羰基化合物在碱性条件下烯醇化，或转化为烯醇醚，酯，烯胺，然后在亲电氟代试剂的作用下，能制备相应的α-氟代羰基化合物，这是比较方便，也用的比较多的一种方法，特别在甾体化合物的合成中用的比较多。所用的氟代试剂包括CF₃OF，CH₃COOF，CsSO₄F，XeF₂，Tos-IF₂以及以Selectfluor为主的大部分含N­-F键的化合物等。

β－二羰基化合物直接氟代，往往得到一氟代和二氟代的混合物，如果延长时间，生成的主产物是更稳定的二氟代产物，如果分步氟代，则能缩短时间，提高效率。

如果想要得到单氟代的产物，Tos-IF₂是一个很好的选择。反应选择性很高，没有二氟代的产物生成。

【Yoshida, M. et al. ARKIVOC. 2003, (vi) 36.】

反应实例

3-Methoxy-17-trimethylsiloxy-1,3,5(10)-16-estratetraene. A 125-mL, two-necked round-bottomed flaskequipped with a reflux condenser and a magnetic stirrer is purged with argonand charged with 6.8 g (0.024 mol) of estrone 3-methyl ether, 50 mL of drybenzene, and 4.0 mL (2.9 g, 0.029 mol) of triethylamine. The solution is stirred, 4.9 mL (5.6 g,0.025 mol) of trimethylsilyl triflate isadded through a syringe, and the mixture is refluxed for 1.5 hr. The reactionmixture is allowed to cool to room temperature, whereupon it separates into twolayers. Dry hexane (40 mL)is added, and the upper hexane–benzene layer is separated, washed successivelywith saturated sodium bicarbonate and water, andthen dried over magnesium sulfate. The drying agentis removed by filtration, and the filtrate is transferred to a 125-mL, round-bottomed, tared flask. The solution isevaporated to a constant weight with a rotary evaporator, initially atwater-aspirator pressure and then at 0.5–1 mm,to leave 8.6 g(100%) of pale-yellow enol trimethylsilylether. This material is used immediately in Part C without purification.

16α-Fluoro-3-methoxy-1,3,5(10)-estratrien-17-one (16α-fluoroestrone 3-methyl ether). The 125-mL, round-bottomed flaskcontaining the enol silyl ether from Part B is purged with argon, and 50 mL of dry dichloromethane is added. N-Fluoropyridiniumtriflate (6.5 g,0.026 mol) is added in one portion, and the mixture is stirred at 20–25°C for 8 hr. The reaction mixture ispoured into water and extracted with three 60-mL portionsof dichloromethane. The combined organicextracts are washed with saturated sodium bicarbonateand then with water, and dried over magnesium sulfate.The drying agent is removed by filtration and the solution is evaporated todryness with a rotary evaporator. The resulting pale-yellow solid iscolumn-chromatographed on silica gel (250 g, 60 × 4.5-cm column) using dichloromethane eluant to give 950mg (14%) of estrone3-methyl ether starting material and 4.8 g (66%) of 16α-fluoroestrone 3-methylether as a colorless solid, mp 157°C.

【Umemoto,T; Tomita, K; Kawada, K. Organic Syntheses.Coll. Vol. 8, 286.】

本文非原创内容，版权归原作者所有，如涉及版权问题，请联系删除。