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Synlett 2009(4): 589-594  
DOI: 10.1055/s-0028-1087924
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Micellar-System-Mediated Direct Fluorination of Ketones in Water

Gaj Stavbera, Marko Zupana, Stojan Stavber*b
a Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
b Laboratory of Organic and Bioorganic Chemistry, Jo˛ef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
Fax: +386(1)423-5400; e-Mail: stojan.stavber@ijs.si;
Further Information

Publication History

Received 12 November 2008
Publication Date:
16 February 2009 (online)

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Abstract

A micellar system was developed and applied for direct regioselective fluorination of a variety of cyclic and acyclic ketones to α-fluoroketones in water as reaction medium with Selectfluor F-TEDA-BF4 as fluorinating reagent. The inexpensive ionic amphiphile sodium dodecyl sulfate (SDS) was found to be an excellent promoter for fluorofunctionalization of hydrophobic ketones without prior activation or use of acid catalysts.

Key words

ketones - halogenation - micelles - F-TEDA-BF4 - water

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General Procedure for the Direct Fluorination of Ketones in SDS Aqueous Micellar System
Ketone (1 mmol) was placed in a glass flask (25 mL) equipped with a magnetic stirrer. Then, H2O (5 mL) was added and stirred for a few minutes. An appropriate amount of SDS (144 mg, 0.5 mmol or 288 mg, 1 mmol; see Table  [³] ) was then added to the heterogeneous reaction system and heated to 80 ˚C during rapid stirring. When the reaction system reached 80 ˚C, F-TEDA-BF4 (390 mg, 1.1 mmol) was added in two portions over an interval of 1 h, and stirred and held at 80 ˚C until the KI test showed consumption of the fluorinating reagent. When reaction was complete, the reaction system was cooled to r.t., and the resulting suspension was extracted with Et2O (2 × 15 mL). The combined ether phases were dried over anhyd Na2SO4. After the removal of the solvent under reduced pressure, the crude products obtained were identified with ¹H NMR, ¹9F NMR, and MS analysis and purified by silica gel column chromatography or preparative TLC (SiO2, CH2Cl2, and a few drops of EtOH) to afford pure α-fluoro ketones. The spectroscopic data of the products were in agreement with those reported in the literature.
Spectroscopic Data for Representative Compounds
1-Fluoro-1-phenylpropan-2-one ²² (21)
Liquid product. ¹H NMR (300 MHz, CDCl3): δ = 2.23 (d, J = 4.0 Hz, 3 H, Me), 5.68 (d, J = 48.7 Hz, 1 H, CHF), 7.40 (br s, 5 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -183.14 (dq, J = 48.7, 4.0 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 25.13 (Me), 95.84 (d, J = 187.8 Hz, C-1), 126.00 (d, J = 7.0 Hz), 128.9, 129.36 (d, J = 2.3 Hz), 133.94 (d, J = 20.6 Hz), 204.55 (d, J = 26.7 Hz, CO). MS (EI, 70eV):
m/z (%) = 152 (6) [M+], 110 (10), 109 (100), 83 (20).
1-Fluoro-1,1-diphenyl-propan-2-one ²³ (23)
Mp 58.5-60.0 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.41 (d, J = 5.9 Hz, 3 H, Me), 7.37 (br s, 10 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -143.62 (q, J = 5.9 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 26.71 (Me), 102.17 (d, J = 185.8 Hz,
C-1), 126.64 (d, J = 7.4 Hz), 128.34, 128.77 (d, J = 2.0 Hz), 137.54 (d, J = 22.8 Hz), 206.43 (d, J = 32.7 Hz, CO).
MS (EI, 70eV): m/z (%) = 185 (100) [M+ - COMe], 151 (11).
3-Fluoro-4-phenylbutan-2-one ²4 (27)
Liquid product. ¹H NMR (300 MHz, CDCl3): δ = 2.13 (d, J = 4.9 Hz, 3 H, Me), 3.01-3.21 (m, 2 H, CH2), 4.93 (ddd, J = 48.5, 6.0, 3.0 Hz, 1 H, CHF), 7.21-7.34 (m, 5 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -188.66 (dtq, J = 48.5, 23.2, 5.0 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 26.42 (Me), 38.10 (d, J = 20.6 Hz, C-4), 95.89 (d, J = 187.3 Hz,
C-3), 127.10, 128.57, 129.49, 135.28, 209.98 (d, J = 26.7 Hz, CO). MS (EI, 70eV): m/z (%) = 166 (100) [M+], 146 (100), 123 (15), 91 (77), 77 (41).