From carboxylic acids or their derivatives to amines and ethers: modern decarboxylative approaches for sustainable C–N and C–O bond formation

Amines and ethers represent essential structural motifs in pharmaceuticals, natural products, organic materials, and catalytic systems. The development of novel, environmentally friendly, and cost-effective strategies for constructing C–N and C–O bonds is therefore of significant importance for the synthesis of these compounds. In recent years, carboxylic acids and their derivatives have emerged as attractive, inexpensive, non-toxic, and readily available synthetic building blocks, serving as promising alternatives to aryl halides. Growing evidence has demonstrated that decarboxylative amination and etherification of carboxylic acid derivatives offer a powerful approach for the synthesis of amines and ethers. These transformations proceed via three principal mechanistic pathways, each offering high atom economy. Specifically, carbanions (or organometallic species) generated through heterolytic decarboxylation can react with suitable electrophiles to form C–heteroatom bonds. In contrast, carbon-centred radicals produced through homolytic decarboxylation can couple with heteroatom-based reagents via radical recombination or oxidative trapping. Additionally, carbocations are typically formed via electrochemical oxidation of carboxylic acids: oxidative decarboxylation first yields a carbon radical, which is then further oxidized at the anode to generate a carbocation. This highly electrophilic intermediate can subsequently be intercepted by heteroatom nucleophiles to construct C–N or C–O bonds. This review highlights recent advances in the field, with a focus on transition metal catalysis, photoredox catalysis, and electrochemical methods for decarboxylative amination and etherification.