在化合物中引入三氟甲基一種重要方法就是通過CF3-的親核反應(yīng)實(shí)現(xiàn)，主要包括兩大類：基于CuCF3對鹵代苯的親核取代和TMSCF3對羰基化合物的親核取代。
最早發(fā)現(xiàn)的方法是基于CuCF3作為CF3- 源對鹵代苯（通常為溴代苯或碘代苯，后者活性更高）的親核取代，從而合成三氟甲基取代的芳基化合物。這個方法是由McLoughlin于1969年首先報導(dǎo)，經(jīng)過多年的發(fā)展，成為三氟甲基化最主要的方法之一。
CuCF3可以通過多種方法，在Cu的存在下現(xiàn)制現(xiàn)用。
其中最常用的是CuI/MeO2CCF2SO2F和CuI/KF/ClCF2CO2Me這兩個體系。反應(yīng)操作很簡單，收率較高。需要注意的是產(chǎn)物和原料在TLC上有時不會有明顯的差異，需要做核磁來辨別（13C-NMR和19F-NMR）。
反應(yīng)實(shí)例
The mixture of PhI (2.04 g, 10 mmol), CuI (3.83 g, 20 mmol) and MeO2CCF2SO2F (4.75 g, 25 mmol) in dry DMF(50 mL) was stirred at 70oCovernight. Then 50 mL water was added to the reaction mixture,the resulting mixture was extracted with EA, washed with water and brine, theorganic phase was concentrated under reduced pressure. The residue was purified by columnchromatography on silica gel to give the desired product (1.22 g, 84%).
【Chen, Q, Y; Wu, S, W.J. Chem. Soc. Chem. Commun. 1989, 705】
A mixture of dry KF (0.58 g, 10 mmol), CuI (2.0 g,10 mmol), PhI (2.04 g,10 mmol) and DMF (30 mL) was placed in a 50 mL three-necked round-bottomedflask fitted with stirrer bar, dry ice condenser and thermometer. The solution was heated to 120 “C under an N2 atmosphere for 0.5 h. Then ClCF2CO2Me (2.89 g,10 mmol) was added over 3 h and thecontents stirred for a further 4 h. After reaction was completed, the reactants were poured into ice water(200 mL). The solution was filtered andthe residue washed with ethyl ether (3×20 mL) and the aqueous layer wasextracted with ethyl ether (3×20 mL). The combined extract was washed with water (30 mL) and dried over Na2SO4. After evaporation of the ether, distillationgave the desired product (1.3 g, 88%).
【Duan, J, X; Su, D, B;Chen, Q, Y. J. Fluo. Chem. 1993, 21, 279】
另一個方法就是TMSCF3（Prakash試劑）對羰基化合物的親核取代。具體內(nèi)請點(diǎn)擊查看：Prakash試劑。
另外，近來Dolbier等使用CF3I/TDAE體系，在溫和的條件下也成功地實(shí)現(xiàn)了對親電物種的三氟甲基化。
【 (a) Ait-Mohand, N, T; Medebielle,M; Dolbier, W, R, Jr. Tetrahedron Lett. 2002, 43, 4317.
(b) Dolbier, W, R, Jr.;Medebielle, M; Pooput, C. Org. Lett. 2004, 6, 301.
(c) Xu, W; Dolbier, W, R, Jr. J. Org. Chem. 2005, 70, 4741.】
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