The palladium catalyzed trifluoromethylation of aryl chlorides is reported by Stephen Buchwald and co-workers, Massachusetts Institute of Technology, USA. They used a phosphine ligand, BrettPhos, along with palladium, the CF3– source, triethylsilyl-CF3, and KF in dioxane at 120 °C for 6 – 12 h.
Both electron-poor and electron-rich aryl chlorides were shown to be suitable substrates and provide the trifluoromethylated products in good yields. Also, heteroaromatic substrates such as indoles, carbazoles, quinolines, and benzofuranes can be efficiently transformed into their trifluoromethylated analogs.
Mechanistic studies suggest that the reaction proceeds via a classical Pd(0)-Pd(II) catalytic cycle.
The high functional group tolerance means the process should be applicable to late stages of intermediate or drug synthesis.
- The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides
E. J. Cho, T. D. Senecal, T. Kinzel, Y. Zhang, D. A. Watson, S. L. Buchwald.
Science 2010, 328 (5986), 1679 – 1681.