Harnessing the power of α-diazo compounds: emerging strategies and expanding applications

Abstract

α-Diazo compounds have long been recognized as versatile reagents in organic synthesis, traditionally employed in metallocarbene chemistry. Recent advances have expanded their scope beyond conventional carbene-based transformations, leading to diverse applications in heterocycle synthesis and functionalization strategies. This review highlights the evolution of α-diazo compounds as key reagents in modern synthetic methodologies, focusing on their unique reactivity patterns, including cycloadditions, homologations, ring expansions, and carbene-free functionalizations. The development of in situ generation protocols has addressed safety concerns, making highly reactive diazo species such as trifluorodiazoethane and diazoacetonitrile more accessible. Their increasing significance in pharmaceutical and material sciences stems from their crucial role in synthesizing fluorinated and cyano-functionalized scaffolds. These reagents facilitate the construction of diverse heterocyclic frameworks, including three-, four-, five-, six-, and seven-membered rings, as well as small carbocycles and fused heterocycles. Additionally, multicomponent reactions (MCRs) involving diazo compounds have emerged as a powerful strategy for synthesizing complex molecular scaffolds efficiently and sustainably. This review explores recent advances in α-diazo chemistry, focusing on new applications in organic synthesis and future research directions.