Amano-PS-IM-Catalyzed Mechanochemical Enzymatic Acylative Kinetic Resolution of Secondary Alcohols

Abstract

Mechanochemical enzymatic acylative kinetic resolution of secondary alcohols using ball milling represents a highly efficient and sustainable approach for the synthesis of chiral esters and alcohols with high enantioselectivity. Previously reported protocols have predominantly relied on lipase B from Candida antarctica (CALB). However, its relatively high cost and its applicability restricted to methyl-substituted secondary alcohols leave significant room for improvement in terms of practicality, sustainability, and substrate scope. Herein, we report a mechanochemical protocol for acylative kinetic resolution catalyzed by less-expensive Amano Lipase PS-IM (immobilized on diatomaceous earth). A broad range of secondary alcohols were efficiently converted to the corresponding acylated products in high yields with excellent enantioselectivities, through the careful optimization of the mechanochemical conditions. Notably, this protocol is applicable to ethyl- and other longer alkyl-substituted secondary benzylic alcohols, which are scarcely reactive under conventional CALB-catalyzed conditions.