Assembly of (hetero)aryl thioethers via simple nucleophilic aromatic substitution and Cu-catalyzed coupling reactions with (hetero)aryl chlorides and bromides under mild conditions

Abstract

The requirement of higher reaction temperatures for an S_NAr reaction between thiols and less reactive electron-poor aryl halides described in earlier reports has triggered intensive studies on the development of metal- and photo-catalyzed methods to promote this transformation. We report here that an S_NAr reaction of thiols with most electron-poor aryl halides takes place at RT–60 °C under the action of K₂CO₃ and DMAc. Both the bases and the solvents play an essential role in such mild conditions. For (hetero)aryl halides that are unreactive toward an S_NAr reaction, two oxalic diamide ligands that are more powerful were identified to make their Cu-catalyzed coupling reactions proceed with low catalytic loadings. A combination of these two methods offers a very attractive approach for preparing (hetero)aryl thioethers.