Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles

Raymond F Turro; Julie L H Wahlman; Z Jaron Tong; Xiahe Chen; Miao Yang; Emily P Chen; Xin Hong; Ryan G Hadt; K N Houk; Yun-Fang Yang; Sarah E Reisman

doi:10.1021/jacs.3c02649

Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles

J Am Chem Soc. 2023 Jul 12;145(27):14705-14715. doi: 10.1021/jacs.3c02649. Epub 2023 Jun 26.

Authors

Affiliations

¹ The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
² College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
³ Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China.
⁴ Arthur Amos Noyes Laboratory of Chemical Physics, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
⁵ Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.

Abstract

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp³) activation changes from a Ni-mediated process when benzyl chlorides and Mn⁰ are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a Ni^II-alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

Abstract

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