Enantioselective Copper-Catalyzed Radical Ring-Opening Cyanation of Cyclopropanols and Cyclopropanone Acetals

A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper-catalyzed radical relay processes has been developed. Various cyclopropanols and cyclopropanone acetals are compatible to the catalytic conditions, providing beta-carbonyl nitriles with excellent enantioselectivity. These products can be readily converted to chiral gamma-amino acids derivatives and drugs such as (R)-baclofen. Preliminary mechanistic studies have supported a ring-opening process for cyclopropanoxy radicals followed by copper-catalyzed enantioselective cyanation of benzylic radicals to form the C-CN bonds in an enantioselective manner.