羰基化合物在堿性條件下烯醇化，或轉化為烯醇醚，酯，烯胺，然后在親電氟代試劑的作用下，能制備相應的α-氟代羰基化合物，這是比較方便，也用的比較多的一種方法，特別在甾體化合物的合成中用的比較多。所用的氟代試劑包括CF3OF，CH3COOF，CsSO4F，XeF2，Tos-IF2以及以Selectfluor為主的大部分含N--F鍵的化合物等。
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，如果延長時間，生成的主產物是更穩定的二氟代產物，如果分步氟代，則能縮短時間，提高效率。
如果想要得到單氟代的產物，Tos-IF2是一個很好的選擇。反應選擇性很高，沒有二氟代的產物生成。
【Yoshida, M. et al. ARKIVOC. 2003, (vi) 36.】
反應實例
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.】
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