Enyne Metathesis Approach towards the Cyclopentane Motif of Jatrophane Diterpenes

Christoph Lentsch; Rita Fürst; Uwe Rinner

doi:10.1055/s-0033-1339923

Synlett, Inhaltsverzeichnis

Synlett 2013; 24(20): 2665-2670
DOI: 10.1055/s-0033-1339923

letter

Enyne Metathesis Approach towards the Cyclopentane Motif of Jatrophane Diterpenes

Christoph Lentsch

Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria Fax: +43(1)42779521 eMail: uwe.rinner@univie.ac.at

,

Rita Fürst

Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria Fax: +43(1)42779521 eMail: uwe.rinner@univie.ac.at

,

Uwe Rinner*

Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria Fax: +43(1)42779521 eMail: uwe.rinner@univie.ac.at

› Institutsangaben

Abstract

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Abstract

A short and efficient synthesis of the cyclopentane moiety of the jatrophane diterpene Pl-3 has been developed. The route features an enyne metathesis reaction, and a stereoselective palladium-catalyzed reductive epoxide opening as key steps.

Key words

metathesis - palladium - natural products - stereoselective synthesis - terpenoids

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Referenzen

References and Notes
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30 Preparation of Alcohol 9: Acetylene 14 (1.0 g, 5.15 mmol, 1.0 equiv) was dissolved in freshly distilled 2-propanol (45 mL; degassed by three pump-freeze-thaw cycles prior to use). The solution was stirred at 40 °C and catalyst 17 (20 mg, 0.003 mmol, 0.0065 equiv; for preparation see Supporting Information), dissolved in 2-propanol (1 mL), was added via a syringe pump over 6 h. After consumption of the starting material the reaction was reduced in vacuo (30 °C, 40 mbar) and the residue (ca. 3 mL) was purified by flash column chromatography (hexane–EtOAc, 9:1) to afford 9 (950 mg, 95%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 5.77–5.87 (m, 1 H), 5.02–5.10 (m, 2 H), 4.28 (dd, J = 5.44, 5.44 Hz, 1 H), 2.33–2.40 (m, 1 H), 1.97–2.04 (m, 1 H), 1.78–1.86 (m, 2 H), 1.00 (s, 3 H), 0.18 (br s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.17 (CH), 116.65 (CH₂), 105.76 (C), 90.65 (C), 66.98 (CH), 39.40 (CH), 36.86 (CH₂), 15.08 (Me), 0.03 (Me). HRMS (ESI): m/z [M – Me]⁺ calcd for C₁₀H₁₇OSi: 181.1049; found: 181.1044 ±5 ppm. [α] _d ²⁰ +3.8° (c = 1.630, CHCl₃). IR (ATR): 3351, 2960, 2352, 2171, 1640, 1376, 1249, 983, 947, 911, 838, 759, 698, 638 cm^–1.
31 Preparation of Cyclopentene 19: Toluene (1.5 L) was degassed by an argon purge of approximately 1 h. Enyne 9 (3.00 g, 15.28 mmol, 1 equiv) was added and the solution was purged with argon for 10 min and with ethene for 10 min. Grubbs 2nd generation catalyst (0.649 g, 0.764 mmol, 0.005 equiv) was added in one portion and the solution was purged with ethene for 15 min. The mixture was heated to 80 °C for 16 h at positive pressure of ethene. After total consumption of the starting material, the mixture was reduced in vacuo (40 °C, 60 mbar) to a volume of approximately 70 mL. This volume was applied on a column and eluted with hexane (300 mL). After purification by flash column chromatography (hexane–EtOAc, 19:1), 19 (2.80 g, 93%) was isolated as a slightly brownish fluid. ¹H NMR (400 MHz, CDCl₃): δ = 5.92 (d, J = 2.80 Hz, 1 H), 5.79 (dd, J = 2.69, 2.69 Hz, 1 H), 5.52 (d, J = 2.69 Hz, 1 H), 4.54 (br s, 1 H), 2.72–2.79 (m, 1 H), 2.11–2.20 (m, 1 H), 1.90–1.96 (m, 1 H), 1.51 (br s, 1 H), 1.09 (d, J = 7.12 Hz, 3 H), 0.17 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 146.23 (C), 145.72 (C), 130.73 (CH), 125.82 (CH₂), 84.31 (CH), 41.47 (CH), 38.97 (CH₂), 19.71 (Me), –0.59 (Me). HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₂₀NaOSi: 219.1181; found: 219.1183 ±5 ppm. [α] _d ²⁰ −89.1° (c = 1.030, CHCl₃).
