在化合物中引入三氟甲基一种重要方法就是通过CF3-的亲核反应实现，主要包括两大类：基于CuCF3对卤代苯的亲核取代和TMSCF3对羰基化合物的亲核取代。
最早发现的方法是基于CuCF3作为CF3- 源对卤代苯（通常为溴代苯或碘代苯，后者活性更高）的亲核取代，从而合成三氟甲基取代的芳基化合物。这个方法是由McLoughlin于1969年首先报导，经过多年的发展，成为三氟甲基化最主要的方法之一。
CuCF3可以通过多种方法，在Cu的存在下现制现用。
其中最常用的是CuI/MeO2CCF2SO2F和CuI/KF/ClCF2CO2Me这两个体系。反应操作很简单，收率较高。需要注意的是产物和原料在TLC上有时不会有明显的差异，需要做核磁来辨别（13C-NMR和19F-NMR）。
反应实例
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】
另一个方法就是TMSCF3（Prakash试剂）对羰基化合物的亲核取代。具体内请点击查看：Prakash试剂。
另外，近来Dolbier等使用CF3I/TDAE体系，在温和的条件下也成功地实现了对亲电物种的三氟甲基化。
【 (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.】
本文非原创内容，版权归原作者所有。
