Chem. Rev. 2009, 109, 3817–3858
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Grubbs’ Ruthenium-Carbenes Beyond the Metathesis Reaction: Less Conventional Non-Metathetic Utility Benito Alcaide,*,† Pedro Almendros,*,‡ and Amparo Luna† Departamento de Quı´mica Orga´nica I, Facultad de Quı´mica, Universidad Complutense de Madrid, 28040 Madrid, Spain, and Instituto de Quı´mica Orga´nica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain Received April 13, 2009
Chem. Rev. 2009.109:3817-3858. Downloaded from pubs.acs.org by KAOHSIUNG MEDICAL UNIV on 10/06/18. For personal use only.
Contents 1. Introduction 2. Kharasch Additions 3. Oxidation Processes 3.1. Dehydrogenation Reactions 3.2. Dihydroxylation Reactions 3.3. Ketohydroxylation Reactions 3.3.1. Preparation of R-Methyl Ketones 4. Activation Reactions 4.1. Activation of Silanes By Grubbs’ Carbenes 4.2. Hydrosilylation of Terminal Alkynes 4.3. Direct Arylation-Hydrosilylation Sequence 5. Hydrogenation Reactions 5.1. Reduction of Olefins Using Ru-1 and Silanes 5.2. One-Pot RCM and CM-Hydrogenation Using Ru-1 and Ru-2 5.3. Transfer Reductions of Ketones With Alcohols 6. Cyclopropanation Reactions 6.1. Tandem Cyclopropanation-RCM of Dienynes 6.2. One-Pot Enyne Metathesis-Cyclopropanation in the Presence of Diazoacetates 6.3. One-Pot RCM/ Isomerization-Cyclopropanation Reaction 7. Cycloaddition Reactions 7.1. RCEYM/Diels-Alder Reaction Sequence 7.2. [2 + 2 + 2]-Cycloaddition Reactions 7.3. [3 + 2]-Cycloaddition Reactions Catalyzed By Grubbs’ Carbene Complexes 8. Olefin Isomerizations 8.1. Isomerization in Diversely Functionalized Compounds 8.2. Deprotection of N-Allyl Amines, N-Allyl Ethers, and N-Propargyl Amines 8.2.1. Deprotection of N-Allyl Amines 8.2.2. Deprotection of N-Allyl Ethers 8.2.3. Deprotection of N-Propargyl Ethers 8.3. Ring-Closing Metathesis Followed By Isomerization 8.4. Isomerization Followed By Ring-Closing Metathesis 8.5. Cross-Metathesis Followed By Isomerization 8.6. Isomerization Followed By Cross-Metathesis 9. Miscellaneous * E-mail:
[email protected];
[email protected]. † Universidad Complutense de Madrid. ‡ CSIC.
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9.1. 9.2. 9.3. 9.4.
Isomerization/Cyclization Isomerization/Claisen Rearrangement Cross-Metathesis/Wittig Olefination Tandem Cross-Metathesis/Intramolecular Hydroarylation 9.5. Cycloisomerization 9.6. Reactivity of Alkynes in the Presence of Carboxylic Acids 9.7. Allylic Alkylation 9.8. Vinylcyclopropane Epimerization 9.9. Diol Cleavage 9.10. Dehydration 10. Conclusions 11. Abbreviations 12. Acknowledgments 13. References
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1. Introduction Metal-catalyzed olefin metathesis has become one of the most widely used organometallic transformations for carbon-carbon formation in organic synthesis. For this reason, the Royal Swedish Academy of Sciences decided to award the Nobel Prize in chemistry for 2005 to Yves Chauvin, Robert H. Grubbs, and Richard Schrock “For the development of the metathesis method in organic synthesis”. In particular, Grubbs has developed powerful new catalysts, stable in air, for metathesis that enabled custom synthesis of many new molecules, such as pharmaceuticals and new polymers with novel properties. Metathesis has developed to industrial and pharmaceutical methods that are more efficient and less polluting. The recognition of this chemistry suggests a big step in the development of new green methods for the synthesis of essential chemicals. Metathesis is an example of how chemistry has been applied for the benefit of man, society, and the environment. During the past decade, olefin chemistry has seen explosive growth as a synthetic tool; this growth can be attributed by the large number of articles appearing on this subject but also by the development of new catalysts such as rutheniumbased carbenes 1-4 (Figure 1), which combine high reactivity with very good tolerance to a wide range of functional groups.1 The large number of successful metathesis reactions (CM, ROM, RCM, RRM, and RCEYM) has been intensively investigated (Scheme 1).2 Besides, nonmetathetic applications promoted by ruthenium-carbene complexes have been observed,3 often as side reactions due to special reaction conditions or to decomposition of ruthenium catalysts. These
10.1021/cr9001512 CCC: $71.50 2009 American Chemical Society Published on Web 07/02/2009
3818 Chemical Reviews, 2009, Vol. 109, No. 8
Benito Alcaide was born in Aldea del Rey, Ciudad Real, Spain, in 1950. He received his B.S. degree (1972) and his Ph.D. (1978) from the Universidad Complutense de Madrid (UCM) under the supervision of Prof. Franco Ferna´ndez. His thesis work included synthesis and chiroptical properties of model steroid ketones. After a four-year period working on the chemistry of R-iminoketones and related compounds with Prof. Joaquı´n Plumet, he began working on β-lactam chemistry. In 1984 he assumed a position of Associate Professor of Organic Chemistry and in 1990 was promoted to Full Professor at the UCM. His current recent interests includes β-lactam chemistry, asymmetric synthesis of compounds of biological interest, free radicals, cycloaddition reactions, allenes, carbenes, metal-promoted cyclizations, C-C coupling reactions, and organocatalysis.
