磺酸酯參與的氟化反應

磺酸酯，如甲磺酸酯，對甲苯磺酸酯在極性非質子溶劑（DMF，CH3CN, DMSO等）中與鹼金屬氟化物發生親核取代反應，得到氟化合物。

鹼金屬氟化物在非質子溶劑中活性如下：CsF>KF>NaF>LiF。CsF的活性最高，但由於KF價格相對便宜，所以最常用。

反應體系中加入冠醚等相轉移催化劑會加快反應進行，提高產率。

有的底物在離子液體中進行反應，能得到很好得結果。如下這個反應在離子液體[bmim]BF4中進行，產率相當高。

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

黃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】

反應例項

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】

對甲苯磺酸酯與TBAF反應

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】

甲磺酸酯與TBAF反應

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】

甲磺酸酯與CsF反應

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】

甲磺酸酯與TBAF(tBuOH)4反應

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】

相關連結

本文轉自公眾號：Labnetwork

【氟化反應】磺酸酯參與的氟化反應

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