Non-decarboxylative functionalization of free carboxylic acids: Strategies for C–O bond formation via photo- and electrochemical approaches

Abstract

Carboxylic acids are among the most readily available, bench-stable, and cost-effective building blocks in organic chemistry. However, the low reactivity of free carboxyl group in both electrophilic and nucleophilic transformations significantly limits the direct use of carboxylic acids in coupling reactions. Typically, additional synthetic steps are required to convert carboxylic acids into activated derivatives to achieve the desired transformations, thereby compromising atom- and step-economy. In recent years, organic photochemistry and electrochemistry have emerged as powerful and sustainable platforms for harnessing carboxylic acids directly in synthetic transformations. Beyond the extensively studied decarboxylative pathways, direct non-decarboxylative couplings between carboxylic acids and external carbon-centered partners have received considerably less attention. Several challenges impede the development of such reactions, including the inherently weak nucleophilicity of the carboxyl group, the instability of carboxyl-derived radical or anionic intermediates toward decarboxylation, and the propensity of carboxyl radicals to undergo reverse hydrogen atom transfer. Nevertheless, rapid progress in photochemical and electrochemical methodologies has enabled the development of increasingly innovative and environmentally benign strategies to overcome these limitations. This review focuses on advances in photo- and electrochemically mediated C–O bond-forming reactions between non-prefunctionalized carboxylic acids and various intermolecular carbon-based partners, encompassing studies published from 2010 to 2025.