Utilizing 1,4-Dihydropyridines for C–N Bond Activation: A Photoredox-Catalyzed Deaminative Approach toward Benzylic Quaternary Carbon Centers

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Authors: Holly L. Hutchinson, Samantha L. Goldschmid, Trevor C. Sherwood, Candice L. Joe, Eric R. Welin, Tomislav Rovis
Cited by: 4
References: 44

Abstract

Primary amines are widely found in natural products, synthetic building blocks, and therapeutics. Accordingly, their structural diversity and low cost render them as highly attractive building blocks in organic synthesis. Recent advances in deaminative functionalization methodologies, particularly those that leverage redox-active Katritzky salts and redox-active imines, have revitalized interest in C–N bond activation. While these methods have been highly enabling for developing valuable bond forming reactions, methods that liberate and functionalize tertiary benzylic radicals in a controlled and selective fashion remain elusive. Herein, we report the C–N bond cleavage of 1,4-dihydropyridines, a substrate class readily synthesized from primary amines, to generate tertiary benzylic radicals for selective radical trapping. Using photoredox catalysis, this method serves as a valuable strategy for constructing quaternary carbon centers. Scope studies reveal broad tolerance of primary amines with electron-neutral, electron-rich, and electron-withdrawing substituents on the benzylic moieties. Mechanistic investigations support the cleavage of the C–N bond via single-electron oxidation of the 1,4-dihydropyridine. Finally, the comparison of this method to other deaminative methods further illuminates the substrate tolerance and mechanistic nuances between amine activation platforms.

Fields of Study & Subjects

Radical Photochemical Reactions Catalytic C–H Functionalization Methods Oxidative Organic Chemistry Reactions

Publication details

Journal / source
ACS Catalysis
Publisher
American Chemical Society (ACS)
Volume
16
Issue
3
Pages
2588–2595
Publication date
19 January 2026
Language
EN