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Synlett 2002(6): 0996-0998
DOI: 10.1055/s-2002-31912
LETTER
© Georg Thieme Verlag Stuttgart · New York

First Synthesis of 4,4-Difluoro-1,3-oxathiolan-5-one

Sonia Gouault, Jean-Claude Pommelet, Thierry Lequeux*
Laboratoire de Chimie Moléculaire et Thio-organique, Université de Caen - ISMRA, UMR CNRS 6507, 6 Boulevard du Maréchal Juin 14050 Caen cedex, France
Fax: +33(0231)452877; e-Mail: Thierry.Lequeux@ismra.fr;
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Publication History

Received 13 March 2002
Publication Date:
07 February 2007 (online)

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Abstract

The synthesis of a novel 4,4-difluoro-1,3-oxathiolanone was reported from α,α-difluorosulfoxide. This route involved a fluorination of a symmetrical sulfide, a Pummerer rearrangement, and a ring closure mediated by organic acids.

Key words

halogenation - fluorine - sulfoxides - rearrangements - heterocycles

12

A degradation of the sulfoxide 9b occurred during the purification. It is preferable to use it without purification in the next step.

16

Despite a quantitative conversion, a lost of 11 was observed during the distillation.

19

Experimental:
Methyl 2,2-difluoro-2-(methoxycarbonyl-trifluoro-acetoxymethylsulfanyl) acetate(10): To a solution of difluoroester(8b) [8] [20] (2.00 g, 9.34 mmol) in CH2Cl2 (40 mL) was added NaHCO3 (1.57 g, 18.7 mmol) followed by meta-chloroperoxybenzoic acid (2.42 g, 14.0 mmol). The resulting mixture was stirred at r.t. for 70 min and then poured into a mixture of sat. aq NaHCO3 (25 mL) and sodium thiosulfate (25 mL). The layers were separated and the aq phase was extracted with CH2Cl2 (5 × 40 mL). The combined organic extracts were washed with sat. aq NaHCO3 (4 × 40 mL) and brine (40 mL), dried over MgSO4 and concentrated under vacuum to give the crude product(9b) (1.53 g, 6.65 mmol) in 71% yield.(9b): 1H NMR (CDCl3): δ = 3.83 (s, 3 H, CH 3O), 3.95 (s, 2 H, CH2), 4.00 (s, 3 H, CH 3O); 13C NMR (CDCl3): δ = 53.1 (t, 3 J CF = 4.6 Hz, CH2), 53.4 (CH3), 54.7 (CH3), 118.6 (t, 1 J CF = 302 Hz, CF2), 160.2 (t, 2 J CF = 28 Hz, CO-CF2), 164.7 (CO); 19F NMR (CFCl3, CDCl3): δ = -109.6 (d, 2 J FF = 235 Hz, 1 F), & ndash;110.8 (d, 2 J FF = 235 Hz, 1 F). The crude sulfoxide(9b) (1.53 g, 6.65 mmol) was stirred at r.t. in the presence of trifluoroacetic anhydride (2.82 mL, 0.020 mol). After 48 h, the mixture was concentrated under vacuum, diluted with CH2Cl2 (20 mL) and washed with brine. The crude product was distilled under reduced pressure (70 °C/0.07 mm Hg) to afford(10) (1.5 g, 4.60 mmol) in 70% yield.1H NMR (CDCl3): δ = 3.87 (s, 3 H, CH 3O), 3.94 (s, 3 H, CH 3O), 6.63 (s, 1 H, CH); 13C NMR (CDCl3): δ = 54.4 (CH3), 54.6 (CH3), 74.8 (t, 3 J CF = 3.9 Hz, CH), 114.1 (q, 1 J CF = 228 Hz, CF3), 118.8 (t, 1 J CF = 292 Hz, CF2), 156 (q, 2 J CF = 44.5 Hz, COCF3), 161.2 (t, 2 J CF = 32 Hz, COCF2), 164.0 (CO); 19F NMR (CDCl3): δ = -75.4 (s, 3 F, CF3), -81.6 (d, 2 J FF = 224 Hz, 1 F), -83.3 (d, 2 J FF = 224 Hz, 1 F); IR (NaCl): ν = 1802 (CO), 1772 (CO), 1762 (CO) cm-1; MS (EI, 70 eV): m/z (%) = 326(9) [M+], 239(33), 213(70), 179(22), 129(42), 103(100), 69(69), 45(44).
Methyl 4,4-difluoro-5-oxo-[1,3]-oxathiolane-2-carboxyl-ate(11): To a solution of(10) (1.48 g, 4.54 mmol) in CHCl3 (20 mL) under nitrogen was added triflic acid (0.60 mL, 6.81 mmol). After stirring overnight at r.t. the mixture was diluted wih CH2Cl2, washed with NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried over MgSO4 and concentrated under vaccum. The crude residue (745 mg, 3.76 mmol) was distilled under reduced pressure (65 °C/1 mbar) to afford(11) (445 mg, 2.45 mmol) in 50% yield. 1H NMR (CDCl3): δ = 3.92 (s, 3 H, CH3), 5.91 (d, 1 H, 4 J HF = 5.8 Hz, CH); 13C NMR (CDCl3): δ = 54.2 (CH3), 70.3 (d, 3 J CF = 1.9 Hz, CH), 121.8 (t, 1 J CF = 280 Hz, CF2), 161.7 (t, 2 J CF = 30.5 Hz, CO), 166.3 (CO); 19F NMR (CDCl3): δ = -71.8 (dd, 2 J FF = 243 Hz, 4 J HF = 5.8 Hz, 1 F), -80.1 (d, 2 J FF = 243 Hz, 1 F); IR (CHCl3/NaCl): ν = 1818 (CO), 1762 (CO), 1124, 1084, 1056 cm-1; MS (EI, 70 eV): m/z (%) = 198(7) [M+], 179(16), 139(35), 116(64), 95(18), 83(56), 63(63), 45(100); HMRS (EI) calcd for C5H4SO4F2 [M+]: 197.9798. Found: 197.9780.