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Formal Reductive Amination of Carboxylic Acids via Iron-Catalyzed Photoredox Decarboxylative α-Aminomethylation

Jinxi Huang, Donghui Xing, Xiaohong Li, Liangbin Huang

2025Organic Letters5 citationsDOI

Abstract

Here we report an iron-catalyzed photocatalytic protocol utilizing ligand-to-metal charge transfer (LMCT) for efficient decarboxylative reductive amination to synthesize tertiary alkylamines. The method employs readily available carboxylic acids and N, O -acetals under mild conditions (room temperature, 390 nm LED), achieving excellent yields (up to 89%) across diverse alkyl carboxylic acid substrates, including primary, secondary, and tertiary types (>40 examples). Furthermore, the protocol exhibits good tolerance toward sensitive functional groups and enables late-stage functionalization of pharmaceutical compounds, providing a practical synthetic tool for complex alkylamine construction.

Topics & Concepts

ChemistryReductive aminationAlkylAminationCombinatorial chemistryOrganic chemistryCarboxylic acidSurface modificationFunctional groupPhotocatalysisPrimary (astronomy)DecarboxylationReaction conditionsPhotoredox catalysisReductive eliminationMoleculeRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and Catalysis
Formal Reductive Amination of Carboxylic Acids via Iron-Catalyzed Photoredox Decarboxylative α-Aminomethylation | Litcius