Diverting C–H Annulation Pathways: Nickel-Catalyzed Dehydrogenative Homologation of Aromatic Amides

Direct homologation of aromatic amides with internal alkynes has been accomplished via a nickel-catalyzed sequential C–H activation reaction. The use of a rigid chelating group and a strong aprotic polar solvent successfully divert the classical [4 + 2] annulation to the [2 + 2 + 2] homologation pathway. This transformation is promoted by a simple nickel catalyst without the need of stoichiometric metal oxidants. Mechanistic studies support an unusual substrate-assisted ligand exchange process. NMR and X-ray data suggest a [5,5] Ni-bridged metallacycle as the catalyst resting state. Substrate assisted directing group swap plays an important role for the subsequent meta-C-H insertion. In contrast, [4 + 2] annulation can be accomplished using a bulky, electron-rich phosphine ligand, which favors rapid reductive C–N elimination.