scaffolds (Scheme 159). Wilkinson’s catalyst in combination with AgOTf was the “first generation” catalyst for the intramolecular [5 + 2] cycloaddition. Later, the carbonyl rhodium complex [Rh(CO)2Cl]2 was found to be a more efficient catalyst, which allowed for greater functional group compatibility, improved selectivity, and shortened reaction times.236 Other cationic rhodium complexes capable of catalyzing [5 + 2] cycloaddition even at room temperature were developed by Gilbertson237 (Rh(DIPHOS)(CH2Cl2)2SbF6) and Zhang238 ([Rh(dppb)Cl]2/AgSbF6). Furthermore, Wender reported that rhodium arene complex 521 is an exceptionally effective and general catalyst for the intramolecular [5 + 2] cycloaddition of alkynyl- and alkenyltethered VCPs 520 (Scheme 160).239 It enables reaction at room temperature within minutes, providing superior chemoselectivity and higher yields of 522 compared to the previously reported catalyst systems. Furthermore, employment of this catalyst allowed for suppressing the undesired olefin isomerization, which was previously observed in the presence of [Rh(CO)2Cl]2 catalyst. In search of a more affordable alternative to the expensive Rh complexes, Trost found an efficient Ru catalyst, CpRu(NCCH3)3]PF6, which enables [5 + 2] cycloaddition of cyclopropylenynes 523 at room temperature (Scheme 161).29,240



Scheme 164

Scheme 162

A general mechanism of [5 + 2] cycloaddition is summarized in Scheme 162.29 Both species 524 and 525 were initially proposed to be putative intermediates for Rhcatalyzed cycloaddtion.28,241 However, recent computational studies by Wender and Houk suggested that cyclopropyl ring cleavage to form metallacyclohexene 524 followed by alkyne insertion is the most viable pathway for the [Rh(CO)2Cl]2catalyzed reaction.242 In contrast, Ru-catalyzed [5 + 2] cycloaddition is believed to preferentially proceed via metallacyclopentene species 525.29 It was demonstrated that, in most cases, stereochemistry in [5 + 2] cycloaddition is transferred from the substrate to the product, whereas regiochemistry often depends on the catalyst used. Thus, for the trans-cyclopropane series (526), cycloadducts with either 1,4- (527) or 1,5-stereorelationships (528) can be obtained as single diastereomers with moderate to high degrees of regioselectivity by employing different catalysts (Scheme 163).243 For the cis-series (529), formation of complementary diastereomers 530 and 531 to that obtained from trans-cyclopropanes 526 was observed (Scheme 164). Also, regardless of the catalyst used, products 530 with 1,4stereorelationships were obtained predominantly or exclusively.243 To explain the observed regio- and diastereoselectivity, Wender proposed the reversible formation of diastereomeric

cyclometalated complexes 532a and 532b (Scheme 165). It was suggested that, for efficient cleavage of the cyclopropyl ring via formal σ-bond metathesis, it is necessary to ensure the parallel arrangement of the C-M bond and one of the two proximal C-C bonds of the ring, which can be achieved by rotation around the C-C bond. Cleavage of the more substituted bond in diastereomeric complexes 533a and 533b via corresponding metallacyclooctadienes 535a and 535b leads to cycloadducts 537 and ent-537 with 1,5-regiochemistry. Alternatively, cleavage of the less substituted bond in diastereomeric complexes 534a and 534b leads to the regioisomeric cycloadducts 538 and ent-538. It was presumed that the regioselectivity in [5 + 2] cycloaddition arises from the relative stability of conformers 533a,b vs 534a,b or from the difference in kinetic rates for the first irreversible step, i.e., formation of cyclometalated complexes 535a,b vs 536a,b (Scheme 165). Remarkably, the diastereomeric information in this reaction is translated without loss from the original configuration of the cyclopropane moiety (i.e., cis or trans) to the cycloaddition product, as a result of a concerted ring expansion.243,244 Analogous investigations of the regioselectivity of [5 + 2] in the presence of Ru catalyst performed by Trost29,245 revealed that cis-substituted cyclopropanes 539 afford product 540 with very high regioselectivity for most substituents tested. trans-Cyclopropyl substrates 542 appeared to be less selective, providing poor regioselectivity of cycloaddition (Scheme 166). It was proposed that reaction with the transsubstrates is affected predominantly by electronic rather than steric factors, while, in cis-cyclopropyl substrates, steric effects govern the reaction. In contrast to the Rh-catalyzed reaction, in the Ru-catalyzed [5 + 2] cycloaddition of transcyclopropanes 542 bearing an electron-withdrawing R group, products 544 were obtained as mixtures of two diastereomers (Scheme 166).29 Exceptional control of diastereoselectivity in [5 + 2] cycloaddition could be achieved through the selection of appropriate substituents in the substrate. Thus, Trost demonstrated very high anti-selectivity in the Ru-catalyzed reactions of alkoxy-substituted substrates 545, which was


Rubin et al.

Scheme 165

Scheme 166

explained by “inside alkoxy effect”246 in terms of the Stork/ Houk-Ja¨ger model (Scheme 167).247 Application of the Rucatalyzed [5 + 2] cycloaddition to bicylic substrates allowed for expeditious access to complex tricyclic scaffolds 546 with high yields and remarkable diastereoselectivities (Scheme 168).29,248 Wender has also shown that, similarly to alkynyl VCPs, olefin-tethered analogues 547 also underwent smooth [5 + 2] cycloaddition to produce bicyclic cis-five-seven and trans-six-seven fused ring systems (548, Scheme 169), as a result of preferential formation of cis- and trans-fused metallacyclopentane intermediates (analogues of 525, Scheme 162), respectively.241,249 Notably, this cycloaddition proceeded well in the presence of Wilkinson’s catalyst, while the usually more efficient carbonyl rhodium complex [Rh(CO)2Cl]2 did not produce any reaction. The possibility of employing Ru catalyst for [5 + 2] cycloaddition of olefin-tethered VCPs was explored by Trost. The cycloaddition of 549, however, did not provide any desired products; instead Ru complex 551 has been isolated in good yield when 0.5 equiv of cyclopentadienylruthenium complex 550 was employed (Scheme 170).250 The mechanism of this transformation is believed to involve initial conversion of VCP into a ruthenacyclohexene followed by

olefin insertion and allylic C-H activation of a 1,6cyclodecadienene (Scheme 170). Wender further demonstrated that allene-tethered VCPs 552 can also be successfully employed in the intramolecular [5 + 2] cycloaddition.251 Notably, optically active allenes underwent this reaction with complete chirality transfer. This method provides easy access to synthetically valuable bicyclic synthons 553 with an exocyclic double bond in the seven-membered ring (Scheme 171). The power of this methodology was demonstrated by Wender in several asymmetric total syntheses. Thus, in the total synthesis of (+)-Dictamnol,252 the stereochemical outcome in the key step was rationalized through preferential formation of rhodabicyclo[5.3.0]octane species 554, in which the larger substituent at C-8 (OH) occupies the less hindered exo face (Scheme 172). (+)-Aphanamol I is another target molecule, of which an elegant asymmetric synthesis was accomplished via the described cycloaddition strategy.253 Remarkably, the key transformation, [5 + 2] cycloaddition of the rather bulky VCP 555 tethered to a tetrasubstituted allene moiety, proceeded highly efficiently with exceptional chemo-, exo/ endo, and diastereoselectivity. Perfect regio- and stereocontrol is believed to be a result of an overruling steric effect



Scheme 170


of a large isopropyl substituent, which, analogously to the previous example, resides in the less encumbered exo face (Scheme 173).253 A Rh-catalyzed [5 + 2] cycloaddition reaction was also employed by Wender for highly selective assembly of the tricyclic core of cyathane diterpenes 556 (Scheme 174)254 and by Martin for the key step in the enantioselective syntheses of Tremulenediol A and Tremulenolide A (Scheme 175).255 The [5 + 2] cycloaddition methodology was adapted to aqueous media through the use of a modified rhodium catalyst bearing a water-soluble phosphine ligand (Scheme 176).256 These new conditions allowed for efficient recovery and reuse of the catalyst, easy isolation of reaction products by simple extraction, and significant elimination of organic solvent waste. The use of water as solvent was also beneficial for achieving pseudo-high-dilution conditions, which allowed

for suppression of the polymerization of starting material, a side process often encountered in this reaction. Recently, Wender disclosed enantioselective intramolecular [5 + 2] cycloaddition of olefin-tethered VCPs.257 Structure-selectivity studies revealed that the enantioselectivity of the cycloaddition was strongly dependent on the substitution pattern of both VCP and tethered alkene moieties in 557 (Scheme 177). Thus, moderate degrees of enantioselectivity were achieved with unsubstituted VCP (557a), whereas introduction of at least one substituent (R1 or R2) dramatically improved enantioinduction (558b-d, Scheme 177). The substrate tether also influenced the enantioselectivity of cycloaddition: superior ee’s were obtained for the




Scheme 174

Scheme 175

Scheme 179

Scheme 176

TsN-tethered VCP 559, compared to the malonate derivative 557a. Attempts at asymmetric [5 + 2] cycloaddition of alkyne-tethered VCPs were less successful, leading to modest ee’s only.257

4.2.2. Intermolecular [5 + 2] Cycloaddition with Alkynes and Allenes The first intermolecular version of [5 + 2] cycloaddition was demonstrated by Wender on siloxy-258 and alkoxy-

vinylcyclopropanes 560.259 This reaction displayed remarkable generality with respect to the alkyne component, as electron rich, electron poor, internal, and terminal alkynes provided corresponding cycloadducts 561 in good to excellent yields (Scheme 178). Wender and de Meijere reported that, in contrast to alkynes, nonactivated allenes did not undergo intermolecular [5 + 2] cycloaddition. However, introduction of an additional conjugated coordinating group, such as an alkynyl, alkenyl, or cyano substituent, allowed for smooth cycloaddition at the distal double bond of allene 562, providing substituted alkylidenecycloheptanones 563 as mixtures of E- and Zisomers (Scheme 179).260 Interestingly, when nonconjugated cyanoallenes with one and three methylene groups between the allene and the nitrile moiety were subjected to this



Scheme 180

Scheme 181

Scheme 183

Scheme 184

Scheme 182

Scheme 185

reaction, mixtures of addition products to distal and proximal double bonds were obtained (Scheme 180).260 In contrast to the facile cycloaddition of alkoxyvinylcyclopropanes, the reaction of simple and alkyl-substituted VCPs 564 (R1 ) H, Alk) required assistance by steric factors. Thus, introduction of a large substituent R1, such as an isopropyl group, at C-1, as well as incorporation of substituents R2 and R3 at the double bond of VCP, allowed for smooth cycloaddition of unactivated VCPs with a variety of terminal alkynes (Scheme 181).261 It was also found that the use of 2,2,2-trifluoroethanol (TFE) as a cosolvent allowed for both increased reaction rates and yields of cycloheptadienes 565. The exceptional regioselectivity observed in this reaction was rationalized by Wender through minimization of steric repulsion (Scheme 182) in either of the two mechanistic pathways described above (Scheme 162).261 Wender further demonstrated that cycloaddition of enynes 567 and alkoxyvinylcyclopropanes 566 affords dienes that can further react without isolation with a variety of activated dienophiles in [4 + 2] cycloaddition fashion to produce an array of functionalized polycyclic products 568 (Scheme 183).262 It was found that cascade [5 + 2]/[4 + 2] cycloaddition proceeds more efficiently when all three components

are added at once, thereby preventing decomposition of the diene and allowing for improved yields of products (Scheme 183). Wender has also developed a hetero-[5 + 2] cycloaddition of cyclopropyl imines 569 with dimethylacetylenedicarboxylate en route to dihydroazepines 570 (Scheme 184).263 It was also shown that dihydroazepines can be directly obtained from the corresponding aldehydes 571 via a convenient and efficient one-pot imination/aza-[5 + 2] cycloaddition protocol (Scheme 185).263

4.2.3. Multicomponent Reactions Involving [5 + 2] Cycloaddition A very efficient approach to eight-membered ring systems via a three-component [5 + 2 + 1] cycloaddition of alkoxyvinylcyclopropane 572, alkyne 573, and CO was


Rubin et al.

