另一个方法就是TMSCF₃(Ruppert-Prakash试剂)对羰基化合物的亲核取代。此方法是在1984年由Ruppert首先报道，随后Prakash对其应用做了大量的工作¹，这是从羰基化合物合成三氟甲基化合物最便捷的方法，反应条件温和，操作方便，产率较高，在有机合成中的应用也很广泛。TMSCF₃自身不与羰基化合物发生反应，三氟甲基负离子必须在引发剂的存在下才能参与反应。

氟负离子引发

将催化量的四丁基氟化铵（TBAF）加入到羰基化合物以及TMSCF₃在某种溶剂中的混合物中，最初生成Me₃SiF以及被四丁基胺正离子稳定的烷氧基加合物，随后该加合物又作为亲核试剂进攻另一分子TMSCF₃产生五配位中间体，然后五配位中间体与底物反应得到三氟甲基硅醚产物，同时再生成另一分子中间体完成循环¹。

反应加入少量氟化物（如TBAF, CsF等）催化，TMSCF₃对羰基的缺电子碳进行亲核取代，最后生成三氟甲基取代的化合物，如果是酯作为底物，水解后则生成三氟甲基酮²。

反应示例²：

To the solution of methyl benzoate (1.36 g, 10 mmol) and TMSCF₃ (1.78g, 12.5 mmol) in dry toluene (20 mL) was added the initiator anhydrous tetrabutyl ammonium fluoride (TBAF; 2.5 mol% in THF) -78 ^oC, and the reaction mixture was then allowed to warm slowly to room temperature, stirred for 18 h. The resulting mixture was treated with 2M hydrochloric acid (5 mL), extracted with EA, washed with water and brine, the organic phase was concentrated under reduced pressure.The residue was purified by column chromatography on silicagel to give 1,1,1-trifluoroacetophenone (1.65 g, 95%).

由于许多合成药物中含氮，亚胺的三氟甲基化也受到了广泛的关注。例如活化的N-磺酰基亚胺可以在TBAT的存在下与TMSCF₃发生三氟甲基化，产率中等到良好³。

反应实例³：

In a typical reaction, 0.36 mmol TBAT was dissolved in 4 mL of dry THF and cooled to 0 °C under inert conditions. In a separate flask, 0.3 mmol of the imine and 0.39 mmol TMSCF₃ were mixed in 3 mL THF. The mixture of imine and TMSCF₃ was slowly added via a syringe to the solution of TBAT. The reaction mixture was stirred for 45 min to 1 h while maintaining the reaction temperature at 0-5 °C. Saturated NH₄Cl (2 mL) was added at 0 °C and the reaction mixture was slowly warmed to ambient temperature. The quenched reaction mixture was extracted three times with ethyl acetate and the combined organic layer was dried over anhydrous Na₂SO₄. Evaporation of the solvent under vacuum followed by column chromatography gave the desired product.

【参考文献】

1.(a)Ruppert, I.; Schlich, K.; Volbach, W. TetrahedronLett. 1984, 25, 2195-2198.

   (b) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J. Am.Chem. Soc. 1989, 111,     393-395.

   (c)Krishnamurti,R.; Bellew, D.R.;Prakash, G. K. S. J. Org. Chem. 1991,56,       984-989.

2.Wiedemann,J.; Heiner, T.; Mloston, G.; Prakash, G. K. S. Olah, G. A. Angew. Chem. Int. Ed. 1998, 37,820-821.

3.Prakash, G.K.S.; Mandal, M.; Olah, G.A. Synlett2001, 1, 77-78.

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