Difluorocarbene Chemistry: Synthesis of gem-Difluorocyclopropenyl Ketones and gem-Difluorinated Dihydrofurans

Zhan-Ling Cheng; Qing-Yun Chen

doi:10.1055/s-2006-926266

LETTER

Difluorocarbene Chemistry: Synthesis of gem-Difluorocyclopropenyl Ketones and gem-Difluorinated Dihydrofurans

Zhan-Ling Cheng, Qing-Yun Chen*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, 200032 Shanghai, P. R. of China
e-Mail: chenqy@mail.sioc.ac.cn;

Abstract

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Abstract

The cycloaddition reactions of difluorocarbene, generated by the decomposition of FSO₂CF₂CO₂SiMe₃, with α,β-acetylenic ketones give gem-difluorocyclopropenyl ketones in good yields. Treatment of these gem-difluorocyclopropenyl ketones with aqueous potassium carbonate results in the formation of gem-difluorinated dihydrofurans.

Key words

difluorocarbene - gem-difluorocyclopropenes - gem-difluorocyclopropenyl ketones - gem-difluorinated dihydrofurans

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References

References and Notes

<A NAME="RW08105ST-1A">1a</A> Chemistry of Organic Fluorine Compounds II Hudlicky M. Pavlath AE. American Chemical Society; Washington D.C.: 1995.

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Prepared according to the literature:

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<A NAME="RW08105ST-4B">4b</A> Yoshikazu K. Steven L. J. Org. Chem. 1982, 2493

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gem -Difluorocyclopropenyl Ketone 2a: α,β-Acetylenic ketone 1a (0.73 g, 3.55 mmol), NaF (19 mg, 10 mol%), and DG (2 mL) were added under a N₂ atmosphere to a Schlenk tube charged with a magnetic stirring bar and a pressure-equalized dropping funnel. After the mixture was heated to about 120 °C (oil bath), TFDA (2.71 g, 3 equiv) was added dropwise. The mixture was stirred at this temperature for about 3 h. Then the mixture was cooled to r.t. and purified by flash column chromatography on silica gel; yield: 0.67 g (89%) [recovered 1a: 0.12 g (conversion 83%)]; solid; mp, 80-85 °C. IR (film): 1759, 1681, 1650, 1597,1577, 1494, 1450, 1313, 1299, 1226 cm^-1. ¹H NMR (CDCl₃, 300 MHz): d = 8.15-8.18 (m, 2 H), 8.01-8.05 (m, 2 H), 7.52-7.72 (m, 6 H). ¹⁹F NMR (CDCl₃, 282 MHz): δ = -103.74 (s, 2 F). MS: m/z (%) = 256 (M⁺, 11.37), 228 (6.99), 151 (6.11), 105 (100), 77 (40.21). Anal. Calcd for C₁₆H₁₀OF₂: C, 75.00; H, 3.93; F, 14.83. Found: C, 75.06; H, 3.82; F, 14.86. X-ray crystallographic data for 2a: crystal system, monoclinic; space group, P2 (1)/n; unit cell dimensions: a = 8.4778 Å, b = 9.0567 Å, c = 17.022 Å, α = 90°, β = 103.462°, γ = 90°, Z = 4, F(000) = 528, R1 = 0.0623, wR2 = 0.1635 (all data), CCDC No. 287907.

<A NAME="RW08105ST-6A">6a</A> Abdo BT. Alberts IL. Attfield CJ. Banks RE. Blake AJ. J. Am. Chem. Soc. 1996, 118: 209

<A NAME="RW08105ST-6B">6b</A> Brisdon AK. Crossley IR. Flower KR. Pritchard RG. Warren JE. Angew. Chem. Int. Ed. 2003, 42: 2398

Difluorinated Dihydrofuran 3c: To a solution of 2c (50 mg, 0.18 mmol) in MeOH (5 mL) was added 10% aq K₂CO₃ (0.1 mL). The mixture was stirred at r.t. and the progress of the reaction was monitored by ¹⁹F NMR spectroscopy. When the reaction had reached completion, H₂O (10 mL) was added and the reaction was extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over MgSO₄. After the solvent was removed under reduced pressure, the residue was purified by flash column chromatography on silica gel; yield: 45 mg (80%); white solid. IR (film): 3117, 2935, 1650, 1616, 1579, 1515, 1494, 1452, 1343, 1285, 1271, 1149, 1071, 1047, 968, 731 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 2.40 (s, 3 H), 3.39 (s, 3 H), 5.69 (s, 1 H), 7.23-7.50 (m, 7 H), 7.75-7.80 (m, 2 H). ¹⁹F NMR (CDCl₃, 282 MHz): δ = -82.27 (d, J = 247 Hz, 1 F), -111.31 (d, J = 248 Hz, 1 F). MS: m/z (%) = 302 (M⁺, 10.13), 283 (12.21), 282 (10.24), 271 (24.50), 243 (14.40), 177 (9.80), 152 (100), 151 (65.65), 119 (59.20), 105 (93.95), 84 (99.36). Anal. Calcd for C₁₈H₁₆O₂F₂: C, 71.51; H, 5.33. Found: C, 71.52; H, 5.64.

X-ray crystallographic data for 3a: C₁₇H₁₄F₂O₂, M 288.28; monoclinic; space group, P2 (1)/n; unit cell dimensions: a = 13.6673 Å, b = 7.1944 Å, c = 14.8156 Å, α = 90°, β = 92.034°, γ = 90°, Z = 4, D_calcd = 1.315 g/cm³, F(000) = 600, R1 = 0.0812, wR2 = 0.1246, CCDC No. 287908.