Compound 21

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InChIKey DFBTWPHVMHWAPR-NGWIZALZSA-N

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

Diisobutylaluminum hydride (5.8 mL, 1M in hexane, 5.82 mmol) was added dropwise to a stirred solution of the E-enoate 20a (1.17 g, 1.94 mmol) in CH₂Cl₂ (50 mL) at −78 °C. The reaction was stirred at this temperature for an additional ca. 2 hours and then quenched by the slow addition of methanol (0.79 mL, 19.4 mmol). Silica gel was added to the reaction mixture and the solvent was removed in vacuo to afford the crude product immobilized on silica gel. Purification by flash chromatography (silica gel, 50–100% ethyl acetate in hexane) provided the allylic alcohol (1.01 g, 93%) as a colorless oil: R_f = 0.15 (TLC, 1:1 diethyl ether/petroleum ether); [α]_D²⁰ −0.6 (c = 1.50, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 5.70 (dt, J = 15.0, 7.3 Hz, 1H), 5.55 (dd, J = 15.7, 6.2 Hz, 1H), 5.46 (t, J = 6.6 Hz, 1H), 4.72 (q, J = 5.1 Hz, 1H), 4.65 (d, A of AB, J_AB = 6.8 Hz, 1H), 4.64 (d, A of AB, J_AB = 6.7 Hz, 1H), 4.63 (d, B of AB, J_AB = 6.7 Hz, 1H), 4.62 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.16 (dd, A of ABX, J_AB = 12.7 Hz, J_AX = 6.7 Hz, 1H), 4.13 (dd, B of ABX, J_AB = 12.9 Hz, J_BX = 6.3 Hz, 1H), 4.08–4.04 (m, 1H), 3.87 (app. quintet, J = 6.1Hz, 1H), 3.80–3.68 (m, 3H), 3.35 (s, 6H), 2.35 (dd, A of ABX, J_AB = 14.0 Hz, J_AX = 6.6 Hz, 1H), 2.29 (app. t, J = 6.3 Hz, 2H), 2.13 (dd, B of ABX, J_AB = 13.8 Hz, J_BX = 6.6 Hz, 1H), 1.75–1.70 (m, 2H), 1.70 (s, 3H), 1.66–1.49 (m, 4H), 1.36–1.29 (m, 1H), 1.33 (d, J = 5.2 Hz, 3H), 1.18 (d, J = 6.1 Hz, 3H), 0.86 (s, 9H), 0.05 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 135.53 (e), 132.70 (o), 128.27 (o), 126.49 (o), 98.56 (o), 95.86 (e), 95.37 (e), 76.76 (o), 74.83 (o), 74.68 (o), 71.22 (o), 67.44 (o), 59.38 (e), 55.72 (o), 55.46 (o), 46.02 (e), 45.92 (e), 43.10 (e), 38.04 (e), 36.65 (e), 26.06 (o), 21.31 (o), 21.27 (o), 18.17 (e), 17.04 (o), −3.86 (o), −3.92 (o); IR (neat) 3375 (br, w), 2929 (w), 2886 (w), 2856 (w), 1669 (w), 1442 (w), 1409 (w), 1375 (w), 1255 (w), 1130 (m), 1097 (m), 1032 (s), 969 (m), 946 (m), 918 (m), 834 (m), 774 (m) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₂₉H₅₆O₈NaSi 583.3642, found 583.3651.

Tetrapropylammonium perruthenate (32 mg, 5 mol%) was added to a suspension of the allylic alcohol (1.01 g, 1.81 mmol), N-methylmorpholine N-oxide (424 mg, 3.62 mmol) and 4Å molecular sieves (2.0 g) in CH2Cl2 (50 mL) at room temperature. The reaction mixture was stirred for ca. 4 hours, quenched by the addition of silica gel and concentrated in vacuo to afford the crude product immobilized on silica gel. Purification by flash chromatography (silica gel, 30–50% diethyl ether in petroleum ether) provided the α,β-unsaturated aldehyde (0.98 g, 97%) as a colorless oil: Rf = 0.30 (TLC, 1:1 diethyl ether/petroleum ether); [α]2D3 −3.4 (c = 1.02, CHCl3); 1H NMR (500 MHz, CDCl₃) δ 10.00 (d, J = 8.0 Hz, 1H), 5.91 (dd, J = 8.1, 1.0 Hz, 1H), 5.71 (dt, J = 14.9, 7.2 Hz, 1H), 5.54 (dd, J = 15.6, 6.2 Hz, 1H), 4.72 (q, J = 5.1 Hz, 1H), 4.65 (d, A of AB, J_AB = 6.9 Hz, 1H), 4.64 (d, A of AB, J_AB = 6.9 Hz, 1H), 4.63 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.62 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.11–4.06 (m, 1H), 3.89–3.83 (m, 2H), 3.75–3.67 (m, 2H), 3.37 (s, 6H), 2.47 (dd, A of ABX, J_AB = 14.4 Hz, J_AX = 7.8 Hz, 1H), 2.31 (dd, B of ABX, J_AB = 14.9 Hz, J_BX = 4.7 Hz, 1H), 2.29 (app. t, J = 6.3 Hz, 2H), 2.20 (d, J = 1.2 Hz, 3H), 1.71 (ddd, J = 13.8, 7.4, 6.1 Hz, 1H), 1.63 (ddd, J = 14.1, 7.8, 5.2 Hz, 1H), 1.58–1.48 (m, 3H), 1.39 (app. dt, J = 13.1, 11.3 Hz, 1H), 1.31 (d, J = 5.1 Hz, 3H), 1.17 (d, J = 6.2 Hz, 3H), 0.86 (s, 9H), 0.05 (s, 6H); 13C NMR (125 MHz, CDCl₃) δ 191.21 (o), 159.91 (e), 132.33 (o), 129.31 (o), 128.59 (o), 98.64 (o), 95.89 (e), 95.38 (e), 76.58 (o), 74.80 (o), 74.16 (o), 71.20 (o), 67.44 (o), 55.74 (o), 55.47 (o), 46.59 (e), 46.04 (e), 43.11 (e), 38.03 (e), 36.75 (e), 26.07 (o), 21.28 (o), 21.22 (o), 18.53 (o), 18.19 (e), −3.84 (o), −3.91 (o); IR (neat) 2929 (w), 2886 (w), 2856 (w), 1675 (m), 1634 (w), 1442 (w), 1409 (w), 1375 (w), 1255 (m), 1098 (m), 1031 (s), 917 (m), 834 (m), 774 (m) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₂₉H₅₄O₈NaSi 581.3486, found 581.3509.

