Copper-catalyzed synthesis of heterocycles <i>via</i> single and two-electron pathways

Heterocyclic compounds serve as indispensable frameworks in pharmaceuticals, agrochemicals, and advanced materials, yet achieving their efficient and sustainable synthesis continues to pose a central challenge in modern organic chemistry. Copper, owing to its natural abundance, low toxicity, and unique ability to access multiple oxidation states (Cu(0), Cu(I), Cu(II), and Cu(III)), has emerged as a powerful and sustainable alternative to precious-metal catalysts for constructing these architectures. This review comprehensively surveys copper-catalyzed heterocycle synthesis published between 2015 and 2024, with particular emphasis on mechanistic diversity, including single-electron transfer and two-electron pathways, such as oxidative addition and reductive elimination. We systematically examine how copper-mediated C–H functionalization, multicomponent reactions, cycloisomerizations, and click chemistry enable the assembly of nitrogen-, oxygen-, and sulfur-containing heterocycles—including pyrroles, furans, thiophenes, indoles, benzimidazoles, benzofurans, and triazoles—under mild conditions, frequently without ligands or solvents. Key advances in microwave-assisted and flow-chemistry protocols that align with green chemistry principles are highlighted. Mechanistic rationale and structure–reactivity relationships are discussed to aid catalyst design. The review further identifies current challenges, proposes strategies to address them, and outlines future directions, including integration with photoredox and electrochemical techniques, to underscore the industrial relevance and scalability of copper-catalyzed heterocyclic synthesis.