10332
H. C. Hailes et al. / Tetrahedron 57 12001) 10329±10333
chromatography )eluent: petroleum spirits 30±408C/diethyl
ether, 20:1) yielding the cis-ring fused title compound 7, a
colourless oil, as a mixture of inseparable diastereoisomers
)2.55 g, 81%). nmax)®lm)/cm21 2961s, 2956s and 1638w;
major diastereoisomer dH )400 MHz; CDCl3) 0.03 )6H, s,
2£Si±Me), 0.87 )9H, s, tBu), 1.56±1.63 )2H, m), 1.65 )3H,
s, CvCCH3), 1.80±2.10 )8H, m), 4.23 )1H, ddd, J6.4, 5.6
and 5.6 Hz, CHOSi) and 5.41 )1H, s, CvCH); dC )100
MHz; CDCl3) 24.9 )Si±Me), 24.7 )Si±Me), 18.1
)C)CH3)3), 21.5, 23.9, 25.8 )C)CH3)3), 28.1, 32.0, 32.8,
34.7, 40.1, 76.5 )COSi), 119.3 )CvCH) and 131.9
)CvCH); m/z )EI) 266 )M1, 5%), 209 )M2C)CH3)3, 40),
133 )50) and 75 )100).
of sodium hypobromite was prepared by the addition of
molecular bromine )0.50 g, 3.1 mmol) to aqueous sodium
hydroxide solution )3.1 M, 4 ml). The solution was then
added dropwise to 8 )193 mg, 0.596 mmol) in dioxane
)3 ml), and the mixture left to stand overnight at rt. A
solution of sodium sul®te )130 mg, 1.03 mmol) in water
)1 ml) was added and the dioxane removed in vacuo. The
crude mixture was then extracted with diethyl ether
)1£30 ml). The aqueous phase was acidi®ed with sulfuric
acid )25%, 3 ml, to pH 2±3) and extracted with diethyl ether
)3£30 ml). These extracts were dried )MgSO4) and concen-
trated in vacuo. The acid was puri®ed by column chroma-
tography )eluent: petroleum spirits 40±608C/ethyl acetate,
10:1) to afford 3-hydroxy-2-)pent-2Z-enyl-cyclopentyl)-
acetic acid )epicucurbic acid) as a colourless oil )112 mg,
3.1.4. 1-[3-ꢀtert-Butyldimethylsilyl)oxy-2-pent-2Z-enyl-
cyclopentyl]-propan-2-one ꢀ8). Molecular oxygen was
bubbled though a stirred solution of the silylether )1.00 g,
3.70 mmol) in dichloromethane )20 ml) at 2788C. After
5 min ozone was bubbled through the reaction mixture
until a faint blue colouration persisted )ca. 30 min). Nitro-
gen was then bubbled through the mixture for 30 min,
dimethyl sul®de )2 ml, 21.1 mmol) was added at 2788C
and the mixture stirred for 3 h, gradually increasing the
temperature to rt. The mixture was concentrated in vacuo
and the crude viscous oil of [2-1tert-butyldimethylsilyl)oxy-
5-12-oxopropyl)-cyclopentyl]acetaldehyde was used with-
out further puri®cation. nmax)®lm)/cm21 2979s, 2955s,
2890s, 1734s and 1718m; major diastereoisomer dH
)400 MHz; CDCl3) 0.03 )6H, s, 2£Si±Me), 0.88 )9H, s,
C)CH3)3), 1.25±1.28 )1H, m), 1.44±1.89 )5H, m), 2.12
)3H, s, COCH3), 2.13±2.20 )1H, m), 2.21±2.35 )1H, m),
2.48±2.65 )2H, m), 4.23±4.25 )1H, m, CHOSi) and 9.53
)1H, m, CHO).
89%).27,28
n
max)®lm)/cm21 3520br s, 2956s, 1712s and
1651w; major epi-diastereoisomer dH )400 MHz; CDCl3)
0.97 )3H, t, J6.6 Hz, CH2CH3), 1.41±1.49 )1H, m),
1.60±1.68 )2H, m), 1.80±2.00 )5H, m), 2.08±2.18 )1H,
m), 2.20±2.48 )4H, m), 4.14±4.22 )1H, m, 1-H), 5.32±
5.38 )2H, m, CHvCH) and 8.70 )1H, br s, COOH); m/z
)EI) 212.1408 )M1, 4%. C12H20O3 requires 212.1412), 210
)25) and 184 )22).
To a stirred solution of epi-cucurbic acid )120 mg,
0.566 mmol) in methanol )10 ml) was added sulpuric acid
)14 M, 0.5 ml) and the mixture was heated at re¯ux for 12 h.
The mixture was diluted with diethyl ether )30 ml) and brine
)10 ml) added. The product was then extracted with diethyl
ether )3£20 ml), dried )MgSO4) and evaporated in vacuo.
