Synthesis of 1,1-Difluoroalkanes via Phase Transfer Catalysed Reaction of 1,1-bis-Triflates with KF in the Presence of Cocatalyst - Ph₃SnF

Abstract

1,1-bis-Triflates treated with KF in the presence of tri­phenyltin fluoride and tetrabutylammonium hydrogen sulfate give 1,1-difluoroalkanes

Key words

phase transfer catalysis - tin compound - fluorination

References

• 1a Fluorine-containing Molecules. Structure, Reactivity, Synthesis and Applications   Liebman JF. Greenberg A. Dolbier WR. VCH; New York: 1988. 
• 1b Filler R. Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications, Studies in Organic Chemistry 48   Filler R. Elsevier; New York: 1993.  p.1-23 
• 2 Hasek WR. Smith WC. Engelhardt V. J. Am. Chem. Soc.  1960,  82:  543 
• 3 Middleton WJ. J. Org. Chem.  1975,  40:  574 
• 4 Schaffer F. Verevkin SP. Rieger HJ. Beckhaus HD. Rü chardt C. Liebigs Ann. Chem.  1997,  1333 
• 5 Rozen S. Zamir D. J. Org. Chem.  1991,  56:  4695 
• 6 García Martínez A. Osío Barcina J. Rys AZ. Subramanian LR. Tetrahedron Lett.  1992,  33:  7787 
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8

Typical Procedure: Dried powdered KF (3.094 g, 53.3 mmol), Ph₃SnF (98 mg, 0.27 mmol) Bu₄N⁺HSO₄ ^- (91 mg, 0.27 mmol) and a freshly prepared solution of RCH(OTf)₂ in CH₂Cl₂ (2.7 mmol in 4.5 mL) were vigorously stirred at r.t. till the reaction was completed (16-48 h). The reaction mixture was diluted with ether (25 mL), the solid was filtered off, washed with diethyl ether (3 × 8 mL). The ether extracts were combined and the solvent was distilled using a 20 cm Vigreux column. The products were purified by chromatography (silica gel, n-pentane or n-pentane/CH₂Cl₂).
1,1-Difluorooctane: ¹H NMR (200 MHz, CDCl₃): 0.89 (t, J [¹H-¹H] = 6.5 Hz, 3 H CH₃), 1.25-1.50 (m, 10 H), 1.65-1.95 (m, 2 H), 5.79 (tt, ^² J [¹⁹F-¹H] = 57 Hz; J [¹H-¹H] = 4.5 Hz, 1 H, CHF₂). ¹⁹F NMR (178 MHz, CDCl₃): -116.2 (dt, ^² J [¹⁹F-¹H] = 57 Hz; ^³ J [¹⁹F-¹H] = 17.5 Hz), MS (EI, 70 eV): 150 (M⁺, <1), 130 (M-HF, 1); 84(20), 81(17), 73(15), 71(21), 69(14), 68(12), 59(12), 57(60), 56(36), 55(37), 43(100), 42(23), 41(65).
1,1-Difluorodecane: ¹H NMR (200 MHz, CDCl₃): 0.88 (t, J [¹H-¹H] = 6.5 Hz, 3 H CH₃), 1,23-1,50 (m, 14 H), 1.65-1.95 (m, 2 H), 5.79 (tt, ^² J [¹⁹F-¹H] = 57 Hz; J [¹H-¹H] = 4.5 Hz, 1 H, CHF₂). ¹⁹F NMR (178 MHz, CDCl₃): -116.2 (dt; ^² J [¹⁹F-¹H] = 57 Hz, ^³ J [¹⁹F-¹H] = 17.5 Hz). MS (EI, 70 eV): 178 (M⁺, 3), 107(13), 85(31), 84(16), 83(11), 82(15), 81(10), 73(16), 71(34), 70(21), 69(17), 57(80), 56(24), 55(34), 43(100), 42(15), 41(43).
1,1-Difluoro-2-phenyl-ethane: ¹H NMR (200 MHz, CDCl₃): 3.07 (td, ^³ J [¹⁹F-¹H] = 17.3 Hz, J [¹H-¹H] = 4.6 Hz, 2 H; Ph-CH₂-CHF₂), 5.85 (tt, ^² J [¹⁹F-¹H] = 56 Hz, J [¹H-¹H] = 4.6 Hz, 1 H, CHF₂), 7.15-7,32 (m, 5 H, Ph). ¹⁹F NMR (178 MHz, CDCl₃): -115,5 (dt, ^² J [¹⁹F-¹H] = 56.6 Hz, ³ J [¹⁹F-¹H] = 17.3 Hz). MS (EI, 70 eV): 142 (M⁺, 33), 91(100), 65(14).
1,1-Difluoro-3-phenyl-propane: ¹H NMR (200 MHz, CDCl₃): 2.01- 2.29 (m, 2 H, CH₂-CHF₂), 2.78 (t, J [¹H-¹H] = 7.9 Hz, 2 H, Ph-CH₂), 5.80 (tt, ^² J [¹⁹F-¹H] = 56.7 Hz, J [¹H-¹H] = 4.5 Hz, 1 H, CHF₂), 7.16-7.36 (m, 5 H, Ph). ¹⁹F NMR (178 MHz, CDCl₃): -117.7 (dt, ^² J [¹⁹F-¹H] = 56.8 Hz, ^³ J [¹⁹F-¹H] = 17.1 Hz). MS (EI, 70 eV): 156 (M⁺, 28), 92(11), 91(100), 65(11).
2-Ethyl-1,1-difluorohexane: ¹H NMR (200 MHz, CDCl₃): 0.85-1.03 (m, 6 H), 1.25-1.55 (m, 8 H), 1.90-2.10 (1 H, CHCHF₂), 5.71 (td, ^² J [¹⁹F-¹H] = 58.0 Hz, J [¹H-¹H] = 4.0 Hz, 1 H, CHF₂). ¹⁹F NMR (178 MHz, CDCl₃): -123.43 (dd, ^² J [¹⁹F-¹H] = 57.0 Hz, ^³ J [¹⁹F-¹H] = 15.7 Hz). MS (EI, 70 eV): 130 (M⁺ - HF, 1), 57(100), 56(11), 55(16), 43(49), 42(22), 41(48), 39(13).
Difluoromethylcyclohexane: ¹H NMR (200 MHz, CDCl₃): 1.01-1.38 (m, 6 H), 1.61-1.84 (m, 5 H), 5.52 (td, ^² J [¹⁹F-¹H] = 56.7 Hz, J [¹H-¹H] = 4.2 Hz, 1 H, CHF₂). ¹⁹F NMR (178 MHz, CDCl₃): -123.82 (dd, ^² J [¹⁹F-¹H] = 56.8 Hz, ^³ J [¹⁹F-¹H] = 14.1 Hz).