Hybrid Palladium Catalyst Assembled from Chiral Phosphoric Acid and Thioamide for Enantioselective β-C(sp3)-H Arylation

Abstract

A hybrid palladium catalyst assembled from a chiral phosphoric acid (CPA) and thioamide enables a highly efficient and enantioselective beta-C(sp(3))-H functionalization of thioamides (up to 99 % yield, 97 % ee). A kinetic resolution of unsymmetrical thioamides by intermolecular C(sp(3))-H arylation can be achieved with high s-factors. Mechanistic investigations have revealed that stereocontrol is achieved by embedding the substrate in a robust chiral cavity defined by the bulky CPA and a neutral thioamide ligand.