Intermolecular Amidation of Unactivated sp² and sp³ C−H Bonds via Palladium-Catalyzed Cascade C−H Activation/Nitrene Insertion

This communication describes the Pd(OAc)2-catalyzed intermolecular amidation reactions of unactivated sp2 and sp3 C−H bonds using primary amides and potassium persulfate. The substrates containing a pendent oxime or pyridine group were amidated with excellent chemo- and regioselectivities. It is noteworthy that reactive C−X bonds were well-tolerated and a variety of primary amides can be effective nucleophiles for the Pd-catalyzed C−H amidation reactions. For the reaction of unactivated sp3 C−H bonds, β-amidation of 1° sp3 C−H bonds versus 2° C−H bonds is preferred. The catalytic reaction is initiated by chelation-assisted cyclopalladation involving C−H bond activation. Preliminary mechanistic study suggested that the persulfate oxidation of primary amides should generate reactive nitrene species, which then reacted with the cyclopalladated complex.