Copper-Catalyzed Site-Selective Intramolecular Amidation of Unactivated C( sp3) - H Bonds

The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper-catalyzed sp(3) CH bond functionalization process. The reaction favors predominantly the CH bonds of -methyl groups over the unactivated methylene CH bonds. Moreover, a preference for activating sp(3) CH bonds of -methyl groups, via a five-membered ring intermediate, over the aromatic sp(2) CH bonds was also observed in the cyclometalation step. Additionally, sp(3) CH bonds of unactivated secondary sp(3) CH bonds could be functionalized by favoring the ring carbon atoms over the linear carbon atoms.