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

Kinetic resolution of racemic carboxylic acids is a reliable method to enantioselectively prepare chiral carboxylic acids. Although efficient catalytic kinetic resolutions of chiral alpha-tertiary carboxylic acids have been reported, the kinetic resolution of alpha-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 alpha-quaternary carboxylic acids via a chiral bifunctional sulfide-catalyzed bromolactonization of alkynes. The ability of chiral sulfides to recognize alpha-quaternary carboxylic acids was evaluated via the catalytic enantioselective desymmetrizing bromolactonization of achiral alpha,alpha-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 alpha-propargyl carboxylic acids that bear an all-carbon quaternary stereocenter.

Automated summary

This article reports a method for the kinetic resolution of α-quaternary carboxylic acids through the bromolactonization of alkynes catalyzed by a chiral sulfide. This method provides a solution to the challenging task of separating α-quaternary carboxylic acids and shows promising results.