O-Ethyl-S-(1,2,2,2-Tetrafluoroethyl)-Dithiocarbonate: A Convenient Reagent for the Generation and Capture of 1,2,2,2-Tetra­fluoroethyl Radicals

Affectionately dedicated to Professor Steve Ley on the occasion of his 70^th birthday

Abstract

The synthesis of a new fluorinated reagent O-ethyl S-(1,2,2,2-tetrafluoroethyl) carbonodithioate (xanthate) and its use for the generation and capture of the hitherto unexplored 1,2,2,2-tetrafluo­roethyl radicals is described. This reagent allows the convenient introduction of the rare CF₃CHF motif onto various olefinic substrates with a high functional-group tolerance.

Key words

organofluorine - xanthates - alkenes - radical addition - indolines

• References and Notes

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• 14 Synthesis of O-Ethyl-1-fluoro-2,2,2-trifluoroethyl) Xanthate (7) Potassium O-ethyl xanthate (1.97 g, 12 mmol) was dissolved in TFA (30 mL). The solution was cooled to 0 °C in an ice bath, and trifluoroacetaldehyde methyl hemiacetal (15 mmol, 1.25 equiv) was added dropwise under a nitrogen atmosphere. After 30 min, the reaction was allowed to reach r.t. and was stirred for 1 h. Pentane (10 mL) and H₂O were added. The aqueous layer was extracted with pentane (2 × 10 mL), and the combined organic layers were washed with brine and dried over anhydrous MgSO₄. After filtering, the pentane solution was cooled to 0 °C under nitrogen atmosphere, and DAST (1.8 mL, 1 equiv) was added dropwise. The reaction was stirred at this temperature for 3 h. Keeping the reaction mixture cold, H₂O (10 mL) was added carefully, and the solution was subjected to steam distillation, following strictly these times and temperatures to divide fractions (the temperatures correspond to those of the oil bath): (1) first fraction, after 30 min at 90 °C: pentane and xanthate 7; (2) second fraction, after 3 h at 120 °C: xanthate 7 and H₂O; (3) third fraction, after 1 h at 130 °C: xanthate 7 + O-ethyl xanthic anhydride. The second fraction was extracted with a minimum of pentane and dried over anhydrous MgSO₄. The pentane was removed under reduced pressure (bath temperature: 20 °C) to afford xanthate 7. The product was stored in the refrigerator. ¹H NMR (400 MHz, CDCl₃): δ = 1.48 (t, J = 8 Hz, 3 H), 4.74 (q, J = 8 Hz, 2 H), 6.80 (dq, J ₁ = 8 Hz, J ₂ = 48 Hz, 1 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 13.5, 71.9, 94.7–97.3 (dq, J ₁ = 37 Hz, J ₂ = 185 Hz), 119.8–122.9 (m), 205.6 ppm. ¹⁹F NMR (376 MHz, CDCl₃): δ = –70.7 (J _F–F = 18 Hz, J _F–H = 6 Hz, 3 F), –170.4 (m, 1 F) ppm. General Procedure for the Addition Reaction The starting olefin (n mmol) and xanthate 7 (1.5–2 n mmol) were dissolved in n mL of EtOAc. The solution was refluxed for 10 min in a preheated bath, under a nitrogen atmosphere. Dilauroyl peroxide (DLP; 10 mol% with respect to the olefin, where the amount of DLP was calculated with respect to the xanthate) was then added every hour until total conversion of starting material was observed (TLC). The mixture was cooled to r.t., and the solvent was removed under reduced pressure. Products 9a–k were purified by flash chromatography (all the adducts were isolated as a mixture of diastereoisomers). General Procedure for the Ring Closing The xanthate adduct 9g–i (n mmol) was dissolved in EtOAc (10n mL) and refluxed for 10 min under a nitrogen atmosphere. DLP (1.2 n mmol) was then added portionwise (20 mol%) every hour. Once reaction was complete (TLC), the mixture was allowed to cool to r.t., and the solvent was evaporated under reduced pressure. The corresponding indolines 10g–i were purified by flash column chromatography and isolated as a mixture of diastereoisomers. 2-[(Ethoxycarbonothioyl)thio]-4,5,5,5-tetrafluoropentyl Acetate (9a) Isolated yield 161 mg (0.5 mmol, 100%). ¹H NMR (400 MHz, CDCl₃): δ = 1.36 (t, J = 8 Hz, 3 H), 2.02 (s, 3 H), 4.36–3.88 (m, 8 H), 4.59 (q, J = 8 Hz, 2 H), 4.73 (m, 1 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 13.7, 20.7, 31.3–33.2 (m), 47.2, 65.5–66.2 (m), 70.5, 170.6, 212.5 ppm. ¹⁹F NMR (376 MHz, CDCl₃): δ = –79.9 (J _F–F = 18 Hz, J _F–H = 6 Hz, 3 F), –200.7 (m, 1 F) ppm. HRMS: m/z calcd for C₇H₉F₄O₂ [M – SCSOEt]: 201.0533; found: 201.0537. tert-Butyl {2-[(Ethoxycarbonothioyl)thio]-4,5,5,5-tetrafluoropentyl}carbamate (9b) Isolated yield: 151 mg (0.4 mmol, 80%). ¹H NMR (400 MHz, CDCl₃): δ = 1.41 (s, 3 H), 1.42 (t, J = 8 Hz, 3 H), 2.20 (m, 2 H), 3.44 (m, 1 H), 3.62 (m, 1 H), 4.07 (m, 1 H), 4.65 (q, J = 8 Hz, 2 H), 4.86 (m, 1 H), 5.13 (m, 1 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 13.7, 28.2, 29.6, 41.7, 47.0, 70.4, 85.5–87.0 (m), 121.3–123.9 (m), 156.0, 211.4 ppm. ¹⁹F NMR (376 MHz, CDCl₃): δ = –79.6 (m, 3 F), –201.1 (m, 1 F) ppm. HRMS: m/z calcd for C₁₀H₁₆F₄NO₂ [M – SCSOEt]: 258.1112; found: 258.1114; m/z calcd for C₁₇H₁₉F₇N₃O [M – SCSOEt]: 414.1411; found: 414.1409. 1-[5-Bromo-3-(2,3,3,3-tetrafluoropropyl)indolin-1-yl]ethanone (10g) Isolated yield: 63 mg (0.18 mmol, 60%). ¹H NMR (400 MHz, CDCl₃): δ = 2.13 (m, 2 H), 2.23 (s, 3 H), 3.60 (d, J = 8 Hz, 1 H), 3.81 (dd, J ₁ = 8 Hz, J ₂ = 12 Hz, 1 H), 4.27 (t, J = 12 Hz, 1 H), 4.77–4.94 (m, 1 H), 7.27 (d, J = 12 Hz, 1 H), 7.36 (dd, J ₁ = 4 Hz, J ₂ = 12 Hz, 1 H), 8.11 (d, J = 4 Hz, 1 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 24.0, 33.3 (d, J = 20 Hz), 36.7, 55.4, 86.7–88.9 (dq, J ₁ = 32 Hz, J ₂ = 185 Hz), 116.1, 118.7, 126.9, 131.7, 134.6, 141.6, 168.6 ppm. HRMS: m/z calcd for C₁₃H₁₂BrF₄NO [M – SCSOEt]: 353.0038; found: 353.0027.