Silicon guided rearrangement of epoxydecalines to spirocyclic compounds. Synthesis of gleenol and axenol from carvone

Article abstract of DOI:10.1016/j.tet.2005.09.025

The synthesis of the spirocyclic sesquiterpenes (-)-gleenol and (-)-axenol in enantiomerically pure form has been achieved starting from R-(-)-carvone. The key step is the silicon guided acid-promoted rearrangement of a 9-trimethylsilyl-5,6-epoxy-noreudesmane prepared from 3- trimethylsilyldihydrocarvone in several steps involving Robinson annulation, enone deconjugation and epoxidation. Acid treatment of the epoxy-noreudesmane gave a norspiroaxane as the main product, which was used as intermediate for the synthesis of two naturally occurring sesquiterpenes gleenol and axenol.

Full text of DOI:10.1016/j.tet.2005.09.025

Tetrahedron 61 (2005) 10853–10860
Silicon guided rearrangement of epoxydecalines to spirocyclic
compounds. Synthesis of gleenol and axenol from carvone
*
´ ´
˜
Gonzalo Blay, Ana M. Collado, Begona Garcıa and Jose R. Pedro
´
`
´
`
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Departament de Quımica Organica, Facultat de Quımica, Universitat de Valencia, E-46100-Burjassot (Valencia), Spain
Received 8 July 2005; revised 6 September 2005; accepted 8 September 2005
Available online 26 September 2005
Abstract—The synthesis of the spirocyclic sesquiterpenes (K)-gleenol and (K)-axenol in enantiomerically pure form has been achieved
starting from R-(K)-carvone. The key step is the silicon guided acid-promoted rearrangement of a 9-trimethylsilyl-5,6-epoxy-noreudesmane
prepared from 3-trimethylsilyldihydrocarvone in several steps involving Robinson annulation, enone deconjugation and epoxidation. Acid
treatment of the epoxy-noreudesmane gave a norspiroaxane as the main product, which was used as intermediate for the synthesis of two
naturally occurring sesquiterpenes gleenol and axenol.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
eudesmanes with special structural features such as hydroxy
enones to spirovetivanes,6 and a,b-epoxy ketones to
spirovetivanes or eremophilanes,7 and the rearrangement
of an epoxy eudesmanolide to an eremophilanolide.8
It is generally accepted that many biogenetic pathways
leading to natural products involve the Wagner–Meerwein
rearrangement of carbocationic intermediates. In the early
past century, Robinson suggested that eremophilanes were
formed in nature from C-5 cationic eudesmanoid precursors
via a route involving methyl migration (Fig. 1, path a, XZ
YZH).1 A similar intermediate has been proposed as
biogenetic precursor of sesquiterpenes bearing the
spiro[4,5]decane framework, that is, spirovetivanes (path
b, XZYZH) and spiroaxanes (path c, XZYZH, RZMe
and R0ZH, or RZH and R0ZMe), via processes involving
migration of C-1 or C-9 methylenes with concomitant
contraction of the A or B ring, respectively.2 Following our
research on the synthesis of bioactive sesquiterpenes3 we
became interested in the use of such rearrangements in the
laboratory as a synthetic route toward naturally occurring
compounds. In particular, we were interested in the
rearrangement of 4,5-epoxydecalins as a way to obtain
5-methyldecalin or spiro[4,5]decane-based compounds
functionalized at C-4. Although such biomimetic approach
has received some attention in the past,4 the task, however,
has been shown to be difficult and only very few successful
examples have been described in the literature. Among
them, we can mention the photochemical rearrangement of
dienones leading to 1,2-methylene or 1,2-methyl migration
products,5 the thermal or acid-catalyzed rearrangements of
This fact may be due to one or more of these reasons: (a)
lack of selectivity of the migrating group; (b) 1,2-
elimination of the hydroxyl group before rearrangement9
and; (c) a Grob-type rearrangement of the 1,3-hydroxy-
carbocations that result after the initial rearrangement in the
case of epoxides.10 In previous articles, we have shown that
some of these drawbacks can be overcome and selectivity
during migration can be gained by introducing a TMS group
in the vicinity of the migrating group, so methylene
migration is preferred if the epoxide and the TMS group
are on the same ring while methyl migration is the main
pathway if they are on diferent rings of the decalin system.11
For instance we have used the rearrangement of a
1-trimethylsilyl-4,5-epoxyeudesmane in a synthesis of
spirovetivanes from santonin12 and a similar strategy was
used by Hwu13 in a synthesis of solavetivone from carvone
(Fig. 1, path b, XZMe3Si, YZH). In these cases the TMS
group at C-1 promoted the migration of the methylene group
C-9 toward the C-5 carbocation by stabilizing the forming
carbocation at C-10 (b-effect), at the time it prevented
further rearrangements in the resulting carbocation by
rapidly eliminating the TMS group to form a double bond
between C-1 and C-10 (super proton behavior).14 According
to these results it was envisaged that a similar rearrangement
directed by a TMS group located at C-9 in the eudesmane
framework should favor migration of methylene C-1,
therefore, permitting the synthesis of spiroaxane type
Keywords: Spiroaxane sesquiterpenes; Wagner–Merweein rearrangement;
Epoxides; Silicon; Carbocation.
*
Corresponding author. Tel.: C34 963544329; fax: C34 963544328;
e-mail: jose.r.pedro@uv.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.025

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G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
Figure 1. Cationic rearrangement of eudesmanes to eremophilanes and spirocyclic sesquiterpenes.
sesquiterpenes (Fig. 1, path c, XZH, YZMe3Si). In this
article, we present our results in this subject and its
application to the synthesis of (K)-gleenol and its C-6
epimer, (K)-axenol, which is the enantiomer of the
naturally occurring (C)-axenol. (K)-Gleenol has been
isolated from Picea glehni,15 Picea koraiensis,16 Cripto-
meria japonica,17 Juniperus oxycedrus,18 and the brown
alga Taonia atomaria.19 Its enantiomer (C)-gleenol and the
C-6 epimer of this, (C)-axenol, have been isolated from
New Zealand Eurypon sp. sponges.20 (C)-Gleenol shows
termiticidal and antihelmintic activities,21 and growth
regulation effects on plant seeds. In recent years, some
syntheses of gleenol and its C-6 epimer have been
reported.22
3-trimethylsilyldihydrocarvone 2 in 91% yield. The stereo-
chemistry of C-3 in this compound was initially assigned
according to the preference of the reagent for axial addition
to cyclic enones, and was ascertained in further steps of the
synthetic sequence (see below). In the next steps, the decalin
system was built up via a Robinson annulation. Treatment of
2 with methyl vinyl ketone (MVK) in the presence of
Ph3CSbCl24 gave a mixture from which compound 3 was
isolated in 52% yield besides 27% of unreacted starting
material. The reaction could not be extended until total
consumption of 2 because of the formation of by-products
resulting from Michael reaction between the formed
compound 3 and MVK (compound 10). Cyclization to the
decalin was achieved by treatment of 3 with methanolic
KOH in 94% yield.25 The stereochemistry of compound 4
was established by NOE experiments. Thus, a NOE was
observed between the signal at d 0.91, corresponding to H-9,
and the signal at d 4.73 corresponding to the one of the
olefinic protons of the isopropylidene chain. Furthermore,
irradiation at the frequency of the methyl group signal
(d 1.28) gave NOEs with the signals corresponding to H-6a
(d 2.65) and H-7 (d 2.57–2.46) proton, therefore, indicating
the cis disposition of the TMS group and the trans
disposition of the isopropylidene side chain relative to
the bridgehead methyl, respectively. This result is similar to
the one obtained with other Robinson annulation with
3-substituted dihydrocarvone.26 Once the decalin system
was obtained, the double bond in the side chain was
selectively hydrogenated with the Wilkinson catalyst to give
noreudesmane 5 (Scheme 2).
