N. Krause, S. Ebert
a sample of the reaction mixture was treated with a small amount 1742 (s, CϭO). Ϫ MS: m/z (%) ϭ 194 (1) [Mϩ], 83 (100). Ϫ HRMS
FULL PAPER
of Me2S and examined by TLC. After 3 min. reaction time, the
starting material was consumed completely, and the mixture was
purged with argon for 5 min. before addition of 0.1 mL (1.4 mmol)
of Me2S. After warming to room temperature, the solvent was re-
moved in vacuo, and the residue was dissolved in diethyl ether and
washed with water. The aqueous phase was washed three times with
diethyl ether, and the combined organic layers were dried with
MgSO4. Purification of the crude product by column chromato-
graphy (SiO2; cyclohexane/diethyl ether, 3:2) provided 72 mg (50%)
of cis-3-(2-oxoethyl)-2-(2-pentyn-1-yl)cyclopentanone as a colorless
oil which was used immediately in the next step. The diastereomeric
ratio was determined by GC to be cis:trans ϭ 72:28 (tR: cis:
9.21 min; trans: 8.88 min.).
calcd. for C13H22O 194.1670; found 194.1667.
cis-3-(2-Oxoethyl)-2-pentylcyclopentanone: Similar to the prepara-
tion of cis-3-(2-oxoethyl)-2-(2-pentyn-1-yl)cyclopentanone, ozone
was passed through a solution of 8 (cis:trans ϭ 94:6; 291 mg,
1.5 mmol) in 20 mL of methanol at Ϫ80 °C until an intense blue
color persisted (ca. 15 min.). The mixture was then purged with
argon for 5 min. before addition of 0.2 mL (2.7 mmol) of Me2S.
After warming to room temperature, the solvent was removed in
vacuo, and the residue was dissolved in diethyl ether and washed
with water. The aqueous phase was washed three times with diethyl
ether, and the combined organic layers were dried with MgSO4.
Purification of the crude product by column chromatography
(SiO2; cyclohexane/diethyl ether, 3:2) provided 206 mg (70%) of cis-
cis-3-(2-Methoxycarbonylmethyl)-2-(2-pentyn-1-yl)cyclopentanone 3-(2-oxoethyl)-2-pentylcyclopentanone as a colorless oil. The dia-
(6):[1b,24a,25] A solution of NaH2PO4·H2O (0.14 g, 1.0 mmol) and
stereomeric ratio was determined by GC to be cis:trans ϭ 91:9 (tR:
H2O2 (30%; 0.05 mL, 0.5 mmol) in 2 mL of water was added to a cis: 9.23 min; trans: 8.67 min.). Ϫ 1H NMR (C6D6): δ ϭ 0.89 (t,
solution of cis-3-(2-oxoethyl)-2-(2-pentyn-1-yl)cyclopentanone (cis:-
trans ϭ72:28; 70 mg, 0.36 mmol) in 5 mL of acetonitrile. A solu-
J ϭ 7.1 Hz, 3 H, 5Ј-H), 1.10Ϫ2.35 (m, 16 H), 9.18 (s, 1 H, 2ЈЈ-H).
Ϫ
13C NMR (C6D6): δ ϭ 14.3 (ϩ, C-5Ј), 22.9, 25.2, 25.7, 27.5,
tion of NaClO2 (80%; 85 mg, 0.75 mmol) in 7 mL of water was then 32.2, 33.0, 34.8 (7Ϫ, C-4, C-5, C-1Ј, C-2Ј, C-3Ј, C-4Ј, C-1ЈЈ),33.0
added dropwise with slight cooling, and the mixture was stirred at
room temperature for 24 h. After addition of a small amount of
sodium sulfite, the mixture was washed three times with diethyl
ether, and the combined organic phases were dried with MgSO4.
Removal of the solvent in vacuo provided 90 mg crude acid which
was dissolved in 2 mL of diethyl ether; after addition of 2 drops of
methanol, an ethereal diazomethane solution was added until the
evolution of nitrogen had ceased and the reaction mixture re-
mained yellow. The mixture was left at room temperature for 30
min. and then purged with argon; removal of the solvent in vacuo
gave 80 mg of crude keto ester 6 as a yellow oil which was used
without purification in the next step. GC analysis revealed a cis:-
trans ratio of 72:28 (tR: cis-6: 11.78 min; trans-6: 11.42 min.).
(ϩ, C-3), 52.1 (ϩ, C-2), 199.7 (ϩ, C-2ЈЈ), 216.6 (x, C-1).
(؎)-Methyl Dihydroepijasmonate (2):[20g,21] The oxidation of cis-3-
(2-oxoethyl)-2-pentylcyclopentanone (cis:trans ϭ 91:9; 147 mg,
0.75 mmol) with NaH2PO4·H2O (0.21 g (1.5 mmol), H2O2 (30%;
0.08 mL, 0.8 mmol) and NaClO2 (80%; 0.12 g, 1.1 mmol), as well
as the subsequent esterification of the crude acid (0.17 g) with di-
azomethane, were carried out according to the preparation of 6.
Purification of the crude product by column chromatography
(SiO2; cyclohexane/diethyl ether, 3:2) yielded 151 mg (89%) of 2 as
a colorless liquid. According to GC analysis, the cis:trans ratio was
91:9 (tR: cis-2: 11.87 min; trans-2: 11.42 min.). Ϫ 1H NMR (C6D6):
δ ϭ 0.85 (t, J ϭ 7.0 Hz, 3 H, 5Ј-H), 1.00Ϫ2.55 (m, 16 H), 3.31 (s,
3 H, OMe). Ϫ 13C NMR (C6D6): δ ϭ 14.3 (ϩ, C-5Ј), 22.9, 25.0,
25.7, 27.5, 32.2, 33.6, 34.8 (7Ϫ, C-4, C-5, C-1Ј, C-2Ј, C-3Ј, C-4Ј,
C-1ЈЈ), 35.8 (ϩ, C-3), 51.1 (ϩ, OMe), 52.4 (ϩ, C-2), 172.5 (x, C-
2ЈЈ), 216.9 (x, C-1).
