亲核性的氟代试剂如HF，包括HF的盐(HF/Pyridine，Bu4NH2F3 ，Et3 N.3HF,Me3N.2HF)，SbF3 , SbF5 ，FBr3 ，MF(M为碱金属)，MoF6 ，SiF 4 ，SF4 ，Ishikawa reagent和DAST及其衍生物Deoxo-Fluor等，能对含氧和含硫底物（如环氧，醇，醛，酮，酸，酯，硫醇，硫羰基化合物，磺酸酯）发生亲核取代，生成相应的氟化合物。

1、环氧开环合成氟化合物

    环氧化合物在HF/Pyridine，Bu4NH2F3 ，Et3N.3HF，Me3N.2HF，SiF4 ，DAST等亲核试剂作用下开环，生成邻位氟代的醇。HF/Pyridine在温和的条件下高产率的使环氧开环，有些底物的区域选择性和立体选择性也不错。

    SiF4 是更温和的一个试剂，很多官能团如双键，醚键，C-Si键在这个条件下也不会断裂。

反应示例

    The mixture of epoxide (1.56 g, 10 mmol) and Me3N.2HF (1.48 g, 15 mmol) in CH2Cl2(50 mL) was heated to reflux for 2 hours. The resulting mixture was extracted with CH2Cl2 and washed with aq. K2CO3 solution and brine, the organic phase was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel to give the desired product (1.1 g, 63%).

2、氧被氟取代合成氟化合物

     含氧官能团如羟基，醛，酮，羧酸及其衍生物在亲核氟代试剂作用下，氧原子被氟原子取代，生成相应的氟化合物，是合成氟化合物最常用的方法之一。常用试剂包括HF/Pyridine，Bu4NH2F3 ，Et3N.3HF，SbF3 , SbF5 ，FBr3 ，MoF6 ，SF4 等，最常用的有三种：Ishikawa reagent，SF4 和DAST及其衍生物如Deoxo-Fluor等，其中DAST的应用最为广泛。

Ishikawa 试剂

     Ishikawa 试剂能将伯醇，仲醇和叔醇转化为相应的氟化合物，对羰基没有影响。其中伯醇反应性能比较好，仲醇和叔醇会有消除或偶联的副产物产生。反应通常在乙醚或二氯甲烷中进行。

      用Ishikawa试剂氟代条件比较温和，选择性也很好，如下面这个分子的全合成中，环氧，双键和保护基都没被破坏。

反应示例

   To a solution of Ishikawa reagent (3 g, 13.5 mmol) in dry dichloromethane (30 mL), a solution of 3-nitrobenzyl alcohol (1.5 g, 9.6 mmol) in dichloromethane (10 ml) vas added dropvise at room temperature. After stirring for 6 h, the reaction mixture vas left overnight. It vas then poured into water and the oily product vas extracted with diisopropyl ether. The ether extract vas washed with water, dried over anhydrous sodium carbonate, filtered, and evaporated to remove the solvent. The residue was distilled to give the desired product (1 g,48%).

DAST

      DAST是液体，在干燥情况下室温或冰箱能长期保存，DAST在 90 o C会分解，处理不当会有爆炸的危险。但由于操作简单和通用性强，DAST是使用得最广泛的氟代试剂之一。这个试剂能将羟基化合物转化为单氟代化合物，醛和酮转化为二氟代化合物。而对羧酸及其衍生物的羰基则没有影响。

      所以在羧酸及其衍生物如酯，内酯，酰胺，内酰胺等存在下，能选择性的取代羟基，醛和酮 

     脂肪族和芳香族的伯，仲，叔醇都能高产率的转化为相应的氟化合物。反应通常用二氯甲烷，一氟三氯甲烷等作溶剂，取代羟基通常在较低温度下反应（－78 o C），取代羰基一般在 0 ℃－40 ℃反应。

     仲醇在取代时可能会发生碳正离子重排，所以异丁醇氟代后得到氟代异丁烷和氟代叔丁烷的混合物。烯丙醇类化合物同样会发生重排

    仲醇在取代的过程中会发生构型翻转，为手性合成提供了一个方法，如 (S)-2-辛醇在反应中构型完全翻转，得到 (R)-2-氟辛 烷，ee％为 97.6% 33 。这个方法在糖类和甾体的合成中应用较多。

