Asymmetric Alkoxycarbonyl-Cyanation of Styrenes via Photoredox and Copper Catalysis

A photoredox and copper dual-catalyzed alkoxycarbonyl-cyanation of styrenes is developed. With this method, a wide range of chiral β-aryl-substituted β-cyanoester derivatives is obtained in good yields with high enantioselectivities. Optically pure β-cyanoesters can be readily converted to the corresponding chiral β-substituted γ-amino acid derivatives. With this strategy in mind, two marketed drugs, (R)-baclofen and (R)-phenibut, are synthesized through the efficient transformation of their corresponding chiral β-aryl-substituted β-cyanoesters. We expect that this efficient and convenient method for synthesizing structurally diverse chiral β-cyanoester derivatives can accelerate the drug development process.