This reaction is mechanistically related to the transition metal-catalyzed nucleophilic addition described above (Scheme 148). Thus, initial nucleophilic attack of palladium at the double bond of VCP results in cyclopropyl ring cleavage and formation of the zwitterionic π-allyl palladium complex 585. The latter undergoes Michael addition with electrondeficient alkenes 583 to give 586, which upon subsequent intramolecular nucleophilic attack of the carbanion at the π-allylpalladium moiety of 586 produces cyclopentane 584. Scheme 189

explored by Wender.264 This reaction proceeds via initial intermolecular [5 + 2] cycloaddition of 574 and 575 to give metallacyclooctadiene species 576, which, upon CO insertion, affords cyclooctadienone 577. The latter undergoes spontaneous transannular closure to produce bicyclo[3.3.0]octenone derivatives 578 in good yields with excellent regioselectivity (Scheme 186). Analogously, four-component [5 + 1 + 2 + 1] cycloaddition allows for a dramatic increase of molecular complexity and involves two consecutive CO insertions to produce conjugated cyclononatrienone 580, which, after a transannular aldol reaction, affords hydroxyindanone derivative 579 (Scheme 187).265 Highlighting the power of this methodology is a bidirectional seven-component cycloaddition involving the efficient construction of ten new bonds in a single step to form the bridged bis-indanone 581 (Scheme 188).265

4.2.4. Miscellaneous Cycloaddition Reactions Tsuji reported palladium-catalyzed [3 + 2] cycloaddition of VCPs 582 to R,β-unsaturated esters and ketones 583, leading to cyclopentane derivatives 584 (Scheme 189).266 Scheme 187

Scheme 188

de Meijere demonstrated that allenylcyclopropanes 587 undergo cascade Heck-type arylation-Diels-Alder cycloaddition with activated dienophiles to produce isomeric vinylcyclohexene derivatives 588 and 589 (Scheme 190).212,267 The first step of this sequential transformation involves arylpalladation of the allenyl moiety in 587 to afford π-allylpalladium species 590, which, upon consecutive β-carbon and β-hydride elimination, produces unstable triene 591. The latter undergoes [4 + 2] cycloaddition with activated dienophiles, which presumably proceeds stepwise via a mesomerically stabilized 1,6-zwitterionic intermediate 592, to give a diastereomeric mixture of 588 and 589, with the thermodynamically more favorable 588 being a major product (Scheme 190).212,267



Scheme 190

Scheme 192

Scheme 191

Scheme 193

+ 1] cycloaddition proceeds regioselectively with cleavage of bond a and predominant formation of product 598 with net retention of configuration at the stereogenic center. This transformation was employed by Taber as a key step in the total synthesis of (+)-delobanone (Scheme 193).270

4.3. Cycloisomerization Reactions 4.3.1. Cycloisomerization into Cyclobutanes

de Meijere also reported that VCPs 593 undergo [5 + 1] cocyclization with carbon monoxide, both in stoichiometric mode with octacarbonyldicobalt and catalytically in the presence of Co- and Rh-carbonyl complexes (Scheme 191).30 It was found that unsubstituted VCP (R1-R4 ) H) did not undergo this reaction, whereas aryl- and vinyl-substituted substrates reacted efficiently only in the presence of stoichiometric amounts of the cobalt octacarbonyl complex. The mechanism of this transformation was rationalized through the initial formation of metallacyclopropane species 595, followed by β-carbon elimination to produce cobaltocyclohexene 596, which after CO insertion and reductive elimination affords cyclohexenone 594. The analogous transformation mediated by an iron pentacarbonyl complex has been known for almost three decades.32,268 However, only recently, Taber investigated the regiochemistry of this reaction with respect to the β-carbon elimination step (i.e., cleavage of either proximal bond a or b) on a series of 2-substituted VCPs 597 (Scheme 192).269 Thus, cleavage of bond a would provide ferracyclohexene complex 600, which, after CO insertion and reductive elimination, would give β-substituted nonconjugated ketone 601. The latter can be easily isomerized into a more stable conjugated ketone 598 upon treatment with DBU. An alternative process involving cleavage of bond b would provide isomeric R-substituted ketone 599 (Scheme 192). Accordingly, it was demonstrated that Fe(CO)5-mediated [5

Efficient asymmetric cycloisomerization of vinylcyclopropanols 602 into vinylcyclobutanones 604 in the presence of catalytic amounts of Pd2(dba)3 and chiral bidentate phosphine ligand (R,R)-605 was recently demonstrated by Trost (Scheme 194).271 This transformation takes advantage of the extremely facile Wagner-Meerwein-type ring expansion of a cyclopropylmethyl cation, which is stabilized in the form of a π-allylpalladium complex (603, Scheme 195).271 The enantioselectivity of this reaction is rationalized through preferential coordination of the chiral palladium complex to the allylic cation from the Si-face. The resulting π-allylpalladium species 603a, leading to the S-enantiomer of cyclobutanone 604, is believed to be thermodynamically more favorable over its diastereomer 603b, which experiences steric repulsion between one of the aryl rings of the chiral ligand and the bulky cyclopropanol moiety (Scheme 194). Vinylcyclopropanols bearing a large R-substituent (such as aryl) dramatically decrease the stability of complex 603a as a result of steric repulsion between the R group and the PPh2 moiety of the ligand. This leads to the observed deterioration of enantioselectivity in the reaction with such substrates.271 A related gold-catalyzed rearrangement of alkynylcyclopropanols 606 into exo-alkylidene cyclobutanones 608 was recently disclosed by Toste.272 Cationic gold(I) species generated in the presence of AgSbF6 additive renders the alkynyl moiety in 607 highly electrophilic, thereby triggering a 1,2-alkyl shift with cleavage of the more substituted proximal bond to produce conjugated ketones 608 in excellent yields (Scheme 196).272


Rubin et al.

Scheme 194

Scheme 195

Scheme 199

Scheme 196

Scheme 200

Scheme 197

Scheme 198

4.3.2. Cycloisomerization into Cyclopentenes Rearrangement of vinylcyclopropane into cyclopentene under pyrolytic conditions and in the presence of a stoichiometric amount of Rh complex was investigated by Hudlicky (Scheme 197).273 It was found that the stereoselectivity of the Rh-promoted reaction was superior to that observed in the analogous thermal rearrangement and was in favor of the less concave diastereomer 609. This cycloisomerization was employed in the expeditious synthesis of terpenoid hirsutene (Scheme 198).273,274 Doyle showed that vinylcyclopropylcarboxylates 611 undergo rearrangement in the presence of copper catalyst to

give a mixture of cyclopentenes 612 and 613 accompanied by isomeric dienes 614 (Scheme 199).275 It was proposed that this rearrangement involves oxidative addition of copper into the C-C bond of “push-pull” cyclopropane 611 to produce metallacyclobutane species 615, which rearranges into η1-pentadienyl species E-616 upon β-hydride elimination. The latter undergoes hydrometalation to give η3cyclopentenyl species 617, which after reductive elimination produces cyclopentenes 612 and 613. The ring-opened side products E- and Z-614 resulted from reductive elimination of copper from the stereoisomeric intermediates, η1-pentadienylcopper complexes E-616 and Z-616, respectively (Scheme 200).275 Palladium-catalyzed rearrangement of activated dienylcyclopropanes 618 proceeded efficiently at ambient or slightly elevated temperature, affording isomeric mixtures of vinylcyclopentenes 620 in good yields (Scheme 201).276 The mechanism of this transformation was rationalized through the formation of the zwitterionic π-pentadienylpalladium intermediate 619, which collapses to produce the five-membered cyclic product 620 exclusively. Likewise, Hiroi demonstrated that activated optically active VCPs 621 rearrange into nonracemic cyclopentene deriva-



Scheme 206

Scheme 202

Scheme 203

Scheme 204

Suginome and Ito observed isomerization of unactivated VCPs into cyclopentenes as a side process in the Ni(acac)2catalyzed silaboration (section 4.1.1).280 A test experiment in the absence of silaborane reagent demonstrated almost quantitative conversion of 626 into 627 at 90 °C in the presence of Ni catalyst, catalytic amounts of diisobutylaluminum hydride, and tricyclohexylphosphine (Scheme 205).280 Recently, Louie reported that Ni(II) catalyst in combination with heterocyclic carbene ligand 630 enables mild and very efficient rearrangement of unactivated VCPs 628 into cyclopentenes 629 (Scheme 206).281 In the presence of just 1 mol % of the catalyst, 1,1-disubstituted olefins isomerized smoothly at room temperature, while trisubstituted analogues required slight activation by heat. In contrast, 1,2-disubstituted olefins appeared to be much less reactive and, in most cases, did not afford any products even at 100 °C. It was also shown that bicyclic cyclopentenes can be obtained using this methodology in very high yields and complete retention of stereochemistry (Scheme 206).281,282

4.4. Metathesis Reactions tives in the presence of Pd, Pt, or Ni catalysts. The stereoselectivity of this rearrangement depends on the catalyst used, providing the best results with Pd catalysts (Scheme 202).277 Furthermore, it was shown that palladium-catalyzed rearrangement of racemic dienylcyclopropanes 622 possessing a chiral sulfoxide moiety at the diene terminus provided optically active vinylcyclopentenes 623 (Scheme 203).278 Coordination of the sulfinyl group to the palladium center in the π-allylpalladium intermediate of type 619 (Scheme 201) was proposed to account for the observed diastereoselectivity. Among several bidentate phosphine ligands tested, good yields and selectivities were obtained with ligands having shorter tethers (dppe, dppp). Saigo investigated analogous rearrangement of allenylcyclopropanes in the presence of Rh catalysts (Scheme 204).279 When a substituent was present at the cyclopropyl moiety (R2 * H), the formation of two regioisomeric products 624 and 625 was observed, as a result of competitive cleavage of two different proximal bonds a and b, respectively. It was reported that, depending on the nature of the substituents and the catalyst used, either of the regioisomers could be obtained with very high selectivity (Scheme 204).

The olefin metathesis reaction has become a convenient and efficient method for incorporation of a vinylcyclopropane unit into complex frameworks. This approach was employed in a number of total syntheses and synthetic studies toward biologically active molecules and natural products. Thus, in synthetic studies toward ambruticin, Pietruszka investigated cross-metathesis of optically active vinylcyclopropylboronic ester 631 with styrene and methyl acrylate in the presence of a first-generation Grabbs catalyst (Scheme 207).283 It was found that VCP 631 smoothly underwent cross-metathesis with styrene, providing 633a as a single chemo- and stereoisomer in high yield. However, the analogous reaction with electron-deficient olefin 632b proved much more sluggish and less selective, affording crossmetathesis product 633b in moderate yield only, accompanied by notable amounts of bis-cyclopropylethylene 634b.283 When 631 was subjected to the same reaction conditions in the absence of an external olefin, bis-cyclopropylethylene 634b was obtained in 81% yield as a single stereoisomer. En route to the same natural product, Donaldson investigated cross-metathesis between vinylcyclopropane 635 and monosubstituted olefins 636 and 638 (Scheme 208).284 It was shown that the first-generation Grubbs catalyst enabled efficient reaction of 635 with linear olefin 636, affording


Rubin et al.

Scheme 207

Scheme 208

Scheme 209

Ring-closing metathesis (RCM) between vinylcyclopropane and a monosubstituted olefin was employed to assemble the macrocyclic core of the highly potent antiviral agent BILN 2061 (Scheme 210).287 Remarkably, it was found that the nature of the Ru catalyst significantly affected not only the yield but also the stereochemical outcome of the macrocyclization. Thus, the first-generation Grubbs catalyst 646 produced the desired product 644, along with notable amounts of diastereomeric macrocycle 645 as a mixture of E/Z-isomers. The mechanism of this unusual Ru-catalyzed epimerization at the C-2 center of the cyclopropane accompanying the RCM reaction remains unclear. In contrast, employment of the second-generation catalyst 647 afforded 644 as a sole reaction product, albeit in moderate yield only, whereas use of Hoveyda’s complex 648 enabled a very efficient and highly selective reaction producing 644 in very good yield (Scheme 210).287 Scheme 211

rac-637 in good yield as a mixture of E/Z-isomers, whereas attempts to use the same catalyst for cross-metathesis of (+)635 with a more sterically hindered alkene 638 resulted in no reaction. However, the second-generation Grubbs catalyst produced the desired product (+)-639 along with substantial amounts of homodimers. Employment of a large excess of olefin 638 suppressed homodimerization of vinylcyclopropane 635, providing a good yield of cross-metathesis product (+)-639. Two consecutive metathesis reactions involving VCPs were employed by Zercher in the formal total synthesis of FR-900848 (Scheme 209).285 Initially, exposure of 640 to Grubb’s catalyst afforded bis-cyclopropylethylene 641 in good yield and very high trans-selectivity. Subsequent crossmetathesis of 641 with oligocyclopropane fragment 642 efficiently provided 643, one of the key building blocks previously employed by Barrett in the total synthesis of FR900848.286 Scheme 210

Danishefsky employed RCM on vinylcyclopropanes in the synthesis of the resorcinylic macrolide cycloproparadicicol and its analogues (Scheme 211).288 In order to circumvent the unfavorable orientation of the two reacting olefin units in 649, the alkynoate moiety was protected with a dicobalt hexacarbonyl complex. Nonetheless, substantial amounts of second-generation Grubbs catalyst were required to produce


Scheme 213

macrocycles 650 in reasonable yields, which were obtained as mixtures of two diastereomers, presumably due to the above-mentioned epimerization of the adjacent cyclopropane chiral center during RCM.288 Ring-closing metathesis was also explored by Barrett as an approach to coronanes 652 (Scheme 212).289 Interestingly, isomeric styrenes 651a-c displayed significant differences in reactivity toward RCM. Thus, both para- and metasubstituted styrenes 651a and 651b underwent macrocyclization with ca. 50% conversion, whereas orthosubstituted analogue 651c failed to react under these conditions.

5. Reactions of Other Cyclopropanes 5.1. Cross-Coupling Reactions Transition metal-catalyzed cross-coupling reactions are widely employed for functionalization of cyclopropanes and for introduction of a cyclopropyl moiety into more advanced building blocks. Two modes of cross-coupling protocols have been demonstrated on cyclopropyl-containing substrates: reactions between cyclopropylmetal species (nucleophilic component) and aryl or vinyl halides, and reactions between cyclopropylhalides (electrophilic component) and organometallic reagents (Scheme 213). An overwhelming number of examples of cross-coupling involving cyclopropanes belong to the first type. A few reports on Suzuki-Miyaura cross-coupling reactions utilizing the latter approach will be discussed in the corresponding section (Vide infra). Alkylmetal species are generally considered very challenging substrates for palladium-catalyzed cross-coupling reactions. The major shortcoming of these reactions lies in the competing facile β-hydride elimination occurring from an alkylmetal intermediate bearing β-hydrogen atoms, which leads to the formation of an olefin and a reduced electrophilic component. A partial solution to this problem involves the use of electron-deficient ligands that accelerate the reductive Scheme 214


elimination step.290 Another approach entails employment of ligands with π-acceptor properties to stabilize a low-valent state of the transition metal.290 This allows for both acceleration of the reductive elimination and suppression of the β-hydride elimination process.291 Finally, employment of bulky phosphine ligands, which prevent free rotation around the C-C bond toward the syn-orientation of the β-H and the Pd-Ar moiety required for β-hydride elimination,292 substantially expanded the scope of successful cross-coupling reactions involving alkylmetal species. Fortunately, transition metal-catalyzed cross-coupling reactions involving cyclopropylmetals are free from the aforementioned complications. First, the increased s-character of the C-M bond in cyclopropylmetal species accelerates both transmetalation and reductive elimination steps. Second, β-hydride elimination from cyclopropylpalladium species is highly unfavorable in this case from a thermodynamic standpoint, as it would lead to a strained cyclopropene product. On the other hand, the significant steric demand of the cyclopropyl moiety brings complications at the transmetalation step, making crosscoupling of multisubstituted cyclopropylmetals fairly impossible. Nevertheless, quite a few successful examples of crosscoupling involving cyclopropylmetal species catalyzed by Pd and Ni complexes have been reported. These examples are discussed in this section, classified by the type of the main group metals at the nucleophilic coupling component: Mg (Kumada-Corriu coupling), B (Suzuki-Miyaura coupling), Zn, In (Negishi coupling), Si (Hiyama coupling), and Sn (Stille coupling).

