High-Valent Cobalt-Catalyzed C-H Activation/Annulation of 2-Benzamidopyridine 1-Oxide with Terminal Alkyne: A Combined Theoretical and Experimental Study

The multiple possible pathways of high-valent cobalt catalyzed C-H activation/annulation of 2-benzamidopyridine 1-oxide with terminal alkyne were investigated in this combined theoretical and experimental study. The calculated results indicated that CoIII catalyzed C-H activation occurs via a concerted-metalation deprotonation (CMD) process and that the subsequent annulation involves the CoIV intermediate generated through a proton-coupled electron transfer (PCET) process in DMSO solvent or through an intermolecular single electron transfer (SET) process in trifluoroethanol (TFE) solvent. Moreover, the theoretical calculations also revealed that CoIII is the actual catalyst, and the solvent controls the chemoselectivity in the annulation stage, triggering a switch between five- and six-membered ring products. Kinetic isotope effect (KIE), electron paramagnetic resonance (EPR), and TEMPO inhibition experiments were performed to confirm the computational results. The mechanistic insights should be valuable for understanding the PCET and SET processes involved in transition metal-catalyzed C-H functionalizations.