A comprehensive review on organometallic catalysis in modern organic synthesis: Bridging inorganic design and sustainable organic applications

Organometallic chemistry occupies a central position at the interface of inorganic and organic chemistry, functioning as a cornerstone of modern synthetic methodology. This comprehensive review provides an in-depth analysis of the role of organometallic complexes spanning noble metals such as palladium and ruthenium to emerging earth-abundant alternatives like nickel, iron, cobalt, and copper in facilitating transformative carbon-carbon and carbon-heteroatom bond-forming reactions. We systematically explore the fundamental mechanisms, catalytic cycles, substrate scope, and inherent limitations of pivotal transformations, including the Suzuki-Miyaura, Heck, Stille, Negishi, and Kumada cross-couplings, as well as olefin metathesis. Special emphasis is placed on the critical influence of ligand architecture ranging from phosphines and N-heterocyclic carbenes (NHCs) to pincer and bidentate systems on catalytic efficiency, selectivity, and stability. The development of air- and moisture-stable pre-catalysts has significantly enhanced practicality, enabling broader application in both academic and industrial settings. The review further examines the ongoing paradigm shift toward sustainable and green catalytic processes. This includes the strategic replacement of scarce and expensive noble metals with abundant first-row transition metals, the adoption of environmentally benign solvents (e.g., water, ethanol, 2-MeTHF), and the integration of energy-efficient activation methods such as photoredox and electrochemical catalysis. Advances in heterogeneous catalysis, catalyst immobilization, and continuous-flow technologies are highlighted as key enablers of recyclability, scalability, and reduced environmental impact. Industrial and pharmaceutical applications are rigorously evaluated through case studies of high-value therapeutics, including Sitagliptin (Januvia®), Valsartan (Diovan®), and Lapatinib (Tykerb®), illustrating how organometallic catalysis underpins the synthesis of complex drug molecules. Concurrently, we address persistent challenges such as residual metal contamination (in compliance with ICH Q3D guidelines), catalyst deactivation, and the economic burden of precious metal use. By synthesizing insights from mechanistic inorganic chemistry and synthetic organic applications, this review not only provides a state-of-the-art overview but also offers a forward-looking perspective on the future of catalysis where sustainability, efficiency, and innovation converge to redefine the frontiers of chemical synthesis.