Synlett 2007(7): 1148-1152  
DOI: 10.1055/s-2007-977439
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© Georg Thieme Verlag Stuttgart · New York

Regioselective Anodic Fluorination of α-(Arylthio)benzylphosphonate Esters, α-(Arylthio)methylphosphonate Esters and Their Analogues

Asami Hidaka, Bakenova Zagipa, Hirokatsu Nagura, Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan
Fax: +81(45)9245406; e-Mail: fuchi@echem.titech.ac.jp;
Further Information

Publication History

Received 5 January 2007
Publication Date:
13 April 2007 (online)

Abstract

Regioselective anodic α-fluorination of α-(arylthio)benzylphosphonate esters and [(arylthio)methyl]- and [(heteroaryl­thio)methyl]phosphonate esters was successfully carried out at a glassy carbon anode or platinum anode in dimethoxyethane and ­nitromethane to provide the corresponding α-fluorophosphonate ­esters in excellent to moderate yields.

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Typical procedure for anodic fluorination: Anodic oxidation of 1 (0.5 mmol) was carried out in an undivided cell equipped with a GC plate anode (2 × 2 cm2) and platinum plate cathode (2 × 2 cm2) in Et4NF·3HF-DME (1 M, 5 mL) at r.t. Constant current (2.5 mA/cm2) was passed until the starting material 1 was almost consumed (monitored by TLC). After electrolysis, the electrolytic solution was passed through a short column filled with silica gel using EtOAc as an eluent to remove fluoride salts. The eluent was evaporated under reduced pressure, and the residue was further purified by column chromatography on silica gel using EtOAc to give pure fluorinated products. The products were identified by spectroscopic data.

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Diethyl α-Fluoro-α-(phenylthio)benzylphosphonate (2a): 1H NMR (CDCl3): δ = 1.11 (t, J = 7.09 Hz, 3 H), 1.31 (t, J = 7.09 Hz, 3 H), 3.69-3.79 (m, 1 H), 3.91-4.02 (m, 1 H), 4.05-4.22 (m, 2 H), 7.13-7.55 (m, 10 H); 13C NMR (CDCl3): δ = 16.3 (d, J PC = 11.7 Hz), 16.4 (d, J PC = 11.7 Hz), 64.4 (dd, J FC = 0.02 Hz, J PC = 7.27 Hz), 64.6 (dd, J FC = 0.02 Hz, J PC = 7.27 Hz), 106.2 (dd, J PC = 175.7 Hz, J FC = 234.3 Hz), 126.3 (t, J = 3.91 Hz), 126.4 (t, J = 3.91 Hz), 127.7 (t, J PC = J FC = 1.68 Hz), 128.3, 128.7 (d, J = 1.68 Hz), 129.0, 134.8 (d, J = 22.4 Hz), 135.9 (d, J = 2.24 Hz); 19F NMR (CDCl3): δ = -67.3 (d, J PF = 90.4 Hz); HRMS: m/z calcd for C17H20FO3PS: 354.0855; found: 354.0843.

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Diethyl α-Fluoro-α-(phenylthio)-4-methoxybenzylphos-phonate (6): 1H NMR (CDCl3): δ = 1.14 (t, J = 6.75 Hz, 3 H), 1.32 (t, J = 6.75 Hz, 3 H), 3.80 (s, 3 H), 3.91-3.97 (m, 1 H), 4.07-4.19 (m, 1 H), 4.29-4.33 (m, 2 H), 6.83 (d, J = 8.64 Hz, 2 H), 7.36-7.58 (m, 5 H), 7.63 (d, J = 7.83 Hz, 2 H); 13C NMR (CDCl3): δ = 16.1 (d, J PC = 5.56 Hz), 16.3 (d, J PC = 5.56 Hz), 64.6 (dd, J FC = 1.68 Hz, J PC = 7.25 Hz), 65.2 (d, J PC = 6.70 Hz), 106.4 (dd, J PC = 162.3 Hz, J FC = 229.2 Hz), 113.4 (t, J PC = J FC = 1.68 Hz), 113.6 (t, J PC = J FC = 1.68 Hz), 127.7 (d, J PC = 3.35 Hz), 127.8 (d, J PC = 3.35 Hz), 130.4, 134.1, 134.5 (d, J = 2.80 Hz), 160.6; 19F NMR (CDCl3): δ = -89.0 (d, J PF = 68.3 Hz); HRMS: m/z calcd for C18H22FO6PS: 416.0859; found: 416.0862.

