Work

Amide synthesis via molecular shuffling of carboxylic acids

Year: 2026

Type: article

Abstract: The amide bond is fundamental in chemistry and biology and its classical construction from carboxylic acids and amines is limited by positional connectivity of the carboxylic acid group. Herein, we report an approach to amide synthesis that relies on molecular shuffling of carboxylic acid group. In this reaction, amino benzoic acids engage in oxidative addition to a Pd(0) complex, and CO from decarbonylation inserts into the C–Pd bond formed by alkene insertion before the last reductive elimination, achieving carbonyl shuttle amidation. This amide synthesis is precisely controlled by ligand selection, where the reaction pathway can be fully switched to a divergent amine synthesis by decarbonylative amination. This method features wide substrate scope and excellent functional-group tolerance. Moreover, it is scalable and applicable to linear amides, highlighting its synthetic value. The study opens avenues for amide synthesis by carbonyl reshuffling and advances their use as critical building blocks in chemical science. The amide bond represents the most fundamental functional group in chemistry and biology. Herein, the authors report an approach to amide synthesis that relies on molecular shuffling of carboxylic acid functional group.

Source: Nature Communications

DOI: 10.1038/s41467-026-77092-0