5.1.1. Kumada−Corriu Cross-Coupling The first example of a Ni-catalyzed cross-coupling reaction with cyclopropyl Grignard reagents was demonstrated by Luh. In his studies of the Ni-catalyzed reaction of aryl dithioacetals with cyclopropyl magnesium bromide to produce aryl 1,3-butadienes 654 and 657, it was found that halide substituents in the aryl rings of substrates 653 and Scheme 215

656 underwent cross-coupling with excess Grignard reagent, affording arylcyclopropanes 655 and 658 in high yields (Scheme 214).293 Later, Ogle employed Ni-catalyzed


Rubin et al.

Scheme 216

Scheme 217

Scheme 219

Scheme 218

Scheme 220

Kumada-Corriu coupling for preparation of isomeric cyclopropyl toluenes 659 (Scheme 214).294 A moderately efficient palladium-catalyzed Kumada-Corriu coupling between cyclopropylmagnesim bromide and arylbromide 660 was used as a final step in the synthesis of a potent inhibitor of cholesteryl ester transfer protein (CETP), 661 (Scheme 215).295 Nickel-catalyzed cross-coupling of Grignard reagent 662 derived from strained bicyclobutane was demonstrated by Szeimies. Various hetaryl and alkenyl halides were used as electrophilic components in this reaction, allowing for efficient synthesis of a series of strained tricyclic compounds 663a-d (Scheme 216). Twofold cross-coupling with mdichlorobenzene afforded product 664 in moderate yield.296 An analogous reaction between 662 and alkynyl halides to give alkynyl-substituted tricyclic compound 665 in moderate yields was reported by Hashmi (Scheme 216).297 A quite unusual Ni-catalyzed cross-coupling reaction of various alkyl- and alkenylmagnesium halides with arylnitriles involving activation of a C-CN bond was shown by Dankwardt. Among other Grignard reagents, cyclopropylmagnesium bromide reacted smoothly with benzonitrile 666 in the presence of lithium alkoxide or lithium thiophenolate, affording arylcyclopropane 667 in fair to good yields (Scheme 217).298 Nakamura reported cross-coupling of cyclopropylcuprates, readily available via syn-specific carbocupration of cyclopropenone acetals.11 Thus, cuprate 668, generated upon vinylcupration of 147, was treated with hexenyliodide in the presence of Pd catalyst to afford cis-divinylcyclopropane 669. The latter underwent a facile Cope rearrangement into

cycloheptadiene 670 (Scheme 218).299 Similarly, cyclopropylcopper species 672, prepared by diastereoselective methylcupration of cyclopropenone acetal 671 bearing a chiral auxiliary, underwent Pd-catalyzed coupling with chloroformate to give optically active cyclopropyl carboxylate 673 (Scheme 219).300

5.1.2. Negishi Cross-Coupling The palladium-catalyzed cross-coupling reaction of organylzinc reagents (Negishi coupling) tolerates a broader range of functional groups compared to the Kumada-Corriu coupling reaction. The first examples of this reaction involving cyclopropylzinc species were demonstrated by Piers (Scheme 220).301 Cyclopropylzinc reagents 675 were generated in situ from the corresponding cyclopropylstannanes 674 upon stereoselective tin-lithium exchange,47 followed by treatment with anhydrous zinc chloride. SubScheme 221

Scheme 222



Scheme 223

Scheme 224

most likely proceeds stepwise via the classical mechanism.

5.1.3. Stille Cross-Coupling sequent addition of Pd catalyst and vinyl iodides 676 allowed for preparation of vinylcyclopropanes 677,301,302 which were used as advanced intermediates in the total synthesis of (()prezizanol and (()-prezizaene (Scheme 220).301 Carpita and Rossi demonstrated that the cross-coupling reaction can be sometimes complicated by the ring opening of cyclopropane. Thus, reaction between cis-substituted cyclopropylzinc species 678 and vinyl iodide 679 afforded predominantly diene 681 along with traces of the desired vinylcyclopropane 680 (Scheme 221).303 Cyclopropylzinc reagents can also be efficiently coupled with different aryl bromides and aryl iodides. Thus, Campbell used this approach to obtain cyclopropyl anthranilonitrile 682 in very high yield (Scheme 222).304 Brandsma took advantage of the Negishi reaction for stereoselective preparation of trans-diarylcyclopropanes 683 (Scheme 222).305 Recently, Knochel demonstrated that iodocyclopropylcarboxylates 684 undergo facile halogen-magnesium exchange with i-PrMgCl to form cis-cyclopropylmagnesium species 685. The bulky isopropyl group prevents nucleophilic addition to the ester substituent, which serves as an efficient chelating group, ensuring configurational stability of the ciscyclopropylmetal species 685. The latter was transmetalated with retention of configuration with ZnBr2 to give cyclopropyl zinc species 686, which in turn was used in Negishi cross-coupling with 4-iodobenzoate to afford cis-cyclopropane 687 in excellent overall yield (Scheme 223).306 Sarandeses investigated the palladium-catalyzed crosscoupling reaction of various triorganylindium compounds with aryl and vinyl triflates and iodides. Tricyclopropyl indium 688 was also tested in this reaction and afforded the corresponding cross-coupling products in excellent yields (Scheme 224).307 It was demonstrated that all three cyclopropyl groups can be efficiently transferred from the indium reagent, due to significant energy release upon formation of In-Hal bonds. Independently prepared R2InCl and RInCl2 species were equally effective and provided high yields of the cross-coupling products,307 indicating that this reaction Scheme 225

In contrast to other cyclopropylmetal reagents, cyclopropylstannanes display very poor reactivity in cross-coupling reactions, primarily due to sluggish transmetalation of a weakly nucleophilic and very sterically encumbered trialkylstannylcyclopropane. As a result, most of the known examples of Stille reactions involving cyclopropylstannanes exhibit low yields of the coupling products. Thus, crosscoupling of triflate 689 with tributylstannylcyclopropane 690 proved inefficient even in the presence of a very electronrich and labile triphenylarsine ligand (Scheme 225). Apparently, the significant steric bulk created by two orthosubstituents at the aryl ring further diminished the efficacy of this reaction, leading to cross-coupling product 691 in very low yield.308 Attempts at cross-coupling of neat tributylstannylcyclopropane with the very electron-poor aryl iodide 692 under various conditions were unsuccessful (Scheme 225).309 Tetracyclopropylstannane also failed to react with 692. Likewise, cross-coupling of 690 with triflate 693 led to the cleavage of triflate, affording the corresponding phenol derivative only.309 Furthermore, reaction of triflate 694 with 690 provided coupling product 695 with disappointingly low yield (Scheme 226).310 Scheme 226

Likewise, the syntheses of cyclopropyluracil 699 and cyclopropylcytosine 698 via Stille cross-coupling of bromides 696 with cyclopropylstannane 690 provided low yields of the desired cyclopropane derivatives 698 and 699, accompanied by formation of substantial amounts of the dehalogenated side products 697 (Scheme 227).311 Acceleration of Stille cross-coupling in the presence of copper iodide,312 known as the “copper effect”, allowed for significant improvement of yields. Thus, in studies toward




Scheme 229

Scheme 230

Curacin A, Romo employed the Stille cross-coupling reaction to install a cyclopropyl moiety in the thiazoline ring (Scheme 228). It was found that, although a Pd catalyst alone provided 2-cyclopropylthiazoline 700 in very low yield as an inseparable mixture with pyrroline, addition of copper iodide increased the yield of the desired product up to 49% (Scheme 228).313 de Meijere showed that various aryl iodides reacted with trans-aminocyclopropylstannanes 701 in the presence of Pd and Cu catalysts, providing corresponding arylcyclopropylamines 702 in moderate to good yields (Scheme 229).314 However, sterically encumbered o-iodotoluene failed to produce any coupling product.314 Marko applied the same conditions for a double-fold Stille cross-coupling between trans-cyclopropyldistannane 703 and phenyl iodide. Employment of an equimolar amount of phenyl iodide led to an inseparable mixture of mono- and bis-substituted products 704 and 705; however, reaction with 4 equiv of the electrophilic component afforded transdiphenylcyclopropane 705 as the sole product in 55% yield (Scheme 230).315

5.1.4. Suzuki−Miyaura Cross-Coupling Among all transition metal-catalyzed coupling methodologies, the Suzuki-Miyaura cross-coupling reaction has several important advantages that make it a very general synthetic method. Mild reaction conditions and excellent tolerance of a broad range of functional groups are the key features of the Suzuki-Miyaura reaction. Readily available by a variety of methods, organoboron compounds are much less toxic than stannanes, are easily isolable and storable (as opposed to lithium or zinc reagents), yet are reactive enough to

undergo efficient transmetalation and provide high yields of cross-coupling products with a wide range of electrophilic reagents. Thus, not surprisingly, the Suzuki-Miyaura reaction is the most popular choice for cross-coupling with cyclopropane derivatives. The substrates for Suzuki-Miyaura coupling, cyclopropylboronic esters, are usually obtained via cyclopropanation of alkenylboronic esters, which in turn are readily accessible from terminal alkynes316 or alkynylboronates317 with both E- and Z-geometries.316-318 Employment of chiral auxiliaries allows for preparation of enantiomerically enriched substrates via diastereoselective cyclopropanation.319 The first example of Suzuki-Miyaura coupling of transsubstituted cyclopropyl boronates 706 with aryl halides 707 was reported by Marsden (Scheme 231).320 It was found that efficient activation of the boron center in dioxaborinane 706 takes place in the presence of 2 equiv of t-BuOK in t-BuOH, affording trans-disubstituted cyclopropanes 708 in varying yields (Scheme 231).320 The same reaction conditions were used by Pietruszka for preparation of dicyclopropyl compound 710 from dioxaborinate 709 (Scheme 231).38 Interestingly, under the described conditions, boronic ester 709 appeared to be more reactive than the parent boronic acid. This is in striking contrast to other numerous examples, in which the reactivity of cyclopropylboronic acids in SuzukiMiyaura cross-coupling was generally higher than that of the more sterically hindered boronates (Vide infra). Pietruszka also employed palladium-catalyzed crosscoupling between boronic ester 711 and aryl iodides in the synthesis of conformationally constrained non-natural amino acid 712 and its analogues (Scheme 232).321 Suzuki-Miyaura cross-coupling of cyclopropylboronates 713 with benzylbromides was developed by Deng. Upon activation of the boronates by combination of Ag2O and KOH, the reaction proceeded smoothly to afford the corresponding trans-disubstituted cyclopropanes 714 in high yields (Scheme 233).322 de Meijere demonstrated an efficient cross-coupling reaction of trans-2-cyclopropylcyclopropyl borolane 715 with vinyl and aryl bromides and with aryl iodides, leading to the corresponding vinyl- and arylcyclopropanes 716 and 717



Scheme 234

Scheme 237


in good yields. Twofold and even threefold coupling with 1,2-dibromo-, 1,3-dibromo-, and 1,3,5-tribromobenzenes was attempted; however, it provided polycyclopropylarenes 718, 719, and 720 in low yields only (Scheme 234).323 Cyclopropylboronic acids, readily available by hydrolysis of the corresponding boronates, are stable compounds which can be easily handled and purified by recrystallization from water. They are generally more reactive than boronic esters in the Suzuki-Miyaura cross-coupling due to lower steric demands and a more electrophilic boron moiety. Deng extensively investigated the Suzuki-Miyaura cross-coupling reaction of racemic and optically active cyclopropylboronic acids with various electrophilic counterparts, such as aryl halides,36 aryl sulfonates,324 hetaryl halides,325 hetaryl triflates,326 alkenyl halides,327 enol triflates,328 and allyl329 and acyl halides.330 Reactions were normally carried out in the presence of 3-5 mol % of a palladium catalyst with PPh3 or AsPh3 as ligand and KOH, KF, K3PO4‚3H2O, or CsCO3 as base. In many cases, activation by Ag2O was necessary for achieving high yields of products. Cross-coupling of cyclopropylboronic acids with allyl bromides and acyl chlorides gave no reaction in the presence of PPh3; however, they proceeded smoothly when an electron-rich dppf ligand was employed.329,330 Likewise, Wallace found that replacement of PPh3 with a bulky electron-rich PCy3 ligand was beneficial for achieving good yields in Suzuki-Miyaura cross-coupling of a nonsubstituted cyclopropylboronic acid (Scheme 235).331 It was also noted that addition of water caused significant acceleration of the Suzuki-Miyaura reaction.331 Recently, Doucet reported a very efficient palladium catalyst bearing tetradentate ligand Tedicyp for crosscoupling of cyclopropylboronic acid with substituted aryl bromides and aryl chlorides 721 (Scheme 236).332 This complex is believed to possess the right combination of steric and electronic properties that are particularly suitable for the efficient coupling of cyclopropylboronic acids. Thus, while

no reaction occurred with isopropyl- or any cycloalkylboronic acids with different ring sizes, cyclopropyl derivatives afforded very high yields of the corresponding coupling products 722. The reaction was found to be practically insensitive to the nature of the electrophilic component, proceeding equally well with both electron-poor and electronrich aryl halides. Turnover numbers, which are somewhat lower with aryl chlorides, reach impressive values of a few thousands with aryl bromides, ensuring nearly quantitative yields for catalyst loadings of 0.1-0.4 mol % (Scheme 236).332 All the successful examples of the Suzuki-Miyaura reaction described above involved unsubstituted or transsubstituted cyclopropylboronates only. Analogous reactions with cis-substituted cyclopropylboronates are scarce, as a result of a significant decrease of the reaction rates caused by cis-substitution to the B(OH)2 group. This problem was recently addressed by Gevorgyan, who showed that enantiomerically enriched cis-substituted boronic acids 723 activated by CsF can be efficiently coupled in the presence of Pd(0) catalyst bearing a P(But)3 ligand to afford the corresponding optically active aryl- and vinylcyclopropanes 724 (Scheme 237).49 Later, Deng reported that air stable trifluoroborates 725 and 727, obtained by treatment of cyclopropylboronic acids with excess KHF2, are very active substrates for SuzukiMiyaura cross-coupling with aryl bromides. Both trans- and cis-isomers reacted smoothly, affording disubstituted cyclopropanes 726 and 728 in high yields with complete retention of configuration (Scheme 238).333 Application of this methodology to the synthesis of enantiomerically pure arylcyclopropanes was recently demonstrated by Pietruszka.334 Cyclopropyl derivatives of 9-BBN can also undergo a Suzuki-Miyaura cross-coupling reaction when activated by nucleophilic attack of hydroxide or alkoxide anion. Thus,




