Toward the Total Syntheses of Pepluanin A and Euphosalicin: Concise Route to a Highly Oxygenated Cyclopentane as a Common Intermediate

Michael W. Gilbert; Anna Galkina; Johann Mulzer

doi:10.1055/s-2004-834822

LETTER

Toward the Total Syntheses of Pepluanin A and Euphosalicin: Concise Route to a Highly Oxygenated Cyclopentane as a Common Intermediate

Michael W. Gilbert, Anna Galkina, Johann Mulzer*
Institut für Organische Chemie, Währingerstrasse 38, 1090 Wien, Austria
Fax: +43(1)427752189; e-Mail: johann.mulzer@univie.ac.at;

Abstract

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Abstract

A substrate controlled asymmetric synthesis is described of a highly functionalized cyclopentanyl vinyl triflate which serves as an advanced intermediate in the total synthesis of the novel multidrug resistance reversing jatrophanes pepluanin A and euphosalicin. Key steps are a Claisen-Eschenmoser rearrangement followed by hydroxy-lactonization, intramolecular trans-lactonization, Davis hydroxylation and regioselective enoltriflate formation.

Keywords

oxygenated cyclopentanes - Eschenmoser-Claisen rearrangement - lactonization - Davis oxidation - enol triflate

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References

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Experimental Details.
2-[(1 S ,5 R )-5-( tert -Butyldimethylsilyloxy)-3-methylcyclo-pent-2-enyl]- N , N -dimethylacetamide ( 11). To a stirred solution of alcohol 4 (13.9 g, 61.0 mmol) in toluene (30 mL) N,N-dimethlyacetamide dimethoxy acetal (24.6 g, 183.0 mmol) was added dropwise. The mixture was heated to reflux for 48 h, during which time the generated MeOH was allowed to distill out. The volatiles were removed under reduced pressure and the resulting crude material was purified by flash chromatography (5:1 hexane-EtOAc) to give amide 11 (15.5 g, 52.0 mmol, 85% yield) as a clear yellow oil: R _f = 0.31 (hexane-EtOAc = 2:1); [α]_D ²⁰ +24.4 (c 1.1, acetone). IR (thin film): n = 3035, 2929, 2856, 1652, 1471, 1397 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.01 (s, 3 H), 0.03 (s, 3 H), 0.86 (s, 9 H), 1.68 (s, 3 H), 2.10-2.25 (m, 2 H), 2.43 (dd, J = 16.0, 6.7 Hz, 1 H), 2.62 (dd, J = 16.0, 6.8 Hz, 1 H), 2.92 (s, 3 H), 2.97 (s, 3 H), 3.09-3.17 (m, 1 H), 4.48-4.54 (m, 1 H), 5.25-5.30 (m, 1 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = -5.1, -4.7, 17.0, 18.1, 25.8, 32.3, 35.3, 37.1, 45.6, 46.1, 73.6, 127.0, 137.7, 172.8 ppm. MS (EI, 70eV): m/z (%) = 297 (1) [M⁺], 240 (42), 72 (100). HRMS (EI, 70 eV): m/z calcd for C₁₆H₃₁NO₂Si [M⁺]: 297.2124; found: 297.2127.
