1990年Umemoto报道化合物1和2的合成及应用^[1]，随后Umemoto报道了化合物3和4的合成及应用^[2]。

这几个化合物是稳定的晶体，具有良好的稳定性。苯并环是很好的离去基团，在取代过程中容易离去，有利反应进行。反应易于处理，特别是化合物4，反应生成后的磺酸是水溶性的，极易除去。这种三氟甲基化并不是通过CF₃^＋进行，也不是S_N2取代，可能是通过SET机理产生三氟甲基自由基，然后对碳负离子的亲电加成。

这种方法通用型强，通过这种方法，可以在多种亲核性化合物上引入三氟甲基。但这几个试剂制备困难，价格较高，限制了其应用。

反应示例^[2a]：

Under an argon atmosphere, to a solution of Ethynyl-benzene (1.02 g, 10 mmol) was dropped n-BuLi (2.5M, 6 mL, 15 mmol) at –78 ^oC, the mixture was stirred for 1 h,  trifluoromethyl onium salt 3 (11 mmol) was added in several portions.  The reaction mixture was stirred for another 1 h at room temperature, then quenched by saturated NH₄Cl solution, and extracted with EA. The combined organic layer was dried over Na₂SO₄, concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give the desired product (0.58 g, 58%).

随后Jin-QuanYu报道了在Pd催化下，苯基吡啶、苯基嘧啶、苯基咪唑、苯基噻唑等使用化合物2, 3和5的邻位三氟甲基化^[3]。

反应示例：

General Procedure for Pd(OAc)₂-Catalyzed ortho-trifluoromethylation:

In a 20 mL sealed tube, 2-phenyl pyridine 2a (0.2 mmol, 1.0 equiv.), Pd(OAc)₂ (4.5mg, 0.02 mmol, 0.1 equiv.), Cu(OAc)₂ (36.3 mg, 0.2 mmol, 1.0 equiv.) and 5-(Trifluoromethyl)-dibenzothiophenium tetrafluoroborate 1b (102.0mg, 0.3 mmol, 1.5equiv.) were dissolved in 1.0 mL dry dichloroethane under air, and then trifluoroacetic acid (148.6 μl, 2.0 mmol, 10 equiv.) was added. The tube was sealed with a Teflon lined cap and the reaction mixture was stirred at 110 °C for 48 hours. After cooling to room temperature, the mixture was quenched with aqueous NaOH (2 N, 8 mL) and saturated Na₂S solvent (8 mL), and extracted with dichloromethane (15 mL × 3) carefully. The solvent was removed under vacuum and the residue was purified by column chromatography on silicagel with a gradient eluant of hexane and ethyl acetate to afford product 3a(yield 50%).

【参考文献】

1. Umemoto, T; Ishihara, S. Tetrahedron Lett. 1990,31, 3579.

2. (a) Umemoto, T; Ishihara, S. J. Am. Chem. Soc. 1993, 115, 2156. (b) Umemoto, T; Ishihara, S; Adachi,K. J. Fluorine Chem. 1995, 74, 77.

3. Xisheng Wang, Larry Truesdale, and Jin-Quan Yu, J. Am. Chem. Soc. 2010, 132, 3648–3649