Ruthenium‐Catalyzed Nitrile‐Acrylate Reductive Coupling by 2‐Propanol: Synthesis of Enantioenriched β‐Amino Esters

Abstract

ABSTRACT Using a ruthenium catalyst derived from RuHCl(CO)(PPh 3 ) 3 and Cy‐BIPHEP, 2‐propanol‐mediated reductive coupling of phenyl acrylate with aromatic or aliphatic nitriles occurs to form α,β‐unsaturated β‐amino esters. Although the reaction products, which incorporate acyclic tetrasubstituted alkenes, are challenging substrates for asymmetric hydrogenation, trifluoroethanol (TFE) enabled rhodium‐Walphos‐catalyzed hydrogenation occurs with high levels of enantioselectivity. Thus, through successive transfer hydrogenative coupling‐asymmetric hydrogenation events, abundant nitrile and acrylate feedstocks are converted to enantioenriched β‐amino esters. This method represents a new catalytic transformation of nitriles and the first reductive C─C coupling of nitriles beyond the use of stoichiometric metals or metalloids.