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33 Preparation of 21: NaH (60% dispersion in mineral oil, 0.224 g, 5.60 mmol, 2.2 equiv) was added to HMPA (1.66 mL, 9.57 mmol, 3.75 equiv) in one portion. After 5 min, a solution of 19 (0.500 g, 2.55 mmol, 1 equiv) in THF (1.66 mL) was added. After consumption of the starting material as indicated by TLC analysis (60 min) the reaction was quenched via addition of a sat. aqueous solution of NH₄Cl. The solution was acidified to pH 2 by addition of HCl (1 M) and stirred for approximately 20 min. The aqueous solution was extracted with CH₂Cl₂ (3 × 20 mL) and dried over MgSO₄. Silica was added and the solvent was reduced in vacuo. The crude product was purified by flash column chromatography (dry loading; pentane–Et₂O, 10:1). The solvent was carefully reduced under reduced pressure (700 mbar, 35 °C) to yield 21 (260 mg, 82%) as a colorless liquid. Note: The product is highly volatile; thus, yields vary between 40% and 82%. ¹H NMR (400 MHz, CDCl₃): δ = 6.45 (dd, J = 17.73, 11.00 Hz, 1 H), 5.82 (dd, J = 2.63, 2.63 Hz, 1 H), 5.41–5.46 (m, 1 H), 5.14 (dd, J = 10.89, 0.84 Hz, 1 H), 4.52 (br s, 1 H), 2.71–2.78 (m, 1 H), 2.14–2.23 (m, 1 H), 1.87–1.94 (m, 1 H), 1.51 (br s, 1 H), 1.10 (d, J = 7.16 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.58 (C), 133.11 (CH), 131.87 (CH), 115.01 (CH₂), 83.20 (CH), 42.56 (CH), 38.60 (CH₂), 19.67 (Me). HRMS (ESI): m/z [M + Na]⁺ calcd for C₈H₁₂NaO: 147.0786; found: 147.0788 ±5 ppm. [α] _d ²⁰ −70° (c = 0.2250, CHCl₃). IR (ATR): 3316, 2954, 2924, 2868, 1641, 1454, 1374, 1260, 1021, 988, 905, 813 cm^–1.
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45 Preparation of 23a: The reaction was carried out in Schlenk flasks using degassed solvents. A Schlenk flask containing Pd₂(dba)₃·CHCl₃ (4.4 mg, 2.5 mol%) and (R,R)-DACH ([138517-61-0], 8.7 mg, 7.5 mol%) was purged with argon five times before CH₂Cl₂ (0.6 mL) was added. After 5 min a mixture of Et₃N (117 μL, 0.844 mmol, 5.0 equiv) and formic acid (32 μL, 0.844 mmol, 5.0 equiv) in CH₂Cl₂ (0.6 mL) was added and stirring was continued for additional 5 min before epoxide 22 (50 mg, 0.169 mmol, 1.0 equiv) was added neat followed by CH₂Cl₂ (0.1 mL). The reaction was stirred until TLC analysis showed total consumption of the starting material (3 h). A sat. aqueous solution of NH₄Cl was added and the mixture was extracted with CH₂Cl₂ (3 × 20 mL), the organic extracts were dried over MgSO₄, filtered and reduced in vacuo. The crude product was purified by flash column chromatography (hexane–EtOAc, 40:1) delivering the desired product 23a (43 mg, 86%) as a colorless oil as sole isolable product. ¹H NMR (400 MHz, CDCl₃): δ = 6.20–6.26 (m, 1 H), 5.22–5.24 (m, 1 H), 5.20 (d, J = 0.78 Hz, 1 H), 4.07–4.11 (m, 1 H), 3.98 (br d, J = 3.90 Hz, 1 H), 3.25 (d, J = 11.16 Hz, 1 H), 2.36–2.40 (m, 1 H), 2.32–2.36 (m, 1 H), 2.25 (ddd, J = 14.42, 8.99, 0.95 Hz, 1 H), 1.51 (ddd, J = 14.37, 5.37, 5.37 Hz, 1 H), 1.05–1.13 (m, 21 H), 0.97 (d, J = 7.32 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 135.16 (CH), 117.43 (CH₂), 85.48 (CH), 78.18 (CH), 52.81 (CH), 43.47 (CH₂), 41.40 (CH), 20.87 (Me), 18.21 (Me), 18.16 (Me), 12.37 (CH). HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₃₄NaO₂Si: 321.2226; found: 321.2223 ±5 ppm. [α] _d ²⁰ −5° (c = 1.0900, CHCl₃). IR (ATR): 3531, 2943, 2866, 2359, 2342, 1636, 1463, 1419, 1383, 1119, 1060, 1014, 997, 912, 881, 847, 823, 729, 678 cm^–1.

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Supporting Information