(3a S ,4 R ,6 R ,6a R )-4-( tert -Butyldimethylsilyloxy)-6-hydroxy-6-methyl-hexahydrocyclopenta[ b ]furan-2-one ( 13). To a cool (0 °C), stirred solution of amide 11 (15.0 g, 50.3 mmol) and 18-crown-6 ether (1.0 g, 3.8 mmol) in a mixture of 1:1:1 CH₂Cl₂-acetone-H₂O (450 mL) was added NaHCO₃ (32.0 g, 381 mmol) portionwise over 20 min. A solution of oxone (60.0 g, 100 mmol) in H₂O (300 mL) was added dropwise over 1 h. The resulting mixture was allowed to stir for another 2 h at 0 °C, EtOAc (200 mL) was then added and the layers were separated. Usual workup and flash chromatography (2:1 hexane-EtOAc gave lactone 13 (11.5 g, 40.2 mmol, 80% yield) as a clear colorless oil: R _f = 0.17 (hexane-EtOAc = 2:1); [α]_D ²⁰ -26.6 (c 0.95, acetone). IR (thin film): ν = 3440, 2957, 2931, 1778, 1472 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.04 (s, 6 H), 0.88 (s, 9 H), 1.40 (s, 3 H), 1.53-1.65 (m, 2 H), 1.97 (dd, J = 13.6, 6.3 Hz, 1 H), 2.44 (dd, J = 18.8, 10.9 Hz, 1 H), 2.98 (dd, J = 18.8, 2.9 Hz, 1 H), 3.09-3.18 (m, 1 H), 4.41 (dd, J = 6.6, 1.5 Hz, 1 H), 4.52-4.59 (m, 1 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = -5.0, -4.8, 18.0, 23.6, 25.7, 28.0, 41.4, 45.3, 71.1, 78.4, 89.9, 177.6 ppm. MS (EI, 70eV): m/z (%) = 229 (41) [M - t-Bu]⁺, 137 (42), 75 (100). HRMS (EI, 70 eV): m/z calcd for C₁₀H₁₇O₄Si [M - t-Bu]⁺: 229.0896; found: 229.0901.
(3a S ,4 R ,6 R ,6a R )-4-( tert -Butyldimethylsilyloxy)-6-(methoxymethoxy)-6-methyl-hexahydrocyclo-penta[ b ]furan-2-one ( 14). To a cool (0 °C), stirred solution of alcohol 13 (11.2 g, 39.3 mmol) and i-Pr₂NEt (25.2 g, 194 mmol) in dry CH₂Cl₂ (100 mL) was added MOMCl (9.5 g, 118 mmol) dropwise over 15 min. The resulting mixture was allowed to warm to r.t. and stirred for 48 h. Sat. aq NaHCO₃ (25 mL) was added and usual workup including flash chromatography (3:1 hexane-EtOAc) gave MOM ether 14 (10.5 g, 31.8 mmol, 81% yield) as a clear colorless oil: R _f = 0.39 (2:1 hexane-EtOAc); [α]_D ²⁰ -21.3 (c 1.2, acetone). IR (thin film): n = 2957, 2823, 1789, 1471 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.05 (s, 6 H), 0.88 (s, 9 H), 1.37 (s, 3 H), 1.50 (dd, J = 13.9, 9.3 Hz, 1 H), 2.18 (dd, J = 13.9, 6.4 Hz, 1 H), 2.45 (dd, J = 18.7, 10.9 Hz, 1 H), 2.98 (dd, J = 18.7, 2.9 Hz, 1 H), 3.05-3.08 (m, 1 H), 3.37 (s, 3 H), 4.50 (ddd, J = 9.3, 8.3, 6.4 Hz, 1 H), 4.58 (dd, J = 6.6, 1.5 Hz, 1 H), 4.65-4.70 (m, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = -5.1, -4.7, 18.0, 18.9, 25.7, 28.0, 41.4, 43.7, 55.7, 71.0, 83.8, 88.5, 91.3, 177.4 ppm. MS (EI, 70eV): m/z (%) = 273 (21) [M - t-Bu]⁺, 243 (100). HRMS (EI, 70 eV): m/z calcd for C₁₂H₂₁O₅Si [M - t-Bu]⁺: 273.1158; found: 273.1161.
(3a S ,4 R ,5 R ,6a R )-4-Hydroxy-5-(methoxymethoxy)-5-methyl-hexahydrocyclopenta[ b ]furan-2-one ( 16). To a stirred solution of silyl ether 14 (9.50 g, 28.8 mmol) in dry THF (40 mL) was added a solution of TBAF (1 M in THF, 43.2 mL, 43.2 mmol). The mixture was stirred at r.t. for 18 h. The solvent was removed under reduced pressure and the resulting crude material was subjected to flash chromatography (1:1 hexane-EtOAc) to give alcohol 16 (5.47 