Highly Enantioselective Michael Addition of Nitroalkanes to Enones and Its Application in Syntheses of (R)-Baclofen and (R)-Phenibut

Abstract

A highly enantioselective Michael addition of nitroalkanes to α,β-unsaturated ketones was developed. In the presence of a chiral primary amine–thiourea catalyst based on dehydroabietic amine, γ-nitro ketones were obtained with excellent enantioselectivities (up to 99% ee) and in up to 96% yield. This protocol was successfully applied in asymmetric syntheses of (<i>R</i>)-baclofen and (<i>R</i>)-phenibut with high yields and excellent enantioselectivities.