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Synlett 2006(15): 2480-2482  
DOI: 10.1055/s-2006-949641
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Unified Strategy for the Regiospecific Assembly of Homoallyl-Substituted Butenolides and γ-Hydroxybutenolides: First Synthesis of Luffariellolide

John Boukouvalas*, Joël Robichaud, François Maltais
Département de Chimie, Université Laval, Quebec City, Quebec G1K 7P4, Canada
Fax: +1(418)6567916; e-Mail: john.boukouvalas@chm.ulaval.ca;
Further Information

Publication History

Received 31 May 2006
Publication Date:
08 September 2006 (online)

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Abstract

The first synthesis of the antiinflammatory marine ­natural product luffariellolide has been achieved by a convergent pathway involving sp3-sp3 cross-coupling and silyloxyfuran oxyfunctionalisation as key steps. An illustration of the inherent ­flexibility of this strategy is provided by a simple synthesis of α,β-acariolide and its γ-hydroxylated derivative from a common silyl­oxyfuran precursor.

Key words

cross-coupling - Grignard reagents - lactones - oxyfunctionalisation - 2-silyloxyfurans

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Data for 8: TLC, R f = 0.42 (100% hexanes). 1H NMR (300 MHz, CDCl3): δ = 6.85 (s, 1 H), 5.22 (s, 1 H), 4.38 (s, 2 H), 1.23 (m, 3 H) 1.09 (d, J = 7.1 Hz, 18 H). 13C NMR (75 MHz, CDCl3): δ = 167.5, 129.6, 123.5, 84.2, 38.1, 17.4, 12.0.

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Experimental Procedure: Magnesium turnings (212 mg, 8.70 mmol) were activated by washing successively with aq 10% HCl, H2O, acetone and Et2O, and dried in a vacuum desiccator. The turnings were then flame-heated under an atmosphere of dry nitrogen, allowed to cool, and 1,2-dibromoethane (75 µL, 0.87 mmol) and anhyd THF (4 mL) were added. The mixture was heated to reflux, stirred for 15 min, and the THF was cannulated out and replaced with anhyd THF (3 mL). The resulting suspension was cooled to 0 °C and silyloxyfuran 8 (835 mg, 2.89 mmol), which was purified on a short column (SiO2) before use, was added. Stirring was continued at 0 °C for 1 h, at which time no more starting material was detected by TLC. Anhyd THF (2 mL) was added, and the mixture was divided into two equal parts and placed into two separate dry vials at 0 °C. In each vial was then added prenyl chloride (9; 80 µL, 0.70 mmol) at 0 °C, followed immediately by a solution of Li2CuCl4 (0.1 M, 350 µL, 0.035 mmol) in THF. Each reaction mixture was stirred for 20 min at 0 °C and then poured (in parallel fashion) into H2O (50 mL) and Et2O (50 mL), and a solution of aq sat. NH4Cl was added until the two layers separated. The product was extracted with Et2O (3 × 50 mL), washed with brine (25 mL), dried (MgSO4), and concentrated in vacuo to afford silyloxyfuran 10 as a yellowish oil that was carried forward without further purification. TLC, R f = 0.81 (EtOAc-hexanes, 1:9). 1H NMR (300 MHz, CDCl3): δ = 6.57 (s, 1 H), 5.12 (t, J = 7.0 Hz, 1 H), 5.02 (s, 1 H), 2.31 (m, 2 H), 2.18 (t, J = 7.3 Hz, 2 H), 1.66 (s, 3 H), 1.57 (s, 3 H), 1.24 (m, 3 H), 1.07 (d, J = 7.0 Hz, 18 H). 13C NMR (75 MHz, CDCl3): δ = 156.5, 131.6, 127.5, 126.5, 123.9, 85.1, 28.1, 25.8, 25.5, 17.4, 15.1, 12.0.
Preparation of α,β-Acariolide (11): To a solution of 10 (112 mg) in acetone (10 mL) and H2O (5 drops) was added Amberlyst-15 (25 mg) and the mixture was stirred at r.t. for 45 min. The resin was filtered, washed with acetone (15 mL), and the solvent was evaporated in vacuo. The resulting oil was purified by flash chromatography (EtOAc-hexanes, 15:85, then 2:8) to afford 11 as a colourless oil (98 mg, 84%); TLC: R f = 0.24 (EtOAc-hexanes, 2:8), whose NMR data matched those reported in ref. 13.
Preparation of γ-Hydroxybutenolide 12: To a solution of 10 (112 mg) in anhyd CH2Cl2 (10 mL) at -78 °C was added an acetone solution of DMDO (ca. 0.1 M, 0.4 mL). The mixture was stirred at -78 °C for 1 h and concentrated in vacuo at -78 °C. The crude oil was dissolved in acetone (10 mL) and H2O (5 drops) was added followed by Amberlyst-15 (25 mg). The mixture was stirred at r.t. for 1.5 h, the resin was filtered off, washed with acetone (15 mL), and the solvent was evaporated in vacuo. The resulting oil was purified by flash chromatography (EtOAc-hexanes, 2:8, then 25:75) to afford 12 as a colourless oil (88 mg, 75%); TLC: R f = 0.32 (EtOAc-hexanes, 3:7), whose NMR data matched those reported in ref. 14.

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Data for 16: TLC, R f = 0.77 (100% hexanes). 1H NMR (300 MHz, CDCl3): δ = 6.58 (s, 1 H), 4.94-5.21 (m, 3 H), 1.89-2.37 (m, 14 H), 1.53-1.65 (m, 11 H), 1.42 (m, 2 H), 1.17-1.31 (m, 3 H), 1.09 (d, J = 7.1 Hz, 18 H), 1.06 (s, 6 H). 13C NMR (75 MHz, CDCl3): δ = 156.5, 137.1, 135.9, 135.3, 127.6, 126.8, 126.5, 123.8, 123.5, 85.1, 40.2, 39.7, 39.6, 34.9, 32.6, 29.6, 28.5, 28.0, 27.8, 26.5, 25.9, 19.7, 19.4, 17.4, 15.9, 12.1, 10.5.