g, 25.3 mmol, 88% yield) as a clear colorless oil: R _f = 0.3 (100% EtOAc); [α]_D ²⁰ -15.1 (c 1.2, CHCl₃). IR (thin film): n = 3443, 2940, 2825, 1769, 1644, 1454 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (s, 3 H), 2.03 (dd, J = 14.8, 3.5 Hz, 1 H), 2.39 (dd, J = 14.8, 6.8 Hz, 1 H), 2.56 (dd, J = 18.4, 11.1 Hz, 1 H), 2.60 (br s, 1 H), 2.81 (dd, J = 18.4, 2.8 Hz, 1 H), 3.18-3.26 (m, 1 H), 3.38 (s, 3 H), 3.97 (dd, J = 6.5, 2.6 Hz, 1 H), 4.63 (d, J = 7.6 Hz, 1 H), 4.75 (d, J = 7.6 Hz, 1 H), 4.99 (ddd, J = 7.5, 6.8, 3.5 Hz, 1 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 17.8, 28.7, 41.3, 42.4, 55.8, 77.9, 83.2, 86.7, 91.3, 177.9 ppm. MS (EI, 70eV): m/z (%) = 216 (1) [M⁺], 171 (46), 153 (65), 57 (100). HRMS (EI, 70 eV): m/z calcd for C₁₀H₁₆O₅ [M⁺]: 216.0998; found: 216.0993.
(3a R ,4 R ,5 R ,6a R )-4,5- Bis (methoxymethoxy)-5-methyl-hexahydrocyclopenta[ b ]furan-2-one ( 4). To a cool (0 °C), stirred solution of alcohol 16 (950 mg, 4.40 mmol) and i-Pr₂NEt (2.84 g, 22.00 mmol) in dry CH₂Cl₂ (20 mL) was added MOMCl (1.06 g, 13.20 mmol) dropwise over 15 min. NaI (20 mg, 0.13 mmol) was added and the resulting mixture was heated to reflux for 18 h. The mixture was allowed to cool to r.t., sat. aq NaHCO₃ (10 mL) was added. Usual workup and flash chromatography (1:1 hexane-EtOAc) gave MOM ether 4 (984 mg, 3.79 mmol, 86% yield) as a clear colorless oil: R _f = 0.38 (100% EtOAc); [α]_D ²⁰ +28.5 (c 1.1, CHCl₃). IR (thin film): ν = 2947, 2896, 1772, 1451 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.36 (s, 3 H), 1.93 (dd, J = 14.8, 4.2 Hz, 1 H), 2.44 (ddd, J = 14.8, 7.2, 1.3 Hz, 1 H), 2.58 (dd, J = 18.0, 10.1 Hz, 1 H), 2.68 (dd, J = 18.0, 2.8 Hz, 1 H), 3.10-3.25 (m, 1 H), 3.33 (s, 3 H), 3.41 (s, 3 H), 3.86 (d, J = 5.8 Hz, 1 H), 4.55-4,70 (m, 4 H), 4.97 (dd, J = 7.5, 7.5, 4.3 Hz, 1 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 18.4, 29.5, 41.6, 42.7, 55.7, 56.6, 83.7, 85.3, 87.3, 91.4, 98.2, 177.5 ppm. MS (EI, 70eV): m/z (%) = 260 (2) [M⁺], 240 (25), 215 (74), 198 (100). HRMS (EI, 70 eV): m/z calcd for C₁₂H₂₀O6 [M⁺]: 260.1260; found: 260.1264.
(3 R ,3a R ,4 R ,5 R ,6a R )-3-Hydroxy-4,5- bis (methoxy-methoxy)-5-methyl-hexahydrocyclopenta[ b ]furan-2-one ( 19). To a cold (-78 ºC), stirred solution of lactone 4 (850 mg, 3.27 mmol) in dry THF (40 mL) was added a solution of KHMDS (0.5 M in toluene, 9.80 mL, 4.90 mmol). The mixture was stirred for 1 h at -78 ºC and a cold (-78 ºC) solution of Davis’ reagent [2-benzenesulfonyl-3-(3-nitro-phenyl)oxaziridine] (1.28 g, 4.90 mmol) in dry THF (5 mL) was added via a cannula. The mixture was stirred for an additional 30 min at -78 ºC and a solution of CSA (1.14 g, 4.90 mmol) in dry THF (5 mL) was added via a cannula. The resulting mixture was allowed to warm to r.t. over 1 h and sat. aq NH₄Cl (15 mL) was added. The layers were separated and the aqueous