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. 2023 Feb 15;145(6):3294-3300.
doi: 10.1021/jacs.2c12767. Epub 2023 Feb 1.

Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp2)-Bromides as HAT Reagents

Xiao Zhang  1 , Yangyang Shen  1 , Tomislav Rovis  1
Affiliations

Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp2)-Bromides as HAT Reagents

Xiao Zhang et al. J Am Chem Soc. .

Abstract

N-Demethylation of trialkylamines is a useful transformation, but typically requires harsh reaction conditions and stepwise procedures, as well as judicious protection of labile functional groups. Herein we report a mild, catalytic approach for the demethylation of trialkylamines by utilizing photoinduced nickel catalysis wherein C(sp2)-bromides serve as hydrogen-atom transfer (HAT) reagents. This method achieves direct demethylation of trialkylamines with wide functional group compatibility, making it highly suitable for late-stage derivatization of complex molecules. Mechanistic investigations provide evidence that C(sp2) radicals generated via photoinduced Ni-C(sp2) bond homolysis are involved in hydrogen atom abstraction from trialkylamines. Utilizing steric control of the C(sp2)-bromides, our HAT approach achieves demethylation with excellent site selectivity in the presence of benzyl-substituted amines, which is complementary to the selectivity of classical approaches that afford debenzylation product instead.

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Figures

Scheme 1.
Scheme 1.
Reaction Design
Scheme 2.
Scheme 2.
Mechanistic Investigations
See this image and copyright information in PMC

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