Compound 4

View in PubChem | MDL Molfile | ChemDraw

InChIKey YQBVTKFFGXWKMA-SQNIBIBYSA-N

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

A solution of diiodomethane (1.91 mL, 23.67 mmol) in THF (6 mL) was added dropwise to a stirred suspension of samarium powder (7.12 g, 47.3 mmol) in THF (114 mL) at room temperature and the resulting mixture was stirred for ca. 2 hours. The acyclic ketone 11 (2.80 g, 10.76 mmol) in methanol (12 mL) was then added to the freshly prepared samarium diiodide solution and the resulting reaction mixture stirred at room temperature overnight. The reaction mixture was then filtered through Celite and the filtrate partitioned between saturated aqueous Na₂S₂O₃ solution and diethyl ether. The combined organic phases were washed with saturated aqueous NaCl solution, dried (MgSO₄), filtered and concentrated in vacuo to afford the crude product. Purification by flash chromatography (silica gel, 20–60% diethyl ether in petroleum ether) provided the secondary alcohol (2.60 g, 92%) as a colorless oil: R_f = 0.30 (TLC, 2:3 diethyl ether/petroleum ether); [α]_D²² +15.8 (c = 0.88, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 5.78 (ddt, J = 17.2, 10.2, 7.2 Hz, 1H), 5.09–5.03 (m, 2H), 4.69 (d, A of AB, J_AB = 6.8 Hz, 1H), 4.68 (d, A of AB, J_AB = 6.6 Hz, 1H), 4.65 (d, B of AB, J_AB = 6.8 Hz, 1H), 4.62 (d, B of AB, J_AB = 6.8 Hz, 1H), 4.12–4.06 (m, 1H), 4.00–3.93 (m, 1H), 3.89 (ddt, J = 8.8, 5.9, 3.4 Hz, 1H), 3.38 (s, 3H), 3.37 (m, 3H), 3.10 (br s, 1H), 2.36–2.24 (m, 2H), 1.60–1.49 (m, 4H), 1.19 (d, J = 6.3 Hz, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 134.52 (o), 117.61 (e), 96.47 (e), 95.55 (e), 75.06 (o), 71.29 (o), 64.34 (o), 55.85 (o), 55.61 (o), 44.46 (e), 41.97 (e), 39.78 (e), 20.78 (o); IR (neat) 3484 (br, w), 3073 (w), 2932 (w), 2846 (w), 2820 (w), 1641 (w), 1442 (w), 1377 (w), 1211 (m), 1145 (m), 1097 (m), 1028 (s), 914 (s) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₁₃H₂₆O₅Na 285.1678, found 285.1673.

Imidazole (244 mg, 3.58 mmol) and tert-butyldimethylsilyl chloride (0.54 g, 3.58 mmol) were sequentially added to a stirred solution of the secondary alcohol (0.47 g, 1.79 mmol) in DMF (6 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred for ca. 33 hours, then quenched with MeOH. The reaction mixture was diluted with 30% diethyl ether in petroleum ether, washed with a saturated aqueous NH4Cl solution, dried (MgSO₄), filtered and concentrated in vacuo to afford the crude product. Purification by flash chromatography (silica gel, 0–5% diethyl ether in petroleum ether) furnished the tert-butyldimethylsilyl ether 4 (0.65 g, 96%) as a colorless oil: R_f = 0.80 (TLC, 3:2 diethyl ether/petroleum ether); [α]_D²² +15.2 (c = 1.18, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 5.81 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.11–5.06 (m, 2H), 4.67 (d, A of AB, J_AB = 7.1 Hz, 1H), 4.66 (d, A of AB, J_AB = 6.9 Hz, 1H), 4.65 (d, B of AB, J_AB = 7.1 Hz, 1H), 4.63 (d, B of AB, J_AB = 6.9 Hz, 1H), 3.92–3.86 (m, 1H), 3.79–3.70 (m, 2H), 3.37 (s, 3H), 3.36 (s, 3H), 2.36–2.26 (m, 2H), 1.74 (ddd, A of ABXY, J_AB = 13.7 Hz, J_AX = 7.7 Hz, J_AY = 6.1 Hz, 1H), 1.67–1.63 (m, 1H), 1.59 (ddd, J = 14.1, 7.1, 4.8 Hz, 1H), 1.53 (ddd, B of ABXY J_AB = 13.8 Hz, J_BX = 6.7 Hz, J_BY = 5.5 Hz, 1H), 1.18 (d, J = 6.2 Hz. 3H), 0.87 (s, 9H), 0.06 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 134.60 (o), 117.51 (e), 95.91 (e), 95.37 (e), 74.84 (o), 71.21 (o), 67.41 (o), 55.71 (o), 55.47 (o), 46.02 (e), 43.03 (e), 39.66 (e), 26.06 (o), 21.27 (o), 18.19 (e), −3.87 (o), −3.93 (o); IR (neat) 2929 (w), 2886 (w) , 2857 (w), 1642 (w), 1464 (w), 1378 (w), 1255 (w), 1153 (m), 1097 (m), 1034 (s), 917 (m), 834 (m), 808 (w), 774 (m) cm⁻¹; HRMS (ESI, [M+Na]⁺) calcd for C₁₉H₄₀O₅NaSi 399.2543, found 399.2552.