Decarboxylative aldol reaction catalysed by lipases and a protease in organic co-solvent mixtures and nearly anhydrous organic solvent media

Abstract

The effects of the choice of lipase, reaction medium, immobilization, presence of additives and temperature on conversion and stereoselectivity during a lipase catalysed decarboxylative aldol reaction were examined. It was shown that Candida antarctica lipase B (CALB) catalysed a decarboxylative aldol reaction between 4-nitrobenzaldehyde and ethyl acetoacetate in a 60% acetonitrile–40% aqueous buffer co-solvent mixture. Interestingly, free and immobilized forms of CALB showed opposite enantioselectivity in this media. The addition of 30 mol% imidazole increased the reaction rate from 8.5 to 55.7 μM min− 1 mg− 1. A 98% conversion could be achieved in 14 h (instead of 168 h) by adding imidazole. Other lipases also catalysed this reaction in different reaction media to a varying extent. With Mucor javanicus lipase in 30% DMSO, 20% enantiomeric excess (ee) of the (R)-product was observed. CALB also catalysed this reaction in nearly anhydrous acetonitrile. In the presence of cross-linked protein coated microcrystals of CALB, 90% conversion was obtained in this media in 24 h. A commercially available protease, alcalase, was also found to catalyse this reaction. While low water media gave poor conversion, the reaction in aqueous–60% acetonitrile co-solvent mixture gave 99% conversion in 72 h, provided imidazole was used as an additive.