Non-Enzymatic Kinetic Resolution and Desymmetrization of α-Quaternary Carboxylic Acids via Chiral Bifunctional Sulfide-Catalyzed Bromolactonization

Abstract

Abstract Kinetic resolution of racemic carboxylic acids is a reliable method to enantioselectively prepare chiral carboxylic acids. Although efficient catalytic kinetic resolutions of chiral α-tertiary carboxylic acids have been reported, the kinetic resolution of α-quaternary carboxylic acids bearing an all-carbon quaternary stereocenter has remained a formidable challenge. Herein, we report a precious example of a kinetic resolution of α-quaternary carboxylic acids via a chiral bifunctional sulfide-catalyzed bromolactonization of alkynes. The ability of chiral sulfides to recognize α-quaternary carboxylic acids was evaluated via the catalytic enantioselective desymmetrizing bromolactonization of achiral α,α-dipropargyl carboxylic acids, which is a reaction that is related to target kinetic resolution. The optimum chiral sulfide was successfully applied to the efficient kinetic resolution of α-propargyl carboxylic acids that bear an all-carbon quaternary stereocenter.