Copper-catalyzed enantioselective allylic alkylation with alkylmetals. Synthesis of tertiary and quaternary all-carbon stereocenters

Chapter 1: Catalytic asymmetric allylic alkylation reactions with alkylmetal reagents. Allylic alkylations represent a powerful class of C-C bond forming reactions. Over the past several years a number of research groups have initiated research programs focused on the development of metal-catalyzed enantioselective additions of alkylmetal reagents to allylic substrates. Representative related methods are highlighted and reviewed in this chapter.; Chapter 2: Development of asymmetric Cu-catalyzed allylic alkylation reactions of cinnamyl phosphates with dialkylzinc reagents and modular amino acid based ligands. The aim of my doctoral studies has been to apply modular amino acid based ligands and novel high throughput screening strategies to the development new asymmetric Cu-catalyzed allylic substitution reactions. In our initial studies we examined the asymmetric Cu-catalyzed allylic alkylation of cinnamyl phosphates with dialkylzinc reagents. Application of our screening protocols allowed us to synthesize libraries of amino acid based ligands and identify an optimal system that allows for the synthesis of tertiary and quaternary all-carbon stereogenic centers in high optical purity, yield and regioselectivity. The utility of the method was demonstrated in the first catalytic asymmetric synthesis of (R)-(-)-sporochnol A.*; Chapter 3: Efficient asymmetric Cu-catalyzed synthesis of alpha-alkyl-beta,gamma-unsaturated esters. Next, we sought to expand the Cu-catalyzed enantioselective method to the synthesis of alpha-alkyl-beta,gamma-unsaturated esters. Successful application of our ligand optimization protocols identified a new catalyst system that afforded the desired products in excellent enantioselectivities (up to 97% ee). With this method, we have gained access to a useful class of compounds, and we demonstrated the utility of the compounds in a catalytic asymmetric synthesis of (R)-(-)-elenic acid.*; Most recently, we have extended this method to the synthesis of quaternary carbon stereogenic centers, specifically alpha,alpha'-dialkyl-beta,gamma-unsaturated esters and alpha-alkyl-alpha-aryl-beta,gamma-unsaturated esters. Our method has been applied to the formal synthesis of ethosuximide and aminoglutethimide in addition to the synthesis of quaternary beta2-amino acids.*; *Please refer to dissertation for diagrams.