New concepts and catalysts for enantioselective synthesis of carbon-carbon, carbon-silicon, and carbon-boron bonds

Chapter 1. The development of chiral monodentate N-heterocyclic carbenes (NHCs) is presented. Structurally varied twenty-eight new chiral imidazolinim salts, NHC precursors, were synthesized and characterized.;Chapter 2. The first example of Cu-catalyzed enantioselective conjugate additions of alkyl- and arylzinc reagents to unactivated cyclic beta-substituted enones is presented. Transformations are promoted in the presence of 2.5--15 mol % of a readily available chiral NHC-based Cu complex, affording the desired products bearing all-carbon quaternary stereogenic centers in 67--98% yield and in up to 97% ee. Catalytic enantioselective reactions can be carried out on a benchtop, with undistilled solvent and commercially available (not further purified) Cu salts.;Chapter 3. A new class of enantioselective conjugate addition (ECA) reactions that involve aryl- or alkenylsilylfluoride reagents and are catalyzed by chiral non-C2-symmetric Cu-based NHC complexes are presented. Transformations have been designed based on the principle that a catalytically active chiral NHC--Cu--aryl or NHC--Cu-alkenyl complex can be accessed from reaction of a Cu-halide precursor with in situ- generated aryl- or alkenyl-tetrafluorosilicate. Reactions proceed in the presence of 1.5 equivalents of the aryl- or alkenylsilane reagents and 1.5 equivalents of tris(dimethylamino)sulfonium difluorotrimethylsilicate. Desired products are isolated in 63--97% yield and 73.5:26.5--98.5:1.5 enantiomeric ratio (47%--97% ee).;Chapter 4. An efficient Cu-catalyzed protocol for enantioselective addition of a dimethylphenylsilanyl group to a wide range of cyclic and acyclic unsaturated ketones, esters, acrylonitriles and alpha,beta,gamma,delta-dienones is presented. Reactions are performed in the presence of 1--5 mol % of commercially available and inexpensive CuCl, a readily accessible monodentate imidazolinium salt as well as commercially available (dimethylphenylsilyl)pinacolatoboron. Cu-catalyzed 1,4- and 1,6-conjugate additions afford the enantiomerically enriched silanes in 72%--98% yield and 90:10-->99:1 enantiomeric ratio (er) with up to >25:1 of Z:E selectivity.;Chapter 5. A Cu-catalyzed method for enantioselective boronate conjugate additions to trisubstituted alkenes of acyclic alpha,beta-unsaturated carboxylic esters, ketones, and thioesters is presented. All transformations are promoted by 5 mol % of a chiral monodentate NHC--Cu complex, derived from a readily available C1-symmetric imidazolinium salt, and in the presence of commercially available bis(pinacolato)diboron. Reactions are efficient (typically, 60% to >98% yield after purification) and deliver the desired beta-boryl carbonyls in up to >98:2 enantiomer ratio (er). In addition, metal-free, nucleophilic activation of a B.B bond has been exploited in the development of a highly efficient method for conjugate additions of commercially available bis(pinacolato)diboron to cyclic or acyclic alpha,beta-unsaturated carbonyls. Reactions are readily catalyzed by 2.5--10 mol % of a simple NHC. A variety of cyclic and acyclic unsaturated ketones and esters can serve as substrates. Transformations deliver beta-boryl carbonyls bearing tertiary as well as quaternary B-substituted carbons in up to >98% yield.