NHC-Cu-Catalyzed Silyl Conjugate Additions to Acyclic and Cyclic Dienones and Dienoates. Efficient Site-, Diastereo- and Enantioselective Synthesis of Carbonyl-Containing Allylsilanes.

Efficient and highly diastereo- and enantioselective conjugate additions of phenyldimethylsilyl units to acyclic and cyclic dienones and dienoates are disclosed. The C-Si bond forming reactions are catalyzed by 2.0-2.5 mol % of a copper complex of a chiral monodentate N-heterocyclic carbene; the requisite reagent, PhMe(2)Si-B(pin), is commercially available or can be easily prepared. Transformations generate allylsilanes in up to 98% yield and >99:1 enantiomeric ratio, and proceed with complete 1,4-selectivity, unless the dienone or dienoate carries a trisubstituted alkene conjugated to the carbonyl group; in the latter cases, 1,6-addition products are obtained exclusively and in up to >98% Z selectivity.

[1]  P. Melchiorre,et al.  Aminocatalytic enantioselective 1,6 additions of alkyl thiols to cyclic dienones: vinylogous iminium ion activation. , 2012, Angewandte Chemie.

[2]  A. Hoveyda,et al.  Metal-free catalytic enantioselective C-B bond formation: (pinacolato)boron conjugate additions to α,β-unsaturated ketones, esters, Weinreb amides, and aldehydes promoted by chiral N-heterocyclic carbenes. , 2012, Journal of the American Chemical Society.

[3]  A. Hoveyda,et al.  Metal-free catalytic C-Si bond formation in an aqueous medium. Enantioselective NHC-catalyzed silyl conjugate additions to cyclic and acyclic α,β-unsaturated carbonyls. , 2011, Journal of the American Chemical Society.

[4]  A. Hoveyda,et al.  Enantioselective synthesis of boron-substituted quaternary carbons by NHC-Cu-catalyzed boronate conjugate additions to unsaturated carboxylic esters, ketones, or thioesters. , 2010, Journal of the American Chemical Society.

[5]  Tamio Hayashi,et al.  Iridium/chiral diene-catalyzed asymmetric 1,6-addition of arylboroxines to alpha,beta,gamma,delta-unsaturated carbonyl compounds. , 2010, Journal of the American Chemical Society.

[6]  A. Hoveyda,et al.  Enantioselective conjugate silyl additions to cyclic and acyclic unsaturated carbonyls catalyzed by Cu complexes of chiral N-heterocyclic carbenes. , 2010, Journal of the American Chemical Society.

[7]  R. Fröhlich,et al.  Rhodium(I)-catalyzed enantioselective 1,4-addition of nucleophilic silicon , 2009 .

[8]  A. Hoveyda,et al.  Monodentate non-C(2)-symmetric chiral N-heterocyclic carbene complexes for enantioselective synthesis. Cu-catalyzed conjugate additions of aryl- and alkenylsilylfluorides to cyclic enones. , 2009, The Journal of organic chemistry.

[9]  A. Hoveyda,et al.  Efficient C-B bond formation promoted by N-heterocyclic carbenes: synthesis of tertiary and quaternary B-substituted carbons through metal-free catalytic boron conjugate additions to cyclic and acyclic alpha,beta-unsaturated carbonyls. , 2009, Journal of the American Chemical Society.

[10]  M. M. Díaz‐Requejo,et al.  Asymmetric β-Boration of α,β-Unsaturated Esters with Chiral (NHC)Cu Catalysts , 2009 .

[11]  A. Alexakis,et al.  Regiodivergent 1,4 versus 1,6 asymmetric copper-catalyzed conjugate addition. , 2008, Angewandte Chemie.

[12]  M. Kanai,et al.  Asymmetric synthesis of tertiary alcohols and alpha-tertiary amines via Cu-catalyzed C-C bond formation to ketones and ketimines. , 2008, Chemical reviews.

[13]  B. Feringa,et al.  Catalytic enantioselective 1,6-conjugate addition of Grignard reagents to linear dienoates. , 2008, Angewandte Chemie.

[14]  M. Oestreich,et al.  Catalytic asymmetric C-Si bond formation to acyclic alpha,beta-unsaturated acceptors by Rh(I)-catalyzed conjugate silyl transfer using a Si-B linkage. , 2008, Angewandte Chemie.

[15]  Stephanie A. Kazane,et al.  Enantioselective synthesis of allylsilanes bearing tertiary and quaternary Si-substituted carbons through Cu-catalyzed allylic alkylations with alkylzinc and arylzinc reagents. , 2007, Angewandte Chemie.

[16]  E. Fillion,et al.  Asymmetric Cu-catalyzed 1,6-conjugate addition of dialkylzinc reagents to 5-(3-aryl-2-propenylidene) Meldrum’s acids , 2006 .

