Asymmetric Conjugate Addition of Alkylzirconium Reagents to α,β-Unsaturated Lactones

Abstract

The asymmetric synthesis of β-substituted lactones by catalytic asymmetric conjugate addition of alkyl groups to α,β-unsaturated lactones is reported. The method uses alkylzirconium nucleophiles prepared in situ from alkenes and the Schwartz reagent. Enantioselective additions to 6- and 7-membered lactones proceed at rt, tolerate a wide variety of functional groups, and are readily scalable. The method was used in a formal asymmetric synthesis of mitsugashiwalactone.