Copper‐ and Silver‐Catalyzed Reactions of Active Methylene Isocyanides: Facile Access to Highly Substituted Five‐ and Six‐Membered Heterocycles

Copper- and silver-catalyzed reactions of active methylene isocyanides provide powerful and versatile strategies for the construction of heterocyclic architectures relevant to pharmaceutical and materials science. Owing to their unique ambiphilic reactivity, active methylene isocyanides serve as key building blocks for the synthesis of fused, bicyclic, polycyclic, and spirocyclic heterocycles under mild catalytic conditions. This review summarizes recent advances in the copper- and silver-catalyzed transformation of functionalized isocyanides toward multi-substituted five- and six-membered heterocyclic frameworks. Particular emphasis is placed on [3+n] cycloaddition reactions, as well as tandem processes involving cycloaddition, annulation, alkylation, and insertion pathways. In addition, emerging strategies that exploit nonfunctionalized isocyanides, strained alkene surrogates, and multi-isocyanide reaction manifolds are discussed, highlighting new opportunities for complexity generation and asymmetric heterocycle synthesis.