2. Results and discussion
Our synthetic strategy was based on the rearrangement of a
C-5 cationic decalinic intermediate guided by a silicon
group located at C-9 of the decalin skeleton. Accordingly,
the retrosynthetic analysis outlined in Scheme 1 was
designed. R-(K)-carvone (1) was chosen as starting
material, which would provide the B ring of the decalin
system. Treatment of this compound with Me3SiLi in THF
at K78 8C in the conditions described by Still23 gave
In order to achieve the cationic rearrangement of the decalin
and to leave a functional group at C-6 we needed an epoxide
in the C(5)–C(6) position, which means that deconjugation
of the enone double bond was required. A first attempt to do
so by treatment of 5 with strong base (potassium tert-
butoxide) and reduction of the ketone27 gave a complex
reaction mixture. Therefore, deconjugation was achieved
via acetal 6, which was obtained by treatment of 5 with
ethyleneglycol and p-toluenesulfonic acid (TsOH). Epoxi-
dation of 6 with acetone–oxone gave only the a-epoxide 7 in
89% yield. However, all attempts to deprotect the acetal
(HCl–acetone or montmorillonite KSF) were unsuccessful
as they gave rise to the cleavage of the oxirane ring
providing the 3,6-diketone 8 or the corresponding
g-hydroxyenone 9. Therefore, we decided to carry out the
Scheme 1. Retrosynthetic analysis for axenol and gleenol and numbering
system.

G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
10855
Scheme 2. Synthesis of epoxydecaline 7.
cationic rearrangement to the spiroscyclic skeleton with
compound 7.
(5%) quantitatively gave two epimeric compounds 14 and
15 in 7:5 ratio, respectively. The stereochemistry of the new
stereogenic center was assigned by NOE experiments. Thus,
upon irradiation on the signal of the axial H-6 proton (d
3.63, d, JZ10.0 Hz) in compound 14, NOE was observed
with the isopropyl group (d 0.80, d, JZ7.0 Hz) and with the
H-14 methyl group indicating that both H-6 and methyl
H-14 are in the b-side of the molecule. A similar irradiation
of H-6 (d 3.24, d, JZ10.5 Hz) in compound 15 did not give
NOE with H-14 (d 0.89, d, JZ6.8 Hz). Although
compounds 14 and 15 were difficult to separate, upon
protection of the hydroxyl groups as trimethylsilyl (TMS)
ethers in the hydrogenation mixture both compounds could
be very easily separated affording compound 16 (50%) and
17 (30%). Introduction of the methyl group at C-2 required
the use of cerium reagents28 since MeMgBr and MeLi
brought about quantitative enolization of the ketone.
Treatment of compound 17 with MeLi in the presence of
CeCl3 gave a 1:1.5 mixture of two alcohols in 96% yield.
Subsequent dehydration of the mixture with mesyl chloride
and triethylamine afforded a mixture of alkenes, which were
According to our previous findings,11,12 we expected that
rearrangement catalyzed by a Lewis acid and directed by the
silicon group at C-9 would take place with preferential
migration of the C-1 methylene group. Treatment of
compound 7 with BF3$Et2O in different solvents gave
product mixtures in which rearrangement via the C-5
carbocation was the main reaction pathway (Scheme 3). As
we expected, the presence of the silicon group on the same
ring of the epoxide favored the migration of methylene C-1
to give spirocompound 12 in a 4–5:1 ratio towards the
methyl migration product 11. Cleavage of the epoxide could
not be completely avoided and compound 8 was also
obtained after acidic treatment. Besides, a compound 13
resulting from cleavage of the acetal moiety was obtained.
A possible mechanism for the formation of this compound is
given in Scheme 4.
Compound 12, obtained in this way was used as a synthetic
intermediate for the synthesis of (K)-gleenol (23) and (K)-
axenol (21). Hydrogenation of the double bond on Pd/C
1
separated by chromatography. The H NMR of compound
18 showed an AB system composed by two broad doublets
at d 2.22 and d 1.78 with a geminal coupling of 16.4 Hz
corresponding to the two H-1 allylic protons, as well as an
ABX system formed by a signal at d 2.36 (ddd, JZ16.4, 4.8,
2.4 Hz) and a broad doublet at d 2.03 (JZ16.4 Hz)
Scheme 3. Rearrangement of compound 7.
Scheme 4. Proposed mechanism for the formation of compound 13.

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G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
Scheme 5. Synthesis of (K)-axenol (21) and (K)-gleenol (23) from compound 12.
corresponding to two H-4 allylic protons, and the olefinic
H-3 signal at 5.07 (br s). Accordingly, the D2,3 structure was
3. Experimental
3.1. General
assigned to this compound. Alkene 19 showed two doublets
at d 4.69 (JZ1.9 Hz) and d 4.64 (JZ1.9 Hz) characteristics
of an exomethylene group. Finally, compound 20 showed a
triplet at d 2.15 (JZ7.4 Hz) corresponding to the two H-3
allylic protons, therefore, the D1,2 structure was assigned
(Scheme 5).
All melting points are uncorrected. Column chromato-
graphy was performed on silica gel (SDS, silica gel 60,
0.035–0.070 mm particle size). Commercial reagents and
solvents were analytical grade or were purified by standard
procedures, prior to use.29 All reactions involving air or
moisture sensitive materials were carried out under argon
atmosphere. Specific rotations were measured in CHCl3. IR
were recorded as liquid film in NaCl for oils and as KBr
discs for solids. NMR were run in CDCl3 at 400 MHz for 1H
and at 75 MHz for 13C NMR, and referenced to the solvent
as internal standard. The carbon type was determined by
DEPT experiments. EIMS were run at 70 eV.