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Diethyl α-Fluoro-α-(phenylthio)-4-iodebenzylphos-phonate (7): 1H NMR (CDCl3): δ = 1.09 (t, J = 7.09 Hz, 3 H), 1.29 (t, J = 7.09 Hz, 3 H), 3.69-3.78 (m, 1 H), 3.93-4.01 (m, 1 H), 4.09-4.22 (m, 2 H), 7.13-7.25 (m, 5 H), 7.40 (d, J = 7.03 Hz, 2 H), 7.54 (d, J = 7.03 Hz, 2 H); 13C NMR (CDCl3): δ = 16.2 (d, J FC = 11.7 Hz), 16.4 (d, J PC = 11.7 Hz), 64.3 (dd, J FC = 1.68 Hz, J PC = 7.27 Hz), 64.6 (dd, J FC = 1.68 Hz, J PC = 7.27 Hz), 106.0 (dd, J PC = 174.6 Hz, J FC = 233.7 Hz), 126.3 (t, J PC = J FC = 7.83 Hz), 126.4 (t, J PC = J FC = 7.83 Hz), 127.7 (t, J PC = J FC = 1.68 Hz), 128.3, 128.6 (d, J = 7.83 Hz), 129.0, 134.9 (d, J = 22.9 Hz), 135.8 (d, J = 1.68 Hz); 19F NMR (CDCl3): δ = -67.3 (d, J PF = 64.5 Hz); HRMS: m/z calcd for C17H19FIO3PS: 479.9821; found: 479.9809.

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Diethyl [Fluoro(2-naphthyl)(phenylthio)methyl]phos-phonate (8): 1H NMR (CDCl3): δ = 1.07 (t, J = 7.02 Hz, 3 H), 1.28 (t, J = 7.02 Hz, 3 H), 3.65-3.78 (m, 1 H), 3.91-4.04 (m, 1 H), 4.12-4.25 (m, 2 H), 7.07-7.16 (m, 3 H), 7.41-7.47 (m, 4 H), 7.47-7.79 (m, 4 H), 7.94 (m, 1 H); 13C NMR (CDCl3): δ = 16.3 (d, J PC = 5.56 Hz), 16.4 (d, J PC = 5.56 Hz), 64.5 (d, J PC = 7.26 Hz), 65.2 (d, J PC = 7.26 Hz), 106.2 (dd, J PC = 176.8 Hz, J FC = 234.3 Hz), 124.0 (dd, J PC = 2.80 Hz, J FC = 5.59 Hz), 125.8 (dd, J PC = 5.59 Hz, J FC = 9.50 Hz), 126.1, 126.5, 127.4, (d, J FC = 6.10 Hz), 128.4, 128.5, 128.8, 132.4 (t, J FC = 11.1 Hz), 132.8, 135.8; 19F NMR (CDCl3): δ = -65.9 (d, J PF = 92.5 Hz); HRMS: m/z calcd for C21H22FO3PS: 404.1011; found: 404.1007.

