Compound 6

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InChIKey IHKMSIIPHCIKIZ-PDTNFJSOSA-N

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Phosphorus tribromide (0.7 mL, 7.41 mmol) in CH₂Cl₂ (5 mL) was added via addition funnel to a stirred solution of the dienol 18 (1.93 g, 7.41 mmol) in CH₂Cl₂ (35 mL) at 0 °C. The resulting clear yellow solution was stirred at 0 °C for ca. 40 minutes, which resulted in the formation of a suspension. The reaction mixture was quenched with a saturated aqueous NaHCO₃ solution and partitioned with ethyl acetate. The combined organic phases were dried (MgSO₄), filtered and concentrated in vacuo to afford the crude product. The crude product was suspended in ethyl acetate, filtered and the solid washed with diethyl ether to provide the dienyl bromide (1.90 g, 79%) as a yellowish solid: mp = 143–145 °C; R_f = 0.4 (TLC, 3:7 ethyl acetate/petroleum ether); ¹H-NMR (500 MHz, CDCl₃) δ 7.74 (d, J = 15.6 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 6.74 (dd, J = 15.6, 10.7 Hz, 1H), 6.57 (dd, J = 15.0, 10.7 Hz, 1H), 6.04 (dt, J = 15.2, 7.7 Hz, 1H), 4.09 (d, J = 8.0 Hz, 2H), 1.71 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 160.51 (e), 157.10 (e), 141.26 (e), 135.30 (o), 132.37 (o), 131.52 (o), 130.66 (o), 121.16 (o), 116.72 (o), 110.98 (e), 105.46 (e), 33.20 (e), 25.78 (o); IR (neat) 3063 (w), 3002 (w), 2942 (w), 1720 (s), 1681 (w), 1607 (w), 1593 (w), 1572 (m), 1474 (m), 1320 (m), 1272 (m), 1235 (m), 1203 (m), 1048 (w), 1021 (m), 1004 (m), 967 (w), 929 (w), 826 (w), 799 (w), 687 (w) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₁₅H₁₅O₃Na⁷⁹Br 345.0102, found 345.0099.

The dienyl bromide (1.25 g, 3.87 mmol) and trimethyl phosphite (2.29 mL, 19.34 mmol) were dissolved in toluene (5 mL) and heated at reflux for ca. 3 hours. The resulting homogeneous yellowish reaction mixture was cooled to room temperature, diluted with diethyl ether and the precipitate filtered to afford the phosphonate 6 (1.10 g, 81%) as a light yellow solid: mp = 79–80 °C; Rf = 0.10 (TLC, 1:3 ethyl acetate/hexane); ¹H-NMR (500 MHz, CDCl₃) δ 7.66 (dd, J = 15.7, 1.9 Hz, 1H), 7.44 (t, J = 8.1 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.76 (dd, J = 15.6, 10.7 Hz, 1H), 6.46 (ddd, J = 15.2, 10.5 Hz, ⁴JH,P = 4.8 Hz, 1H), 5.82 (app. dq, J = 15.1, 7.6 Hz, ³JH,P = 7.6 Hz, 1H), 3.77 (d, ³JH,P = 10.8 Hz, 6H), 2.74 (dd, ²JH,P = 22.8 Hz, J = 7.8 Hz, 2H), 1.71 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 160.56 (e), 157.06 (e), 141.60 (e, d, J_C,P = 1.8 Hz), 135.72 (o, d, J_C,P = 14.8 Hz), 135.24 (o), 132.40 (o, d, J_C,P = 4.9 Hz), 130.12 (o, d, J_C,P = 4.6 Hz), 124.17 (o, d, J_C,P = 12.9 Hz), 120.93 (o), 116.32 (o), 110.85 (e), 105.36 (e), 52.96 (o, d, J_C,P = 8.5 Hz), 30.16 (e, d, J_C,P = 140.8 Hz), 25.76 (o); IR (neat) 2999 (w), 2954 (w), 2851 (w), 1725 (s), 1595 (w), 1574 (m), 1475 (m), 1391 (w), 1378 (w), 1318 (m), 1271 (s), 1209 (m), 1039 (s), 1029 (s), 812 (m) cm⁻¹; HRMS (CI, [M+NH4]⁺) calcd for C₁₇H₂₅NO₆P 370.1420, found 370.1414.