Lipase-catalyzed dynamic kinetic resolution of dimethyl (1,3-dihydro-2H-isoindol-1-yl)phosphonate

Abstract

A simple dynamic kinetic resolution of dimethyl (1,3-dihydro-2H-isoindol-1-yl)phosphonate has been developed by means of a lipase-catalyzed alkoxycarbonylation reaction. The influence of reaction parameters such as solvent, type and amount of alkoxycarbonylating agent, source and loading of enzyme, substrate concentration, temperature, and reaction time has been studied. The best results were found in the biocatalyzed reaction using Candida antarctica lipase type A and allyl 3-methoxyphenyl carbonate in toluene at 30 °C, yielding the (R)-allyl carbamate in 58% isolated yield and 96% enantiomeric excess. Remarkably, this procedure does not require external auxiliaries for the racemization of the slow-reacting aminophosphonate enantiomer and occurs under mild reaction conditions.