Compound 1a

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

General procedure A: To a suspension of K₂CO₃ (40 mmol) and TBAI (if X ≠ I, 3 mmol) in DMF (10 mL) under vigorous stirring was added the ketoester or malonate (10 mmol) at room temperature. After 5 min, the appropriate homoallylic or propargylic halide (23 mmol) was added and the mixture was stirred at room temperature or 60 °C until TLC monitoring showed completion (16-72 h). The mixture was diluted with Et₂O (60 mL) and washed with H₂O (3 x 75 mL), and the aqueous layers were extracted with Et₂O (30 mL). The combined organic layers were washed with brine (2 x 15 mL), dried over MgSO₄ and concentrated. The crude product was purified as described below to afford the title compound.

Prepared according to general procedure above using methyl acetoacetate (1.09 mL, 10 mmol), 4-bromobut-1-ene (2.40 mL, 23 mmol), K₂CO₃ (5.32 g, 40 mmol) and TBAI (1.11 g, 3 mmol) at room temperature. After a reaction time of 36 h, purification by careful column chromatography (pentane/Et₂O 98:2 to 95:5) gave 1a as a colorless oil (1.44 g, 64%). ¹H NMR (400 MHz, CDCl₃) δ 5.83–5.71 (m, 2 H, CH=CH₂), 5.03 (d, 2 H, J = 17.2 Hz, CH=CH_cisH_trans), 4.97 (d, 2 H, J = 10.3 Hz, CH=CH_cisH_trans), 3.73 (s, 3 H, CO₂CH₃), 2.14 (s, 3 H, (C=O)CH₃), 2.06–1.80 (m, 8 H, CH₂CH₂CH=CH₂ + CH₂CH₂CH=CH₂); ¹³C NMR (100 MHz, CDCl₃) δ204.9 (CH₃C=O), 172.8 (CO₂CH₃), 137.4 (CH=CH₂), 115.2 (CH=CH₂), 62.9 (CCO₂CH₃), 52.4 (CO₂CH₃), 30.6 (CH₂CH₂CH=CH₂), 28.2 (CH₂CH₂CH=CH₂), 26.8 (CH₃C=O); IR ν_max (neat/cm^-1): 2953, 1741, 1710, 1641, 1434, 1356, 1256, 1202, 1138, 993, 911, 879, 806, 760, 645; HRMS (ESI) calcd for C₁₃H₂₀O₃Na, [M+Na]⁺: 247.1305, found 247.1307.