Mechanistic Insight into the Photoredox-Nickel-HAT Triple Catalyzed Arylation and Alkylation of α-Amino Csp3–H Bonds
KAUST DepartmentKAUST Catalysis Center (KCC)
Physical Science and Engineering (PSE) Division
Chemical Science Program
Online Publication Date2020-09-09
Print Publication Date2020-10-07
Embargo End Date2021-09-09
Permanent link to this recordhttp://hdl.handle.net/10754/665080
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AbstractWe report here a comprehensive computational analysis of the mechanisms of the photoredox-nickel-HAT (HAT: hydrogen atom transfer) catalyzed arylation and alkylation of α-amino Csp3–H bonds developed by MacMillan and coworkers. Different alternatives for the three catalytic cycles were tested to identify unambiguously the operative reaction mechanism. Our analysis indicated that the IrIII 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 α-amino Csp3‒H bond of the substrate is facile and selective relative to activation of a β-amino Csp3‒H bond. Finally, our analysis of the nickel cycle indicated that both arylation and alkylation of α-amino Csp3–H bonds occurs via the sequence of nickel oxidation states NiI-NiII-NiI-NiIII, and of elementary steps: radical addition-SET-oxidative addition-reductive elimination.
CitationMaity, B., Zhu, C., Yue, H., Huang, L., Harb, M., Minenkov, Y., … Cavallo, L. (2020). Mechanistic Insight into the Photoredox-Nickel-HAT Triple Catalyzed Arylation and Alkylation of α-Amino Csp3–H Bonds. Journal of the American Chemical Society. doi:10.1021/jacs.0c05010
SponsorsWe acknowledge King Abdullah University of Science and Technology (KAUST) for support and the KAUST Supercomputing Laboratory for providing computational resources of the supercomputer Shaheen II.
PublisherAmerican Chemical Society (ACS)