The crude oil was puri®ed by column chromatography
)eluent: petroleum spirits 40±608C/ethyl acetate, 10:1),
to afford methyl )3-hydroxy-2-pent-2Z-enylcyclopentyl)-
acetate )methyl epicucurbate) as a colourless oil )118 mg,
To a solution of sodium bis)trimethylsilyl)amide )1.0 M,
2.4 ml, 2.4 mmol) in tetrahydrofuran )10 ml), was
added n-propyltriphenylphosphonium bromide )925 mg,
2.40 mmol). The reaction mixture was cooled to 2308C
and a solution of the crude aldehyde from above in tetra-
hydrofuran )2 ml) added dropwise. The reaction mixture
was maintained at 2308C for further 2 h before it was
warmed to rt. After a further 1 h of stirring the reaction
mixture was diluted with methanol )1 ml) and brine
)5 ml). The product was extracted with ether )3£20 ml),
dried over )MgSO4) and concentrated in vacuo. The crude
oil was puri®ed by column chromatography )eluent:
petroleum spirits 40±608C/ethyl acetate, 20:1) yielding the
methyl ketone 8 )0.773 g, 67% over two steps). nmax)®lm)/
cm21 2997s, 2956s, 1714s and 1711m; major diastereo-
isomer dH )400 MHz; CDCl3) 20.05 )6H, s, 2£Si±Me),
0.89 )9H, s, C)CH3)3), 0.96 )3H, t, J6.3 Hz, CH2CH3),
1.25±1.95 )6H, m), 2.00±2.12 )4H, m), 2.10 )3H, s,
COCH3), 2.41±2.49 )1H, m), 2.52±2.58 )1H, m), 4.10±
4.14 )1H, m, CHOSi) and 5.31±5.38 )2H, m, CHvCH);
dC )100 MHz; CDCl3) 25.1 )Si±Me), 24.6 )Si±Me), 14.2
)CH2CH3), 18.0 )C)CH3)3), 20.8, 23.3, 25.9 )C)CH3)3), 29.6,
30.4, 34.1, 34.9, 46.5, 48.5, 75.3 )C±OSi), 128.3
)CHvCHCH2CH3), 131.9 )CHCH2CH3) and 209.7
)COMe); m/z )EI) 324 )M1, 2%), 281 )24), 210 )25) and
147 )100).
92%).27,28 max)®lm)/cm21 3418br s, 2956s, 1732s and
n
1641w; major epi-diastereoisomer dH )400 MHz; CDCl3)
0.98 )3H, t, J7.2 Hz, CH2CH3), 1.42±1.46 )1H, m),
1.59±1.65 )2H, m), 1.81±1.95 )3H, m), 2.05±2.13 )3H,
m), 2.21±2.30 )1H, m), 2.36±2.50 )3H, m), 3.68 )3H, s,
OMe), 4.11±4.19 )1H, m, CHOH), 5.38±5.50 )2H, m,
CHvCH); m/z )EI) 227.1660 )M11H, 18%. C13H23O3
requires 227.1647), 209 )42) and 135 )100).
To a stirred solution of methyl epicucurbate )150 mg,
0.664 mmol) in dichloromethane )5 ml) was added 1,1,1,-
triacetoxy-1,1-dihydro-1,2-benziodoxol-3-1H-one24 )400 mg,
0.942 mmol). The reaction was stirred for 30 min, the white
solid removed by ®ltration and the ®ltrate concentrated in
vacuo to give a pale yellow oil. The oil was puri®ed by
chromatography )eluent: petroleum spirits 40±608C/ethyl
acetate, 10:1), to afford methyl epijasmonate )2) as a colour-
less oil )141 mg, 94%). nmax)®lm)/cm21 2959s, 1735s, and
1642w; dH )400 MHz; CDCl3) 0.94 )3H, t, J7.4 Hz,
CH2CH3), 1.78±1.86 )1H, m), 2.01±2.07 )2H, m, CH2CH3),
2.09±2.44 )8H, m), 2.72±2.95 )1H, m), 3.65 )3H, s, OCH3),
5.19±5.29 )1H, m, HCvCHCH2CH3), 5.40±5.50 )1H, m,
HCvCHCH2CH3); dC )100 MHz; CDCl3) 14.0 )CH2CH3),
20.6 )CH2CH3), 22.8, 25.5, 33.5, 35.0 )CHCHCO), 35.7,
51.5 )O±CH3), 52.2 )CHCO), 125.3 )CHvCHCH2CH3),
134.1 )CHvCHCH2CH3), 172.5 )COOMe) and 218.9
)CvO); m/z )EI) 224.1408 )M1, 25%. C13H20O3 requires
224.1412), 194 )M2OCH2, 22), 151 )M2CH2CO2Me, 40)
and 83 )100).
3.1.5.
Methyl
2-ꢀ2-pent-2Z-enyl)-3-oxo-cyclopentyl
acetate ꢀmethyl epijasmonate) ꢀ2).26±28 A stirred solution