A SIMPLE AND EFFICIENT PREPARATION OF (ARYLPHOSPHINYL)-METHYLPHOSPHONATES

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• A representative experimental is given for 3d: A mixture of methyl 4-iodobenzoate (1d) (160 mg, 0.607 mmol), diethyl (ethoxyphosphinyl)methylphosphonate (2) (163 mg, 0.668 mmol), NMM (0.20 mL, 1.82 mmol) and Pd(PPh3)4 (34 mg) in acetonitrile (2 mL) were stirred at 90°C in a sealed tube under an atmosphere of Ar for 3 h. The reaction mixture was then concentrated, and the residue partitioned between 0.5 N aq HCl and CH2Cl2. The layers were separated, and the aqueous layer was reextracted three times with CH2Cl2. The combined extracts were washed with saturated aq NaCl, dried over MgSO4, and concentrated. The crude product was purified by flash chromatography on silica gel. Gradient elution from 10% MeOH–CH2Cl2 to 25% MeOH–CH2Cl2 afforded 177 mg (77%) of 3d as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.16–8.13 (m, 2H), 7.97–7.90 (m, 2H), 4.24–4.05, 4.04–3.97 (m, 6H), 3.95 (s, 3H), 2.73–2.59 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.1 (d, J = 7 Hz), 19.1 (d, J = 7 Hz); Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 379 [M + H]. Anal. Calcd. for C15H24O7P2: C, 47.62; H, 6.39. Found: C, 47.59; H, 6.32. Products 3a–c: 1H NMR (300 MHz, CDCl3) δ 7.89–7.82 (m, 2H), 7.59–7.46 (m, 3H), 4.21–3.95 (m, 6H), 2.69–2.56 (m, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.8 (d, J = 8 Hz), 19.6 (d, J = 8 Hz); Electrospray mass spectrum (50 : 50 acetonitrile: water + 0.1% NH4OH): m/z 321 [M + H]. Anal. Calcd. for C13H22O5P2: C, 48.75; H, 6.92. Found: C, 48.72; H, 6.90. Products 3e,f: 1H NMR (300 MHz, CDCl3) δ 8.33 (dd, J = 8.7, 2.6 Hz, 2H), 8.09 (dd, J = 11.7, 8.7 Hz, 2H); 4.27–3.96 (m, 6H), 2.73–2.60 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 31.5, 18.6; Anal. Calcd. for C13H21NO7P2: C, 42.75; H, 5.80; N, 3.83. Found: C, 42.67; H, 5.70; N, 3.77. Product 3g: 1H NMR (300 MHz, CDCl3) δ 7.49–7.37 (m, 3H); 7.16–7.13 (m, 1H), 4.26–3.95 (m, 6H), 3.88 (s, 3H), 2.86–2.60 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 35.2, 19.4; Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 351 [M + H]. Anal. Calcd. for C14H24O6P2: C, 48.00; H, 6.91. Found: C, 47.84; H, 6.85. Product 3h: 1H NMR (300 MHz, CDCl3) δ 7.81 (dd, J = 12.0, 8.7 Hz, 2H), 7.02 (dd, J = 8.7, 2.9 Hz, 2H), 4.23–3.91 (m, 6H), 3.88 (s, 3H), 2.78–2.53 (m, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 34.8, 19.8; Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 351 [M + H]. Anal. Calcd. for C14H24O6P2: C, 48.00; H, 6.91. Found: C, 47.95; H, 6.90. Product 3i: 1H NMR (300 MHz, CDCl3) δ 7.77–7.62 (m, 4H), 4.21–3.92 (m, 6H), 2.67–2.53 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H), 1.31 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.0 (d, J = 7 Hz), 19.2 (d, J = 7 Hz); Anal. Calcd. for C31H21BrO5P2: C, 39.12; H, 5.30. Found: C, 39.00; H, 5.26.
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• The authors wish to thank Dr. Raji Sundaramoorthi for the preparation of 3i.
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