Advancements in multicomponent reactions of α-diazo compounds: expanding beyond metal-carbene chemistry

Multicomponent reactions (MCRs) are pivotal in synthetic organic chemistry, efficiently enabling the rapid synthesis of complex molecules. Diazo compounds, which have been valuable synthetic reagents for over a century in both academic and industrial research, are commonly employed in MCRs due to their diverse reactivity. While the MCRs of diazo compounds involving metallocarbene intermediates have been extensively studied and reviewed, this review focuses on α-diazo compounds in MCRs that operate without metallocarbene intermediates. These compounds are known for their high reactivity and ease of preparation, facilitating a variety of transformations under MCR conditions, including [3 + 2] cycloadditions, [2 + 1] cycloadditions, gem-difunctionalizations, and Wolff rearrangements. Additionally, they can act as C-nucleophiles or undergo the simultaneous addition of both electrophiles and nucleophiles to the terminal nitrogen of the diazo group, pathways that are also utilized in MCRs. Despite their extensive use, certain pathways, such as [2 + 1] cycloaddition and gem-difunctionalization, remain underexplored. The development of new catalysts and ligands will further advance this field. This review comprehensively analyzes all peer-reviewed literature on MCRs of diazo compounds that do not involve metallocarbene intermediates, up to 2025, with the aim of stimulating further interest and innovative applications. Special emphasis is placed on classifying existing MCRs of diazo compounds and systematically analyzing their reaction mechanisms.