Treatment of compound 20 with aqueous acid brought about
deprotection of the hydroxyl group to give compound 21,
which showed spectral features coincident with those
described for natural (C)-axenol and opposite optical
rotation sign. Compound 21 has been also described by
Caine as an intermediate for the synthesis of axisonitrile
3.22a For the synthesis of 23, the inversion of C-6 was
required. Initial attempts using the Mitsunobu protocol
failed, probably because of the steric hindrance in the
proximity of the hydroxyl group. Therefore, inversion was
carried in two steps. Oxidation of the hydroxyl group with
NMO-TPAP in compound 21 gave the corresponding
ketone 22 in 89% yield. Finally, the ketone was
reduced with L-selectride affording compound 23 in 75%
yield together with 15% of the previous alcohol 21.
Compound 23 had spectral features coincident with natural
(K)-gleenol.
3.1.1. (3R,5S)-5-Isopropenyl-2-methyl-3-trimethylsilyl-
cyclohexanone (2). A solution obtained from 1.6 M MeLi
in diethyl ether (32.6 mL, 53.3 mmol) and dry THF
(100 mL) was added to a frozen solution of hexamethyldi-
silane (13.6 mL, 66.6 mmol) in HMPA (20 mL) at K78 8C
under argon. Then, the reaction flask was introduced in an
ice bath and the frozen solution left to melt. After 15 min of
stirring at 0 8C, the reaction mixture was cooled at K78 8C
and a solution of R-(K)-carvone (4.0 g, 26.6 mmol) in THF
(25 mL) was added dropwise. After 1 h at this temperature,
water (30 mL) was added, the mixture was left to reach
room temperature, THF was removed under reduced
pressure and the aqueous solution was extracted with
diethyl ether (3!100 mL). The organic layer was washed
with water, brine, dried over Na2SO4, and concentrated
under reduced pressure. Column chromatography eluting
with hexane/diethyl ether 9:1 afforded 5.41 g (91%) of
compound 2: an oil; [a]1D9C7.8 (c 1.3); MS m/z 224 (MC,
12), 209 (50), 195 (22), 181 (30), 73 (100); HRMS 224.1589
(MC), C13H24OSi required 224.1596; IR (NaCl) 3076,
In summary, we have presented here the first cationic
rearrangement of a 5,6-epoxy-noreudesmane into a
norspiroaxane with concomitant contraction of ring B in
the decalin system. This rearrangement is guided by a
silicon group at C-9, which allows a selective migration of
the C-1 methylene group towards migration of the bridge-
head methyl group in a 5:1 ratio. The synthetic utility of
this rearrangement is illustrated by the synthesis of two
spiroaxanes, the naturally occurring (K)-gleenol, and (K)-
axenol, which is the enantiomer of natural (C)-axenol,
which have been prepared from carvone in ca. 0.5%
overall yield.
1708, 1441, 1252, 847 cmK1; H NMR (300 MHz) d 4.80
(1H, br s), 4.70 (1H, br s), 2.57 (1H, m), 2.49 (1H, dd, JZ
1.6, 6.8 Hz), 2.34 (1H, ddd, JZ1.1, 8.1, 14.0 Hz), 2.01 (1H,
1

G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
10857
dddd, JZ1.1, 4.1, 7.8, 14.0 Hz), 1.74 (1H, m), 1.68 (3H, s),
1.40 (1H, ddd, JZ4.0, 6.0, 8.1 Hz), 1.12 (3H, d, JZ7.3 Hz),
0.00 (9H, s); 13C NMR d 213.4 (s), 146.7 (s), 110.9 (t), 46.6
(d), 44.0 (d), 43.8 (t), 28.8 (t), 27.8 (d), 21.0 (q), 14.7 (q),
K1.0 (q).
171.1 (s), 124.9 (s), 43.0 (d), 38.9 (s), 38.1 (t), 36.8 (t), 34.0
(t), 33.3 (d), 26.7 (t), 26.0 (d), 20.7 (q), 20.7 (q), 20.4 (q),
0.3 (q).
3.1.5. (7S,9R,10R)-3,3-Ethylenedioxy-9-trimethylsilyl-
15-nor-5-eudesmene (6). A solution containing compound
5 (3.07 g, 11.0 mmol), ethyleneglycol (6.5 mL, 117 mmol)
and TsOH (1.06 g, 3.3 mmol) in benzene (110 mL) was
heated at reflux temperature overnight using a Dean–Stark
system. The reaction mixture was washed with cold satd
aqueous NaHCO3 and the aqueous layer extracted with
EtOAc. The combined organic layers were washed with
brine, dried and concentrated under reduced pressure.
Column chromatography eluting with hexane/EtOAc 9:1–
7:3 afforded 2.82 g (79%) of acetal 6 and 558 mg (18%) of
starting material.
3.1.2. (2R,3R,5S)-5-Isopropenyl-2-methyl-2-(3-oxobu-
tyl)-3-(trimethylsilyl)cyclohexanone (3). A mixture of
compound
2
(2.04 g, 9.1 mmol), MVK (1.5 mL,
18.2 mmol) and Ph3CSbCl3 (264 mg, 0.46 mmol) was
stirred at 0 8C, under argon in the dark. After 24 h, the
reaction mixture was diluted with EtOAc and the solvent
removed under reduced pressure. Column chromatography
eluting with hexane/EtOAc (10:0–7:3) allowed to obtain
556 mg (27%) of starting material, 1.40 g (52%) of
compound 3:30 an oil; [a]2D1C39.5 (c 1.8); MS m/z 294
(MC, 2), 237 (36), 236 (49), 223 (32), 143 (38), 131 (16),
130 (100), 115 (38), 73 (86); HRMS 294.2011, C17H30O2Si
required 294.2015; IR (NaCl) 3085, 1705, 1426, 1377,
Compound 6. Mp 95–97 8C; [a]2D1C67.0 (c 1.1); MS m/z
322 (MC, 7), 279 (22), 117 (14), 107 (14), 99 (100), 73 (87);
HRMS 322.2318, C19H34O2Si required 322.2328; IR (KBr)
1
1252, 837 cmK1; H NMR (300 MHz) d 4.79 (1H, s), 4.66
1
(1H, s), 2.52–2.38 (4H, m), 2.10 (3H, s), 2.01–1.84 (4H, m),
1.70 (3H, s), 1.23 (1H, dd, JZ4.4, 7.1 Hz), 1.08 (3H, s),
0.04 (9H, s); 13C NMR d 215.2 (s), 208.2 (s), 146.9 (s),
110.8 (s), 49.8 (s), 43.6 (d), 42.5 (t), 38.2 (t), 32.0 (t), 31.6
(d), 29.9 (q), 27.1 (t), 22.3 (q), 20.9 (q), 0.5 (q).
