A Comprehensive Review on Cross-Coupling Reactions: Catalytic Systems, Mechanistic Pathways, and Industrial Relevance

Transition-metal-catalyzed cross-coupling reactions, particularly those mediated by palladium, nickel, and copper, represent some of the most powerful and widely used strategies for the formation of carbon–carbon and carbon–heteroatom bonds in modern organic synthesis. Over the past five decades, these transformations have played a pivotal role in the synthesis of pharmaceuticals, advanced materials, functional polymers, and organic electronic components. Continuous advances in catalytic system design, ligand development, and mechanistic understanding have significantly expanded substrate scope, enabling the activation of less reactive electrophiles such as aryl chlorides, esters, amides, and sp³-hybridized substrates. This comprehensive review focuses on three interconnected aspects of cross-coupling chemistry: catalytic systems, mechanistic pathways, and industrial relevance. Classical palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Heck, Buchwald–Hartwig, and Sonogashira reactions, are discussed alongside emerging methodologies such as cross-electrophile coupling, decarboxylative coupling, metallaphotoredox catalysis, and nickel-catalyzed reductive processes. Particular attention is devoted to the role of advanced ligands, including bulky biaryl phosphines and N-heterocyclic carbenes, in enhancing catalyst activity, stability, and selectivity. From a mechanistic perspective, both canonical catalytic cycles involving oxidative addition, transmetalation, and reductive elimination, as well as non-classical pathways such as radical-mediated, single-electron transfer, and noncanonical mechanisms are critically examined. In addition, the industrial implementation of cross-coupling reactions is analyzed with emphasis on process development, scalability, metal residue control, solvent effects, and green chemistry considerations. By bridging fundamental mechanistic insights with practical applications, this review provides an up-to-date and integrated perspective on the current state and future directions of cross-coupling chemistry.

کلیدواژه ها:

ZSM-۵ zeolite ، photocatalysis ، dye degradation ، metal doping ، advanced oxidation process ، environmental remediation