New methods for catalytic enantioselective conjugate addition of dialkylzinc reagents to alpha,beta-unsaturated carbonyls: Discovery and use of new catalysts

This thesis will discuss the discovery and application of new catalyst systems for enantioselective conjugate addition of dialkylzinc reagents. There will also be a discussion of other catalytic systems for effecting these transformations.; Chapter one. Catalytic enantioselective conjugate addition to alpha,beta-unsaturated carbonyls. The first chapter will be a review of methods available for catalytic enantioselective conjugate addition of carbon-based nucleophiles, with an emphasis on the use of these methods in the total synthesis of complex natural and non-natural products.; Chapter two. Copper-catalyzed ECA of dialkylzinc reagents to alpha,beta-unsaturated N-acyl oxazolidinones. Beginning with a review of related methods from the literature, this chapter will discuss the discovery of new peptidic phosphine amides as effective ligands in the Cu-catalyzed enantioselective conjugate addition of dialkylzinc reagents to alpha,beta-unsaturated N-acyl oxazolidinones. The screening methods which allowed for the identification of the catalyst will be discussed. The new triamide ligand will be compared to the bisamide Schiff bases which are effective in other Cu-catalyzed ECA reactions. Reaction scope and limitations of the new catalytic system, as well as conversion of the products into optically enriched carboxylic acid derivatives will be given.; Chapter three. Catalytic enantioselective formation of all-carbon quaternary stereogenic centers by copper-catalyzed ECA of dialkylzinc reagents to beta-disubstituted alpha,beta-unsaturated ketones. A new class of ligands, peptidic anthranilic amides, was developed for the Cu-catalyzed enantioselective conjugate addition of dialkylzinc reagents to beta-disubstituted enones, yielding all-carbon quaternary stereogenic centers. The ligand screening cascade is described as well as a rationale for the decisions made en route. Substrate scope and limitations will be presented, followed by methods for functionalization of the products into other small molecule building blocks containing all-carbon stereogenic centers. The last part of the chapter will focus on new, highly potent N-heterocyclic Ag and Cu complexes for ECA of dialkylzinc reagents to simple beta-disubstituted enones.