[Rh(CO]2Cl]2 has been shown to catalyze sequential, mechanistically- distinct transformations in one pot. Tandem allylic alkylation/cycloisomerization sequences have been developed to access valuable, complex structures from relatively simple substrates. A methodology for the enantioselective conjugate addition of 2-heteroaryl nucleophiles to a variety of Michael acceptors has been developed. This method was used successfully in an ongoing approach to the synthesis of cortistatin A. 10 linear steps have been completed towards the synthesis of cortistatin A, including a highly regioselective propargylation to install a quaternary carbon and a diastereoselective intramolecular Diels-Alder reaction. / text

This report details the discovery of a method for rhodium catalyzed asymmetric conjugate additions of heteroaryl nucleophiles to α,β-unsaturated carbonyl compounds. This work has successfully employed heteraryl titanates in enantioselective conjugate addition to α,β-unsaturated carbonyl compounds for the first time. Moreover, the utility of benzofuranyl, benzothiophenyl, and pyrrolo zinc reagents has been exemplified in enantioselective conjugate additions. We have found that the precatalyst [Rh(COD)acac]/OMeBIPHEP is broadly effective for enantioselective conjugate additions. Each heterocycle tested exhibited unique reactivity with respect to both conversion and enantioselectivity; reactivities of heteroaryl zinc reagents and heteroaryl titanates in enantioselective conjugate additions to α,β-unsaturated carbonyl compounds are sometimes complementary. Efforts directed towards the development of a method for rhodium-free enantioselective conjugate addition of furan to α,β-unsaturated carbonyl compounds are also described. / text

Thesis advisor: Amir H. Hoveyda / 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 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 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 a,b-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 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 a,b-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 boryl carbonyls bearing tertiary as well as quaternary B-substituted carbons in up to >98% yield. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

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