Scheme 241

Scheme 244

corresponding products 740 in good yields. Remarkably, cis739 reacted readily as well, providing the corresponding cyclopropylboronic ester 741 (Scheme 243).339 The obtained boronic esters 740 and 741 can further be utilized as nucleophilic components in the second Suzuki-Miyaura cross-coupling reaction or in other stereoselective transformations of cyclopropyl boronates, such as oxidation into cyclopropanols340 or Matteson homologation.38,321,341 Soderquist demonstrated that hydroxyborate 729, readily available via hydroboration/cyclization of propargylbromide,335 underwent cross-coupling with aryl and alkenyl bromides in the presence of catalytic amounts of Pd(PPh3)4 to give 730 in good to excellent yields (Scheme 239).336 In a similar transformation reported by Fu¨rstner, a combination of Pd(OAc)2 with imidazolium salt 732 was employed as a catalyst, which allowed for efficient cross-coupling of alkoxyborate 731 with aryl chlorides (Scheme 240).337 As mentioned in the introductory part, cyclopropylhalides can undergo cross-coupling reaction as electrophilic partners. Indeed, facile oxidative addition of palladium to cyclopropyliodide makes it a suitable electrophilic component for Suzuki-Miyaura cross-coupling with a wide range of boronic acids and esters. Thus, cross-coupling between cyclopropylboronates 733 and cyclopropyliodides 734 was employed by Charette to assemble oligocyclopropane building blocks 735 in synthetic studies toward natural oligocyclopropanes U-106305 and FR-900848 (Scheme 241).338 He also reported efficient cross-coupling of cyclopropyliodides 736 with aryl-, hetaryl-,37 and alkenylboronates to produce the corresponding aryl- (737) and alkenylcyclopropanes (738) in reasonable to high yields (Scheme 242).37 Pietruszka demonstrated that the optically active 2-iodocyclopropylboronic esters cis- and trans-739 can be used as ambiphilic cyclopropyl building blocks. A bulky chiral auxiliary at boron efficiently suppressed homocoupling of trans-739, allowing for selective cross-coupling between the cyclopropyl iodide and external boronic acid to give the

5.1.5. Oxidative Homocoupling of Cyclopropylmetal Species An example of oxidative homocoupling of two cyclopropyltin units was demonstrated by Itoh (Scheme 244).342 These conditions, originally reported by Liebeskind for the palladium-catalyzed oxidative dimerization of stannylquinones,343 were successfully applied for homocoupling of 742, furnishing the corresponding bis-cyclopropanes 743 in 66% yield. Related copper-catalyzed oxidative homocoupling of cyclopropyllithium species 745, generated in situ from bromocyclopropane 744, afforded quatercyclopropane 746 (Scheme 245).344,345 The latter was used as an advanced intermediate in Falck’s total synthesis344 of the polycyclopropane antibiotic FR-900848 (Scheme 241). Scheme 245

5.2. Miscellaneous Reactions 5.2.1. C−H Activation Reactions An interesting example of palladium(II)-catalyzed asymmetric iodination of cyclopropane in the presence of



Scheme 246

Scheme 247

PhI(OAc)2 was recently reported by Yu.346 Reaction of oxazoline 747 derived from cyclopropane carboxylic acid and tert-leucinol provided cis-iodocyclopropane 748 in good yield and excellent diastereoselectivity (Scheme 246). In contrast to the preferential activation of a C-H bond in the methyl group observed in the reactions with acyclic and nonstrained cyclic substrates, the cyclopropyl analogue 747 demonstrated a reversed reactivity pattern, favoring C-H activation in the methylene moiety, producing iodocyclopropane 748 as a sole product. It was proposed that this transformation involves initial formation of a trinuclear coordination complex 749, which, upon dissociation of HOAc and diastereoselective activation of the cis-C-H bond, provided cyclopropylpalladium complex 750. The latter upon reaction with iodine immediately produced 748 and a PdI2 complex, which is catalytically inactive but can be transformed into Pd(OAc)2 by reaction with PhI(OAc)2 (Scheme 246).346

5.2.2. Rearrangement of Acylcyclopropanes into Dihydrofurans Acylcyclopropane to dihydrofuran rearrangement represents a heteroanalogue of vinylcyclopropane to cyclopentene rearrangement described in section 4.3.2. Activated pushpull substrates possessing an electron-donating group vicinal to the acyl function readily undergo this transformation in uncatalyzed fashion, as shown by Wenkert,347 Alonso,348 and Davies.349 In the case of nonactivated substrates, Lewis acid or transition metal catalysis is required for efficient re-

Scheme 248

arrangement.350 Thus, Johnson reported Ni(0)-catalyzed cycloisomerization of 1-acyl-2-vinylcyclopropanes 751, which proceeds at room temperature, affording dihydrofurans 753 in high yields (Scheme 247).351 It was proposed that Ni(0) triggers cyclopropane ring opening, producing π-allylmetal species 752, which undergoes intramolecular nucleophilic attack by the pendant enolate moiety leading to dihydrofuran 753 (Scheme 247). Interestingly, employment of a nonracemic substrate 754 led to the formation of optically active product 755 with retention of configuration, presumably via a standard double-inversion mechanism.352 Attempted asymmetric rearrangement using nonracemic Ni(0) catalysts failed to afford enantioenriched products (Scheme 247).351

5.2.3. Cycloaddition of Nitrones to Cyclopropanes Sibi reported enantioselective Ni-catalyzed [3 + 3] cycloaddition of activated cyclopropanes to nitrones (Scheme 248).353 In the presence of Ni(II) perchlorate and chiral


Rubin et al.

Scheme 249

Scheme 250

bisoxazoline ligand 758, cyclopropyldicarboxylates 756 readily reacted with 757, affording the corresponding tetrahydrooxazines 759 in excellent yields and high enantioselectivity.

5.2.4. [3 + 2] Cycloaddition of Activated Cyclopropanes to Enones An elegant approach toward cyclopentanes 761 and 764 via the [3 + 2] cycloaddition of activated cyclopropanes 760 and 762 with conjugated enones 763 was recently independently disclosed by Montgomery354 and Ogoshi and Kurosawa355 (Scheme 249). It was shown that, in the presence of Ni catalyst, cyclopropane 760 afforded homocycloaddition product 761 with very high diastereoselectivity (Scheme 249). In contrast, slow addition of external enone 763 to a reaction mixture containing 762 allowed for the crosscycloaddition product 764 exclusively. Accordingly, it was proposed that this reaction proceeds via the cyclic nickel enolate 765, which in the absence of 763 undergoes reductive elimination to produce enone 766 (Scheme 250). The latter, upon [3 + 2] cycloaddition with another molecule of enolate 765, affords nickelacycle 767, which after reductive elimination gives dimer 761. Alternatively, the reaction of 765 with external conjugated enone 763 produces, via analogous metallacyclic intermediate 768, cross-cycloaddition product 764 (Scheme 250).354,356 Interestingly, when this reaction was carried out at room temperature, enonenickel dimeric complex 769 was isolated in high yield, thus confirming the intermediacy of conjugated enone 766.355

more, a diverse reactivity pattern resulting from the significant strain energy accounts for the use of small carbocycles as convenient models for investigation of organic and organometallic reaction mechanisms. There is also a growing interest in small carbocycles from the related fields of medicinal and biological chemistry. Thus, rigid threemembered cyclic units incorporated into biologically important molecules are now widely used for elucidation of mechanisms and identification of critical enzyme binding sites. Employment of transition metals has revolutionized the chemistry of small cycles by making highly chemoselective reactions possible, addressing the regio- and stereocontrol, thereby dramatically expanding the scope of available transformations. In addition to protocols employing wellestablished catalysts, such as Pd, Rh, and Ru complexes, efficient Cu-, Pt-, and Au-catalyzed transformations of strained carbocycles have recently emerged as exciting new directions of research in this area. Transition metal-catalyzed chemistry of three-membered carbocycles is now ubiquitous and vigorously developing, spanning highly stereoselective addition, cycloaddition, and cycloisomerization reactions, efficient cross-coupling protocols, C-H activation, and metathesis reactions. Along with these methodologies, novel approaches toward synthesis of diversely substituted optically active three-membered carbocycles are being extensively developed. Altogether, this opens new exciting opportunities for organic synthesis and guarantees a prolific future for the transition metal chemistry of small rings.

7. Abbreviations 6. Conclusion The importance of strained carbocycles has long been recognized in organic chemistry. Due to the limited degrees of freedom in the system, these conformationally constrained molecules have very pronounced steric, stereoelectronic, and directing effects, which make them versatile probes for the study of regio-, diastereo-, and enantioselectivity. Further-

Ac acac Alk Ar BARF BBN BINAP bipy

acetyl acetylacetonate alkyl aryl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate 9-borabicylo[3.3.1]nonane 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene 2,2′-bipyridyl

Transition Metal Chemistry of Cyclopropenes Bn bnp Boc Bz cat COD Cp Cy dba DBU DCE DCM DIBAH DIOP

benzyl 2,2′-(1,1′-binaphthyl)phosphate tert-butoxycarbonyl benzoyl catalyst, catalytic 1,5-cyclooctadiene cyclopentadienyl cyclohexyl 1,3-dibenzylideneacetone 1,5-diazabicyclo[5.4.0]undec-5-ene dichloroethane dichloromethane diisobutylaluminum hydride O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane DMF N,N-dimethylformamide DMSO dimethylsulfoxide dppb 1,4-bis(diphenylphosphino)butane dppe 1,2-bis(diphenylphosphino)ethane dppf 1,1′-bis(diphenylphosphino)ferrocene dpph 1,6-bis(diphenylphosphino)hexane dppp 1,3-bis(diphenylphosphino)propane E electrophile Et-BPE 1,2-bis(2,5-diethylphospholano)ethane EWG electron-withdrawing group L ligand MCP methylenecyclopropane Mes mesityl MMAO modified methylaluminoxane MOM methoxymethyl MS molecular sieves nbd norbornadiene NMO N-methylmorpholine-N-oxide NMP N-methylpyrrolidinone Nu nucleophile pfb perfluorobutyrate phsp 1-(phenylsulfonyl)prolinate pin pinacol PKR Pauson-Khand reaction PMB p-methoxybenzyl ptpa 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-phenylpropanoate rt room temperature TBAF tetrabutylammonium fluoride TBDPS tert-butyldiphenylsilyl TBS tert-butyldimethylsilyl TDMPP tris(2,5-dimethoxyphenyl)phosphine Tf triflyl, trifluoromethylsulfonyl TFE 2,2,2-trifluoroethanol THF tetrahydrofuran THP tetrahydropyranyl TIPS triisopropylsilyl TMEDA N,N,N′,N′-tetramethylethylenediamine TMS trimethylsilyl Tol-BINAP 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthalene TON turnover number Ts tosyl, p-toluenesulfonyl VCP vinylcyclopropane

8. Acknowledgments Financial support by the University of Kansas (M.R.) and the National Science Foundation CHE-0710749 (V.G.) is gratefully acknowledged.

9. References (1) Latin: much in little. (2) (a) Bach, R. D.; Dmitrenko, O. J. Am. Chem. Soc. 2006, 128, 4598. (b) Khoury, P. R.; Goddard, J. D.; Tam, W. Tetrahedron 2004, 60,


(3)

(4) (5)

(6)

(7) (8) (9)

(10) (11) (12) (13)

(14) (15)

(16)

(17) (18) (19) (20) (21) (22) (23) (24) (25)

(26) (27) (28) (29) (30) (31) (32) (33) (34) (35)

