Published July 12, 2023 | Published + Supplemental Material
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Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles

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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.

Additional Information

© 2023 The Authors. Published by American Chemical Society. Attribution 4.0 International (CC BY 4.0) Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis are gratefully acknowledged for access to analytical equipment. S.E.R. acknowledges financial support from the NIH (R35GM118191). Fellowship support for J.L.H.W. was provided by the NSF (DGE-1144469). K.N.H. is grateful to the National Science Foundation (CHE-1764328) for financial support of this research. R.G.H. acknowledges support from the NIH (National Institute of General Medical Sciences, R35-GM142595). Y.-F. Y. is grateful to the National Natural Science Foundation of China (21978272), the Fundamental Research Funds for the Provincial Universities of Zhejiang (RF-C2022006), and the Province-Ministry Co-Construct State Key Laboratory of Green Chemistry-Synthesis Technology at Zhejiang University of Technology for financial support of this research. The authors would like to thank Dr. David VanderVelde for assistance with NMR experiments, Dr. Jay Winkler for assistance with CV experiments, and Dr. Paul Oyala of Caltech for assistance with EPR measurements. We thank the Dow Next Generation Educator Funds and Instrumentation Grants for their support of the Beckman Institute X-ray Crystallography Facility at Caltech, as well as the Caltech CCE NMR facility and Multiuser Mass Spectrometry Laboratory, which is also supported by the NSF CRIF program (CHE-0541745). The authors declare no competing financial interest.

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Created:
August 22, 2023
Modified:
January 18, 2024