N‐Heterocyclic Carbenes (NHCs): An Emerging Efficient Catalyst in Amide Bond Formation

Abstract

Since the discovery of N‐heterocyclic carbenes (NHCs), their role as ligands and organocatalysts has grown significantly due to their unique umpolung reactivity and strong σ‐donor capabilities. In recent years, the field of amide bond formation has seen notable advancements through NHC catalysis. Given the wide application of amides in pharmaceuticals, agrochemicals, and materials science, several NHC‐based strategies have emerged for synthesizing amides from substrates such as aldehydes, alcohols, esters, and nitriles. This review highlights the sustainable and efficient nature of NHC‐catalyzed amide bond formation. Both metal–NHC complexes and metal‐free NHCs offer diverse catalytic pathways, with Ru–NHC systems proving especially effective in redox‐neutral amidations. NHCs promote reactions through mechanisms involving acyl azolium, hemiaminal, and Breslow intermediates, enabling high selectivity under mild conditions. Many of these methods align with green chemistry principles, featuring high atom economy and minimal waste generation. The versatility and tunability of NHC catalysts allow broad substrate compatibility, and recent innovations include metal‐free organocatalysis, continuous flow processes, and electrochemical amidation strategies. This review presents a comprehensive analysis of NHC‐catalyzed amide formation, summarizing key mechanisms, substrate scope, and catalyst design, emphasizing their dual role in metal‐based and organocatalytic sustainable amidation methods.