Kinetic Resolution of alpha-Acetoxy-N-Acyl Oxazolidinethiones by a Chiral O-Nucleophilic Acyl Transfer Catalyst

Abstract

We recently described a series of catalysts bearing a hydroxyl group in close proximity to a basic amine which effect the methanolysis of para-nitrophenyl (PNP) esters.1 These catalysts, an example of which is provided in Scheme 1, operate by an Onucleophilic mechanism in which the hydroxyl group of the catalyst (1) undergoes base-catalyzed acylation by the PNP ester (2) to give an acyl-transferred intermediate (3). This intermediate then undergoes base-catalyzed deacylation to provide the product (4) and regenerate the catalyst (1). In the course of our studies, we found that the deacylation step of the catalytic cycle is turnover-limiting, and that catalysts containing alcohols with a proximal electron withdrawing group are more active, probably due to their enhanced leaving group ability. The catalysts we studied are chiral, and in this communication we describe the use of two such catalysts for the kinetic resolution of chiral α-acetoxy oxazolidinethione imides.