Exploring asymmetric catalytic transformations

In Chapter 2, we report a highly enantioselective synthesis of β-alkyl-substituted alcohols through a one-pot Cu- catalyzed asymmetric allylic alkylation with organolithium reagents followed by reductive ozonolysis. The synthesis of γ-alkyl-substituted alcohols was also achieved through Cu-catalyzed asymmetric allylic alkylation with organolithium reagents followed by a hydroboration-oxidation. These protocols do not compromise the stereochemical integrity and provide readily access to highly valuable chiral building blocks. In Chapter 3, a highly enantioselective Cu-catalyzed direct allylic arylation using organolithium compounds is described. The use of readily available aryllithium reagents in combination with allylic bromides and use of a copper-NHC catalyst are key factors for the success of this reaction. The only stoichiometric waste produced in this novel transformation is LiBr. The use of n-BuLi was found essential for the preparation of aryllithium compounds. The broad substrate and reagent scope and the application of the new method in the formal catalytic enantioselective synthesis of (R)-tolterodine (Detrol) illustrate the potential of this allylic arylation for the synthesis of important chiral diarylmethane structures. In Chapter 4, we report a highly enantioselective synthesis of quaternary all- carbon stereocenters via Cu-catalyzed direct allylic arylation using organolithium compounds. A Cu(I)-NHC catalytic system proved to be essential for this transformation and allowed the preparation of a wide range of di- and tri-arylated vinyl methane compounds with good to excellent enantioselectivites. This transformation is also highly atom economical as LiBr is the only stoichiometric waste during this transformation.