另一個(gè)方法就是TMSCF3(Ruppert-Prakash試劑)對(duì)羰基化合物的親核取代。此方法是在1984年由Ruppert首先報(bào)道，隨后Prakash對(duì)其應(yīng)用做了大量的工作1，這是從羰基化合物合成三氟甲基化合物最便捷的方法，反應(yīng)條件溫和，操作方便，產(chǎn)率較高，在有機(jī)合成中的應(yīng)用也很廣泛。TMSCF3自身不與羰基化合物發(fā)生反應(yīng)，三氟甲基負(fù)離子必須在引發(fā)劑的存在下才能參與反應(yīng)。
氟負(fù)離子引發(fā)
將催化量的四丁基氟化銨（TBAF）加入到羰基化合物以及TMSCF3在某種溶劑中的混合物中，最初生成Me3SiF以及被四丁基胺正離子穩(wěn)定的烷氧基加合物，隨后該加合物又作為親核試劑進(jìn)攻另一分子TMSCF3產(chǎn)生五配位中間體，然后五配位中間體與底物反應(yīng)得到三氟甲基硅醚產(chǎn)物，同時(shí)再生成另一分子中間體完成循環(huán)1。
反應(yīng)加入少量氟化物（如TBAF, CsF等）催化，TMSCF3對(duì)羰基的缺電子碳進(jìn)行親核取代，最后生成三氟甲基取代的化合物，如果是酯作為底物，水解后則生成三氟甲基酮2。
反應(yīng)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%).
由于許多合成藥物中含氮，亞胺的三氟甲基化也受到了廣泛的關(guān)注。例如活化的N-磺?；鶃啺房梢栽赥BAT的存在下與TMSCF3發(fā)生三氟甲基化，產(chǎn)率中等到良好3。
反應(yīng)實(shí)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.
【參考文獻(xiàn)】
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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