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.

Keywords::

• decarboxylative aldol reaction
• biocatalysis in aqueous-organic co-solvent mixtures
• lipases
• C–C bond formation

Acknowledgements

The authors would like to thank Prof. P. S. Pandey, Dr. N.G. Ramesh, both from Chemistry Dept., IIT Delhi, India for valuable discussions and especially his (PSP) suggestion that we try imidazole instead of triethylamine.

Declaration of interest: The work was supported by grants from the Department of Science and Technology (DST), Govt. of India. M. K. and J. M. thank CSIR, India for providing senior research fellowship and junior research fellowship respectively. Supports from the project funded by Department of Biotechnology (DBT), Govt. of India, is also gratefully acknowledged. The support for our work in this area from UKIERI is also acknowledged. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.