Alcaide et al.
Amparo Luna was born in Veracruz, Mexico, in 1974. She obtained her B.S. degree in Chemical Engineering from the Instituto Tecnolo´gico de Veracruz, Mexico, in 1996 and her Ph.D. degree (2002) from the Universidad de Oviedo (Spain) under the supervision of Prof. Vicente Gotor and Dr. Covadonga Astorga. In 2003 she joined the research group of Prof. Roland Furstoss at Faculte´ des Sciences de Luminy (Lab. Associe´ au CNRS, UMR 6111) in Marseille (France) as a postdoctoral fellow. In 2004 she moved to the research group of Prof. Benito Alcaide (UCM, Madrid) where, in 2006, she was appointed Assistant Professor at the UCM. Her research interests are focused on β-lactam chemistry, asymmetric synthesis, allene chemistry, and metal-catalyzed coupling reactions.
Figure 1. Scheme 1. Successful Metathesis Reactions: CM, ROM, RCM, RRM, and RCEYM
Pedro Almendros was born in Albacete, Spain, in 1966. He received his B.S. degree (1989) and his Ph.D. degree (1994) from the Universidad de Murcia under the supervision of Prof. Pedro Molina and Dr. Pilar M. Fresneda. After three years postdoctoral work for Prof. Eric J. Thomas at the University of Manchester, England, with a Spanish MEC Postdoctoral Fellowship (1995-1997) and an European Marie Curie Postdoctoral Grant (1997-1998), he joined the research group of Prof. Benito Alcaide (UCM, Madrid) in 1998 as Associate Researcher (Contrato de Reincorporacio´n de Doctores y Tecno´logos). Subsequent appointments have included Assistant Professor at the UCM (2000-2002) and Cientı´fico Titular (Tenured Scientist) at the Instituto de Quı´mica Orga´nica General, CSIC, Madrid. In 2007 he was promoted to Investigador Cientı´fico (Researcher Scientist) at the IQOG, CSIC, Madrid. His research interest includes β-lactam chemistry, allene chemistry, asymmetric synthesis, carbenes, metal-promoted heterocyclizations, and C-C coupling reactions.
complexes have been shown to catalyze Kharasch addition,4 oxidation processes,5 activation reactions (hydrosilylations of terminal alkynes and hydrosilylations of carbonyls),6 hydrogenation of olefins,7 cyclopropanation sequences,8 cycloaddition reactions,9 and olefin isomerizations,10 among others. Although the mechanisms of these reactions have not been fully elucidated, they represent an interesting synthetic development. Some of these nonmetathetic reactions have been optimized and show utility in organic synthesis. Indeed, the
usefulness of the Grubbs’ carbenes in deallylation of amines, amides, lactams, imides, pyrazolidinones, hydantoins, and oxazolidinones has been demonstrated.11 The aim of this review is to provide an overview of the field, concentrating on recent advances in the nonmetathetic behavior of Grubbs’ carbenes.
