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 <i>meta</i>-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

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 <i>meta</i>-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

Iridium-Catalyzed Aerobic α,β-Dehydrogenation of γ,δ-Unsaturated Amides and Acids: Activation of Both α- and β‑C–H bonds through an Allyl–Iridium Intermediate

Direct aerobic α,β-dehydrogenation of γ,δ-unsaturated amides and acids using a simple iridium/copper relay catalysis system is described. We developed a new strategy that overcomes the challenging issue associated with the low α-acidity of amides and acids. Instead of α-C–H metalation, this reaction proceeds by β-C–H activation, which results in enhanced α-acidity. Conjugated dienamides and dienoic acids were synthesized in excellent yield with this reaction, which uses a simple reaction protocol. Mechanistic experiments suggest a catalyst resting state mechanism in which both α-C–H and β-C–H cleavage is accelerated