The advancements in cross-coupling chemistry are a considerably powerful tool for the synthesis of pharmaceutical molecules. The formation of catalytic carbon-heteroatom (C-X) and carbon-carbon (C-C) bonds is one of the important reactions in organic synthesis, which plays a key role in the synthesis of biologically active molecules, natural products, heterocycles, and useful compounds. Recently, there has been a significant increase in the development and advancement of environmentally friendly catalysts that serve as a suitable alternative to conventional metalbased catalysts. On the other hand, N-heterocyclic carbenes (NHCs)-metal-based catalysts became suitable for performing a wide range of chemical transformations due to their unique spatial and electronic properties. The NHCs have received much attention as ligands due to their important properties. The present review aimed to discuss the recent advances in the application of NHCs in cross-coupling chemistry in the last six years. The present study focused on the catalytic application of NHCs in various crosscoupling reactions, such as Suzuki, Heck, Sonogashira, Hiyama, Kumada, Buchwald–Hartwig, Ullmann, and Chan. Moreover, some cross-coupling reactions by selective C-X cleavage catalyzed by NHCs with high catalytic activity were discussed. In addition, several chiral NHCs capable of catalyzing asymmetric cross-coupling reactions were reported. Finally, numerous green protocols for cross-coupling reactions catalyzed by functional and biocompatible NHCs under mild conditions were investigated. These protocols had advantages such as high-yield products, short time, cost-effectiveness, and high catalytic activity.

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