Synthesis of Amidines and Benzoxazoles from Activated Nitriles with Ni(0) Catalysts

Abstract

Amidines and 2-substituted benzoxazoles were synthesized from N-heterocyclic nitriles under mild conditions (50 °C, 48 h, two steps) in an atom-economical process that involves addition of methanol, the solvent, to a nitrile moiety to yield a methyl imidate and the subsequent extrusion of solvent in the presence of amines to afford the title compounds. Methyl imidate formation was achieved by developing a new catalytic pathway using [(dippe)Ni(H)]2 (dippe = 1,2-bis(diisopropylphosphino)ethane), [Ni(cod)2]/dppe, or [Ni(cod)2]/P(OPh)3 (cod = 1,5-cyclooctadiene, dppe = 1,2-bis(diphenylphosphino)ethane, P(OPh)3 = triphenyl phosphite) as the catalyst precursor. Regarding the ligands, for a given substrate, namely 4-cyanopyridine, the best performance for the Ni(0)-catalyzed system was found for the σ-donor bidentate dippe, whereas the monodentate π acceptor P(OPh)3 was less efficient. In relation to the substrates, for a given Ni–dippe system, steric hindrance and, more importantly, substrate electron-withdrawing character control imidate formation and thus the yield of amidines and benzoxazoles.