Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp2)-Bromides as HAT Reagents.
J Am Chem Soc
; 145(6): 3294-3300, 2023 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-36724205
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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Coleções:
01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article