Utilization of C(sp3)-Carboxylic Acids and Their Redox-Active Esters in Decarboxylative Carbon‒Carbon Bond Formation

Over the last several years, radical‐mediated decarboxylative cross‐coupling reactions employing alkyl carboxylic acids have emerged as a powerful tool for the regiospecific construction of carbon−carbon bonds. Under thermal or photocatalytic conditions, a wide variety of C(sp3)‐carboxylic acids and their redox‐active esters undergo decarboxylative C−C bond formation with suitable reactant partners, leading to complex chemical scaffolds with wide‐ranging applications. This synthetic strategy has several advantages over the more conventional organometallic reagents, including abundant starting material availability and high functional group tolerance associated with the mild reaction conditions. This review article highlights recent developments in the functionalization of α‐heteroatom‐substituted carboxylic acids as well as the more challenging unactivated acids, with representative examples discussed against the backdrop of insightful comments on reaction mechanisms. In addition, examples of the synthesis of natural products, drug molecules, and the late‐stage modification of bioactive molecules employing this non‐traditional C−C bond formation strategy are included. This review has been categorized into three main sections that are organized around the type of C−C bond being forged: C(sp3)−C(sp2), C(sp3)−C(sp3), and C(sp3)−C(sp). Further, the reactions of carboxylic acids and their redox‐active esters have been organized separately in each section.