1362, 1247, 1103, 865, 831 cmK1; H NMR (300 MHz) d
5.39 (1H, br s), 3.90 (4H, m), 2.47 (1H, td, JZ2.1, 14.0 Hz),
2.04 (1H, dd, JZ3.0, 14.0 Hz), 1.78 (1H, br s), 1.74 (1H, t,
JZ3.6 Hz), 1.61–1.51 (5H, m), 1.28 (1H, m), 1.05 (3H, s),
0.93 (3H, d, JZ6.3 Hz), 0.85 (3H, d, JZ6.3 Hz), 0.02 (9H,
s); 13C NMR d 141.0 (s), 126.7 (d), 109.3 (s), 64.1 (t), 42.1
(t), 41.4 (d), 38.1 (t), 37.5 (s), 31.7 (d), 31.6 (d), 31.2 (t),
23.8 (t), 21.3 (q), 21.2 (q), 20.7 (q), K0.0 (q).
3.1.3. (7S,9R,10R)-3-Oxo-9-trimethylsilyl-15-nor-4,11-
eudesmadiene (4). A 1 M solution of KOH in MeOH
(17 mL) was added to compound 3 (1.25 g, 4.3 mmol) and
the mixture stirred for 8 h at room temperature, under argon
in the dark. After this time, satd aqueous NH4Cl was added
and the mixture extracted with EtOAc, washed with brine
and dried over MgSO4. Column chromatography eluting
with hexane/EtOAc 9:1 gave 1.11 g (94%) of compound 4:
mp 62–63 8C (hexane/EtOAc); [a]2D1K119.8 (c 1.5); MS
m/z 276 (MC, 8), 233 (11), 208 (11), 176 (14), 132 (25), 73
(100); HRMS 276.1911, C17H28OSi required 276.1909; IR
3.1.6. (5R,6S,7S,9R,10R)-5,6-Epoxy-3,3-ethylenedioxy-9-
trimethylsilyl-15-noreudesmane (7). A solution of
NaHCO3 (6.0 g, 71.1 mmol) in water (55 mL) was added
to a solution of acetal 6 (2.08 g, 6.2 mmol) in 1:1 CH2Cl2/
acetone (110 mL). The mixture was cooled at 0 8C and
18-crown-6 (100 mg, 0.37 mmol) and oxonew (7.08 g,
11.5 mmol) were added. After stirring for 2 h, the mixture
was diluted with CH2Cl2 and washed with satd aqueous
NaHCO3, 10% aqueous Na2SO3 and again with satd
aqueous NaHCO3. The organic layer was dried over
MgSO4, concentrated under reduced pressure and chro-
matographed using hexane/EtOAc 9:1–6:4 to give 1.94 g
(89%) of epoxide 7: an oil; [a]2D5C20.2 (c 1.2); MS m/z 338
(MC, 2), 239 (11), 180 (33), 143 (34), 107 (23), 99 (96), 86
(46), 73 (100); HRMS 338.2267, C19H34O3Si required
338.2277; IR (NaCl) 1249, 1101, 865, 834 cmK1; 1H NMR
(300 MHz) d 3.89 (4H, m), 2.79 (1H, br s), 2.25 (1H, d, JZ
13.6 Hz), 1.80–1.65 (3H, m), 1.63–1.50 (4H, m), 1.35–1.24
(1H, m), 1.15–1.12 (1H, m), 1.14 (3H, s), 1.03 (3H, d, JZ
6.6 Hz), 0.90 (3H, d, JZ6.6 Hz), 0.58 (1H, dd, JZ2.8,
10.9 Hz), 0.02 (9H, s); 13C NMR d 109.2 (s), 66.3 (d), 64.2;
64.1 (t), 63.2 (s), 41.5 (t), 41.0 (d), 36.8 (t), 35.0 (s), 30.9 (t),
30.8 (d), 28.0 (d), 21.1 (q), 20.9 (q), 20.8 (t), 20.5 (q),
0.5 (q).
(NaCl) 1674, 1443, 1250, 871, 834 cmK1 1H NMR
;
(300 MHz) d 5.73 (1H, d, JZ0.9 Hz), 4.88 (1H, s), 4.75
(1H, s), 2.65 (1H, ddd, JZ2.1, 6.3, 9.0 Hz), 2.57–2.46 (2H,
m), 2.36–2.33 (1H, m), 2.30–2.28 (1H, m), 2.03 (1H, ddq,
JZ2.7, 5.1, 13.3 Hz), 1.85–1.84, (2H, m), 1.78 (1H, dt, JZ
4.5, 14.0 Hz), 1.67 (3H, s), 1.28 (3H, s), 0.91 (1H, dd, JZ
4.1, 12.5 Hz), 0.08 (9H, s); 13C NMR d 199.0 (s), 171.6 (s),
145.9 (s), 124.9 (d), 112.9 (t), 40.9 (d), 39.1 (s), 38.0 (t),
36.6 (t), 34.0 (t), 32.2 (d), 26. (t), 22.5 (q), 20.6 (q), 0.4 (q).
3.1.4. (7S,9R,10R)-3-Oxo-9-trimethylsilyl-15-nor-4-
eudesmene (5). A solution of Wilkinson’s catalyst
(150 mg) in benzene (4 mL) was added to a solution of
compound 4 (1.04 g, 3.8 mmol) in benzene (6 mL) under H2
at atmospheric pressure. The mixture was stirred for 3.5 h
and the solvent removed under reduced pressure. The
residue was chromatographed eluting with hexane/EtOAC
9:1 to give 1.0 g (95%) of compound 5: mp 121–122 8C
(hexane/EtOAc); [a]D22K129.2 (c 1.3); MS m/z 278 (MC,
19), 264 (22), 263 (100), 235 (19), 208 (25), 145 (15), 73
(65); HRMS 278.2063, C17H30OSi required 278.2066; IR
3.1.7. Rearrangement of compound 7. (5S,6S,7S)-6-
Hydroxy-3-oxo-15-nor-9-eremophilene (11) and (5R,6S,7S)-
6-hydroxy-7-isopropyl-10-methylspiro[4.5]dec-9-en-2-one
(12). BF3$Et2O (0.8 mL) was added dropwise to a solution
of compound 7 (1.78 g, 5.2 mmol) in CH2Cl2 (100 mL) at
K78 8C under argon. The resulting solution was stirred at
this temperature for 5 min and at 0 8C for additional 35 min.
