Enzyme-Mediated Synthesis of (S)- and (R)-Verapamil.

A lipase-mediated synthesis of (S)- and (R)-verapamil is described. The key steps of the synthetic sequence are the enantioselective acetylation, mediated by Lipase PS, of allylic alcohol (Z)-(+/-)-2, affording the acetate derivative (Z,R)-(-)-3 (ee 92%) and the Ireland-Claisen rearrangement of this latter and of its enantiomer (Z,S)-(+)-3 (ee 92%) to afford acid derivatives (E,R)-(-)-4 (ee 94%) and (E,S)-(+)-4 (ee 93%), pre cursors of (S)- and (R)-verapamil, respectively.