      DAST对羰基的亲核氟代反应，醛作为底物活性比酮的活性高，所以在酮存在下可以选择性的取代醛基。

      除 了 DAST 以 外 ， 其 他 一 些 类 似 物 如 Dimehtylaminosulfur trifluoride ，Diisopropylaminosulfur trifluoride ， Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor)，Morpholinosulfur trifluoride，Tris(dimethylamino)sulfur(trimethylsilyl) difluoride， Piperidinosulfur trifluoride，Pyrrolidinosulfur trifluoride 也能进行亲核氟代。特别是 Morpholinosulfur trifluoride 和 Deoxo-Fluor，其稳定性更好，所以反应能在较高的温度进行。

反应示例

      A dry, 1-L, three-necked, round-bottomed flask is fitted with a 500-mL dropping funnel,thermometer, a magnetic stirrer, and a reflux condenser protected from the atmosphere with a drying tube. The apparatus is flushed with dry nitrogen, and 150 mL of dry dichloromethane and 21 mL (0.16 mole) of diethylaminosulfur trifluoride [Org. Synth., Coll. Vol. 6, 440 (1988)] are added to the flask. The contents of the flask are cooled to 10°, and a solution of 23 g (0.150 mole) of 4-nitrobenzyl alcohol in 450 mL of dichloromethane is added dropwise at a fast rate (45 minutes). The reaction mixture is allowed to come to room temperature and poured into a beaker containing 300 g of ice, decomposing any unreacted diethylaminosulfur trifluoride. The organic layer is separated, and the water layer is extracted twice with 45-mL portions of dichloromethane. The organic layer and extracts are combined, washed with 150 mL of water, and dried over anhydrous magnesium sulfate. Evaporation to dryness under reduced pressure gives 20.9–22.1 g (90–95%) of crude product. Recrystallization from 500 mL of pentane yields 15.5 g. (67%) of 4-nitrobenzyl fluoride as colorless needle-shaped crystals, m.p. 36–37°

SF4

    SF 4 是氟代能力很强的一种试剂，通常和HF一起使用。除了能把羟基化合物转化为单氟代化合物，醛和酮转化为二氟代化合物之外，还能把羧基转化为三氟甲基，是合成三氟甲基化合物的一个重要方法，特别是芳香类三氟甲基化合物。

     SF4 在氟化学的发展史上是很重要的一种氟代试剂，随着DAST等新型氟代试剂的发展，SF 4 在氟化学中的应用逐渐减少，对羟基化合物和醛酮的氟代反应基本已被DAST等试剂取代。

     SF4 最重要的应用就是从羧酸合成三氟甲基化合物。脂肪族羧酸为底物反应收率不高，生成的副产物是醚.

      芳香族羧酸底物的产率还可以，不过反应需要加入20－30当量的HF，反应操作不方便。

反应示例

    Twenty-six grams (0.20 mole) of heptanoic acid is placed in a 145-mL pressure vessel lined with Hastelloy-C. The air in the vessel is displaced with nitrogen, and the head of the vessel is secured in place. The vessel is cooled in a bath of acetone and solid carbon dioxide, and the nitrogen in the vessel is evacuated with a vacuum pump to a pressure of 0.5–1.0 mm. Sixty-five grams (95% pure, 0.57 mole) of sulfur tetrafluoride is transferred to the cold vessel.This is conveniently done by connecting a cylinder containing 65 g of sulfur tetrafluoride to the pressure vessel by a length of copper tubing having a 1/16-in. bore and 1/8-in. outside diameter.

     The pressure vessel is heated with agitation at 100° for 4 hours and at 130° for 6 hours. The vessel is allowed to cool to room temperature and the volatile by-products [ Caution!Toxic!] are vented. The crude, fuming, liquid product is poured into a stirred suspension of 10 g. of finely divided sodium fluoride in 60 mL of pentane, the mixture is filtered, and the filtrate is fractionated through a 6-in. Vigreux column. 1,1,1-Trifluoroheptane is collected at 100–101°/760 mm., n D 25 1.3449. The yield is 21.7–24.6 g. (70–80%).