Construction of Ketenimines through the Reactions between Free Carbenes and Isocyanides and their Synthetic Application

Ketenimines are versatile reactive intermediates in organic synthesis, characterized by their unique cumulative double-bond framework and pronounced synthetic utility. This review provides a comprehensive and systematic overview of recent advances in the synthesis of ketenimines via the coupling of free carbenes with isocyanides, along with the diverse downstream transformations of the resulting ketenimine intermediates. The free carbene species discussed are categorized into four major precursor classes: N-heterocyclic carbenes (NHCs), diazo compounds, silane-based reagents, and other miscellaneous sources, and their electronic properties are examined in the context of reactivity and selectivity. Depending on the substituent patterns and stabilization modes, these carbenes exhibit electrophilic, ambiphilic, or nucleophilic character, which in turn governs the efficiency and outcome of the isocyanide addition. The resulting ketenimines serve as powerful platforms for a wide array of subsequent transformations, including nucleophilic and electrophilic additions, electrocyclizations, and sigmatropic rearrangements, enabling rapid construction of diverse functionalized molecules and heterocyclic scaffolds. This review is intended to serve as a comprehensive reference for researchers in free carbene chemistry and synthetic methodology, and to provide a clear framework for understanding the reactivity and synthetic potential of free carbene–isocyanide coupling chemistry.