[17]  M. Suginome,et al.  Palladium-catalyzed asymmetric silaboration of allenes. , 2006, Journal of the American Chemical Society.

[18]  M. Oestreich,et al.  Rhodium-catalyzed enantioselective conjugate silyl transfer: 1,4-addition of silyl boronic esters to cyclic enones and lactones. , 2006, Angewandte Chemie.

[19]  M. Snapper,et al.  A chiral Ag-based catalyst for practical, efficient, and highly enantioselective additions of enolsilanes to alpha-ketoesters. , 2006, Journal of the American Chemical Society.

[20]  N. Tokunaga,et al.  Rhodium-catalyzed asymmetric 1,6-addition of aryl zinc reagents to dienones. , 2005, Angewandte Chemie.

[21]  Martin D. Eastgate,et al.  Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl ketene acetal to ketones. , 2005, The Journal of organic chemistry.

[22]  J. Panek,et al.  Crotylsilane reagents in the synthesis of complex polyketide natural products: total synthesis of (+)-discodermolide. , 2005, Journal of the American Chemical Society.

[23]  M. Laguerre,et al.  Asymmetric synthesis of cyclic β-hydroxyallylsilanes via sequential allyltitanation-ring closing metathesis , 2004 .

[24]  Y. Landais,et al.  Allylsilanes in Organic Synthesis − Recent Developments , 2004 .

[25]  A. Barbero,et al.  Allylsilanes and vinylsilanes from silylcupration of carbon-carbon multiple bonds: scope and synthetic applications. , 2004, Accounts of chemical research.

[26]  R. Schrock,et al.  Enantioselective synthesis of medium-ring heterocycles, tertiary ethers, and tertiary alcohols by Mo-catalyzed ring-closing metathesis. , 2002, Journal of the American Chemical Society.

[27]  Y. Uozumi,et al.  Modification of Chiral Monodentate Phosphine Ligands (MOP) for Palladium‐Catalyzed Asymmetric Hydrosilylation of Cyclic 1,3‐Dienes , 2001 .

[28]  T. Matsuda,et al.  Convenient Preparation of Silylboranes , 2000 .

[29]  Y. Ito,et al.  Transition-metal-catalyzed additions of silicon-silicon and silicon-heteroatom bonds to unsaturated organic molecules. , 2000, Chemical reviews.

[30]  J. Panek,et al.  Total Synthesis of (−)-Mycalolide A , 2000 .

[31]  J. Panek,et al.  Total Synthesis of Oleandolide , 1999 .

[32]  R. Lerner,et al.  A Catalytic Enantioselective Route to Hydroxy-Substituted Quaternary Carbon Centers: Resolution of Tertiary Aldols with a Catalytic Antibody , 1999 .

[33]  I. Fleming,et al.  Stereochemical Control in Organic Synthesis Using Silicon-Containing Compounds. , 1997, Chemical reviews.

[34]  C. Masse,et al.  Diastereoselective Reactions of Chiral Allyl and Allenyl Silanes with Activated C:X .pi.-Bonds , 1995 .

[35]  Y. Uozumi,et al.  Asymmetric synthesis of allylsilanes by palladium-catalyzed asymmetric reduction of allylic carbonates with formic acid☆ , 1994 .

[36]  K. Yanagi,et al.  Optically-Active Ruthenocenylbis(Phosphines) - New Efficient Chiral Phosphine-Ligands for Catalytic Asymmetric Reactions , 1994 .

[37]  Tamio Hayashi,et al.  Catalytic asymmetric synthesis of β-hydroxy ketones by palladium-catalyzed asymmetric 1,4-disilylation of α,β-unsaturated ketones , 1994 .

[38]  A. Hoveyda,et al.  Siloxanes: versatile templates for acyclic stereocontrol. Synthesis of the C27-C33 segment of rapamycin , 1992 .

[39]  Tamio Hayashi,et al.  Palladium-catalyzed asymmetric 1,4-disilylation of .alpha.,.beta.-unsaturated ketones: catalytic asymmetric synthesis of .beta.-hydroxy ketones , 1988 .

[40]  M. Kumada,et al.  Asymmetric synthesis catalyzed by chiral ferrocenylphosphine-transition metal complexes. 3. Preparation of optically active allylsilanes by palladium-catalyzed asymmetric Grignard cross-coupling , 1986 .

[41]  K. Tamao,et al.  Optically active cyclic allylsilanes: Preparation by asymmetric hydrosilylation and anti stereochemistry in SE' reactions☆ , 1983 .

[42]  M. Kumada,et al.  OPTICALLY ACTIVE ALLYLSILANES. 1. PREPARATION BY PALLADIUM-CATALYZED ASYMMETRIC GRIGNARD CROSS-COUPLING AND ANTI STEREOCHEMISTRY IN ELECTROPHILIC SUBSTITUTION REACTIONS , 1982 .