Then acetone (30 mL) and 2 M HCl (1.6 mL) were added
and stirring continued for 30 min at room temperature. Satd
1
(NaCl) 1674, 1609, 1459, 1250, 871, 834 cmK1; H NMR
(300 MHz) d 5.64 (1H, s), 2.51–2.24 (4H, m), 2.04 (1H, ddd,
JZ2.9, 5.0, 13.4 Hz), 1.77 (1H, dt, JZ3.6, 12.9 Hz), 1.60–
1.40 (2H, m), 1.26 (3H, s), 0.86 (3H, d, JZ6.3 Hz), 0.81
(3H, d, JZ6.6 Hz), 0.07 (9H, s); 13C NMR d 199.0 (s),

10858
G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
aqueous NaHCO3 was added and the mixture extracted with
CH2Cl2, washed with brine and dried. After removal of the
solvent under reduced pressure, chromatography with
CH2Cl2/isopropanol 99:1 eluted in this order, 305 mg
(20%) of diketone 8, 99 mg (9%) of compound 11,
378 mg (33%) of spirocompound 12 and 35 mg (2%) of
ester 13.
Compound 15. Mp 68–70 8C; [a]2D3K15.6 (c 1.3); MS m/z
224 (MC, 14), 181 (22), 142 (22), 123 (30), 83 (100), 81
(22), 69 (20), 55 (27); HRMS 224.1773, C14H24O2 required
224.1776; IR (KBr) 3415, 1729, 1460, 1398, 1177 cmK1
;
1H NMR (300 MHz) d 3.24 (1H, d, JZ10.5 Hz), 2.42 (1H,
dddd, JZ1.7, 7.7, 12.1, 20.0 Hz), 2.31–2.11 (3H, m), 2.05–
1.97 (2H, m), 1.93–1.80 (2H, m), 1.55–1.34 (3H, m), 1.18
(1H, m), 1.05–0.94 (2H, m), 0.89 (3H, d, JZ6.8 Hz), 0.84
(3H, d, JZ6.6 Hz), 0.78 (3H, d, JZ7.0 Hz); 13C NMR d
221.0 (s), 78.9 (d), 53.4 (s), 45.6 (d), 40.0 (d), 38.5 (t), 37.9
(t), 31.2 (t), 31.1 (t), 25.9 (d), 22.5 (t), 21.0 (q), 16.4 (q),
15.5 (q).
Diketone 8. Mp 124–126 8C (hexane/EtOAc); [a]2D5K79.5
1
(c 1.6); IR (KBr) 1705, 1247, 864, 836 cmK1; H NMR
(300 MHz) d 0.99 (3H, s), 0.94 (3H, d, JZ5.7 Hz), 0.72
(3H, JZ5.7 Hz), 0.09 (9H); 13C NMR d 213.0 (s), 211.5 (s),
58.1 (d), 55.7 (d), 43.7 (s), 40.9 (t), 37.6 (t), 37.4 (t), 33.6
(d), 28.2 (d), 27.8 (t), 20.8 (q), 20.7 (q), 14.8 (q), 0.3 (q).
Compound 14. Mp 115–116 8C; [a]2D3K40.7 (c 1.2); MS m/z
224 (MC, 38), 181 (16), 142 (38), 123 (43), 83 (100), 81
(16), 55 (19); HRMS 224.1777, C14H24O2 required
Compound 11. An oil; [a]2D6K72.5 (c 1.5); MS m/z 222
(MC, 28), 137 (25), 136 (100), 123 (12), 94 (18); HRMS
222.1629, C14H22O2 required 222.1620; IR (NaCl) 3445,
224.1776; IR (KBr) 3427, 1729, 1398, 1187 cmK1 1H
;
NMR (300 MHz) d 3.63 (1H, d, JZ10.0 Hz), 2.59 (1H, d,
JZ18.3 Hz), 2.43 (1H, dq, JZ1.5, 8.7 Hz), 2.19–2.10 (2H,
m), 1.99 (1H, d quint, JZ2.3, 7.0 Hz), 1.90 (1H, d, JZ
18.3 Hz), 1.95–1.80 (1H, m), 1.75–1.65 (1H, m), 1.67 (1H,
s), 1.47–1.40 (3H, m), 1.30–1.20 (2H, m), 0.95 (3H, d, JZ
7.1 Hz), 0.90 (3H, d, JZ7.0 Hz), 0.80 (3H, d, JZ7.0 Hz);
13C NMR d 220.7 (s), 74.2 (d), 48.1 (s), 46.6 (t), 46.1 (d),
39.7 (d), 37.5 (t), 33.1 (t), 29.1 (t), 25.7 (d), 21.1 (q), 17.6 (t),
15.7 (q), 14.0 (q).
1
1661, 1056 cmK1; H NMR (300 MHz) d 5.46 (1H, t, JZ
2.4 Hz), 3.45 (1H, d, JZ11.3 Hz), 2.58 (1H, d, JZ13.4 Hz),
2.56 (1H, m), 2.37–2.31 (2H, m), 2.23 (1H, d, JZ13.4 Hz),
2.12 (1H, sext, JZ3.4 Hz), 1.94–1.86 (2H, m), 1.72–1.65
(2H, m), 1.01 (3H, s), 0.90 (3H, d, JZ7.2 Hz), 0.83 (3H, d,
JZ6.8 Hz); 13C NMR d 211.5 (s), 137.4 (s), 121.3 (d), 78.0
(d), 52.8 (t), 44.5 (s), 41.3 (t), 39.4 (d), 31.5 (t), 25.7 (d),
24.0 (t), 20.6 (q), 18.9 (q), 15.2 (q).
Spirocompound 12. Mp 90–91 8C (hexane/EtOAc); [a]2D1K
115.2 (c 1.3); MS m/z 222 (MC, 14), 194 (19), 136 (100),
121 (22), 105 (32), 93 (51), 79 (24); HRMS 222.1616,
C14H22O2 required 222.1620; IR (KBr) 3434, 1725,
3.1.9. (5R,6S,7S,10R)-7-Isopropyl-10-methyl-6-trimethyl-
silyloxyspiro[4.5]decan-2-one (17) and (5R,6S,7S,10S)-7-
isopropyl-10-methyl-6-trimethylsilyloxyspiro[4.5]decan-
2-one (16). The above hydrogenation mixture was dissolved
in pyridine (50 mL) and treated with hexamethyldisilazane
(6.7 mL, 31.8 mmol) and TMSCl (3.2 mL, 25.1 mmol).
After 1 h, the solvent was removed under reduced pressure
and the resulting oil chromatographed eluting with hexane/
EtOAc 1:0–7:3 to give in this order 536 mg (30%) of
compound 17 and 896 mg (50%) of 16.
1181 cmK1 1H NMR (300 MHz) d 5.37 (1H, d, JZ
;
5.1 Hz), 3.58 (1H, d, JZ11.3 Hz), 2.59–2.49 (1H, m), 2.48
(1H, d, JZ17.3 Hz), 2.35–2.11 (2H, m), 2.10–2.02 (3H, m),
1.95–1.83 (2H, m), 1.78 (1H, td, JZ2.5, 11.1 Hz), 1.65 (3H,
br s), 1.53 (1H, m), 0.89 (3H, d, JZ7.0 Hz), 0.81 (3H, d, JZ
6.8 Hz); 13C NMR d 220.3 (s), 136.4 (s), 122.9 (d), 77.8 (d),
49.1 (s), 44.7 (t), 41.5 (d), 38.0 (t), 30.8 (t), 25.5 (d), 23.6 (t),
20.6 (q), 19.3 (q), 15.2 (q).
