Catalytic hydrogenation of unactivated amides enabled by hydrogenation of catalyst precursor

A general method for catalytic hydrogenation of unactivated amides was achieved. During the catalyst induction period, a novel structural change was observed involving full hydrogenation of the interior unsaturated bonds of the pyridines of the Ru-containing catalyst precursor. Based on this observation, the mechanism of amide hydrogenation may involve a two-step pathway, wherein the Ru catalyst having an H–Ru–N–H functionality is generated in the first step, followed by the amide carbonyl group interacting with the outer, rather than the inner, sphere of the Ru catalyst.