Trifluoromethyl-containing aromatic compounds (ArCF3) are important motifs, especially in pharmaceuticals. It is also well-known that the introduction of a trifluoromethyl group into a molecule enhances its biological activity and metabolic stability. Hence, the efficient synthesis of trifluoromethylated arenes is highly important. A number of strategies are available to access ArCF3 compounds; among them a copper-catalyzed/mediated trifluoromethylation of aryl halides. Trifluoromethylation reagents, such as CuCF3, HCF3, and Me3SiCF3, are widely used; however, they are costly and can be unstable.
Zhiqiang Weng and co-workers, Fuzhou University, China, report on the synthesis of the complexes [Cu(O2CCF3)(phen)] and [Cu(phen)2][(O2CCF2Cl)] and their application in the trifluoro- and difluoromethylation of (hetero)aryl halides and phenols.
Such complexes are air stable and can be easily prepared by the reaction of copper tert-butoxide with a diamine ligand and subsequent addition of trifluoro acetic acid (TFA) or chlorodifluoroacetic acid. They serve as robust trifluoromethylating reagents, giving the corresponding products trifluoromethyl (hetero)arenes and (hetero)aryl difluoromethyl ethers in good yields. Mechanistic investigations revealed that radical intermediates are not likely to be involved in the trifluoromethylation reaction.
- Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl],
Xiaoxi Lin, Chuanqi Hou, Haohong Li, Zhiqiang Weng,
Chem. Eur. J. 2016, 22, 2075–2084.