layer was extracted with EtOAc (3 × 20 mL). Usual workup including flash chromatography (1:1 hexane-EtOAc) gave alcohol 19 (665 mg, 2.41 mmol, 74% yield) as a clear colorless oil: R _f = 0.36 (100% EtOAc); [α]_D ²⁰ +21.6 (c 1.1, CHCl₃). IR (thin film): ν = 3385, 2948, 1770, 1640, 1567, 1447 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.33 (s, 3 H), 1.86 (dd, J = 14.5, 5.2 Hz, 1 H), 2.42 (ddd, J = 14.5, 7.2, 1.3 Hz, 1 H), 2.88 (br s, 1 H), 3.16 (ddd, J = 7.9, 6.6, 3.3 Hz, 1 H), 3.35 (s, 3 H), 3.42 (s, 3 H), 4.08 (dd, J = 6.6, 1.3, 1 H), 4.59 (d, J = 3.3 Hz, 1 H), 4.65-4.72 (m, 4 H), 5.10 (ddd, J = 7.9, 7.2, 5.2 Hz, 1 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 18.4, 42.2, 49.7, 55.8, 56.5, 68.9, 82.1, 83.4, 87.0, 91.4, 97.9, 177.6 ppm. MS (EI, 70eV): m/z (%) = 276 (2) [M⁺], 231 (25), 214 (51), 77 (100). HRMS (EI, 70 eV): m/z calcd for C₁₂H₂₀O₇ [M⁺]: 276.1209; found: 276.1217.
(3 R ,3a R ,4 R ,5 R ,6a R )-3-(4-Methoxybenzyloxy)-4,5- bis (methoxymethoxy)-5-methyl-hexahydrocyclo-penta[ b ]furan-2-one ( 20). To a stirred solution of alcohol 19 (505 mg, 1.83 mmol) in dry CH₂Cl₂ (25 mL) was added PMBOC(=N)CCl₃ (780 mg, 2.74 mmol) and CSA (42 mg, 0.18 mmol). The resulting mixture was stirred for 18 h at r.t. Sat. aq NaHCO₃ (10 mL) was then added and the resulting layers were separated. Usual workup including flash chromatography (2:1 hexane-EtOAc) gave PMB ether 20 (630 mg, 1.59 mmol, 87% yield) as a clear colorless oil: R _f = 0.16 (2:1 hexane-EtOAc); [α]²⁰ _D +48.6 (c 1.1, CHCl₃). IR (thin film): ν = 3277, 2948, 1769, 1731, 1613, 1586, 1447 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (s, 3 H), 1.90 (dd, J = 14.9, 4.3 Hz, 1 H), 2.44 (ddd, J = 14.9, 7.3, 1.2 Hz, 1 H), 3.12 (ddd, J = 7.4, 5.9, 1.5 Hz, 1 H), 3.30 (s, 3 H), 3.32 (s, 3 H), 3.80 (s, 3 H), 3.97 (d, J = 6.3 Hz, 1 H), 4.20 (d, J = 1.5 Hz, 1 H), 4.40-4.80 (m, 6 H), 5.10 (ddd, J = 7.4, 7.4, 4.2 Hz, 1 H), 6.9 (d, J = 8.6 Hz, 2 H), 7.30 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 18.2, 42.4, 49.5, 55.3, 55.8, 56.6, 71.7, 74.4, 82.9, 84.3, 87.4, 91.4, 98.0, 113.9, 129.2, 130.1, 159.5, 175.0 ppm. MS (EI, 70eV): m/z (%) = 396 (1) [M⁺], 275 (3), 137 (24), 121 (100). HRMS (EI, 70 eV): m/z calcd for C₂₀H₂₈O₈ [M⁺]: 396.1786; found: 396.1775.
( R )-2-(4-Methoxybenzyloxy)-2-[(1 R ,2 R ,3 R ,5 R )-5-hydroxy-2,3- bis (methoxymethoxy)-3-methylcyclo-pentyl]-1-(pyrrolidin-1-yl)ethanone ( 21). To a stirred solution of lactone 20 (504 mg, 1.27 mmol) in dry toluene (5 mL) was added pyrrolidine (524 µL, 6.40 mmol). The resulting mixture was heated to reflux for 18 h. The mixture was allowed to cool to r.t. and the volatiles were removed under reduced pressure. The resulting crude material was subjected to flash chromatography (EtOAc) to give amide 21 (541 mg, 1.16 mmol, 91% yield) with traces amount of pyrrolidine as a clear orange oil: