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.