Photoredox-Enabled C(sp³)–H Functionalization of Amines through Iminium Ions, Radicals, and Carbanions

Abstract

The direct functionalization of C(sp3)–H bonds in amines has emerged as a powerful and atom-economical strategy for constructing structurally diverse nitrogen-containing molecules without requiring prefunctionalized substrates. Over the past decade, visible-light photoredox catalysis has evolved into a versatile platform for such transformations, offering high functional-group tolerance, mild reaction conditions, and distinct modes of ionic and radical activation. This review provides a comprehensive, mechanism-oriented summary of recent developments in photoredox-catalyzed C(sp3)–H functionalization of amines. We focus on three principal mechanistic pathways: (i) Iminium-ion pathways, involving the reaction of electrophilic iminium intermediates with nucleophiles; (ii) Enamine pathways, wherein iminium intermediates undergo tautomerization to nucleophilic enamine species that react with electrophilic partners;; (iii) Radical pathways, featuring coupling or addition processes mediated by radical species; (iv) Carbanion pathways, where nucleophilic carbanions engage electrophilic partners. These strategies collectively enable a diverse range of C–C and C–X bond-forming reactions—including alkylation, arylation, alkenylation, acylation, phosphonylation, alkynylation, cyanation, carboxylation, amination, boronation, and oxidation. Particular emphasis is placed on advances in asymmetric catalysis, cooperative metal–photoredox systems, and radical–radical cross-coupling. We also critically examine persistent challenges—such as achieving regio- and stereocontrol, expanding substrate scope, and enhancing sustainability—and outline future opportunities for innovation. By integrating mechanistic insight with synthetic scope, this review establishes a framework for the rational design of next-generation catalytic systems, underscoring the transformative potential of photoredox catalysis in late-stage functionalization, medicinal chemistry, and green synthesis.