(؎)-Methyl Epijasmonate (1):[19,20]
A solution of 6 (20 mg,
0.09 mmol) (cis:trans ϭ 72:28) in 5 mL of hexane was treated with
2 mg of Lindlar catalyst (Pd/Pb/CaCO3) and hydrogenated at ambi-
ent pressure for three days. The catalyst was filtered off and the
solvent was removed in vacuo, giving 18 mg (89%) of (Ϯ)-methyl
epijasmonate (cis-1:trans-1 ϭ 72:28 according to GC analysis; tR:
cis-1: 11.56 min; trans-1: 11.15 min.). Ϫ 1H NMR (C6D6): δ ϭ 0.92
(t, J ϭ 7.3 Hz, 3 H, 5Ј-H), 1.60Ϫ2.85 (m, 12 H), 3.61 (s, 3 H,
OMe), 5.32Ϫ5.41 (m, 2 H, 2Ј-H, 3Ј-H). Ϫ 13C NMR (C6D6): δ ϭ
14.1 (ϩ, C-5Ј), 20.3, 22.8, 25.6 (3Ϫ, C-4, C-1Ј, C-4Ј), 33.6, 35.0
(2Ϫ, C-5, C-1ЈЈ), 35.6 (ϩ, C-3), 51.3 (ϩ, OMe), 52.5 (ϩ, C-2), 125.3
(ϩ, C-2Ј), 133.0 (ϩ, C-3Ј), 172.7 (x, C-2ЈЈ), 218.2 (x, C-1).
Acknowledgments
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for financial support of this work, and Dr.
P. Kraft (Givaudan Roure Research Ltd., Geneva, Switzerland) for
the olfactory investigation of our sample of (Ϯ)-methyl dihydroepi-
jasmonate and for the data given in Table 1.
[1] [1a]
E. Demole, E. Lederer, D. Mercier, Helv. Chim. Acta 1962,
cis-2-Pentyl-3-(2-propen-1-yl)cyclopentanone (8): Analogous to the
preparation of 5 with tin-free lithium allylcuprate, compound 7
(152 mg, 1.0 mmol) was treated with the cuprate prepared from
CuI (286 mg, 1.5 mmol), LiCl (64 mg, 1.5 mmol), and allyllithium
(0.86 solution in diethyl ether; 3.5 mL, 3.0 mmol),[28] and the
protonation was carried out with 4 (1.35 g, 10.0 mmol). Workup
with 0.6 mL (10.0 mmol) of acetic acid and purification of the
crude product by column chromatography (SiO2; petroleum ether/
tert-butyl methyl ether, 10:1) yielded 136 mg (70%) of 8 as a slightly
yellow oil (cis:trans ϭ 94:6 according to GC analysis; tR: cis-8:
7.66 min; trans-5: 7.10 min.). Ϫ 1H NMR (C6D6): δ ϭ 0.81 (t, J ϭ
7.0 Hz, 3 H, 5Ј-H), 1.10Ϫ2.39 (m, 16 H), 4.88 (dd, J ϭ 17.0/1.5 Hz,
1 H, 3ЈЈ-H), 4.95 (dd, J ϭ 9.4/1.2 Hz, 1 H, 3ЈЈ-H), 5.76 (m, 1 H,
2ЈЈ-H). Ϫ 13C NMR (C6D6): δ ϭ 14.3 (ϩ, C-5Ј), 22.9, 24.4, 24.8,
27.7, 32.3, 32.9, 34.8 (7Ϫ, C-4, C-5, C-1Ј, C-2Ј, C-3Ј, C-4Ј, C-1ЈЈ),
[1b]
45, 675Ϫ685. Ϫ
E. Demole, M. Stoll, Helv. Chim. Acta.
1962, 45, 692Ϫ703.
R. Nishida, T. E. Acree, J. Agric. Food. Chem. 1984, 32,
1001Ϫ1003.
A. Kobayashi, M. Kawamura, Y. Yamamoto, K. Shimizu, K.
Kubota, T. Yamanishi, Agric. Biol. Chem. 1988, 52,
2299Ϫ2303.
J. L. Ward, M. H. Beale, J. Chem. Soc., Perkin Trans. 1 1993,
2379Ϫ2381.
cis and trans relate to the stereogenic centers at C-2 and C-3
of the cyclopentane ring; the double bond of the pentenyl side
chain always has the (Z)-configuration.
[2]
[3]
[4]
[5]
[6]
R. Nishida, T. E. Acree, H. Fukami, J. Agric. Food. Chem.
1985, 33, 425Ϫ427.
[7] [7a]
E. Demole, in Fragrance Chemistry (Ed.: E. T. Theimer),
[7b]
Academic Press, New York, 1982, pp. 349Ϫ396. Ϫ
G.
38.3 (ϩ, C-3), 53.0 (ϩ, C-2), 116.2 (Ϫ, C-3ЈЈ),137.2 (ϩ, C-2ЈЈ),
´
Frater, J. A. Bajgrowicz, P. Kraft, Tetrahedron 1998, 54,
Ϫ1
[7c]
˜
217.2 (x, C-1). Ϫ IR (neat): ν ϭ 3050 cm (s), 2950 (s, CϪH),
7633Ϫ7703. Ϫ
P. Kraft, J. A. Bajgrowicz, C. Denis, G.
3840
Eur. J. Org. Chem. 2001, 3837Ϫ3841