8103. (c) Fattahi, A.; McCarthy, R. E.; Ahmad, M. R.; Kass, S. R. J. Am. Chem. Soc. 2003, 125, 11746. (a) Walsh, R. Chem. Soc. ReV. 2005, 34, 714. (b) Baird, M. S. Chem. ReV. 2003, 103, 1271. (c) Dolbier, W. R., Jr.; Battiste, M. A. Chem. ReV. 2003, 103, 1071. (d) Sekiguchi, A.; Lee, V. Y. Chem. ReV. 2003, 103, 1429. (e) Chen, K.-C.; Lee, G.-A. Huaxue 2006, 64, 73. Baird, M. S. In Houben-Weyl: Methods of Organic Chemistry, 4th ed.; de Meijere, A., Ed.; Thieme: Stuttgart, 1996; Vol. E17d, pp 2695-2744. For reviews on other methods for the preparation of cyclopropenes, see: (a) Baird, M. S. In Houben-Weyl: Methods of Organic Chemistry, 4th ed.; de Meijere, A., Ed.; Thieme: Stuttgart, 1996; Vol. E17d, pp 2747-2759. (b) Hopf, H. In Houben-Weyl: Methods of Organic Chemistry, 4th ed.; de Meijere, A., Ed.; Thieme: Stuttgart, 1996; Vol. E17d, pp 2745-2746. (a) Doyle, M. P.; Winchester, W. P.; Hoorn, J. A. A.; Lynch, V.; Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968. (b) Doyle, M. P.; Protopopova, M.; Mu¨ller, P.; Ene, D.; Shapiro, E. A. J. Am. Chem. Soc. 1994, 116, 8492. (c) Doyle, M. P.; Ene, D. G.; Peterson, C. S.; Lynch, V.; Angew. Chem., Int. Ed. 1999, 38, 700. (d) Mu¨ller, P.; Imogai, H. Tetrahedron: Asymmetry 1998, 9, 4419. (a) Davies, H. M. L.; Lee, G. H. Org. Lett. 2004, 6, 1233. (b) Nawlan, D. T., III; Singleton, D. A. J. Am. Chem. Soc. 2005, 127, 6190. Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916. (a) Fox, J. M.; Yan, N. Curr. Org. Chem. 2005, 9, 719. (b) Liao, L. A.; Zhang, F.; Yan, N.; Golen, J. A.; Fox, J. M. Tetrahedron 2004, 60, 1803. (c) Liao, L. A.; Zhang, F.; Dmintrenko, O.; Bach, R. D.; Fox, J. M. J. Am. Chem. Soc. 2004, 126, 4490. Rubin, M.; Gevorgyan, V. Synthesis 2004, 796. Nakamura, M.; Isobe, H.; Nakamura, E. Chem. ReV. 2003, 103, 1295. Halton, B. Chem. ReV. 2003, 103, 1327. (a) Staley, S. W.; Norden, T. D. J. Am. Chem. Soc. 1984, 106, 3699. (b) Billups, W. E.; Lin, L.-J.; Casserly, E. W. J. Am. Chem. Soc. 1984, 106, 3698. (c) Maier, G.; Hoppe, M.; Lanz, K.; Reisenauer, H. P. Tertrahedron Lett. 1984, 25, 5645. Yoshida, Z.; Konishi, H. In Houben-Weyl: Methods of Organic Chemistry, 4th ed.; de Meijere, A., Ed.; Thieme: Stuttgart, 1997; Vol. E17d, pp 2983-3078. (a) Jacobsen, H.; Ziegler, T. J. Am. Chem. Soc. 1994, 116, 3667. (b) Windus, T. L.; Gordon, M. S. J. Am. Chem. Soc. 1992, 114, 9559. (c) Khabashesku, V. N.; Kudin, K. N.; Tamas, J.; Boganov, S. E.; Margrave, J. L.; Nefedov, O. M. J. Am. Chem. Soc. 1998, 120, 5005. (a) Johnson, W. T. G.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 5930. (b) Alcami, M.; Mo, O.; Yanez, M. J. Comput. Chem. 1998, 19, 1072. (c) Bach, R. D.; Dmitrenko, O. J. Am. Chem. Soc. 2004, 126, 4444. Samuelson, A. G. Proc.sIndian Acad. Sci., Chem. Sci. 1984, 93, 729. For preparation of MCPs, see: Brandi, A.; Goti, A. Chem. ReV. 1998, 98, 598. de Meijere, A.; Kozhushkov, S. I.; Khlebnikov, A. F. Top. Curr. Chem. 2000, 207, 89. Nakamura, I.; Yamamoto, Y. AdV. Synth. Catal. 2002, 344, 111. (a) Lautens, M.; Ren, Y.; Delanghe, P. H. M. J. Am. Chem. Soc. 1994, 116, 8821. (b) Lautens, M.; Ren, Y. J. Am. Chem. Soc. 1996, 118, 9597. Binger, P.; Buech, H. M. Top. Curr. Chem. 1987, 135, 77. Donaldson, W. A. AdV. Met.-Org. Chem. 1991, 2, 269. Lautens, M.; Ren, Y.; Delanghe, P.; Chiu, P.; Ma, S.; Colucci, J. Can. J. Chem. 1995, 73, 1251. (a) Schleyer, P. v. R.; Buss, V. J. Am. Chem. Soc. 1969, 91, 5880. (b) Wolf, J.; Harch, R. W.; Taft, R. W.; Hehre, W. J. J. Am. Chem. Soc. 1975, 97, 2903. (c) Brown, H. C.; Ravindranathan, M. J. Am. Chem. Soc. 1975, 97, 2895. (a) Gleiter, R. Top. Curr. Chem. 1979, 86, 197. (b) Harada, Y.; Seki, K.; Suzuki, A.; Inokuchi, H. Chem. Lett. 1973, 893. de Meijere, A.; Luttke, W. Tetrahedron 1969, 25, 2047. Wender, P. A.; Gamber, G. G.; Williams, T. J. In Modern RhodiumCatalyzed Organic Reactions; Evans, P. A., Ed.; Wiley: Weinheim, 2005; p 263. Trost, B. M.; Shen, H. C.; Horne, D. B.; Toste, F. D.; Steinmetz, B. G.; Koradin, C. Chem.sEur. J. 2005, 11, 2577. de Meijere, A.; Kurahashi, T. Synlett 2005, 2619. Sarel, S. Acc. Chem. Res. 1978, 11, 208. Khusnutdinov, R. I.; Dzhemilev, U. M. J. Organomet. Chem. 1994, 471, 1. For recent review, see: Wang, S. C.; Tantillo, D. J. J. Organomet. Chem. 2006, 691, 4386. For thermal rearrangements, see: Baldwin, J. E. Chem. ReV. 2003, 103, 1197. Salau¨n, J. Chem. ReV. 2005, 105, 396.

3176 Chemical Reviews, 2007, Vol. 107, No. 7 (36) Zhou, S.-M.; Deng, M.-Z.; Xia, M.-Z.; Tang, M.-H. Angew. Chem., Int. Ed. 1998, 37, 2845. (37) Charette, A. B.; Giroux, A. J. Org. Chem. 1996, 61, 8718. (38) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 2000, 65, 9194. (39) Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006, 1221. (40) Nakamura, M.; Hirai, A.; Nakamura, E. J. Am. Chem. Soc. 2000, 122, 978. (41) Liao, L.; Fox, J. M. J. Am. Chem. Soc. 2002, 124, 14322. (42) Liu, X.; Fox, J. M. J. Am. Chem. Soc. 2006, 128, 5600. (43) Nowlan, D. T., III; Gregg, T. M.; Davies, H. M. L.; Singleton, D. A. J. Am. Chem. Soc. 2003, 125, 15902. (44) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2002, 124, 11566. (45) (a) Nakamura, E.; Machii, D.; Imbushi, T. J. Am. Chem. Soc. 1989, 111, 6849. (b) Yamago, S.; Ejiri, S.; Nakamura, E. Chem. Lett. 1994, 1889. (46) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2004, 126, 3688. (47) Rubina, M.; Gevorgyan, V. Tetrahedron 2004, 60, 3129. (48) Trofimov, A.; Gevorgyan, V. Unpublished results. (49) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 125, 7198. (50) Suginome, M.; Ito, Y. Chem. ReV. 2000, 100, 3221. (51) Pohlmann, T.; de Meijere, A. Org. Lett. 2000, 2, 3877. (52) Trost, B. M.; Sorum, M. T.; Chan, C.; Harms, A. E.; Ruther, G. J. Am. Chem. Soc. 1997, 119, 698. (53) Gevorgyan, V.; Ukkiramapandian, R.; Takeda, A.; Rubina, M.; Rubin, M.; Yamamoto, Y. J. Org. Chem. 2001, 66, 2835. (54) Trost, B. M.; Kottirsch, G. J. Am. Chem. Soc. 1990, 112, 2816. (55) Rubin, M.; Markov, J.; Chuprakov, S.; Wink, D. J.; Gevorgyan, V. J. Org. Chem. 2003, 68, 6251. (56) Yin, J.; Chisholm, J. D. Chem. Commun. 2006, 632. (57) Rubina, M.; Rubin, M.; Gevorgyan, V. Unpublished results. (58) Nakamura, I.; Bajracharya, G. B.; Yamamoto, Y. J. Org. Chem. 2003, 68, 2297. (59) (a) D’yakonov, I. A.; Kostikov, R. R. Zh. Obshch. Khim. 1964, 34, 1383. (b) Henseling, K. O.; Weyerstahl, P. Chem. Ber. 1975, 108, 2803. (c) Franck-Neumann, M.; Miesch, M. Tetrahedron Lett. 1982, 23, 1409. (d) Imogai, H.; Bernardinelli, G.; Gra¨nicher, C.; Moran, M.; Rossier, J.-C.; Mu¨ller, P. HelV. Chim. Acta 1998, 81, 1754. (60) Barrett, A. G. M.; Tam, W. J. Org. Chem. 1997, 62, 7673. (61) (a) Barluenga, J.; Suarez-Sobrino, A. L.; Tomas, M.; Garcia-Granda, S.; Santiago-Garcia, R. J. Am. Chem. Soc. 2001, 123, 10494. (b) Larionov, O. V.; de Meijere, A. Org. Lett. 2004, 6, 2153. (c) Gilligan, P. J.; Folmer, B. K.; Hartz, R. A.; Koch, S.; Nanda, K. K.; Andreuski, S.; Fitzgerald, L.; Miller, K.; Marshall, W. J. Bioorg. Med. Chem. 2003, 11, 4093. (62) Kawamura, N. Jpn. Kokai Tokkyo Koho 1996, JP 08073400 A2 19960319; CAN 125:57975. (63) Nalesnik, T. E.; Orchin, M. J. Organomet. Chem. 1981, 222, C5C8. (64) Nalesnik, T. E.; Freudenberger, J. H.; Orchin, M. J. Organomet. Chem. 1982, 236, 95. (65) Matsui, Y.; Orchin, M. J. Organomet. Chem. 1983, 244, 369. (66) Jessop, P. G.; Ikariya, T.; Noyori, R. Organometallics 1995, 14, 1510. (67) Kireev, S. L.; Smit, V. A.; Ugrak, B. I.; Nefedov, O. M. Bull. Acad. Sci. USSR (Engl. Transl.) 1991, 2240. (68) Witulski, B.; Go¨ssmann, M. Synlett 2000, 1793. (69) (a) Marchueta, I.; Verdaguer, X.; Moyano, A.; Pericas, M. A.; Riera, A. Org. Lett. 2001, 3, 3193. (b) Pericas, M. A.; Balsells, J.; Castro, J.; Marchueta, I.; Moyano, A.; Riera, A.; Vazquez, J.; Verdaguer, X. Pure Appl. Chem. 2002, 74, 167. (70) Nu¨ske, H.; Bra¨se, S.; de Meijere, A. Synlett 2000, 1467. (71) Pallerla, M. K.; Fox, J. M. Org. Lett. 2005, 7, 3593. (72) Diev, V. V.; Kostikov, R. R.; Gleiter, R.; Molchanov, A. P. J. Org. Chem. 2006, 71, 4006. (73) (a) Isaka, M.; Matsuzawa, S.; Shigeru, Y.; Ejiri, S.; Miyachi, Y.; Nakamura, E. J. Org. Chem. 1989, 54, 4727. (b) Isaka, M.; Ejiri, S.; Nakamura, E. Tetrahedron 1992, 48, 2045. (74) Poloukhtine, A.; Popik, V. V. J. Org. Chem. 2003, 68, 7833. (75) Jeong, Y.-T.; Jung, J.-H.; Choi, S.-K. J. Chem. Soc., Perkin Trans. 1 1997, 823. (76) Liao, L.-A.; Yan, N.; Fox, J. M. Org. Lett. 2004, 6, 4937. (77) Untiedt, S.; de Meijere, A. Chem. Ber. 1994, 127, 1511. (78) Xu, W.; Chen, Q.-Y. J. Org. Chem. 2002, 67, 9421. (79) Baird, M. S.; Al Dulayymi, J. R.; Rzepa, H. S.; Thoss, V. J. Chem. Soc., Chem. Commun. 1992, 1323. (80) Cheng, Z.-L.; Chen, Q.-Y. J. Fluor. Chem. 2005, 126, 39. (81) Chuprakov, S.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 3714. (82) For reviews on the Do¨tz reaction, see: (a) Alcaide, B.; Casarrubios, L.; Dominguez, G.; Sierra, M. A. Curr. Org. Chem. 1998, 2, 551. (b) de Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int.

Rubin et al.

(83)

(84) (85) (86) (87) (88) (89) (90)

(91)

(92) (93) (94) (95) (96) (97) (98) (99) (100) (101) (102) (103) (104) (105) (106) (107) (108) (109) (110) (111) (112) (113) (114)

(115) (116) (117) (118) (119) (120)

