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

Using a ruthenium catalyst derived from RuHCl(CO)(PPh3)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.