58. DFT Study on the Mechanism of the Iridium-Catalyzed Benzylamine Ortho C-H Alkenylation with Ethyl Acrylate

Jia, R.; Ling, B.;* Liu, P.; Liu, Y.; Jiang, Y.-Y.; Bi, S.*  ACS Omega 2020, 5, 15446–15453. Download Link

Abstract: Iridium-catalyzed oxidative o-alkenylation of benzylamines with acrylates was enabled by the directing group pentafluorobenzoyl (PFB). Density functional theory calculations were performed to explore the detailed reaction mechanism. The calculated results reveal that N-deprotonation prior to C−H activation is favored over direct C−H activation. Moreover, C−H activation is reversible and not the rate-determining step, which has been supported by the experimental observation. The regio- and stereoselectivity of ethyl acrylate insertion are controlled by the steric effect and the carbon atom with a larger orbital coefficient of the π* antibonding orbital in the nucleophilic attack, respectively. The migratory insertion of ethyl acrylate is computationally found to be rate-determining for the whole catalytic cycle. Finally, the seven-membered ring intermediate IM11 undergoes a sequential Nprotonation and β-H elimination with the assistance of AcOH, rather than β-H elimination and reductive elimination proposed experimentally, to afford the o-alkenylated product. IM11 is unable to directly cyclize through C−N reductive elimination because both sp3-hybridized N and C atoms are unfavorable for N−C reductive elimination. The origin of the directing group PFB preventing the product and intermediates undergoing aza-Michael addition has been explained.