Ed. 2000, 39, 3964. (c) Sola, M.; Duran, M.; Torrent, M. Catal. Met. Complexes 2002, 25, 269. (a) Semmelhack, M. F.; Ho, S.; Steigerwald, M.; Lee, M. C. J. Am. Chem. Soc. 1987, 109, 4397. (b) Semmelhack, M. F.; Ho, S.; Cohen, D.; Steigerwald, M.; Lee, M. C.; Lee, G.; Gilbert, A. M.; Wulff, W. D.; Ball, R. G. J. Am. Chem. Soc. 1994, 116, 7108. Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631. Tomilov, Y. V.; Shapiro, E. A.; Protopopova, M. N.; Ioffe, A. I.; Dolgii, I. E.; Nefedov, O. M. IzV. Akad. Nauk SSSR Ser. Khim. 1985, 631. Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44, 3343. (a) Mu¨ller, P.; Pautex, N.; Doyle, M. P.; Bagheri, V. HelV. Chim. Acta 1990, 73, 1233. (b) Mu¨ller, C.; Gra¨nicher, C. HelV. Chim. Acta 1993, 76, 521. Padwa, A.; Kassir, J. M.; Xu, S. L. J. Org. Chem. 1991, 56, 6971. Mu¨ller, P.; Gra¨nicher, C. HelV. Chim. Acta 1995, 78, 129. (a) Ma, S.; Lu, L.; Lu, P. J. Org. Chem. 2005, 70, 1063. (b) Basak, A.; Mandal, S. Tetrahedron Lett. 2002, 43, 4241. (c) Lee, Y. R.; Suk, J. Y. Tetrahedron Lett. 2000, 41, 4795. (d) Davies, H. M. L.; Cantrell, W. R., Jr.; Romines, K. R.; Baum, J. S. Org. Synth. 1992, 70, 93. (a) Kinder, F. R.; Padwa, A. Tetrahedron Lett. 1990, 31, 6835. (b) Padwa, A.; Kinder, F. R. J. Org. Chem. 1993, 58, 21. (c) Gettwert, V.; Krebs, F.; Maas, G. Eur. J. Org. Chem. 1999, 1213. (d) Snyder, J. P.; Padwa, A.; Stengel, T. J. Am. Chem. Soc. 2001, 123, 11318. Hoye, T. R.; Dinsmore, C. J.; Johnson, D. S.; Korkowski, P. F. J. Org. Chem. 1990, 55, 4518. Padwa, A.; Chiacchio, U.; Garreau, Y.; Kassir, J. M.; Krumpe, K. E.; Schoffstall, A. M. J. Org. Chem. 1990, 55, 414. Mu¨ller, P.; Allenbach, Y. F.; Bernardinelli, G. HelV. Chim. Acta 2003, 86, 3164. Mu¨ller, P.; Gra¨nicher, C.; Klaerner, F.-G.; Breikopf, V. Gazz. Chim. Ital. 1995, 125, 459. (a) Tollari, S.; Palmisano, G.; Cenini, S.; Cravotto, G.; Giovenzana, G. B. Synthesis 2001, 735. (b) Rosenfeld, M. J.; Ravi Shankar, B. K.; Shechter, H. J. Org. Chem. 1988, 53, 2699. Pirrung, M. C.; Blume, F. J. Org. Chem. 1999, 64, 3642. Padwa, A.; Straub, C. S. J. Org. Chem. 2003, 68, 227. Padwa, A.; Straub, C. S. Org. Lett. 2000, 2, 2093. Ma, S.; Zhang, J. J. Am. Chem. Soc. 2003, 125, 12386. Chuprakov, S.; Gevorgyan, V. Unpublished results. Tallarico, J. A.; Randall, M. L.; Snapper, M. L. Tetrahedron 1997, 53, 16511. Singh, R.; Czekelius, C.; Schrock, R. R. Macromolecules 2006, 39, 1316. Michaut, M.; Parrain, J.-L.; Santelli, M. Chem. Commun. 1998, 2567. Statsuk, A. V.; Liu, D.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 9546. For a review, see: Goldschmidt, Z. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1995; Vol. 2, pp 495-695. Isaeva, L. S.; Peganova, T. A.; Petrovskii, P. V.; Kravtsov, D. N. J. Organomet. Chem. 1989, 376, 141. Weiss, H.; Hampel, F.; Donaubauer, W.; Grundl, M. A.; Bats, J. W.; Hashmi, A. S. K.; Schindler, S. Organometallics 2001, 20, 1713. Li, R. T.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1994, 116, 10032. Hughes, D. L.; Leigh, G. J.; McMahon, C. N. J. Chem. Soc., Dalton Trans. 1997, 1301. Huges, R. P.; Reisch, J. W.; Rheingold, A. L. Organometallics 1985, 4, 241. Fo¨rstner, J.; Kakoschke, A.; Stellfeldt, B.; Butenschon, H.; Wartchow, R. Organometallics 1998, 17, 893. Fo¨rstner, J.; Kakoscke, A.; Wartchow, R.; Butenschon, H. Organometallics 2000, 19, 2108. (a) Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1993, 115, 8130. (b) de la Mata, F. J.; Grubbs, R. H. Organometallics 1996, 15, 577. (c) Fujimura, O.; de la Mata, F. J.; Grubbs, R. H. Organometallics 1996, 15, 1865. (d) de la Mata, F. J. J. Organomet. Chem. 1996, 525, 183. (a) Binger, P.; Mu¨ller, P.; Wenz, R.; Mynott, R. Angew. Chem. 1990, 102, 1070. (b) Binger, P.; Mu¨ller, P.; Benn, R.; Mynott, R. Angew. Chem. 1989, 101, 647. Binger, P.; Mu¨ller, P.; Hermann, A. T.; Phillips, P.; Gabor, B.; Langhau, F. Chem. Ber. 1991, 124, 2165. Flatt, B. T.; Grubbs, R. H.; Blanski, R. L.; Calabrese, J. C.; Feldman, J. Organometallics 1994, 13, 2728. Huang, J.-H.; Lee, T.-Y.; Swenson, D. C.; Messerle, L. Inorg. Chim. Acta 2003, 345, 209. Green, M.; Orpen, A. G.; Schaverien, C. J. J. Chem. Soc., Dalton Trans. 1989, 1333. (a) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1992, 114, 3974. (b) Nguyen, S. T.; Grubbs, R. H.;


(121) (122) (123) (124) (125) (126) (127) (128) (129) (130) (131) (132) (133) (134) (135) (136)

(137) (138) (139) (140) (141) (142) (143) (144)

(145) (146) (147)

(148)

(149)

Ziller, J. W. J. Am. Chem. Soc. 1993, 115, 9858. (c) Gagne, M. P.; Grubbs, R. H. Organometallics 1992, 11, 3933. Sanford, M. S.; Valdez, M. R.; Grubbs, R. H. Organometallics 2001, 20, 5455. Gilbertson, R. D.; Weakley, T. J. R.; Haley, M. M. Chem.sEur. J. 2000, 6, 437. Wu, H.-P.; Weakley, T. J. R.; Haley, M. M. Organometallics 2002, 21, 4320. Wu, H.-P.; Weakley, T. J. R.; Haley, M. M. Chem.sEur. J. 2005, 11, 1191. Iron, M. A.; Lucassen, A. C. B.; Cohen, H.; van der Boom, M. E.; Martin, J. M. L. J. Am. Chem. Soc. 2004, 126, 11699. Gilbertson, R. D.; Lau, T. L. S.; Lanza, S.; Wu, H.-P.; Weakley, T. J. R.; Haley, M. M. Organometallics 2003, 22, 3279. Jacob, V.; Weakley, T. J. R.; Haley, M. M. Organometallics 2002, 21, 5394. Gilbertson, R. D.; Weakley, T. J. R.; Haley, M. M. J. Am. Chem. Soc. 1999, 121, 2597. Wu, H.-P.; Lanza, S.; Weakley, T. J. R.; Haley, M. M. Organometallics 2002, 21, 2824. (a) Landorf, C. W.; Jacob, V.; Weakley, T. J. R.; Haley, M. M. Organometallics 2004, 23, 1174. (b) Jacob, V.; Weakley, T. J. R.; Haley, M. M. Angew. Chem., Int. Ed. 2002, 41, 3470. (a) Elliot, G. P.; Roper, W. R.; Waters, J. M. J. Chem. Soc., Chem. Commun. 1982, 811. (b) Elliot, G. P.; McAuley, N. M.; Roper, W. R. Inorg. Synth. 1989, 26, 184. Hughes, R. P.; Trujillo, H. A.; Egan, J. W., Jr.; Rheingold, A. L. J. Am. Chem. Soc. 2000, 122, 2261. Hughes, R. P.; Trujillo, H. A.; Rheingold, A. L. J. Am. Chem. Soc. 1993, 115, 1583. Donovan, B. T.; Egan, J. W., Jr.; Hughes, R. P.; Spara, P. P.; Trujillo, H. A.; Rheingold, A. L. Isr. J. Chem. 1990, 30, 351. Donovan, B. T.; Hughes, R. P.; Trujillo, H. A. J. Am. Chem. Soc. 1990, 112, 7076. (a) Donovan, B. T.; Hughes, R. P.; Trujillo, H. A.; Rheingold, A. L. Organometallics 1992, 11, 64. (b) Donovan-Merkert, B. T.; Tjiong, H. I.; Rhinehart, L. M.; Russel, R. A.; Malik, J. Organometallics 1997, 16, 819. Donovan, B. T.; Hughes, R. P.; Kowalski, A. S.; Trujillo, H. A.; Rheingold, A. L. Organometallics 1993, 12, 1038. Egan, J. W.; Hughes, R. P.; Rheingold, A. L. Organometallics 1987, 6, 1578. Hughes, R. P.; Trujillo, H. A.; Egan, J. W.; Rheingold, A. L. Organometallics 1999, 18, 2766. Donovan, B. T.; Hughes, R. P.; Spara, P. P.; Rheingold, A. L. Organometallics 1995, 14, 489. Hughes, R. P.; Robinson, D. J. Organometallics 1989, 8, 1015. Hughes, R. P.; Trujillo, H. A.; Gauri, A. J. Organometallics 1995, 14, 4319. Grabowski, N. A.; Hughes, R. P.; Jaynes, B. S.; Rheingold, A. L. J. Chem. Soc., Chem. Commun. 1986, 1694. (a) Binger, P.; McMeeking, J. Angew. Chem., Int. Ed. Engl. 1974, 13, 466. (b) Binger, P.; Schroth, G.; McMeeking, J. Angew. Chem., Int. Ed. Engl. 1974, 13, 465. (c) Doyle, M. J.; McMeeking, J.; Binger, P. J. Chem. Soc., Chem. Commun. 1976, 376. (d) Binger, P.; Doyle, M. J.; McMeeking, J.; Kruger, C.; Tsay, Y.-H. J. Organomet. Chem. 1977, 135, 405. (e) Binger, P.; Doyle, M. J. J.Organomet. Chem. 1978, 162, 195. (f) Furman, D. B.; Rudashevskaya, T. Yu.; Kudryashev, A. V.; Ivanov, A. O.; Isaeva, L. S.; Morozova, L. N.; Peganova, T. A.; Bogdanov, V. S.; Kravtsov, D. N.; Bragin, O. V. IzV. Akad. Nauk SSSR, Ser. Khim. 1990, 345. (a) Lukin, K. A.; Zefirov, N. S. Zh. Org. Khim. 1990, 26, 289. (b) Weigert, F. J.; Baird, R. L.; Shapley, J. R. J. Am. Chem. Soc. 1970, 92, 6630. Binger, P.; Biedenbach, B. Chem. Ber. 1987, 120, 601. (a) Tomilov, Yu. V.; Bordakov, V. G.; Tsvetkova, N. M.; Dolgii, I. E.; Nefedov, O. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1987, 1534. (b) Baird, M. S.; Hussain, H. H.; Clegg, W. J. Chem. Soc., Perkin Trans. 1 1987, 1609. For metallacyclization of alkynes, leading to palladacyclopentadienes, see, for example: (a) Tom, Dieck, H.; Munz, C.; Mu¨ller, C. J. Organomet. Chem. 1990, 384, 243. (b) van Belzen, R.; Klein, R. A.; Kooijman, H.; Veldman, N.; Spek, A. L.; Elsevier, C. J. Organometallics 1998, 17, 1812. (c) Yamamoto, Y.; Nagata, A.; Arikawa, Y.; Tatsumi, K.; Itoh, K. Organometallics 2000, 19, 2403. (d) Campora, J.; Lopez, J. A.; Palma, P.; del Rio, D.; Carmona, E.; Valerga, P.; Graiff, C.; Tiripicchio, A. Inorg. Chem. 2001, 40, 4116. (e) Yamamoto, Y.; Nagata, A.; Nagata, H.; Ando, Y.; Arikawa, Y.; Tatsumi, K.; Itoh, K. Chem.sEur. J. 2003, 9, 2469. (f) Canovese, L.; Visentin, F.; Chessa, G.; Uguagliati, P.; Levi, C.; Dolmella, A. Organometallics 2005, 24, 5537. (a) Hashmi, A. S. K. Trends Organomet. Chem. 2002, 4, 33. (b) Hashmi, A. S. K.; Grundl, M. A.; Bats, J. W. Organometallics 2000,


(150) (151) (152) (153) (154) (155) (156) (157) (158) (159) (160) (161) (162) (163) (164) (165) (166) (167) (168) (169) (170) (171) (172)

(173) (174) (175) (176) (177) (178) (179) (180) (181)

(182) (183) (184) (185)

(186)

19, 4217. (c) Hashmi, A. S. K.; Naumann, F.; Bolte, M.; Rivas Nass, A. J. Prakt. Chem. 1998, 340, 240. (d) Hashmi, A. S. K.; Naumann, F.; Bats, J. W. Chem. Ber. 1997, 130, 1457. Peganova, T. A.; Petrovskii, P. V.; Isaeva, L. S.; Kravtsov, D. N.; Furman, D. B.; Kudryashev, A. V.; Ivanov, A. O.; Zotova, S. V.; Bragin, O. V. J. Organomet. Chem. 1985, 282, 283. Hashmi, A. S. K.; Naumann, F.; Probst, R.; Bats, J. W. Angew. Chem., Int. Ed. 1997, 36, 104. Hashmi, A. S. K.; Grundl, M. A.; Bats, J. W.; Bolte, M. Eur. J. Org. Chem. 2002, 1263. (a) Buech, H. M.; Binger, P.; Benn, R.; Rufinska, A. Organometallics 1987, 6, 1130. (b) Binger, P.; Brinkmann, A.; Wedemann, P. Chem. Ber. 1986, 119, 3089. Grobovenko, S. Ya.; Zlobina, V. A.; Surmina, L. S.; Bolesov, I. G.; Lapidus, A. L.; Beletskaya, I. P. Metalloorg. Khim. 1990, 3, 697. Binger, P.; McMeeking, J.; Schuchardt, U. Chem. Ber. 1980, 113, 2372. Binger, P.; Buch, H. M.; Benn, R.; Mynott, R. Angew. Chem., Int. Ed. 1982, 21, 62. (a) Rush, S.; Reinmuth, A.; Risse, W. Macromolecules 1997, 30, 7375. (b) Mathews, N.; Hager, H.; Rush, S.; Risse, W. Polym. Mater. Sci. Eng. 1999, 80, 435. Rush, S.; Reinmuth, A.; Risse, W.; O’Brien, J.; Ferro, D. R.; Tritto, I. J. Am. Chem. Soc. 1996, 118, 12230. Maassarani, F.; Pfeffer, M.; Le Borgne, G.; Grandjean, D. Organometallics 1986, 5, 1511. Loewe, C.; Shklover, V.; Bosch, H. W.; Berke, H. Chem. Ber. 1993, 126, 1769. Schubert, J.; Mock, S.; Schubert, U. Chem. Ber. 1993, 126, 657. Morton, M. S.; Selegue, J. P. J. Organomet. Chem. 1999, 578, 133. Gompper, R.; Bartmann, E. Angew. Chem. 1985, 97, 209. Yarosh, O. G.; Zhilitskaya, L. V.; Yarosh, N. K.; Albanov, A. I.; Voronkov, M. G. Russ. J. Gen. Chem. 2004, 74, 1492. (a) Nishihara, Y.; Itazaki, M.; Osakada, K. Tetrahedron Lett. 2002, 43, 2059. (b) Itazaki, M.; Nishihara, Y.; Osakada, K. J. Org. Chem. 2002, 67, 6889. Bessmertnykh, A. G.; Blinov, K. A.; Grishin, Yu. K.; Donskaya, N. A.; Tveritinova, E. V.; Yur’eva, N. M.; Beletskaya, I. P. J. Org. Chem. 1997, 62, 6069. Lautens, M.; Meyer, C.; Lorenz, A. J. Am. Chem. Soc. 1996, 118, 10676. Chenard, B. L.; Van Zyl, C. M. J. Org. Chem. 1986, 51, 3561. Suginome, M.; Ito, Y. J. Organomet. Chem. 2003, 680, 43. Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org. Chem. 1998, 63, 6458. Nakamura, I.; Itagaki, H.; Yamamoto, Y. Chem. Heterocycl. Compd. 2001, 37, 1532. (a) Siriwardana, A. I.; Kamada, M.; Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2005, 70, 5932. (b) Siriwardana, A. I.; Kathriarachchi, K. K. A. D. S.; Nakamura, I.; Yamamoto, Y. Heterocycles 2005, 66, 333. Shi, M.; Chen, Y.; Xu, B. Org. Lett. 2003, 5, 1225. (a) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 1999, 38, 3365. (b) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2001, 66, 270. Siriwardana, A. I.; Nakamura, I.; Yamamoto, Y. Tetrahedron Lett. 2003, 44, 4547. Smolensky, E.; Kapon, M.; Eisen, M. S. Organometallics 2005, 24, 5495. Nakamura, I.; Saito, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 2661. Nakamura, I.; Siriwardana, A. I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2002, 67, 3445. Tsukada, N.; Shibuya, A.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 8123. Camacho, D. H.; Nakamura, I.; Oh, B. H.; Saito, S.; Yamamoto, Y. Tetrahedron Lett. 2002, 43, 2903. (a) Smit, V. A.; Kireev, S. L.; Nefedov, O. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1987, 2637. (b) Kireev, S. L.; Smit, V. A.; Nefedov, O. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1989, 2061. (c) Smit, V. A.; Kireev, S. L.; Nefedov, O. M.; Tarasov, V. A. Tetrahedron Lett. 1989, 30, 4021. Witulski, B.; Stengel, T. Angew. Chem., Int. Ed. 1998, 37, 489. Stolle, A.; Becker, H.; Salau¨n, J.; de Meijere, A. Tetrahedron Lett. 1994, 35, 3517. Bra¨se, S.; Scho¨menauer, S.; McGaffin, G.; Stolle, A.; de Meijere, A. Chem.sEur. J. 1996, 2, 545. (a) Stolle, A.; Becker, H.; Salau¨n, J.; de Meijere, A. Tetrahedron Lett. 1994, 35, 3521. (b) de Meijere, A.; Becker, H.; Stolle, A.; Kozhushkov, S. I.; Bes, M. T.; Salau¨n, J.; Noltemeyer, M. Chem.s Eur. J. 2005, 11, 2471. Corlay, H.; Fouquet, E.; Magnier, E.; Motherwell, W. B. Chem. Commun. 1999, 183.

