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This review examines the reactivity of bis(α-cyanoacetamides) attached to various spacers in producing heterocyclic and macrocyclic molecules. Bis(α-cyanoacetamides) contain two electrophilic and three nucleophilic sites, allowing for multiple coupling reactions. They are regarded as potent chemical reagents capable of producing various heterocyclic derivatives with potential biological applications. The current review covers all reports where bis(α-cyanoacetamides) are used to prepare heterocycles with mono-, bi-, and tricyclic rings. The review is divided into sections based on the type of annulation system and the number of heteroatoms present. We reviewed all available papers on synthesizing macrocyclic molecular systems using bis(α-cyanoacetamide). The mechanistic postulates of some complex procedures are highlighted.
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