Copper(ii)-catalyzed trifluoromethylation of iodoarenes using Chen's reagent

Abstract

The introduction of a trifluoromethyl group to organic molecules is significant for modern drug discovery; thus practical routes towards catalytic trifluoromethylation are highly desired. Herein, we report the efficient copper(II)-catalyzed nucleophilic trifluoromethylation of various aryl and heteroaryl iodides using methyl fluorosulfonyldifluoroacetate (FO₂SCF₂CO₂Me, Chen's reagent). The use of CuCl₂ instead of CuI resulted in a significant improvement in the original Chen's methodology; specifically, catalytic amounts (10 to 15%) of CuCl₂ were used instead of Cu(I) salts for the generation of CuCF₃ species. The improved trifluoromethylation converts aryl and heteroaryl iodides into the corresponding CF₃-containing molecules with multiple functional groups in moderate to high yields. Moreover, a mechanism was proposed for this new catalytic system.