3178 Chemical Reviews, 2007, Vol. 107, No. 7 (187) Schelper, M.; Buisine, O.; Kozhushkov, S.; Aubert, C.; de Meijere, A.; Malacria, M. Eur. J. Org. Chem. 2005, 3000. (188) Molchanov, A. P.; Diev, V. V.; Magull, J.; Vidoviæ, D.; Kozhushkov, S. I.; de Meijere, A.; Kostikov, R. R. Eur. J. Org. Chem. 2005, 593. (189) Noyori, R.; Odagi, T.; Takaya, H. J. Am. Chem. Soc. 1970, 92, 5780. (190) (a) Binger, P.; Doyle, M.; Benn, R. Chem. Ber. 1983, 116, 1. (b) Binger, P.; Schuchardt, U. Chem. Ber. 1981, 114, 3313. (191) Trost, B. M. Angew. Chem., Int. Ed. 1986, 25, 1. (192) Corlay, H.; Lewis, R. T.; Motherwell, W. B.; Shipman, M. Tetrahedron Lett. 1995, 51, 3303. (193) Yamago, S.; Nakamura, E. J. Chem. Soc., Chem. Commun. 1988, 1112. (194) de Meijere, A.; Nu¨ske, H.; El-Sayed, M.; Labahn, T.; Schroen, M.; Bra¨se, S. Angew. Chem., Int. Ed. 1999, 38, 3669. (195) (a) de Meijere, A.; Kozhushkov, S. I. Eur. J. Org. Chem. 2000, 3809. (b) Binger, P.; Wedemann, P.; Kozhushkov, S. I.; de Meijere, A. Eur. J. Org. Chem. 1998, 113. (196) Kawasaki, T.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2002, 67, 4911. (197) (a) Inoue, Y.; Hibi, T.; Satake, M.; Hashimoto, H. J. Chem. Soc., Chem. Commun. 1979, 982. (b) Binger, P.; Weintz, H.-J. Chem. Ber. 1984, 117, 654. (198) Weintz, H.-J.; Binger, P. Tetrahedron Lett. 1985, 26, 4075. (199) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (b) Chan, D. M. T. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 4, p 217. (c) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem. ReV. 2003, 103, 1213. (200) Nakamura, I.; Oh, B.-H.; Saito, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 1289. (201) Oh, B.-H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Tetrahedron Lett. 2001, 42, 6203. (202) Siriwardana, A. I.; Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2004, 69, 3202. (203) Thormeier, S.; Carboni, B.; Kaufmann, D. E. J. Organomet. Chem. 2002, 657, 136. (204) Delgado, A.; Rodrigues, J. R.; Castedo, L.; Mascarenas, J. L. J. Am. Chem. Soc. 2003, 125, 9282. (205) Lopez, F.; Delgado, A.; Rodrı´gues, J. R.; Castedo, L.; Mascaren˜as, J. L. J. Am. Chem. Soc. 2004, 126, 10262. (206) Saito, S.; Masuda, M.; Komagawa, S. J. Am. Chem. Soc. 2004, 126, 10540. (207) Kurahashi, T.; Wu, Y.-T.; Meindl, K.; Ru¨hl, S.; de Meijere, A. Synlett 2005, 805. (208) Fournet, G.; Balme, G.; Gore, J. Tetrahedron 1988, 44, 5809. (209) Fournet, G.; Balme, G.; Barieux, J. J.; Gore´, J. Tetrahedron 1988, 44, 5821. (210) (a) Bra¨se, S.; de Meijere, A. Angew. Chem., Int. Ed. 1995, 34, 2545. (b) Nu¨ske, H.; Bra¨se, S.; Kozhushkov, S. I.; Noltemeyer, M.; ElSayed, M.; de Meijere, A. Chem.sEur. J. 2002, 8, 2351. (211) Nu¨ske, H.; Noltemeyer, M.; de Meijere, A. Angew. Chem., Int. Ed. 2001, 40, 3411. (212) de Meijere, A.; Schelper, M.; Knoke, M.; Yucel, B.; Su¨nneman, H. W.; Scheurich, R. P.; Arve, L. J. Organomet. Chem. 2003, 687, 249. (213) von Seebach, M.; Grigg, R.; de Meijere, A. Eur. J. Org. Chem. 2002, 3268. (214) Bra¨se, S.; Wertal, H.; Frank, D.; Vidoviæ, D.; de Meijere, A. Eur. J. Org. Chem. 2005, 4167. (215) de Meijere, A.; Bra¨se, S. J. Organomet. Chem. 1999, 576, 88. (216) Fu¨rstner, A.; Aissa, C. J. Am. Chem. Soc. 2006, 128, 6306. (217) Shi, M.; Liu, L.-P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430. (218) (a) Pines, H.; Huntsman, W. D.; Ipatieff, V. N. J. Am. Chem. Soc. 1953, 75, 2315. (b) Conia, J. M.; Robson, M. J. Angew. Chem., Int. Ed. 1975, 87, 505. (219) Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 11107. (220) Trost, B. M.; Frontier, A. J. J. Am. Chem. Soc. 2000, 122, 11727. (221) Ma, S.; Lu, L.; Zhang, J. J. Am. Chem. Soc. 2004, 126, 9645. (222) Kettunen, M.; Abu-Surrah, A. S.; Repo, T.; Leskela, M. Polym. Int. 2001, 50, 1223. (223) (a) Kim, S.; Takeuchi, D.; Osakada, K. J. Am. Chem. Soc. 2002, 124, 762. (b) Kim, S.; Takeuchi, D.; Osakada, K. Macromol. Chem. Phys. 2003, 204, 666. (224) Takeuchi, D.; Yasuda, A.; Osakada, K. Dalton Trans. 2003, 2029. (225) Osakada, K.; Takeuchi, D. Catal. SurV. Asia 2004, 8, 199. (226) Takeuchi, D.; Anada, K.; Osakada, K. Angew. Chem., Int. Ed. 2004, 43, 1233. (227) (a) Takeuchi, D.; Osakada, K. Chem. Commun. 2002, 646. (b) Takeuchi, D.; Anada, K.; Osakada, K. Macromolecules 2002, 35, 9628. (228) Moreau, P.; Maffei, M. Tetrahedron Lett. 2004, 45, 743. (229) Suzuki, M.; Sawada, S.; Yoshida, S.; Eberhardt, A.; Saegusa, T. Macromolecules 1993, 26, 4748. (230) Shimizu, I.; Aida, F. Chem. Lett. 1988, 601. (231) Hughes, G.; Lautens, M.; Wu, J. Synlett 2000, 835.

Rubin et al. (232) Sebelius, S.; Olsson, V. J.; Szabo, K. J. J. Am. Chem. Soc. 2005, 127, 10478. (233) Wang, X.; Stankovich, S. Z.; Widenhoefer, R. Organometallics 2002, 21, 901. (234) Aloise, A. D.; Layton, M. E.; Shair, M. D. J. Am. Chem. Soc. 2000, 122, 12610. (235) Wender, P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995, 117, 4720. (236) Wender, P. A.; Sperandio, D. J. Org. Chem. 1998, 63, 4164. (237) Gilbertson, S. R.; Hoge, G. S. Tetrahedron Lett. 1998, 39, 2075. (238) Wang, B.; Cao, P.; Zhang, X. Tetrahedron Lett. 2000, 41, 8041. (239) Wender, P. A.; Williams, T. J. Angew. Chem., Int. Ed. 2002, 41, 4550. (240) Trost, B. M.; Toste, F. D.; Shen, H. J. Am. Chem. Soc. 2000, 122, 2379. (241) Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A.; Pleuss, N. Tetrahedron 1998, 54, 7203. (242) Yu, Z.-X.; Wender, P. A.; Houk, K. N. J. Am. Chem. Soc. 2004, 126, 9154. (243) Wender, P. A.; Dyckman, A. J. Org. Lett. 1999, 1, 2089. (244) Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.; Kadereit, D.; Love, J. A.; Rieck, H. J. Am. Chem. Soc. 1999, 121, 10442. (245) Trost, B. M.; Shen, H. C. Org. Lett. 2000, 2, 2523. (246) Trost, B. M.; Shen, H. C.; Schulz, T.; Koradin, C.; Schirok, H. Org. Lett. 2003, 5, 4149. (247) (a) Haller, J.; Strassner, T.; Houk, K. N. J. Am. Chem. Soc. 1997, 119, 8031. (b) Houk, K. N.; Moses, S. R.; Wu, Y.-D.; Rondan, N. G.; Jager, V.; Schohe, R.; Fronczek, F. R. J. Am. Chem. Soc. 1984, 106, 3880. (c) Stork, G.; Kahn, M. Tetrahedron Lett. 1983, 24, 3951. (248) Trost, B. M.; Shen, H. C. Angew. Chem., Int. Ed. 2001, 40, 2313. (249) Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1998, 120, 1940. (250) Trost, B. M.; Toste, F. D. Angew. Chem., Int. Ed. 2001, 40, 1114. (251) Wender, P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1999, 121, 5348. (252) Wender, P. A.; Fuji, M.; Husfeld, C. O.; Love, J. A. Org. Lett. 1999, 1, 137. (253) Wender, P. A.; Zhang, L. Org. Lett. 2000, 2, 2323. (254) Wender, P. A.; Bi, C.; Brodney, M. A.; Gosselin, F. Org. Lett. 2001, 3, 2105. (255) Ashfeld, B. L.; Martin, S. F. Org. Lett. 2005, 7, 4535. (256) Wender, P. A.; Love, J. A.; Williams, T. J. Synlett 2003, 1295. (257) Wender, P. A.; Haustedt, L. O.; Lim, J.; Love, J. A.; Williams, T. J.; Yoon, J.-Y. J. Am. Chem. Soc. 2006, 128, 6302. (258) Wender, P. A.; Rieck, H.; Fuji, M. J. Am. Chem. Soc. 1998, 120, 10976. (259) Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.; Scanio, M. J. C. Org. Lett. 2000, 2, 1609. (260) Wegner, H. A.; de Meijere, A.; Wender, P. A. J. Am. Chem. Soc. 2005, 127, 6530. (261) Wender, P. A.; Barzilay, C. M.; Dyckman, A. J. J. Am. Chem. Soc. 2001, 123, 179. (262) Wender, P. A.; Gamber, G. G.; Scanio, M. J. C. Angew. Chem., Int. Ed. 2001, 40, 3895. (263) Wender, P. A.; Pedersen, T. M.; Scanio, M. J. C. J. Am. Chem. Soc. 2002, 124, 15154. (264) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.; Zhang, L. J. Am. Chem. Soc. 2002, 124, 2876. (265) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.; Pham, S. M.; Zhang, L. J. Am. Chem. Soc. 2005, 127, 2836. (266) Shimizu, I.; Ohashi, Y.; Tsuji, J. Tetrahedron Lett. 1985, 26, 3825. (267) (a) Knoke, M.; de Meijere, A. Synlett 2003, 195. (b) Knoke, M.; de Meijere, A. Eur. J. Org. Chem. 2005, 2259. (268) (a) Sarel, S. Acc. Chem. Res. 1978, 11, 204. (b) Schultze, M. M.; Gockel, U. Tetrahedron Lett. 1996, 37, 357. (c) Schultze, M. M.; Gockel, U. J. Organomet. Chem. 1996, 525, 155. (269) (a) Taber, D. F.; Kanai, K.; Jiang, Q.; Bui, G. J. Am. Chem. Soc. 2000, 122, 6807. (b) Taber, D. F.; Joshi, P. V.; Kanai, K. J. Org. Chem. 2004, 69, 2268. (270) Taber, D. F.; Bui, G.; Chen, B. J. Org. Chem. 2001, 66, 3423. (271) Trost, B. M.; Yasukata, T. J. Am. Chem. Soc. 2001, 123, 7162. (272) Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 9708. (273) Hudlicky, T.; Koszyk, F. J.; Kutchan, T. M.; Sheth, J. P. J. Org. Chem. 1980, 45, 5020. (274) Hudlicky, T.; Kutchan, T. M.; Wilson, S. R.; Mao, D. T. J. Am. Chem. Soc. 1980, 102, 6351. (275) Doyle, M. P.; van Leusen, D. J. Org. Chem. 1982, 47, 5326. (276) Morizawa, Y.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982, 23, 2871. (277) Hiroi, K.; Arinaga, Y. Tetrahedron Lett. 1994, 35, 153.

