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

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.

Automated summary

We reported a mild, catalytic approach for the demethylation of trialkylamines using photoinduced nickel catalysis. C(sp2)-bromides serve as hydrogen-atom transfer reagents in this process, achieving direct demethylation with wide functional group compatibility. Mechanistic investigations reveal the involvement of C(sp2) radicals generated via photoinduced Ni-C(sp2) bond homolysis in the hydrogen atom abstraction from trialkylamines. Our approach shows excellent site selectivity in the demethylation reactions of benzyl-substituted amines, complementing the selectivity of classical approaches.