1990年Umemoto報道化合物1和2的合成及應用^[1]，隨后Umemoto報道了化合物3和4的合成及應用^[2]。

這幾個化合物是穩定的晶體，具有良好的穩定性。苯并環是很好的離去基團，在取代過程中容易離去，有利反應進行。反應易于處理，特別是化合物4，反應生成后的磺酸是水溶性的，極易除去。這種三氟甲基化并不是通過CF₃^＋進行，也不是S_N2取代，可能是通過SET機理產生三氟甲基自由基，然后對碳負離子的親電加成。

這種方法通用型強，通過這種方法，可以在多種親核性化合物上引入三氟甲基。但這幾個試劑制備困難，價格較高，限制了其應用。

反應示例^[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%).

隨后Jin-QuanYu報道了在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的鄰位三氟甲基化^[3]。

反應示例：

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%).

【參考文獻】

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