R _f = 0.9 (EtOAc); [α]_D ²⁰ -13.3 (c 1.0, CHCl₃). IR (thin film): ν = 3450, 2957, 2882, 1774, 1631, 1514, 1449 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.44 (s, 3 H), 1.72-1.95 (m, 5 H), 2.44 (dd, J = 14.6, 7.1 Hz, 1 H), 2.77 (m, 1 H), 3.31 (s, 3 H), 3.32-3.38 (m, 1 H), 3.40 (s, 3 H), 3.45-3.60 (m, 4 H), 3.79 (s, 3 H), 4.03 (d, J = 3.8 Hz, 1 H), 4.12-4.20 (m, 1 H), 4.40 (d, J = 10.9 Hz, 1 H), 4.48 (d, J = 10.9 Hz, 1 H), 4.53 (d, J = 11.1 Hz, 1 H), 4.62 and 4.69 (m, 3 H), 4.76 (d, J = 6.6 Hz, 1 H), 6.86 (br d, J = 8.8 Hz, 2 H), 7.24 (br d, J = 8.8 Hz, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 21.0, 23.9, 26.8, 46.7, 46.9, 48.2, 50.0, 55.7, 55.9, 57.0, 71.2, 72.9, 76.9, 86.8, 86.9, 91.9, 99.0, 114.2, 129.7, 130.0, 159.7, 171.2 ppm. MS (EI, 70eV): m/z (%) = 422 (1) [M - MOM]⁺, 210 (13), 137 (27), 121 (100). HRMS (EI, 70 eV): m/z calcd for C₂₂H₃₂O₇N [M - MOM]⁺: 422.2179; found: 422.2191.
( R )-2-[(1 R ,2 R ,3 R ,5 R )-2,3- Bis (methoxymethoxy)-3-methyl-5-(triethylsilyloxy)cyclopentyl]-2-(4-methoxy-benzyloxy)-1-(pyrrolidin-1-yl)ethanone ( 22). To a stirred solution of alcohol 21 (392 mg, 0.84 mmol) in dry CH₂Cl₂ (10 mL) was added pyridine (200 µL, 2.5 mmol). TESCl (212 µL, 1.26 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. Sat. aq NH₄Cl (5 mL) was added. Usual workup including flash chromatography (2:1 hexane-EtOAc) gave TES ether 22 (430 mg, 0.74 mmol, 88% yield) as a clear colorless oil: R _f = 0.21 (hexane-EtOAc = 2:1); [α]_D ²⁰ -34.0 (c 0.6, CHCl₃). IR (thin film): ν = 3854, 3822, 1646, 1613, 1586, 1441 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.51 (q, J = 7.9 Hz, 6 H), 0.91 (t, J = 7.9 Hz, 9 H), 1.40 (s, 3 H), 1.73 (dd, J = 13.8, 5.4 Hz, 1 H), 1.75-1.95 (m, 4 H), 2.38 (dd, J = 13.8, 6.8 Hz, 1 H), 3.28-3.35 (m, 1 H), 3.38 (s, 3 H), 3.39 (s, 3 H), 3.40-3.55 (m, 3 H), 3.58-3.68 (m, 1 H), 3.78 (s, 3 H), 3.85 (d, J = 4.3 Hz, 1 H), 4.29 (d, J = 10.8 Hz, 1 H), 4.49 (d, J = 10.8 Hz, 1 H), 4.51-4.58 (m, 1 H), 4.61-4.72 (m, 4 H), 4.83 (d, J = 6.3 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2 H), 7.20 (d, J = 8.7 Hz, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 4.8, 6.8, 19.7, 24.2, 26.1, 45.3, 45.5, 45.8, 47.6, 55.2, 55.7, 56.4, 66.6, 72.6, 73.7, 85.2, 86.3, 91.4, 98.44, 113.6, 129.3, 130.9, 158.9, 168.3 ppm. MS (EI, 70eV): m/z (%) = 582 (2) [M⁺], 552 (9) [M - Et]⁺, 324 (34), 121 (100). HRMS (EI, 70 eV): m/z calcd for C₂₈H₄₆O₈NSi
[M - Et]⁺: 552.2883; found: 552. 2881.
