Anipamil

Alcs. and nitrile functionalities have widespread applications in biochem. and chem. synthesis.Catalytic transformations involving C-C bond formation relying on unsaturated coupling partners create important pathways for processes in synthetic, material, and medicinal chem.The discovery of a simple and selective coupling of nitriles with allylic alcs. catalyzed by a ruthenium pincer complex is described, which tolerates reactive functional groups such as carbamate, sulfonate, olefin, cyano, and trifluoromethyl-substituted benzyl nitriles.Homo allylic alcs. also provided 1,4-addition products following the isomerization of double bonds.Mechanistic studies supported that the allylic alcs. initially undergo selective oxidation by the catalyst to α,β-unsaturated carbonyl compounds followed by 1,4-conjugate addition of benzyl nitriles catalyzed by a base and subsequent catalytic reduction of carbonyl functionality, leading to the formation of δ-hydroxynitrile products.The catalytic cycle of this tandem process is established by d. functional theory studies.Remarkably, anipamil drug is successfully synthesized using this catalytic protocol.The utility of the δ-hydroxynitrile products in the synthesis of biol. active mols. and their further functionalization are also demonstrated.