Enantioselective synthesis of compounds containing bis-benzylic quaternary stereocenters through palladium-catalyzed conjugate additions of arylboronic acids

Abstract

This thesis describes development of a catalyst system that allows formation of compounds containing bis-benzylic quaternary stereocenters. The work presented herein describes studies towards development of enantioselective, palladium-catalyzed conjugate additions of arylboronic acids to β-aryl, β,β-disubstituted enones to generate ketones containing bis-benzylic quaternary stereocenters. A catalyst generated in situ from palladium trifluoroacetate and a chiral, non-racemic (S)-4-tert-butyl-2-(2-pyridyl)oxazoline ligand ((S)t-BuPyOx) promotes conjugate additions of a wide range of electronically and structurally diverse arylboronic acids to a variety of β-aryl, β,β-disubstituted enones. In this work, we have used iterative addition of the arylboronic acids as a strategy to minimize undesired protodeboronation pathways that leads to efficient formation of the corresponding ketones containing bis-benzylic quaternary stereocenters in up to 92% yield with up to 93% enantioselectivity.