磺酸酯，如甲磺酸酯，对甲苯磺酸酯在极性非质子溶剂（DMF，CH3CN, DMSO等）中与碱金属氟化物发生亲核取代反应，得到氟化合物。

碱金属氟化物在非质子溶剂中活性如下：CsF>KF>NaF>LiF。CsF的活性最高，但由于KF价格相对便宜，所以最常用。

反应体系中加入冠醚等相转移催化剂会加快反应进行，提高产率。

有的底物在离子液体中进行反应，能得到很好得结果。如下这个反应在离子液体[bmim]BF4中进行，产率相当高。

【Kim, D, W. Song, C, E. Chi, D, Y. J. Org. Chem. 2003, 68,4281-4285】

黄原酸酯也能被取代生成氟化物。

【Keon, M, J. LeGuyader, F. J. Chem. Soc.Chem.Commu. 1995, 25,1241】

反应实例

CsF (760 mg, 5 mmol) was added to the mixture of2-(3-methanesulfonyloxypropyl) naphthalene (264 mg, 1.0 mmol), [bmim]-[BF4] (3.0 mL), andH2O (90 íL, 5 mmol) in acetonitrile (3.0 mL). The mixture was stirred at 100 °C for 20 min. The reaction wasmonitored by TLC. The reaction mixture wasextracted from the ionic liquid phase with ethyl ether (7mL× 3). The ether layer was dried over Na2SO4and evaporated under reduced pressure. Theresidue was purified by flash column chromatography on silica gel (5%EtOAc/hexane) to give 2-(3-fluoropropyl)naphthalene (179 mg , 95%) as acolorless oil.

【Kim, D, W. Song, C, E. Chi, D, Y. J. Org. Chem. 2003, 68,4281-4285】

对甲苯磺酸酯与TBAF反应

The solution of tetrabutylammonium fluoride (TBAF) in THF (14 mL, 1M) was added in the solution of tosylate(0.78g, 1.8 mmol) in anhydrous THF (15 mL). The reaction mixture was then refluxed for 4 h. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate (80 mL). The organic solution was washed with water(30 mL), brine (30 mL) and saturated aqueous NaHCO3(30 mL). Then the organiclayer was dried over Na2SO4. After filtration the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography using ethyl acetate/hexane (30/70, v/v) to afford the product(0.29 g, 57%) as a colorless oil.

【Zhude Tu,et al.J. Med. Chem., 2011, 54 (6), 1555–1564】

甲磺酸酯与TBAF反应

TBAF(1 M in THF, 0.20 mL) was added to a solution of 8 (27 mg, 0.05 mmol) inanhydrous THF (10 mL). The mixture was refluxed for 4 h. Afterward, it was cooled to room temperature. After a standard workup with ethyl acetate, the residue was purified by silica gel chromatography (hexane/ethyl acetate = 1:1) to give 22 mg of 9 (94.0%).

【Masahiro Ono, et alJ. Med. Chem., 2011, 54 , 2971–2979】

甲磺酸酯与CsF反应

CsF (456mg, 3.0 mmol) was added to the mixture of 2-(3-methanesulfonyloxypropoxy)naphthalene (280 mg, 1.0 mmol) in t-amyl alcohol(4.0 mL). The mixture was stirred over 6 h at 80 °C. The reaction mixture was triturated with ethyl ether to remove most of ionic salts. The filtrate was evaporated under reduced pressure. The residue was purified by flash column chromatography (20% CH2Cl2/hexanes) to obtain192 mg (94%) of2-(3-fluoropropoxy)naphthalene as a colorless oil with ether byproduct .

【DongWook Kim et al. J. Org. Chem. 2008, 73, 957-962】

甲磺酸酯与TBAF(tBuOH)4反应

Commercially available TBAF hydrate (1.0 g, 3.17mmol) was added to t-BuOH (88 mL) and n-hexane(22 mL). The mixture was stirred for 30 min at 90oC. During this time TBAF dissolved completely. The solution was cooled to room temperature, and a white crystalline solid precipitated. The crystalline solid was filtered and washed rapidly with 40 mL of 70% t-BuOH/hexane. The filtrate was kept in vacuum for 15–20 min to remove residual solvent, and TBAF(tBuOH)4 (1.63 g, 2.92 mmol) was obtained as white crystalline solid in 92% yield.

TBAF(t-BuOH)4(1.1g, 2 mmol) was added to a solution of mesylate (280 mg, 1.0 mmol) in CH3CN(4.0 mL). The mixture was stirred for 1.0 h at 70 oC. The residue was dissolved in water (6.0 mL) and extracted from the aqueous phase with diethyl ether(6.0 mL×3). The organiclayer was dried (sodium sulfate) and evaporated under reduced pressure. The residue was purified by short flash column chromatography (5% EtOAC/hexane) to give 2-(3-fluoropropoxy)-naphthalene (200 mg, 98%) as a colorless oil.

【Dong Wook Kim et al. Angew. Chem. Int. Ed. 2008, 47, 8404 -8406】

相关链接

本文转自公众号：Labnetwork

【氟化反应】磺酸酯参与的氟化反应

版权归原作者所有，如有版权问题，请联系本人删除。