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 sp ³ 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.