Theoretical Study on Ir-Catalyzed α-Amidation of 2-Acylimidazoles: Mechanism and Insertion Selectivity

The mechanism and reactivity of Ir-catalyzed α-amidation of 2-acylimidazoles have been investigated at the B3LYP-D3 level, with the emphasis on nitrene insertion selectivity. The calculation results show that the catalytic mechanism consists of iridacycle formation, CO 2 release, nitrene insertion, and amido protonation processes. Thereinto, nitrene insertion is both rate- and selectivity-determining steps. The origin of the nitrene group favorably inserting into an Ir–C α over C γ –H bond was further unraveled. In addition, this work also explored the α-amidation reactivity difference between α-mono- and α,α-di-substituted 2-acylimidazoles and the source of this difference was identified. These meaningful insights may serve as the basis for the further design and development of transition-metal-catalyzed α-amidation systems featuring high reactivity and selectivity.