Promiscuous acylase-catalyzed aza-Michael additions of aromatic N-heterocycles in organic solvent

A novel and efficient enzymatic promiscuous protocol for aza-Michael addition of aromatic N-heterocycles to α,β-unsaturated compounds has been described. The reactions were catalyzed by promiscuous zinc-active-site acylase in organic solvent at 50 °C. The strategy works with a broad range of N-heterocycles to afford the corresponding Michael adduct with good yields in several hours (0.5–6 h). This catalytic promiscuity is the first example of metal-active-site enzyme-catalyzed aza-Michael addition for aromatic N-heterocycles.