Compound 20a

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InChIKey OJTFIUZFYQZWEX-PERUXTLISA-N

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

Triethyl phosphonoacetate (4.1 mL, 20.65 mmol) was added slowly to a suspension of sodium hydride (0.61 g, 60% in mineral oil, 16.5 mmol) in 1,2-dimethoxyethane (40 mL) and at room temperature and the reaction mixture stirred for ca. 1 hour. The mixture was then cooled to 0 °C and a solution of the ketone 19 (1.1 g, 2.07 mmol) in 1,2-dimethoxyethane (10 mL) was added and the resulting reaction mixture was stirred from 0 °C to room temperature for ca. 48 hours. The reaction was quenched by the addition of silica gel and the solvent removed in vacuo to afford the crude product immobilized on silica gel. Purification by flash chromatography (silica gel, 20–50% diethyl ether in petroleum ether) afforded the E-enoate 20a (0.78 g, 63%) and Z-enoate 20b (0.25 g, 20%) as colorless oils. The pure Z-enoate 20b (0.25 g, 0.42 mmol) was redissolved in THF (3 mL) and treated with a freshly prepared solution of lithium 4-methoxybenzenethiolate, which was prepared by the addition n-BuLi (0.33 mL, 1M in hexane) to p-MeOC₆H₄SH (0.51 mL, 4.15 mmol) in THF (3 mL) at 0 °C. The mixture was allowed to warm to room temperature overnight, quenched with silica gel and concentrated in vacuo to afford the addition product. Purification by flash chromatography (silica gel, 1–30% diethyl ether in petroleum ether) gave the corresponding 3-(arylthio)ester (0.295 g, 96%) as a pale yellow oil and the recovered Z-enoate 20b (5 mg, 2%). The sulphide (0.295 g, 0.40 mmol) was dissolved in CH₂Cl₂ (12 mL) and treated with a solution of m-chloroperoxybenzoic acid (0.11 g, 75%, 0.48 mmol) in CH₂Cl₂ (2 mL) at −78 °C. The resulting mixture was allowed to warm to room temperature and stirred for ca. 8 days to provide a mixture of the E/Z-enoates 20a and 20b (1.3:1), which was quenched by the slow addition of a saturated aqueous sodium bicarbonate solution at 0 °C and partitioned with diethyl ether. The combined organic phases were dried (MgSO₄), filtered and concentrated in vacuo to afford the crude product. Purification by flash chromatography (silica gel, 1–30% diethyl ether in petroleum ether) furnished the E-enoate 20a (0.12 g, 10%) and Z-enoate 20b (0.095 g, 8%). The recovered Z-enoate 20b (0.095g, 0.16 mmol) was resubjected to the equilibration sequence to provide an overall yield of the E-enoate 20a (0.942 g, 76%): R_f = 0.46 (TLC, 1:1 diethyl ether/petroleum ether); [α]_D²⁰ +3.5 (c = 0.70, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 5.74–5.68 (m, 1H), 5.71 (d, J = 0.9 Hz, 1H), 5.55 (dd, J = 15.5, 6.2 Hz, 1H), 4.73 (q, J = 5.1 Hz, 1H), 4.66 (d, A of AB, J_AB = 6.9 Hz, 1H), 4.65 (d, A of AB, J_AB = 6.7 Hz, 1H), 4.64 (d, B of AB, J_AB = 6.5 Hz, 1H), 4.63 (d, B of AB, J_AB = 6.9 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 4.10–4.07 (m, 1H), 3.90–3.80 (m, 2H), 3.76–3.68 (m, 2H), 3.36 (s, 6H), 2.46 (dd, A of ABX, J_AB = 13.8 Hz, J_AX = 7.0 Hz, 1H), 2.30 (app t, J = 6.2 Hz, 2H), 2.23 (dd, B of ABX, J_AB = 13.9 Hz, J_BX = 6.0 Hz, 1H), 2.19 (d, J = 1.2 Hz, 3H), 1.72 (ddd, J = 13.7, J = 7.6, J = 6.1 Hz, 1H), 1.66–1.50 (m, 4H), 1.36 (app. dt, J = 13.1, J = 11.3 Hz, 1H), 1.33 (d, J = 5.1 Hz, 3H), 1.27 (t, J = 7.2 Hz, 3H), 1.18 (d, J = 6.2 Hz, 3H), 0.87 (s, 9H), 0.06 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 166.67 (e), 155.49 (e), 132.49 (o), 128.45 (o), 118.20 (o), 98.63 (o), 95.88 (e), 95.39 (e), 76.64 (o), 74.81 (o), 74.21 (o), 71.21 (o), 67.45 (o), 59.76 (e), 55.73 (o), 55.48 (o), 47.15 (e), 46.04 (e), 43.12 (e), 38.05 (e), 36.68 (e), 26.07 (o), 26.06 (o), 21.29 (o), 21.26 (o), 19.42 (e), 14.45 (o), −3.84 (o), −3.90 (o); IR (neat) 2930 (w), 2886 (w), 2857 (w), 1716 (m), 1649 (w), 1444 (w), 1408 (w), 1374 (w), 1255 (w), 1221 (m), 1140 (m), 1127 (m), 1096 (m), 1032 (s), 969 (m), 945 (m), 918 (m), 834 (m), 774 (m) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₃₁H₅₈O₉NaSi 625.3748, found 625.3723.