Biocatalytic decarboxylative Michael addition for synthesis of 1,4-benzoxazinone derivatives

The Candida antarctica lipase B (Novozym 435) is found to catalyze a novel decarboxylative Michael addition in vinylogous carbamate systems for the synthesis of 1,4-benzoxazinone derivatives. The reaction goes through Michael addition, ester hydrolysis and decarboxylation. A possible mechanism is suggested, with simultaneous lipase-catalyzed Michael addition and ester hydrolysis. The present methodology offers formation of complex products through multi-step reactions in a one pot process under mild and facile reaction conditions with moderate to high yields (51-90%) and no side product formation. The reaction seems to be is a great example of enzymatic promiscuity.

Automated summary

This study reports the Candida antarctica lipase B (Novozym 435) catalyzed novel decarboxylative Michael addition in vinylogous carbamate systems for the synthesis of 1,4-benzoxazinone derivatives. The reaction proceeds through Michael addition, ester hydrolysis, and decarboxylation. A possible mechanism involving simultaneous lipase-catalyzed Michael addition and ester hydrolysis is suggested. The reaction demonstrates enzymatic promiscuity by offering formation of complex products through multi-step reactions in a one pot process under mild and facile reaction conditions with moderate to high yields and no side product formation.