Compound 17. Mp 46–47 8C; [a]2D5C13.2 (c 1.4); MS m/z
296 (MC, 69), 281 (27), 184 (34), 171 (45), 157 (35), 111
(32) 97 (53), 85 (61), 71 (74), 69 (57), 57 (100), 55 (52);
HRMS 296.2178, C17H32O2Si required 296.2172; IR (KBr)
Compound 13. An oil; [a]D25C5.9 (c 0.6); IR (NaCl) 3549–
1
3104, 1733, 1716, 1464, 1250, 851, 835 cmK1; H NMR
1
1742, 1251, 1086, 838 cmK1; H NMR (300 MHz) d 3.24
(300 MHz) d 5.23 (1H, s), 4.78 (1H, s), 4.16 (2H, q, JZ
4.1 Hz), 4.01 (1H, d, JZ10.6 Hz), 3.79 (2H, t, JZ4.6 Hz),
2.22–2.05 (4H, m), 1.70–1.45 (3H. m), 1.15 (3H, s), 0.93
(3H, d, JZ7.0 Hz), 0.85 (3H, d, JZ7.0 Hz), 0.02 (9H, s);
13C NMR d 174.6 (s), 154.9 (s), 106.2 (t), 71.1 (d), 66.1 (t),
61.2 (t), 49.6 (d), 42.5 (s), 34.8 (t), 34.7 (d), 29.3 (t), 27.0
(d), 25.2 (q), 21.1 (t), 21.0 (q), 15.9 (q), 1.3 (q).
(1H, d, JZ10.2 Hz), 2.43 (1H, d, JZ18.5 Hz), 2.27 (1H,
m), 2.23 (1H, d, JZ7.5 Hz), 2.15–1.98 (2H, m), 2.01 (1H, d,
JZ18.5 Hz), 1.72 (1H, m), 1.57–1.35 (3H, m), 1.10–0.90
(3H, m), 0.85 (3H, d, JZ7.2 Hz), 0.81 (3H, d, JZ6.8 Hz),
0.71 (3H, d, JZ7.0 Hz), 0.11 (9H, s); 13C NMR d 221.0 (s),
79.8 (d), 50.2 (s), 46.7 (d), 41.6 (d), 38.9 (t), 37.7 (t), 30.8
(t), 30.7 (t), 25.3 (d), 22.1 (t), 21.4 (q), 16.8 (q), 15.4 (q),
1.0 (q).
3.1.8. (5R,6S,7S,10S)-6-Hydroxy-7-isopropyl-10-methyl-
spiro[4.5]decan-2-one (14) and (5R,6S,7S,10R)-6-
hydroxy-7-isopropyl-10-methylspiro[4.5]decan-2-one
(15). Compound 12 (1.36 g, 6.1 mmol) dissolved in acetone
(50 mL) was hydrogenated over 5% Pd/C (415 mg) for 2 h.
The reaction mixture was filtered though a pad of silica gel
to remove the catalyst and the filtrate concentrated under
reduced pressure to give 1.37 g (100%) of a ca. 7:5 mixture
of two epimeric compounds 14 and 15. For analytical
purposes, compounds 14 and 15 were separated in an
independent run after repeated chromatography eluting with
hexane/EtOAc 9:1–6:4.
Compound 16. Mp 52–53 8C; [a]2D6C55.0 (c 1.2); MS m/z
296 (MC, 100), 171 (96), 157 (54), 75 (26), 73 (67); HRMS
296.2177, C17H32O2Si required 296.2172; IR (KBr) 1744,
1251, 1083, 839 cmK1; 1H NMR (300 MHz) d 3.60 (1H, d,
JZ10.0 Hz), 2.51 (1H, dd, JZ1.0, 17.9 Hz), 2.35–2.13 (2H,
m), 2.06–1.91 (3H, m), 1.90–1.80 (1H, m), 1.40–1.32 (2H,
m), 1.23–1.16 (2H, m), 0.95 (3H, d, JZ7.1 Hz), 0.86 (3H, d,
JZ7.0 Hz), 0.72 (3H, d, JZ6.8 Hz), 0.10 (9H, s); 13C NMR
d 219.9 (s), 74.2 (d), 49.3 (s), 47.2 (d), 45.6 (t), 36.1 (t), 36.0
(d), 29.7 (t), 28.4 (t), 25.1 (d), 21.4 (q), 17.4 (t), 15.6 (q),
14.6 (q), 1.0 (q).

G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
10859
3.1.10. (5S,6S,7S,10R)-7-Isopropyl-2,10-dimethyl-6-tri-
methylsilyloxyspiro[4.5]dec-1-ene (20). A suspension of
anhydrous CeCl3 (300 mg, 1.2 mmol) in dry THF (6 mL)
was stirred overnight under argon and in an ultrasound bath
for 3 h (additional) until the obtention of an homogeneous
suspension of finely divided CeCl3. A solution of compound
17 (98 mg, 0.33 mmol) in THF (1 mL) was added, the
mixture was cooled at 0 8C followed by the addition of a
1.6 M solution of MeLi in diethyl ether (0.65 mL,
1.0 mmol). After 20 min, the reaction was quenched with
satd aqueous NH4Cl, extracted with diethyl ether, washed
with brine, dried over MgSO4, and the solvent removed
under reduced pressure to give 100 mg (96%) of an oil
composed of a ca. 2:3 of two epimeric alcohols. For
analytical purposes both epimers were separated in an
independent run by chromatography with hexane/EtOAc
9:1–5:5.
Compound 19. An oil; [a]2D5K13.2 (c 0.5); 1H NMR
(300 MHz) d 4.69 (1H, d, JZ1.9 Hz), 4.64 (1H, d, JZ
1.9 Hz), 3.20 (1H, d, JZ10.4 Hz), 2.37 (1H, d, JZ16.4 Hz),
2.25 (2H, s, m), 2.03 (2H, m), 1.84 (1H, m), 1.32–1.01 (4H,
m), 0.85 (3H, d, JZ7.2 Hz), 0.82 (3H, d, JZ6.8 Hz), 0.69
(3H, d, JZ7.0 Hz), 0.10 (9H, s).