Transition Metal Chemistry of Cyclopropenes (278) (a) Hiroi, K.; Yoshida, Y.; Kaneko, Y. Tetrahedron Lett. 1999, 40, 3431. (b) Hiroi, K.; Suzuki, Y.; Kaneko, Y.; Kato, F.; Abe, I.; Kawagishi, R. Polyhedron 2000, 19, 525. (279) Hayashi, M.; Ohmatsu, T.; Meng, Y.-P.; Saigo, K. Angew. Chem., Int. Ed. 1998, 37, 837. (280) Suginome, M.; Matsuda, T.; Yoshimoto, T.; Ito, Y. Organometallics 2002, 21, 1537. (281) Zuo, G.; Louie, J. Angew. Chem., Int. Ed. 2004, 43, 2277. (282) Miura, T.; Sasaki, T.; Harumashi, T.; Murakami, M. J. Am. Chem. Soc. 2006, 128, 2516. (283) Garcia, P. G.; Hohn, E.; Pietruszka, J. J. Organomet. Chem. 2003, 680, 281. (284) Lukesh, J. M.; Donaldson, W. A. Chem. Commun. 2005, 110. (285) Verbicky, C. A.; Zercher, C. K. Tetrahedron Lett. 2000, 41, 8723. (286) Barrett, A. G. M.; Kasdorf, K.; Tustin, G. J. J. Am. Chem. Soc. 1996, 118, 11030. (287) (a) Faucher, A.-M.; Bailey, M. D.; Beaulieu, P. L.; Brochu, C.; Duceppe, J.-S.; Ferland, J.-M.; Ghiro, E.; Gorys, V.; Halmos, T.; Kawai, S. H.; Poirier, M.; Simoneau, B.; Tsantrizos, Y. S.; LlinasBrunet, M. Org. Lett. 2004, 6, 2901. (b) Poirier, M.; Aubry, N.; Boucher, C.; Ferland, J.-M.; LaPlante, S.; Tsantrizos, Y. S. J. Org. Chem. 2005, 70, 10765. (288) (a) Yang, Z.-Q.; Danishefsky, S. J. J. Am. Chem. Soc. 2003, 125, 9602. (b) Yang, Z.-Q.; Geng, X.; Solit, D.; Pratilas, C. A.; Rosen, N.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 7881. (289) Barrett, A. G. M.; Hamprecht, D.; James, R. A.; Ohkubo, M.; Procopiou, P. A.; Toledo, M. A.; White, A. J. P.; Williams, D. J. J. Org. Chem. 2001, 66, 2187. (290) (a) Netherton, M. R.; Fu, G. C. Top. Organomet. Chem. 2005, 14, 85. (b) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674. (291) Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2002, 124, 4222. (292) Dubbaka, S. R. Synlett 2005, 709. (293) (a) Ng, D. K. P.; Luh, T. Y. J. Am. Chem. Soc. 1989, 111, 9119. (b) Yu, C. C.; Ng, D. K. P.; Chen, B.-L.; Luh, T.-Y. Organometallics 1994, 13, 1487. (294) Ogle, C. A.; Black, K. C.; Sims, P. F. J. Org. Chem. 1992, 57, 3499. (295) Durley, R. C.; Grapperhaus, M. L.; Hickory, B. S.; Massa, M. A.; Wang, J. L.; Spangler, D. P.; Mischke, D. A.; Parnas, B. L.; Fobian, Y. M.; Rath, N. P.; Honda, D. D.; Zeng, M.; Connoly, D. T.; Heuvelman, D. M.; Witherbee, B. J.; Melton, M. A.; Glenn, K. C.; Krul, E. S.; Smith, M. E.; Sikorski, J. A. J. Med. Chem. 2002, 45, 3891. (296) Kottirsch, G.; Szeimies, G. Chem. Ber. 1990, 123, 1495. (297) Hashmi, A. S. K.; Vollmer, A.; Szeimies, G. Liebigs Ann. 1995, 471. (298) (a) Miller, J. A.; Dankwardt, J. W. Tetrahedron Lett. 2003, 44, 1907. (b) Miller, J. A.; Dankwardt, J. W.; Penney, J. M. Synthesis 2003, 1643. (299) Nakamura, E.; Isaka, M.; Matsuzawa, S. J. Am. Chem. Soc. 1988, 110, 1297. (300) Isaka, M.; Nakamura, E. J. Am. Chem. Soc. 1990, 112, 7428. (301) Piers, E.; Jean, M.; Marrs, P. S. Tetrahedron Lett. 1987, 28, 5075. (302) Piers, E.; Coish, P. D. G. Synthesis 2001, 251. (303) Carpita, A.; Ribecai, A.; Rossi, R.; Stabile, P. Tetrahedron 2002, 58, 3673. (304) Campbell, J. B., Jr.; Firor, J. W.; Davenport, T. W. Synth. Commun. 1989, 19, 2265. (305) De Lang, R.-J.; Brandsma, L. Synth. Commun. 1998, 28, 225. (306) Vu, V. A.; Marek, I.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2002, 41, 351. (307) (a) Perez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123, 4155. (b) Perez, I.; Perez Sestelo, J.; Sarandeses, L. A. Org. Lett. 1999, 1, 1267. (308) Nelson, P. H.; Carr, S. F.; Devens, B. H.; Eugui, E. M.; Franco, F.; Gonzales, C.; Hawley, R.; Loughhead, D. G.; Milan, D. J.; Papp, E.; Patterson, J. W.; Rouhafza, S.; Sjorgen, E. B.; Smith, D. B.; Stephenson, R. A.; Talamas, F. X.; Waltos, A. M.; Weikert, R. J.; Wu, J. C. J. Med. Chem. 1996, 39, 4181. (309) Turner, W. R.; Suto, M. J. Tetrahedron Lett. 1993, 34, 281. (310) Branca, Q.; Jakob-Rotne, R.; Kettler, R.; Rover, S.; Scalone, M. Chimia 1995, 49, 381. (311) Peters, D.; Hornfeldt, A.-B.; Gronowitz, S. J. Heterocycl. Chem. 1991, 28, 1629. (312) (a) Liebeskind, L. S.; Fengl, R. W. J. Org. Chem. 1990, 55, 5359. (b) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S. J. Org. Chem. 1994, 59, 5905. (313) Schmitz, W. D.; Romo, D. Tetrahedron Lett. 1996, 37, 4857. (314) Wiedemann, S.; Rauch, K.; Savchenko, A.; Marek, I.; de Meijere, A. Eur. J. Org. Chem. 2004, 631. (315) Heureux, N.; Marchant, M.; Maulide, N.; Berthon-Gelloz, G.; Hermans, C.; Hermant, S.; Kiss, E.; Leroy, B.; Wasnaire, P.; Marko, I. E. Tetrahedron Lett. 2005, 46, 79.

Chemical Reviews, 2007, Vol. 107, No. 7 3179 (316) (a) Brown, H. C.; Bhat, N. G.; Somayji, V. Organometallics 1983, 2, 1311. (b) Deloux, L.; Srebnik, M. J. Org. Chem. 1994, 59, 6871. (c) Deloux, L.; Skrzypczak-Jankun, E.; Cheeseman, B. V.; Srebnik, M. J. Am. Chem. Soc. 1994, 116, 10302. (d) Quintanilla, R.; Cole, T. E. Tetrahedron 1995, 51, 4297. (e) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000, 122, 4990. (317) Hansen, E. C.; Lee, D. J. Am. Chem. Soc. 2005, 127, 3252. (318) (a) Pietruszka, J.; Schoene, N. Angew. Chem., Int. Ed. 2003, 42, 5638. (b) Lee, T.; Baik, C.; Jung, I.; Song, K. H.; Kim, S.; Kim, D.; Kang, S. O.; Ko, J. Organometallics 2004, 23, 4569. (c) Shirakawa, K.; Arase, A.; Hoshi, M. Synthesis 2004, 1814. (d) Ley, S. V.; Humphries, A. C.; Eick, H.; Downham, R.; Ross, A. R.; Boyce, R. J.; Pavey, J. B. J.; Pietruszka, J. J. Chem. Soc., Perkin Trans. 1 1998, 23, 3907. (319) (a) Imai, T.; Mineta, H.; Nishida, S. J. Org. Chem. 1990, 55, 4986. (b) Pietruszka, J.; Widenmeyer, M. Synlett 1997, 977. (c) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 1999, 64, 8287. (320) Hildebrand, J. P.; Marsden, S. P. Synlett 1996, 893. (321) Pietruszka, J.; Witt, A.; Frey, W. Eur. J. Org. Chem. 2003, 3219. (322) Deng, M.-Z.; Chen, H. J. Chem. Soc., Perkin Trans. 1 2000, 1609. (323) Lohr, S.; de Meijere, A. Synlett 2001, 489. (324) (a) Yao, M.-L.; Deng, M.-Z. Synthesis, 2000, 1095. (b) Yao, M.; Wang, J.; Deng, M. Chin. Sci. Bull. 2001, 46, 1277. (325) Ma, H.-R.; Wang, X.-H.; Deng, M.-Z. Synth. Commun. 1999, 29, 2477. (326) Yao, M.-L.; Deng, M.-Z. New J. Chem. 2000, 24, 425. (327) (a) Zhou, S.-M.; Yan, Y.-L.; Deng, M.-Z. Synlett 1998, 198. (b) Wang, P.-A.; Deng, M. Z.; Pan, R.Q.; Zhang, S. Y. J. Fluor. Chem. 2003, 124, 93. (c) Zhou, S.-M.; Deng, M.-Z. Tetrahedron Lett. 2000, 41, 3951. See, also: (d) Rossi, R.; Carpita, A.; Ribecai, A.; Mannina, L. Tetrahedron 2001, 57, 2847. (328) (a) Yao, M.-L.; Deng, M.-Z. J. Org. Chem. 2000, 65, 5034. (b) Yao, M.-L.; Deng, M.-Z. Heteroat. Chem. 2000, 11, 380. (c) Yao, M.-L.; Deng, M.-Z. Tetrahedron Lett. 2000, 41, 9083. (329) Chen, H.; Deng, M.-Z. J. Org. Chem. 2000, 65, 4444. (330) Chen, H.; Deng, M.-Z. Org. Lett. 2000, 2, 1649. (331) Wallace, D. J.; Chen, C. Tetrahedron Lett. 2002, 43, 6987. (332) Lemhadri, M.; Doucet, H.; Santelli, M. Synth. Commun. 2006, 36, 121. (333) Fang, G.-H.; Yan, Z.-Y.; Deng, M.-Z. Org. Lett. 2004, 6, 357. (334) Hohn, E.; Pietruszka, J.; Solduga, G. Synlett 2006, 1531. (335) Brown, H. C.; Rhodes, S. P. J. Am. Chem. Soc. 1969, 91, 4306. (336) Soderquist, J. A.; Huertas, R.; Leon-Colon, G. Tetrahedron Lett. 2000, 41, 4251. (337) Fu¨rstner, A.; Leitner, A. Synlett 2001, 290. (338) (a) Charette, A. B.; de Freitas-Gil, R. P. Tetrahedron Lett. 1997, 38, 2809. (b) Pietruszka, J. Chem. ReV. 2003, 103, 1051. (c) Faust, R. Angew. Chem., Int. Ed. 2001, 40, 2251. (339) Hohn, E.; Pietruszka, J. AdV. Synth. Catal. 2004, 246, 863. (340) (a) Pietruszka, J.; Rieche, A. C. M.; Wilhelm, T.; Witt, A. AdV. Synth. Catal. 2003, 345, 1273. (b) Pietruszka, J.; Witt, A. Synlett 2003, 91. (341) Pietruszka, J.; Witt, A. J. Chem. Soc., Perkin Trans. 1 2000, 4293. (342) Itoh, T.; Emoto, S.; Kondo, M. Tetrahedron 1998, 54, 5225. (343) Liebeskind, L. S.; Riesinger, S. W. Tetrahedron Lett. 1991, 32, 5681. (344) Falck, J. R.; Mekonnen, J. Y.; Lai, J.-Y. J. Am. Chem. Soc. 1996, 118, 6096. (345) Lincoln, C. M.; White, J. D.; Yokochi, A. F. T. Chem. Commun. 2004, 2846. (346) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem., Int. Ed. 2005, 44, 2112. (347) (a) Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.; Chou, K. J. J. Am. Chem. Soc. 1977, 99, 4778. (b) Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.; Sanchez, E. L. J. Am. Chem. Soc. 1983, 105, 2021. (c) Alonso, M. E.; Jano, P.; Hernandez, M.; Greenberg, R. S.; Wenkert, E. J. Org. Chem. 1983, 48, 3047. (348) Alonso, M. E.; Morales, A.; Chitty, A. W. J. Org. Chem. 1982, 47, 3747. (349) Davies, H. M. L.; Ahmed, G.; Calvo, R. L.; Churchill, M. R.; Churchill, D. G. J. Org. Chem. 1998, 63, 2641. (350) (a) Yadav, V. K.; Balamurugan, R. Org. Lett. 2001, 3, 2717. (b) Young, I. S.; Kerr, M. A. Angew. Chem., Int. Ed. 2003, 42, 3203. (351) Bowman, R. K.; Johnson, J. S. Org. Lett. 2006, 8, 573. (352) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395. (353) Sibi, M. P.; Ma, Z.; Jasperse, C. P. J. Am. Chem. Soc. 2005, 127, 5764. (354) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348. (355) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128, 5350. (356) Lloyd-Jones, G. C. Angew. Chem., Int. Ed. 2006, 45, 6788.

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Transition Metal Chemistry of Cyclopropenes and Cyclopropanes

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