Investigation of lipase-catalyzed Michael-type carbon-carbon bond formations

Conjugate additions of carbon nucleophiles to appropriate acceptor molecules were investigated with respect to the synthetic potential and stereochemistry of the products. Reactions of short-chain α,β-unsaturated ketones and mono-substituted nitroalkenes with CH-acidic carboxylic ester derivatives were catalyzed by various immobilized lipases. Using methyl nitroacetate complete conversion with methyl vinyl ketone and trans-β-nitrostyrene was obtained. The reactions proceeded without enantioselectivity. Evidence for enzyme catalysis is provided by the observation that after denaturation of Candida antarctica lipase B or inhibition no reaction took place. Docking studies with the chiral addition product methyl 2-methyl-2-nitro-5-oxohexanoate did not reveal any specific binding mode for this reaction product, which would have been the requirement for stereoselective additions. These results support the experimental findings that the conjugate addition takes place without enantiopreference.

Graphical abstractDownload full-size imageLipase-catalyzed Michael additions of activated alkenes and carbon-nucleophiles were performed in organic solvents. Conversions up to completion were obtained within 20 h at room temperature. However, no enantioselectivity was observed. Molecular modelling experiments give an insight into the putative catalytic processes.