Micellar-System-Mediated Direct Fluorination of Ketones in Water

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.

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

References and Notes

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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).

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