Transition-Metal-Catalyzed Cross-Coupling Reactions in Green Solvents: Toward Sustainable Synthetic Methodologies

The development of sustainable synthetic methodologies represents a central challenge in modern organic chemistry, particularly in light of the environmental impact associated with the large-scale production of fine chemicals and pharmaceuticals. Among the strategies proposed to address these issues, the design of catalytic processes operating in environmentally benign reaction media has emerged as a powerful approach to minimize the use of hazardous solvents while enhancing the overall efficiency of chemical transformations. This lecture will highlight recent advances in transition-metal-catalyzed cross-coupling reactions performed in green solvents, with a particular focus on water and deep eutectic solvents (DESs). DESs, formed by combining inexpensive hydrogen-bond donors and acceptors, are increasingly recognized as versatile and sustainable alternatives to conventional volatile organic solvents. Their distinctive physicochemical properties enable efficient catalytic transformations under relatively mild conditions, often in the absence of additional ligands, while also facilitating catalyst recycling and process scalability. The potential of these media will be showcased through a range of carbon–carbon and carbon–heteroatom bond-forming reactions catalyzed by palladium, copper, and nickel complexes. These methodologies provide efficient access to structurally diverse molecules and have been successfully applied to the synthesis of pharmaceutically relevant targets. Overall, these studies illustrate how the synergistic combination of green solvents and catalytic strategies can drive the development of more sustainable approaches to chemical synthesis.