The Hudrlik–Peterson Reaction of Secondary cis-TMS-Epoxy Alcohols and its Application to the Synthesis of the Fatty Acid Intermediates

Abstract

As an extension of the study on the Hudrlik–Peterson reaction of trans-TMS-epoxy alcohols with lithium acetylides, four cis-TMS-epoxy alcohols possessing different alkyl substituents were subjected to the reaction with TMS-acetylide. The reaction completed in 1 h at 0 °C to afford cis-enynyl alcohols in good yields. The results indicated that cis-TMS-epoxy alcohols had higher reactivity than the trans-isomers. Anions derived from 1-heptyne and phenylacetylene participated in the reaction as well. The reaction was applied to optically active cis-TMS-epoxy alcohols, and the resulting enynyl alcohols were transformed to the synthetic intermediates of protectin D1, maresin 1, resolvin E1, and leukotriene B₄.

Key words

epoxy alcohol - trimethylsilyl - acetylene - enyne - protectin D1 - maresin 1 - resolvin E1

• References and Notes

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• 15 To an ice-cold solution of trimethylsilylacetylene (0.29 mL, 2.10 mmol) in THF (0.8 mL) was added n-BuLi (1.57 M in hexane, 1.20 mL, 1.88 mmol) dropwise. After 30 min of stirring at 0 °C, HMPA (0.64 mL, 3.68 mmol) and a solution of epoxy alcohol 3a (101 mg, 0.467 mmol) in THF (0.7 mL) were added. The solution was stirred at 0 °C for 1 h and diluted with saturated NH₄Cl solution to afford a mixture of 4a, 9a, and 10a (total 93 mg). A mixture of the products and K₂CO₃ (95 mg, 0.687 mmol) in MeOH (1.6 mL) was stirred at rt for 1 h and diluted with saturated NH₄Cl solution. The mixture was extracted EtOAc three times and purified by chromatography on silica gel (hexane/EtOAc, 4:1) to afford 10a (59 mg, 83% from 3a): liquid; R_f = 0.50 (hexane/EtOAc, 4:1). ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (t, J = 7.2 Hz, 3 H), 1.22–1.67 (m, 8 H), 2.21 (br s, 1 H), 3.12 (dd, J = 2.2 Hz, 0.8 Hz, 1 H), 4.61–4.68 (m, 1 H), 5.50 (ddd, J = 11.2 Hz, 2.2 Hz, 0.8 Hz, 1 H), 5.96 (ddd, J = 11.2 Hz, 8.4 Hz, 0.8 Hz, 1 H). ¹³C–APT NMR (100 MHz, CDCl₃): δ = 14.1 (+), 22.6 (–), 24.8 (–), 31.7 (–), 36.5 (–), 70.0 (+), 79.6 (–), 82.7 (–), 108.8 (+), 147.6 (+). HRMS (EI⁺): m/z calcd for C₁₀H₁₆O [M⁺]: 152.1201; found: 152.1206.