Promiscuous Behavior of Rhizomucor miehei Lipase in the Synthesis of N ‐Substituted β‐Amino Esters

Abstract

A mild and efficient procedure for the aza-Michael addition of amines to acrylates by using lipases as catalysts is reported. Various lipases, mono- and bifunctional amines, alkyl acrylates, and reaction parameters were studied. Under the optimal conditions, Rhizomucor miehei lipase showed high selectivity. It catalyzed the formation of the Michael monoadduct as the only product in high yield and purity. Moreover, when diamines were used as nucleophiles, the lipase catalyzed the addition of only one of the two amino groups, showing in this case high substrate specificity. This promiscuous and highly selective behavior displayed by Rhizomucor miehei lipase allowed us to obtain 22 N-substituted β-amino esters, 15 of them being new products.