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Diethyl α-Fluoro-α-(2-pyridylthio)benzylphosphonate (11): 1H NMR (CDCl3): δ = 1.14 (t, J = 7.02 Hz, 3 H), 1.26 (t, J = 7.02 Hz, 3 H), 3.89 (q, J = 7.29 Hz, 1 H), 4.14 (q, J = 6.48 Hz, 1 H), 4.34 (q, J = 6.9 Hz, 2 H), 6.90-7.56 (m, 8 H), 8.34 (d, J = 4.86 Hz, 1 H); 13C NMR (CDCl3): δ = 16.33 (d, J PC = 10.62 Hz), 16.39 (d, J PC = 10.65 Hz), 64.7 (dd, J PC = 7.29 Hz, J FC = 31.02 Hz), 65.1 (dd, J PC = 6.78 Hz, J FC = 22.87 Hz), 106.21 (dd, J PC = 170.11 Hz, J FC = 230.11 Hz), 126,3 (t, J PC = 3.91 Hz), 126.6 (t, J PC = 3.91 Hz), 127.9 (s), 128.2 (t, J = 1.69 Hz), 129.1 (t, J = 1.68 Hz), 134.5 (d, J = 22.42 Hz), 149.19 (s); 19F NMR (CDCl3): δ = -66.28 (d, J PF = 92.2 Hz); HRMS: m/z calcd for C16H19FNO3PS: 355.0807; found: 355.0800.

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Diethyl α-Fluoro-α-(4-pyridylthio)benzylphosphonate (12): 1H NMR (CDCl3): δ = 1.13 (t, J = 7.02 Hz, 3 H), 1.29 (t, J = 7.02 Hz, 3 H), 3.86 (q, J = 7.29 Hz, 1 H), 4.01 (q, J = 7.02 Hz, 1 H), 4.15 (q, J = 6.95 Hz, 2 H), 7.16-7.53 (m, 5 H), 7.57 (d, J = 6.92 Hz, 2 H), 8.34 (d, J = 5.21 Hz, 2 H); 13C NMR (CDCl3): δ = 16.30 (d, J PC = 10.62 Hz), 16.38 (d, J PC = 10.62 Hz), 64.76 (dd, J PC = 7.25 Hz, J FC = 22.85 Hz), 65.1 (dd, J PC = 6.71 Hz, J FC = 22.31 Hz), 106.1 (dd, J PC = 169.52 Hz, J FC = 229.8 Hz), 126,3 (t, J PC = 3.91 Hz), 126.6 (t, J PC = 3.91 Hz), 127.6 (s), 128.1 (t, J = 1.68 Hz), 128.9 (t, J = 1.68 Hz), 134.1 (d, J = 22.36 Hz), 149.17 (s); 19F NMR (CDCl3): δ = -66.67 (d, J PF = 86.9 Hz); HRMS: m/z calcd for C16H19FNO3PS: 355.0807; found: 355.0789.

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Diethyl [Fluoro(4-pyridylthio)methyl]phosphonate (19): 1H NMR (CDCl3): δ = 1.37 (t, J = 7.09 Hz, 6 H), 4.24-4.36 (m, 4 H), 6.19 (dd, J HF = 53.6 Hz, J HP = 7.56 Hz, 1 H, CHF), 7.34 (d, J = 1.48 Hz, 1 H), 7.36 (d, J = 1.48 Hz, 1 H), 8.53 (d, J = 1.48 Hz, 1 H), 8.55 (d, J = 1.48 Hz, 1 H); 13C NMR (CDCl3): δ = 16.65 (d, J PC = 6.15 Hz), 64.5 (dd, J PC = 6.70 Hz, J FC = 11.7 Hz), 93.7 (dd, J PC = 177.2 Hz, J FC = 232.5 Hz, CHF), 122.9 (d, J FC = 1.68 Hz), 144.5 (d, J PC = 2.80 Hz), 144.7 (d, J PC = 2.80 Hz), 149.9 (s); 19F NMR (CDCl3): δ = -93.6 (dd, J PF = 83.3 Hz, J HF = 53.6 Hz); HRMS: m/z calcd for C10H15FNO3PS: 279.0494; found: 279.0489.