Sodium bis(trimethylsilyl)amide (2.32 mL, 1M in THF, 2.32 mmol) was added dropwise to a stirred solution of the phosphonate 6 (0.817 g, 2.32 mmol) in THF (35 mL) at −78 °C resulting in a dark-blue solution. The ylide was allowed to form in the dark for ca. 1.5 hours and then a solution of the a,b-unsaturated aldehyde (0.96 g, 1.72 mmol) in THF (10 mL) was added slowly over ca. 15 minutes. The resulting mixture stirred for ca 30 minutes, then quenched by the addition of silica gel and the reaction concentrated in vacuo to afford the crude product immobilized on silica gel. Purification by flash chromatography (silica gel, 20–100% diethyl ether in petroleum ether) furnished the monomer 21 (1.33 g, 98%) as a yellow syrup: Rf = 0.50 (TLC, 1:1 diethyl ether/petroleum ether); [α]_D²⁰ −16.3 (c = 0.50, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 7.73 (d, J = 15.5 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 6.86 (dd, J = 15.5, 9.7 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.53–6.43 (m, 3H), 6.26 (dd, J = 14.7, 9.7 Hz, 1H), 5.97 (d, J = 11.2 Hz, 1H), 5.71 (dt, J = 14.9, 7.4 Hz, 1H), 5.56 (dd, J = 15.7, 6.1 Hz, 1H), 4.74 (q, J = 5.1 Hz, 1H), 4.66 (d, A of AB, J_AB = 6.7 Hz, 1H), 4.65 (d, A of AB, J_AB = 6.6 Hz, 1H), 4.63 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.62 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.10–4.04 (m, 1H), 3.88 (app. quintet, J = 6.1 Hz, 1H), 3.80–3.68 (m, 3H), 3.36 (s, 6H), 2.44 (dd, A of ABX, J_AB = 13.7 Hz, JAX = 6.2 Hz, 1H), 2.29 (app. t, J = 6.1 Hz, 2H), 2.20 (dd, B of ABX, J_AB = 13.7 Hz, J_BX = 6.7 Hz, 1H), 1.84 (s, 3H), 1.75–1.70 (m, 1H), 1.71 (s, 6H), 1.67–1.49 (m, 4H), 1.38–1.30 (m, 1H), 1.34 (d, J = 5.1 Hz, 3H), 1.18 (d, J = 6.2 Hz, 3H), 0.87 (s, 9H), 0.06 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 160.59 (e), 157.11 (e), 141.89 (e), 136.52 (e), 135.75 (o), 135.04 (o), 133.70 (o), 132.74 (o), 132.69 (o), 131.58 (o), 130.52 (o), 129.52 (o), 128.25 (o), 128.03 (o), 120.62 (o), 115.87 (o), 110.57 (e), 105.25 (e), 98.57 (o), 95.83 (e), 95.37 (e), 76.77 (o), 74.98 (o), 74.79 (o), 71.19 (o), 67.44 (o), 55.71 (o), 55.45 (o), 46.54 (e), 46.01 (e), 43.10 (e), 38.03 (e), 36.68 (e), 26.06 (o), 25.75 (o), 25.74 (o), 21.31 (o), 21.28 (o), 18.17 (e), 17.75 (o), −3.86 (o), −3.90 (o); IR (neat) 2987 (w), 2929 (m), 2856 (w), 1732 (w), 1666 (w), 1574 (w), 1474 (m), 1444 (w), 1378 (w), 1271 (m), 1249 (w), 1209 (w), 1140 (m), 1126 (m), 1040 (s), 836 (w), 775 (w) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₄₄H₆₈O₁₀NaSi 807.4479, found 807.4518.