Grubbs’ Ruthenium-Carbenes Non-Metathetic Utility Scheme 2. New Reactivity of Ru-1 in Kharasch Addition
Chemical Reviews, 2009, Vol. 109, No. 8 3819 Scheme 4. Generation of Five New Bonds in a Single Reaction Sequence by Olefin Metathesis-Double Kharasch Addition Catalyzed by Ru-1
Scheme 3. Kharasch Addition Catalyzed by Ru-1 Followed by Hydrolysis Reaction
Scheme 5. Tandem RCM-Kharasch Addition Promoted by Grubbs’ Catalyst Ru-1
2. Kharasch Additions The widely used Grubbs’ ruthenium carbene Ru-1, wellknown for its ability to promote olefin metathesis, is also an effective catalyst in radical atom transfer reactions such as Kharasch addition. In 1999, Snapper et al. isolated a product derived not from olefin metathesis but from a metal-catalyzed addition of CHCl3 across an alkene (Scheme 2).12 This chemistry led to the discovery that Ru-1 is an efficient and mild catalyst for the Kharasch addition of CHCl3 to olefins.13 For this reason, they expanded this methodology to several trichloroalkyls groups across a variety of olefins, offering the hydrolysis of the corresponding polyhalogenated adducts a novel access to R,β-unsaturated ketones, aldehydes, or γ-hydroxybutenolides.14 The reaction was carried out using 5-10 mol % of Ru-1 in the presence of excess trichloroalkanes at 65-80 °C. Alkenes less prone to undergo an olefin metathesis, such as styrenes and acrylates, serve as excellent substrates for Kharasch addition, especially with chloroform or 1,1,1-trichloroethane as their reaction partner. Adduct 6a can be converted into aldehyde 7 in 77% yield by heating with 10% H2SO4 in a sealed reaction vessel for 6.5 h (Scheme 3). In comparison to the styrenyl substrates, hydrolysis of the acrylate-derived addition products offered an alternative carbonylation product. Acidic hydrolysis of trichlorinated ester 6b provided γ-hydroxybutenolide 8 in 91% yield (Scheme 3). The two-step sequence represents a convenient method for the attachment of the carbonyl functionality to olefins. Tandem catalysis can involve multiple chemical transformations in a single reaction vessel, effecting multiple bond changes in a single operation.15 As synthetic application of these catalytic reactions, a tandem ruthenium-catalyzed olefin metathesis/Kharasch addition, using complex Ru-1, was developed to convert acyclic halogenated diene precursors into highly functionalized systems. In this process, a single metal precursor, Ru-1, catalyzes the formation of up to three new carbon-carbon and two carbon-halogen bonds in one operation through two mechanistically unique pathways (Scheme 4).4b Bicyclic ring systems [3.3.0], [4.3.0], and [5.3.0] can be prepared from acyclic dienes through a tandem RCM-intramolecular Kharasch addition reaction sequence. The metathesis reaction forms the 5,6-membered rings, at room temperature, followed by a Kharasch addition that generates the 5-membered lactam under more forcing conditions. The
stereochemical outcome of the reaction supports an atom transfer radical mechanism compared to a rutheniummediated oxidative addition/reductive elimination pathway. The high temperature required for this intramolecular Kharasch addition is attributed to the unfavorable amide bond rotamer required for ring closure in the radical cyclization. However, the reactions proceed at lower temperatures in substrates 11a and 11b although requiring longer reaction times when benzyl or tosyl groups are added to the amide functionality. The aliphatic substrate 13 provides the highest yield of a tandem cycloadduct 14. Evidently, the conformational freedom offered by removing the amide linkage more than compensates for the reduced Kharasch activity of the trichloroalkyl functionality. An alternative route to the 5,6ring system is shown with substrate 15. In this case, a RCM is used to prepare the furanyl ring, followed by a Kharasch addition that installs the 6-membered lactam 16 (Scheme 5). An efficient example of tandem processes have been obtained when dienes 9a and 9b are heated in the presence of styrene, generating compounds 17a and 17b selectively in 52% and 78% yields, respectively, as a 1:1 mixture of
3820 Chemical Reviews, 2009, Vol. 109, No. 8 Scheme 6. Tandem RCM-Intramolecular Kharasch Reaction Followed by an Intermolecular Kharasch Addition Catalyzed by Ru-1
Alcaide et al. Scheme 9. Sequential Addition of Substrates to Catalyst Ru-1a
Scheme 7. Intramolecular Competition Experiments (Metathesis Versus Kharasch Reactions)
Scheme 8. Sequential Metathesis-Kharasch Reactionsa
Scheme 10. Metathesis Is Faster than the Alternative Kharasch Reaction Catalyzed by Ruthenium Carbene
benzyl chlorides. In these reactions, Grubbs’ catalyst Ru-1 first effects the RCM and then, upon heating, promotes an intramolecular Kharasch addition, before carrying out an intermolecular Kharasch on 9a or 9b with the addition of styrene. The result is the formation of three new contiguous carbon-carbon bonds, two carbon-halogen bonds, and four new stereogenic centers in a single reaction flask (Scheme 6). Studies in the group of Quayle have revealed that there is an important rate difference between olefin metathesis and Kharasch reactions in substrates exposed to both reactions conditions.16 Amides 18 under thermolysis with Ru-1 afforded the ∆2-pyrrolines 19 in excellent yields and only trace amounts (