( R )-1-[(1 R ,2 R ,3 R ,5 R )-2,3- Bis (methoxymethoxy)-3-methyl-5-(triethylsilyloxy)cyclopentyl]-1-(4-methoxy-benzyloxy)propan-2-one ( 23). To a cool (0 ºC), stirred solution of amide 22 (362 mg, 0.623 mmol) in dry THF (10 mL) was added a solution of MeLi (1.6 M in Et₂O, 0.780 mL, 1.240 mmol) dropwise over 30 min. The mixture was stirred for an additional 15 min at 0 ºC and sat. aq NH₄Cl (5 mL) was added. The aqueous layer was extracted with EtOAc (3 × 10 mL). Usual workup and flash chromato-graphy (5:1 hexane-EtOAc) gave methyl ketone 23 (265 mg, 0.503 mmol, 81% yield) as a clear colorless oil: R _f = 0.42 (2:1 hexane-EtOAc); [α]_D ²⁰ -5.5 (c 1.7, CHCl₃). IR (thin film): ν = 2955, 2878, 1715, 1613, 1586, 1515, 1458 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.58 (q, J = 8.0 Hz, 6 H), 0.95 (t, J = 8.0 Hz, 9 H), 1.34 (s, 3 H), 1.82 (dd, J = 13.6, 7.6 Hz, 1 H), 2.20-2.29 (m, 4 H), 3.00 (m, 1 H), 3.33 (s, 3 H), 3.35 (s, 3 H), 3.80 (s, 3 H), 3.98 (d, J = 5.8 Hz, 1 H), 4.18 (d, J = 7.8 Hz, 1 H), 4.38 (ddd, J = 7.6, 7.5, 7.3 Hz, 1 H), 4.42 (s, 2 H), 4.52-4.72 (m, 4 H), 6.87 (d, J = 8.6 Hz, 2 H), 7.25 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 4.8, 6.7, 20.0, 26.9, 47.0, 49.0, 55.2, 55.4, 56.3, 70.8, 71.1, 81.4, 85.1, 86.0, 91.5, 97.8, 113.8, 129.5, 130.1, 159.2, 210.0 ppm. MS (EI, 70eV): m/z (%) = 497 (0.5) [M - MeO]⁺, 465 (1), 390 (3), 121 (100). HRMS (EI, 70 eV): m/z calcd for C₂₅H₄₁O₈Si [M - MeO]⁺: 497.2571; found: 497.2559.
( R )-1-[(1 S ,2 R ,3 R ,5 R )-2,3- Bis (methoxymethoxy)-3-methyl-5-(triethylsilyloxy)cyclopentyl]-1-(4-methoxy-benzyloxy)prop-2-en-2-yl Trifluoro-methanesulfonate ( 3). To a cold (-78 ºC), stirred solution of methyl ketone 23 (201 mg, 0.381 mmol) in dry THF (10 mL) was added a solution of KHMDS (0.5 M in toluene, 0.84 mL, 0.42 mmol). The mixture was stirred for 1 h at -78 ºC and a cold (-78 ºC) solution of PhNTf₂ (204 mg, 0.57 mmol) in dry THF (1 mL) was added via a cannula. The mixture was stirred for an additional 10 min at -78 ºC and then allowed to warm to r.t. over 1 h. Sat. aq NH₄Cl (5 mL) was added and the resulting layers were separated. Usual workup and flash chromatography (50:10:1 hexane-EtOAc-Et₃N) gave vinyltriflate 3 (229 mg, 0.348 mmol, 91% yield) as a clear colorless oil: R _f = 0.55 (2:1 hexane-EtOAc); [α]_D ²⁰ -3.3 (c 0.9, CHCl₃). IR (thin film): ν = 2956, 1664, 1613, 1515, 1443, 1417 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.56 (q, J = 7.9 Hz, 6 H), 0.96 (t, J = 7.9 Hz, 9 H), 1.39 (s, 3 H), 1.77 (dd, J = 14.2, 4.2 Hz, 1 H), 2.39 (dd, J = 14.2, 6.4 Hz, 1 H), 2.71-2.78 (m, 1 H), 3.31 (s, 3 H), 3.38 (s, 3 H), 3.79 (s, 3 H), 3.89 (d, J = 4.5 Hz, 1 H), 4.18 (d, J = 10.1 Hz, 1 H), 4.32 (d, J = 10.4 Hz, 1 H), 4.37 (ddd, J = 6.9, 6.4, 4.2 Hz, 1 H), 4.59-4.71 (m, 5 H), 5.24 (d, J = 3.4 Hz, 1 H), 5.39 (d, J = 3.4 Hz, 1 H), 6.86 (br d, J = 8.6 Hz, 2 H), 7.28 (br d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ = 4.9, 6.8, 20.0, 48.3, 48.5, 55.2, 55.5, 56.3, 69.9, 71.6, 76.6, 85.9, 86.7, 91.4, 98.9, 108.5, 113.7, 118.4 (q, CF₃), 129.5, 129.9, 152.7, 159.1 ppm. MS (EI, 70eV): m/z (%) = 613 (1) [M - MOM]⁺, 283 (3), 181 (5), 135 (8), 121 (100). HRMS (EI, 70 eV): m/z calcd for C₂₆H₄₀O₉F₃SSi [M - MOM]⁺: 613.2114; found: 613.2097.