Efficient C–H Functionalisation of Thiazole Derivatives Catalyzed by Pd–NHC Complexes

Abstract In this study, benzimidazolium salts were synthesized by introducing a bulky N -(2-ethylhexyl) benzimidazole, while various aryl substituents were incorporated onto the second nitrogen. These salts were employed as N-heterocyclic carbene (NHC) precursors and reacted with Pd(OAc)₂ to afford a series of [PdCl₂(NHC)₂]-type palladium(II) NHC complexes. The catalytic activity of the synthesized complexes were evaluated in the direct C–H arylation of thiazole-derived heteroaromatic compounds. Two different thiazole derivatives, namely 2- n -propylthiazole and 4,5-dimethylthiazole, were selected as substrates, and their reactivity with aryl bromides bearing different electronic properties was systematically investigated. The arylation yields were found to vary significantly depending on both the substitution pattern of the thiazole ring and the nature of the aryl halides. Notably, aryl bromides containing electron-withdrawing groups facilitated the oxidative addition step and afforded higher yields, whereas those bearing electron-donating groups resulted in lower reactivity. These findings suggest that the catalytic performance of the Pd–NHC complexes is influenced not only by the metal center but also by the ligand environment and the electronic characteristics of the substrates involved. In conclusion, this study demonstrates that structurally tunable Pd–NHC complexes can serve as effective homogeneous catalysts for the selective and efficient C–H functionalization of thiazole-based heteroaromatic compounds. The results contribute to the ongoing development of versatile catalyst systems for direct functionalization of electron-rich heterocycles, providing a foundation for future investigations in this area.