Origin of kinetic resolution of hydroxy esters through catalytic enantioselective lactonization by chiral phosphoric acids

Abstract

Kinetic resolution is a widely used strategy for separation and enrichment of enantiomers. Using density functional theory computations, the origin of how a chiral BINOL–phosphoric acid catalyzes the selective lactonization of one of the enantiomers of α-methyl γ-hydroxy ester is identified. In a stepwise mechanism, the stereocontrolling transition state for the addition of the hydroxyl group to the si face of the ester carbonyl in the case of the S isomer exhibits a network of more effective noncovalent interactions between the substrate and the chiral catalyst.