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 sp3 CH bond functionalization process. The reaction favors predominantly the CH bonds of β‐methyl groups over the unactivated methylene CH bonds. Moreover, a preference for activating sp3 CH bonds of β‐methyl groups, via a five‐membered ring intermediate, over the aromatic sp2 CH bonds was also observed in the cyclometalation step. Additionally, sp3 CH bonds of unactivated secondary sp3 CH bonds could be functionalized by favoring the ring carbon atoms over the linear carbon atoms. Getting ahead on tams: The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper‐catalyzed sp3 CH bond functionalization process to deliver β‐lactams. The reaction favors the CH bonds of β‐methyl groups over the unactivated methylene CH bonds, as well as aromatic C(sp2)H bonds and unactivated secondary C(sp3)H bonds of rings.