Theoretical investigation of Co(II)-catalyzed inert C–H bond functionalization in pyridine amide derivatives

Abstract

Density functional theory (DFT) calculations were used to investigate the mechanism of Co(II)-catalyzed functionalization of inert CH bonds in pyridine amide derivatives. The research focused on the influence of substituents on the benzene ring and product selectivity. When the benzene ring contains tert‑butyl and isopropyl substituents, the reaction yields indoline and benzoxazine derivatives, respectively. Through calculations, the distinct mechanisms of these two reaction pathways were revealed: the formation of indoline derivatives follows a concerted metalation/deprotonation (CMD) mechanism, while the formation of benzoxazine derivatives proceeds via a hydrogen transfer mechanism. The key transition states in the corresponding processes have been studied in particular. The transition state structures have been located with relatively low energy barriers, which provide an important basis for understanding the reaction kinetics. In addition, in order to further explore the relationship between different spin multiplicities, the minimum energy crossing points (MECPs) were systematically investigated, which provided a theoretical basis for elucidating the possible spin state transition during the reaction.