38078-09-0 / 氟化試劑：二乙胺基三氟化硫 (DAST)

DAST二乙胺基三氟化硫，一種常用的氟化試劑。常溫下是液體，在干燥情況下室溫或冰箱能長期保存，DAST在90oC會(huì)分解，處理不當(dāng)會(huì)有爆炸的危險(xiǎn)。但由于操作簡單和通用性強(qiáng)，DAST是使用得最廣泛的氟代試劑之一。這個(gè)試劑能將羥基化合物轉(zhuǎn)化為單氟代化合物，醛和酮轉(zhuǎn)化為二氟代化合物[1]。

反應(yīng)機(jī)理：

首先DAST會(huì)和羥基生成一個(gè)中間態(tài)，并生成一分子氟化氫。之后是氟負(fù)離子通過SN1或者SN2方式親核進(jìn)攻羥基碳原子，從而生成產(chǎn)物[2,3]。

反應(yīng)特點(diǎn)：

脂肪族和芳香族的伯，仲，叔醇都能高產(chǎn)率的轉(zhuǎn)化為相應(yīng)的氟化合物。反應(yīng)通常用二氯甲烷，一氟三氯甲烷等作溶劑，取代羥基通常在較低溫度下反應(yīng)（－78oC），取代羰基一般在0oC－40oC反應(yīng)。

仲醇在取代的過程中會(huì)發(fā)生構(gòu)型翻轉(zhuǎn)，為手性合成提供了一個(gè)方法，如(S)-2-辛醇在反應(yīng)中構(gòu)型完全翻轉(zhuǎn)，得到(R)-2-氟辛烷，ee％為97.6%[4]。

文獻(xiàn)示例：

A dry, 1-L, three-necked, round-bottomed flask is fittedwith a 500-mL dropping funnel, thermometer, a magnetic stirrer,and a reflux condenser protected from theatmosphere with a drying tube. The apparatus is flushed with dry nitrogen, and150 mL of drydichloromethaneand21 mL (0.16mole) ofdiethylaminosulfurtrifluoride[5]are added to the flask.The contents of the flask are cooled to 10°, and a solution of23 g (0.150 mole) of4-nitrobenzyl alcoholin450 mL ofdichloromethaneis added dropwise at a fast rate (45 minutes). The reaction mixture is allowed to come toroom temperature and poured into a beakercontaining 300 gof ice, decomposing any unreacted diethylaminosulfurtrifluoride. The organic layer isseparated, and the water layer is extracted twice with45-mL portions ofdichloromethane. The organic layer andextracts 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 from500 mL ofpentaneyields 15.5 g. (67%) of 4-nitrobenzyl fluoride as colorless needle-shapedcrystals, m.p. 36–37°

作者示例：

YJFX-190112-A(10.0 g, 1.0 eq.)was dissolved in CH2Cl2(100 mL), DAST (5.2 g, 1.2 eq.) was dropped slowly into the solutionunder -78 °C. The mixture was stirred for 30 min at -78 °C. The reaction waswarmmed to 30-40 °C and stirred for 1-2h.

Themixture was dropped into aq. NaHCO3(10%, 200mL), and stirred for 20min. Extracted with CH2Cl2(150mL*2), the organic layerwas dried with anhydrous Na2SO4 and concentrated, and the residuewas purified by column chromatography togive product as oil (8.5 g, yield: 84%).

反應(yīng)經(jīng)驗(yàn)：

帶有手性的仲醇，發(fā)生了構(gòu)型翻轉(zhuǎn)。

該反應(yīng)滴加DAST在零下78攝氏度進(jìn)行，而中間態(tài)往產(chǎn)品的轉(zhuǎn)化卻需要升溫進(jìn)行，因此升溫時(shí)必要的（不同底物需要自己摸索了）。上述反應(yīng)的中間態(tài)極性和產(chǎn)品幾乎幾乎無差別（TLC檢測無法分別），導(dǎo)致最初反應(yīng)做的差的原因，延長時(shí)間后，得到改善。

反應(yīng)淬滅過程建議滴加，上述反應(yīng)最開始是倒入，反應(yīng)會(huì)瞬間變雜，控制溫度也不行，改為滴加后，得到改善。

參考文獻(xiàn)：

Bombrun, A. et. al.J. Med. Chem.2003, 46,4365.

Rozen, S. ; Faust, Y. ; Ben-Yakov, H. Tetrahedron Lett. 1979,20, 1823.

Leroy, J.; Hebert, E.; Wakselman, C. J. Org. Chem. 1979, 44,3406.

Middleton, W, J.J. Org. Chem.1975, 40, 574.

Hundlicky, M.Org. React.1988, 34, 513.