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

作者：Lin, Zijie; Zheng, Zhenjie; Xiao, Rongxing; Zheng, Kangcheng; Wang, Juping^*

来源：Organometallics, 2022.

DOI：10.1021/acs.organomet.2c00365

• C-H AMINATION
• TRANSANNULATION
• BONDS
• ACIDS

The mechanism and reactivity of Ir-catalyzed alpha- amidation of 2-acylimidazoles have been investigated at the B3LYPD3 level, with the emphasis on nitrene insertion selectivity. The calculation results show that the catalytic mechanism consists of iridacycle formation, CO2 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 alpha over C gamma-H bond was further unraveled. In addition, this work also explored the alpha-amidation reactivity difference between alpha-mono-and alpha,alpha-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 alpha-amidation systems featuring high reactivity and selectivity.

• 单位
  中山大学; 广东药学院