Compound 20. An oil; [a]2D5K35.0 (c 1.2); MS m/z 294
(MC, 56), 161 (40), 134 (53), 121 (100), 108 (44), 81 (33),
73 (68), 69 (28), 57 (37); HRMS 294.2376, C18H34OSi
1
required 294.2379; IR (NaCl) 1249, 1114, 836 cmK1; H
NMR (300 MHz) d 5.23 (1H, s), 3.23 (1H, d, JZ10.6 Hz),
2.15 (2H, t, JZ7.4 Hz), 2.08 (1H, dq, JZ2.4, 7.0 Hz), 1.97–
1.87 (1H, m), 1.72 (3H, s), 1.64–1.56 (2H, m), 1.43–1.25
(3H, m), 0.87 (3H, d, JZ7.0 Hz), 0.75 (3H, d, JZ6.5 Hz),
0.71 (3H, d, JZ7.0 Hz), 0.11 (9H, s); 13C NMR d 142.9 (s),
123.2 (d), 80.8 (d), 61.4 (s), 46.5 (d), 41.9 (d), 36.6 (t), 32.8
(t), 31.4 (t), 25.5 (d), 22.7 (t), 21.4 (q), 17.1 (q), 16.7 (q),
15.2 (q), 1.1 (q).
Minor isomer. An oil; [a]D25K28.7 (c 1.4); IR (NaCl) 3500,
1
1252, 839 cmK1; H NMR (300 MHz) d 4.04 (1H, s), 3.22
3.1.11. (K)-Axenol (21). Trimethylsilyl ether 20 (35 mg,
0.12 mmol) was stirred in 3:5:10 H2O/AcOH/THF (2.5 mL)
for 45 min at room temperature. The mixture was diluted
with CH2Cl2, washed with satd aqueous NaHCO3 and brine,
and dried. Column chromatography eluting with hexane/
EtOAc 95:5 gave 24 mg (91%) of compound 21: an oil;
[a]2D5K35.0 (c 1.2); MS m/z 222 (MC, 27), 204 (32), 121
(100), 108 (38), 97 (30), 93 (37), 81 (93), 71 (39), 69 (53),
57 (68), 55 (54); HRMS 222.1988, C15H26O required
222.1984; IR (NaCl) 3561, 3474, 1464, 1374, 989 cmK1; 1H
NMR (300 MHz) d 5.12 (1H, d, JZ1.7 Hz), 3.04 (1H, t, JZ
10.4 Hz), 2.21–2.05 (4H, m), 1.76 (3H, br s), 1.51 (2H, m),
1.20–0.98 (4H, m), 0.87 (3H, d, JZ7.1 Hz), 0.77 (3H, d, JZ
7.0 Hz), 0.76 (3H, d, JZ6.6 Hz); 13C NMR d 147.3 (s),
121.7 (d), 78.3 (d), 61.2 (s), 47.1 (d), 40.7 (d), 36.8 (t), 33.1
(t), 31.8 (t), 26.1 (d), 23.1 (t), 21.1 (q), 17.2 (q), 16.9 (q),
15.7 (q).
(1H, d, JZ10.5 Hz), 2.04–1.94 (2H, m), 1.62–1.57 (2H, m),
1.50–1.39 (4H, m), 1.28 (3H, s), 0.85 (3H, d, JZ7.0 Hz),
0.81 (3H, d, JZ6.7 Hz), 0.71 (3H, d, JZ6.9 Hz), 0.19 (9H,
s); 13C NMR d 81.4 (d), 78.7 (s), 53.2 (s), 46.4 (d), 41.8 (d),
41.7 (t), 41.6 (t), 33.5 (t), 30.5 (t), 25.8 (q), 25.1 (d), 22.7 (t),
21.6 (q), 16.3 (q), 16.1 (q), 1.1 (q).
Major isomer. An oil; [a]2D5K26.5 (c 1.4); MS m/z 312
(MC, 37), 295 (28), 294 (100), 211 (28), 204 (41), 117 (76),
161 (62), 157 (38), 121 (50), 73 (36); HRMS 312.2474,
C18H36O2Si requiere 312.2485; IR (NaCl) 3400, 1251,
1
1078, 837 cmK1; H RMN (300 MHz) d 3.20 (1H, d, JZ
10.4 Hz), 2.00 (1H, d quint, JZ2.2, 6.9 Hz), 1.83–1.70 (3H,
m), 1.61–1.55 (2H, m), 1.49–1.37 (2H, m), 1.32 (3H, s),
0.95 (3H, d, JZ6.8 Hz), 0.84 (3H, d, JZ7.0 Hz), 0.68
(3H, d, JZ6.9 Hz), 0.12 (9H, s); 13C RMN d 82.5 (d),
80.6 (s), 53.5 (s), 46.2 (d), 42.0 (t), 41.2 (t), 40.0 (d), 34.5 (t),
32.0 (t), 29.1 (q), 24.8 (d), 22.5 (t), 21.6 (q), 17.7 (q), 16.0
(q), 1.4 (q).
3.1.12. (5S,7S,10R)-(C)-7-Isopropyl-2,10-dimethyl-
spiro[4.5]dec-1-en-6-one (22). Tetrapropylammonium per-
ruthenate (TPAP) (2.7 mg, 0.008 mmol) was added to a
solution of compound 21 (19 mg, 0.076 mmol) and NMO
(22 mg, 0.19 mmol) in CH2Cl2 (0.6 mL). After 1.5 h the
reaction mixture was chromatographed eluting with hexane/
EtOAC 8:2 to give 15 mg (89%) of compound 22: mp 44–
46 8C; [a]2D5C56.8 (c 0.8); MS m/z 220 (MC, 28), 121 (99),
108 (62), 107 (34), 97 (29), 93 (39), 85 (39), 83 (33), 81
(41), 71 (63), 69 (56), 57 (100), 55 (71); HRMS 220.1826,
C15H24O required 220.1827; IR (KBr) 1705, 1458, 1448,
871 cmK1; 1H NMR (300 MHz) d 5.28 (1H, d, JZ1.5 Hz),
2.77 (1H, ddd, JZ4.5, 8.7, 14.4 Hz), 2.19–1.97 (5H, m),
1.70 (3H, d, JZ1.3 Hz), 1.69–1.45 (4H, m), 1.33–1.23 (1H,
m), 0.85 (3H, d, JZ7.0 Hz), 0.85 (3H, d, JZ5.8 Hz), 0.82,
(3H, d, JZ6.8 Hz); 13C NMR d 212.6 (s), 144.8 (s), 123.0
(d), 69.6 (s), 53.3 (d), 43.5 (d), 36.0 (t), 31.7 (t), 28.5 (t),
28.1 (t), 26.2 (d), 21.4 (q), 18.7 (q), 17.0 (q), 16.6 (q).
The resulting alcohol mixture (100 mg, 0.32 mmol) was
dissolved in THF (5 mL) and treated with Et3N (0.23 mL,
1.6 mmol) and MsCl (48 mL, 0.61 mmol) at room tempera-
ture. After 1.5 h, water was added and the mixture extracted
with ether, washed with brine and dried. Column
chromatography eluting with hexane/EtOAc 1:0–9:1
allowed to obtain 38 mg (41%) of 18, 11 mg (12%) of 19
and 22 mg (23%) of 20.
