Stereoselective Synthesis of (E)-α-Fluorovinylphosphonates from α,α-Difluorophosphonates

Abstract

α,α-Difluorophosphonates, which are readily available from alkyl halides and diethyl difluoromethylphosphonate, undergo elimination of hydrogen fluoride using alkali metal alkoxides to provide α-fluorovinylphosphonates in high yields and E/Z selectivities.

Key words

phosphonate - fluorine - elimination

References and Notes

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17

Synthesis of ( E )-1a; Typical Procedure. Trifluoroethanol (0.16 mL, 2.25 mmol, 5 equiv) was added to a mixture of sodium metal (29 mg, 1.26 mmol, 2.8 equiv) in anhydrous THF (2 mL). The mixture was stirred under argon until all sodium reacted. Solvent and excess alcohol were removed under reduced pressure and anhydrous DMF (1.5 mL) was added, followed by the addition of 2a (125 mg, 0.45 mmol, 1 equiv). After stirring for 2 h at r.t., saturated aqueous NH₄Cl (10 mL) was added, the product was extracted into Et₂O (3 × 15 mL) and the combined organic phase was washed with brine (10 mL), dried over anhydrous MgSO₄, and solvent was removed under reduced pressure. Purification of the crude product by silica gel flash chromatography (EtOAc-hexanes, 2:3), afforded pure (E)-1a (115 mg, 98%) as a colorless oil.^¹³a R _f = 0.47 (EtOAc-hexanes, 2:3); IR (film): 3092, 3058, 3029, 2985, 2933, 2910, 1577, 1495, 1450, 1393, 1265, 1165, 1022, 757, 694 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 1.39 (dt, J = 7.1, 0.4 Hz, 6 H, 2 × CH₃), 4.16-4.27 (m, 4H, 2 × CH₂), 6.75 (dd, J = 42.3, 8.6 Hz, 1 H, CH), 7.33-7.43 (m, 3 H, C_ArH), 7.61-7.63 (m, 2 H, C_ArH); ^¹³C NMR (100 MHz, CDCl₃): δ = 16.3 (d, J = 6.2 Hz, CH₃), 63.2 (d, J = 5.4 Hz, CH₂), 123.1 (d, J = 29.9 Hz, CH), 128.7 (C_ArH), 129.5 (d, J = 2.5 Hz, C_ArH), 130.0 (d, J = 7.7 Hz, C_ArH), 131.1-131.3 (m, C_Ar), 150.0 (dd, J = 286.1, 236.1 Hz, CF); ^¹9F NMR (376 MHz, CDCl₃): δ = -127.1 (dd, J = 97.8, 42.3 Hz); ^³¹P NMR (162 MHz, CDCl₃): δ = 5.94 (d, J = 97.8 Hz); MS (EI): m/z (%) = 258 (95) [M]⁺, 195 (17), 185 (70), 167 (18), 149 (89), 129 (64), 118 (61), 102 (100), 93 (30), 65 (45); HRMS (ESI⁺): m/z
[M + H]⁺ calcd for C₁₂H₁₇FO₃P: 259.08939; found: 259.08926.