3-Vinyl-2,5-dihydrofuran Derivatives via Enyne Metathesis

Abstract

Acyclic enynes having the alkyne moiety directly ­connected to the asymmetric carbon atom of an acetal were obtained in two steps. These reactive substrates were then subjected to ruthenium-catalyzed enyne metathesis to produce (5-ethoxy-4-­vinyl-2,5-dihydrofuran-2-yl)methanol derivatives in racemic and enantiomerically pure form. These products are useful glycosyl ­donors for the preparation of d4T analogues.

Key words

enyne - metathesis - carbohydrate - cyclization - furan

References and Notes

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12

RCEYM Reaction of rac -15 and rac -16 - Typical Procedure
The ruthenium catalyst 5 (3% mol) was dissolved in CH₂Cl₂ (26 mL) and ethylene gas was passed through the solution for 20 min. The enyne mixture of rac-15 and rac-16 (400 mg, 0.98 mmol) in CH₂Cl₂ (12 mL) was then added and the mixture was stirred under ethylene at 20 °C during 5 d. The volatiles were eliminated under reduced pressure and the residue was purified by flash chromatography (5% EtOAc in hexane) to give rac-cis-22 (100 mg, 25%) and rac-trans-22 (100 mg, 25%) in order of fractions eluted.

14

Selected physico-chemical data for compound cis-12: R _f = 0.50 (5% EtOAc-hexane). ¹H NMR (300 MHz, CDCl₃): δ = 7.71 (m, 4 H, Ph), 7.45 (m, 6 H, Ph), 6.48 (dd, 1 H, J = 12, 18 Hz, =CH), 6.18 (s, 1 H, H³), 5.87 (s, 1 H, H⁵), 5.46 (d, 1 H, J = 18 Hz, =CH), 5.23 (d, 1 H, J = 12 Hz, =CH), 4.80 (m, 1 H, J = 1 Hz, H²), 3.68 (m, 4 H, OCH ₂CH₃, CH₂OSi), 1.23 (t, 3 H, J = 8 Hz, CH₃), 1.06 (s, 9 H, 3 CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 138.9 (C⁴), 136.0 (Ph), 135.9 (Ph), 133.9 (C³), 133.8 (Ph), 130.4 (=CH), 128.1 (Ph), 118.0 (=CH₂), 107.6 (C⁵), 85.7 (C²), 67.6 (CH₂OSi), 62.6 (OCH₂), 27.2 (CH₃ of t-Bu), 19.6 (Cq of t-Bu), 15.8 (CH₃) ppm. ESI-HRMS: m/z calcd [M + Na⁺]: 431.2018; found: 431.2034.

15

Selected physico-chemical data for compound trans-12: R _f = 0.20 (5% MeOH-CH₂Cl₂). ¹H NMR (300 MHz, CDCl₃): δ = 7.65 (m, 4 H, Ph), 7.38 (m, 6 H, Ph), 6.43 (m, 1 H, J = 12, 18Hz, =CH), 5.98 (s, 1 H, H³), 5.96 (d, 1 H, J = 4 Hz, H⁵), 5.43 (d, 1 H, J = 18, =CH), 5.24 (d, 1 H, J = 12 Hz, =CH), 4.90 (m, 1 H, H²), 3.72 (m, 4 H, OCH ₂CH₃, CH₂OSi), 1.26 (t, 3 H, J = 8 Hz, CH₃), 1.04 (s, 9 H, 3 CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 138.8 (C⁴), 136.0 (Ph), 133.9 (Ph), 130.6 (C³), 130.0 (Ph), 129.0 (=CH), 128.1 (Ph), 118.0 (=CH₂), 107.6 (C⁵), 85.6 (C²), 66.6 (CH₂OSi), 62.1 (OCH₂), 27.2 (CH₃ of t-Bu), 19.6 (Cq of t-Bu), 15.8 (CH₃). ESI-HRMS: m/z calcd [M + Na⁺]: 431.2018; found: 431.2025.