Thiazol-2-ylidenes as N-Heterocyclic carbene ligands with enhanced electrophilicity for transition metal catalysis

N-heterocyclic carbenes are widely exploited as ligands in transition metal catalysis, but are largely limited to N-arylimidazolylidenes. Here, the authors report on the steric and electronic properties of thiazol-2-ylidenes, demonstrating that their enhanced pi-electrophilicity makes them attractive as carbene ligands in transition metal-catalysed electrophilic cyclization reactions. Over the last 20 years, N-heterocyclic carbenes (NHCs) have emerged as a dominant direction in ligand development in transition metal catalysis. In particular, strong sigma-donation in combination with tunable steric environment make NHCs to be among the most common ligands used for C-C and C-heteroatom bond formation. Herein, we report the study on steric and electronic properties of thiazol-2-ylidenes. We demonstrate that the thiazole heterocycle and enhanced pi-electrophilicity result in a class of highly active carbene ligands for electrophilic cyclization reactions to form valuable oxazoline heterocycles. The evaluation of steric, electron-donating and pi-accepting properties as well as structural characterization and coordination chemistry is presented. This mode of catalysis can be applied to late-stage drug functionalization to furnish attractive building blocks for medicinal chemistry. Considering the key role of N-heterocyclic ligands, we anticipate that N-aryl thiazol-2-ylidenes will be of broad interest as ligands in modern chemical synthesis.

Automated summary

This study reports on the catalytic properties of thiazol-2-ylidenes in transition metal catalysis. It demonstrates that thiazol-2-ylidenes, as carbene ligands, possess enhanced pi-electrophilicity and can be used in transition metal-catalysed electrophilic cyclization reactions. The study evaluates the steric and electronic properties of thiazol-2-ylidenes and provides insights into their structural characterization and coordination chemistry. This mode of catalysis has potential applications in late-stage drug functionalization, providing important building blocks for medicinal chemistry.