Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols.

A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pK of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.