Improved process for the enantioselective hydrolysis of prochiral diethyl malonates catalyzed by pig liver esterase

An improved process for the enantioselective hydrolysis of prochiral 2-aryl-2-alkyl-disubstituted diethyl malonates catalyzed by pig liver esterase (PLE) was developed. With diethyl 2phenyl-2-methylmalonate as a model substrate, the highest enantioselectivities (96% ee; R-isomer) were achieved when carrying out the process in the presence of a suitable mixture of cosolvents (buffer-i-PrOH-t-BuOH, 8: 1: 1). The process also works efficiently at higher substrate concentrations. The reaction was carried out on a multi-gram preparative scale, leading to a conversion of > 95%, an enantioselectivity of 96% ee, and a yield of 83% at a substrate concentration of 200 mM.