Compound 14

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InChIKey DTFMTZTYHDQYGA-PLSXKVAHSA-N

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

The alkyl iodide 13 (2.21 g, 5.94 mmol) and zinc dust (3.88 g, 59.4 mmol) were suspended in aqueous THF (25 mL, 1:4) and heated at reflux with vigourous stirring for ca. 1.5 hours. The reaction mixture was then cooled to room temperature, filtered through Celite and the filtrate partitioned between water and diethyl ether. The combined organic phases were dried (MgSO₄), filtered and concentrated in vacuo to afford the crude aldehyde (1.27 g, 99%) as a light yellow oil, which was used in the next reaction without further purification. Purification of a sample for characterization by flash chromatography (silica gel, 5-10% diethyl ether in petroleum ether) gave the aldehyde as a colorless oil: R_f = 0.40 (TLC, 1:9 diethyl ether/petroleum ether); [α]_D²³ −4.2 (c = 1.28, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 9.78 (t, J = 2.4 Hz, 1H), 5.88 (ddd, J = 16.9, 10.6, 6.2 Hz, 1H), 5.27 (app. dt, J = 16.9, 1.3 Hz, 1H), 5.12 (app. dt, J = 10.6, 1.3 Hz, 1H), 4.68–4.64 (m, 1H), 2.62 (ddd, A of ABMX, J_AB = 15.8 Hz, J_AM = 6.9 Hz, J_AX = 2.6 Hz, 1H), 2.53 (ddd, B of ABMX, J_AB = 15.9 Hz, J_BM = 5.1 Hz, J_BX = 2.2 Hz, 1H), 0.94 (t, J = 8.0 Hz, 9H), 0.60 (q, J = 8.1 Hz, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 210.59 (o), 140.16 (o), 114.98 (e), 69.40 (o), 51.47 (e), 6.85 (o), 4.95 (e); IR (neat) 2956 (w), 2913 (w), 2878 (w), 2730 (w), 1726 (m), 1644 (w), 1459 (w), 1414 (w), 1240 (w), 1134 (m), 1087 (m), 1004 (s), 925 (m), 818 (w), 725 (s) cm⁻¹; HRMS (ESI, [M+H]⁺) calcd for C₁₁H₂₃O₂Si 215.1462, found 215.1462.

The crude aldehyde (1.27 g, 5.92 mmol) and acetylmethylenetriphenylphosphorane (2.08 g, 6.52 mmol) were dissolved in toluene (40 mL) and the resulting reaction mixture heated at reflux for ca. 1 hour. The reaction was cooled to ambient temperature and concentrated in vacuo to afford the crude product. Purification by flash chromatography (silica gel, 0–5% diethyl ether in petroleum ether) provided the α,β-unsaurated ketone 14 (1.16 g, 77% over 2 steps from 13) as a colorless oil: R_f = 0.20 (TLC, 1:9 diethyl ether/petroleum ether); [α]_D²⁰ +8.1 (c = 1.00, CHCl₃); ¹H-NMR (500 MHz, CDCl₃) δ 6.78 (dt, J = 16.0, 7.4 Hz, 1H), 6.08 (dt, J = 16.0, 1.2 Hz, 1H), 5.81 (ddd, J = 17.0, 10.6, 6.3 Hz, 1H), 5.20 (app. dt, J = 17.1, 1.3 Hz, 1H), 5.09 (app. dt, J = 10.4, 1.2 Hz, 1H), 4.24 (app. q, J = 6.1 Hz, 1H), 2.42 (app. tt, J = 6.6, 1.5 Hz, 2H), 2.24 (s, 3H), 0.94 (t, J = 8.0 Hz, 9H), 0.61–0.56 (m, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 198.72 (e), 144.61 (o), 140.62 (o), 133.55 (o), 114.88 (e), 72.75 (o), 41.44 (e), 26.78 (o), 6.94 (o), 4.98 (e); IR (neat) 2956 (m), 2911 (m), 2878 (m), 1699 (w), 1678 (s), 1631 (w), 1459 (w), 1417 (w), 1361 (m), 1254 (m), 1128 (w), 1082 (m), 1006 (m), 981 (m), 924 (w), 745 (m) cm⁻¹; HRMS (CI, [M+NH4]⁺) calcd for C₁₄H₃₀O₂SiN 272.2046, found 272.2039.