Highly Controlled Ring-Opening of Siloxydifluorocyclopropanes: A Versatile Route to Cyclic Fluoroketones

Abstract

A convenient access to cyclic fluoroketones that involves base-promoted ring-opening of siloxydifluorocyclopropanes is presented. Selective formation of gem-difluorinated cycloalkanones and monofluorinated enones has been achieved.

Key words

fluorine - silicon - cyclopropane - ring-opening - ketone

• References and Notes

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For recent reports of ring-opening of gem-difluorocyclopropanes, see:
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• 17 Sodium bromodifluoroacetate is available from Tokyo Chemical Industry Co., Ltd. Otherwise, this reagent is prepared by the reaction of bromodifluoroacetic acid (available from SynQuest Laboratories, Inc.) with NaOH; see ref. 16.
• 18 Formation of Siloxydifluorocyclopropanes 2; General Procedure: To a solution of silyl enol ether 1a (851 mg, 5.0 mmol) in diglyme (20 mL), was added a diglyme solution (20 mL) of sodium bromodifluoroacetate (1.48 g, 7.5 mmol) at 150 °C. The reaction mixture was stirred for 10 min at 150 °C, then, after cooling to room temperature, the reaction was quenched by the addition of water. Organic materials were extracted three times with hexane and the combined organic layers were washed with brine and dried over Na₂SO₄. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (hexane–EtOAc, 50:1) to give 2a ¹⁵,¹⁶ (800 mg, 73%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 2.22–2.10 (m, 1 H), 1.96–1.78 (m, 2 H), 1.64–1.40 (m, 2 H), 1.38–1.20 (m, 4 H), 0.17 (s, 9 H). ¹⁹F NMR (376 MHz, CDCl₃, C₆F₆): δ = 25.9 (dd, J _F–F = 161.7, J _H–F = 23.3 Hz, 1 F), 15.4 (d, J _F–F = 161.7 Hz, 1 F). GC-MS: m/z (%) = 220 (4) [M]⁺, 205 (10), 81 (31), 73 (100).
• 19 Formation of gem-Difluorinated Cycloalkanones 3; General Procedure: A mixture containing siloxydifluorocyclopropane 2a (594 mg, 2.7 mmol) and Na₂CO₃ (286 mg, 2.7 mmol) in MeOH (30 mL) was stirred at room temperature under an atmosphere of argon for 30 min. Organic materials were extracted three times with Et₂O, and the combined organic layers were washed with brine and dried over Na₂SO₄. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (hexane–EtOAc, 5:1) to give 3a (283 mg, 71%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 2.70–2.64 (m, 2 H), 2.15–2.03 (m, 2 H), 1.88–1.80 (m, 2 H), 1.76–1.68 (m, 2 H), 1.67–1.60 (m, 2 H). ¹⁹F NMR (376 MHz, CDCl₃, C₆F₆): δ = 56.9 (s, 2 F). ¹³C NMR (75 MHz, CDCl₃): δ = 201.3 (t, J = 24.9 Hz), 118.6 (t, J = 249.2 Hz), 38.8, 33.7 (t, J = 23.7 Hz), 27.5, 23.6, 22.8 (t, J = 5.7 Hz). GC-MS: m/z (%) = 148 (3) [M]⁺, 119 (15), 84 (61), 55 (100). IR (NaCl): 1739 cm^–1. Anal. Calcd for C₇H₁₀F₂O: C, 56.75; H, 6.80. Found: C, 56.41; H, 6.89.
• 20 Formation of Fluorinated Cyclic Enones 4; General Procedure: To a solution of siloxydifluorocyclopropane 2a (66.0 mg, 0.3 mmol) in diglyme (3.0 mL) was added TBAF (1 M in THF, 0.3 mL, 0.3 mmol) at –78 °C under an atmosphere of argon. The reaction mixture was then stirred for 150 min at room temperature. Organic materials were extracted three times with Et₂O and the combined organic layers were washed with brine and dried over Na₂SO₄. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (hexane–EtOAc, 5:1) to give 4a ²¹ (34.9 mg, 91%) as a colorless oil. ¹H NMR (300 MHz, CDCl₃, TMS): δ = 6.25 (dt, J _H–F = 21.6, 6.6 Hz, 1 H), 2.70–2.64 (m, 2 H), 1.89–1.87 (m, 2 H), 1.74–1.62 (m, 4 H). ¹⁹F NMR (282 MHz, CDCl₃, C₆F₆): δ = 43.0 (d, J _H–F = 21.6 Hz, 1 F). GC-MS: m/z (%) = 128 (4) [M]⁺, 85 (64), 72 (100). IR (NaCl): 1698 cm^–1.
• 21 Usuki Y, Iwaoka M, Tomoda S. J. Chem. Soc., Chem. Commun. 1992; 1148