Roads Not Taken: Mechanism and Origins of Regio- and Chemoselectivity of Directed CoIII-Catalyzed Alkenylation of N‑Pyridyl 2‑Pyridone

The mechanism of Co-catalyzed alkenylation of N-pyridyl-2-pyridone with terminal alkynes was probed using density functional theory calculations. The mechanism is predicted to involve three steps: C–H activation ortho to the pyridine directing group, affording a six-membered cobaltacycle intermediate, insertion of the alkyne into the CoIII–aryl bond, resulting in a seven-membered cobaltacycle intermediate, and protodemetalation. Our results demonstrate that attractive dispersion interactions modulate ligand binding energies, thereby affecting the reaction barriers and the magnitude of reaction feasibility. Further, we show that temperature plays a key role in controlling the chemoselectivity of the reaction.