Abstract
We report here a comprehensive computational analysis of the mechanisms of the photoredox-nickel-HAT (HAT: hydrogen atom transfer) catalyzed arylation and alkylation of alpha-amino C-sp3-H bonds developed by MacMillan and co-workers. Different alternatives for the three catalytic cycles were tested to identify unambiguously the operative reaction mechanism. Our analysis indicated that the Ir-III photoredox catalyst, upon irradiation with visible light, can be either reduced or oxidized by the HAT and nickel catalysts, respectively, indicating that both reductive and oxidative quenching catalytic cycles can be operative, although the reductive cycle is favored. Our analysis of the HAT cycle indicated that activation of a alpha-amino C-sp3-H bond of the substrate is facile and selective relative to activation of a beta-amino C-sp3-H bond. Finally, our analysis of the nickel cycle indicated that both arylation and alkylation of alpha-amino Csp3-H bonds occurs via the sequence of nickel oxidation states Ni-I-Ni-II-Ni-I-Ni-III and of elementary steps: radical addition-SET-oxidative addition-reductive elimination.