Compound 18. An oil; [a]2D5K18.3 (c 1.4); MS m/z 294
(MC, 38), 204 (100), 161 (52), 123 (26), 121 (53), 120 (50),
119 (44), 105 (33), 80 (45), 75 (26), 73 (52); HRMS
294.2368, C18H34OSi required 294.2379; IR (NaCl) 1250,
1
1099, 897, 837 cmK1; H NMR (300 MHz) d 5.07 (1H, br
s), 3.23 (1H, d, JZ10.4 Hz), 2.36 (1H, dq, JZ2.4, 16.3 Hz),
2.22 (1H, d, JZ16.4 Hz), 2.03 (2H, m), 1.78 (1H, d, JZ
16.3 Hz), 1.81 (3H, s), 1.48 (1H, dq, JZ3.2, 12.6 Hz), 1.36
(1H, dq, JZ3.2, 12.6 Hz), 1.26–1.05 (3H, m), 0.86 (3H, d, JZ
7.0 Hz), 0.73(3H, d, JZ6.5 Hz), 0.70(3H, d,JZ6.9 Hz), 0.07
(9H, s); 13C NMR d 140.2 (s), 122.2 (d), 80.3 (d), 52.1 (s), 46.5
(d), 43.9 (t), 41.1 (d), 36.9 (t), 30.3 (t), 25.4 (d), 22.3 (t), 21.5
(q), 16.5 (q), 15.9 (q), 15.4 (q), 1.0 (q).
3.1.13. (K)-Gleenol (23). A solution of compound 22
(14 mg, 0.064 mmol) in THF (0.75 mL) was treated with a
1 M solution of L-Selectride in THF (0.32 mL, 0.32 mmol)
at room temperature. After 24 h, a solution of H2O (0.3 mL)
in EtOH (1 mL) was added, the reaction was stirred for
20 min followed by the addition of a mixture of 4 M

10860
G. Blay et al. / Tetrahedron 61 (2005) 10853–10860
10. (a) Hikino, H.; Kohama, T.; Takemoto, T. Tetrahedron 1969,
25, 1037–1045. (b) Mehta, G.; Chetty, G. L.; Nayak, U. R.;
Dev, S. Tetrahedron 1968, 24, 3775–3786.
aqueous NaOH (0.32 mL) and 30% H2O2 (0.65 mL). After
stirring for 2 h, water was added and the mixture extracted
with EtOAc, washed with brine and dried. Column
chromatography eluting with hexane/EtOAc 9:1 gave
2.1 mg (15%) and 9.5 mg (67%) of (K)-gleenol 23: an
oil; [a]2D5K22.9 (c 0.4) [lit.18 [a]2D0K15.02 (c 0.5)]; MS m/z
222 (MC, 16), 204 (28), 121 (100), 108 (38), 107 (28), 93
(30), 81 (80), 69 (31); HRMS 222.1992, C15H26O required
´
11. Blay, G.; Cardona, L.; Collado, A. M.; Garcıa, B.; Pedro, J. R.
Tetrahedron Lett. 2003, 44, 8117–8119.
´
12. Blay, G.; Collado, A. M.; Garcıa, B.; Morcillo, V.; Pedro, J. R.
J. Org. Chem. 2004, 69, 7294–7302.
13. Hwu, J. R.; Wetzel, J. M. J. Org. Chem. 1992, 57, 922–928.
14. Colvin, E. W. Silicon Reagents in Organic Synthesis;
Academic: London, 1988.
1
222.1984; IR (NaCl) 3502, 1463, 1376 cmK1; H NMR
(300 MHz) d 5.15 (1H, d, JZ1.5 Hz), 3.51 (1H, s), 2.20
(1H, m), 1.94–1.74 (1H, m), 1.72 (3H, d, JZ1.3 Hz),
1.80–1.60 (1H, m), 1.70–1.60 (1H, m), 1.41–1.60 (1H, m),
1.50–1.40 (1H, m), 1.30–1.20 (1H, m), 1.20–1.10 (1H, m),
1.14–1.00 (1H, m), 0.90 (3H, d, JZ6.6 Hz), 0.89 (3H, d, JZ
6.6 Hz), 0.73 (3H, d, JZ6.8 Hz); 13C NMR d 142.8 (s),
125.5 (d), 76.4 (d), 58.8 (s), 45.3 (d), 36.3 (t), 34.0 (d), 34.0
(t), 31.7 (t), 29.3 (d), 24.4 (t), 21.2 (q), 20.7 (q), 17.0 (q),
16.2 (q).
15. Kurvyakov, P. I.; Gatilov, Y. V.; Yu, V.; Khan, V. A.;
Dubovenko, Zh. V.; Pentegova, V. A. Khim. Prir. Soedin.
1979, 164–168.
16. Khan, V. A.; Dubovenko, Zh. V.; Pentegova, V. A. Khim. Prir.
Soedin. 1983, 109–110.
17. Nagahama, S.; Tazaki, M.; Nomura, H.; Nishimura, K.;
Tajima, M.; Iwasita, Y. Mokuzai Gakkaishi 1996, 42,
1127–1133.
´
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N.; Barragan, A. Phytochemistry 1991, 30, 1551–1554.
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Acknowledgements
Financial support from the European Commission (FAIR
CT 96-1781) is gratefully acknowledged. A. M. C. thanks
the E.C. for a pre-doctoral grant.
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(6H, m), 2.07 (3H, d, JZ1.2 Hz), 2.04 (3H, d, JZ1.5 Hz), 1.66
(3H, s), 1.32 (1H, d, JZ14.1 Hz), 1.02 (3H, s), 0.00 (9H, s);
13C NMR d 216.0 (s), 211.3 (s), 207.5 (s), 146.9 (s), 110.9 (t),
50.3 (s), 46.6 (d), 43.1 (d), 42.3 (t), 39.9 (t), 39.4 (t), 33.0 (d),
29.8 (q), 29.7 (q), 27.3 (t), 27.0 (t), 22.2 (q), 20.7 (q), 0.3 (q).
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1
Compound 10b. An oil; H NMR (300 MHz) d 4.75 (1H, s),
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4.64 (1H, s), 2.49–2.22 (6H, m), 2.12 (3H, s), 2.04 (3H, s), 1.67
(3H, s), 0.93 (3H, s), 0.00 (9H); 13C NMR d 215.3 (s), 211.4
(s), 207.3 (s), 146.8 (s), 110.5 (t), 50.6 (s), 47.1 (d), 43.6 (d),
42.3 (t), 40.0 (t), 39.3 (t), 33.2 (d), 29.8 (q), 29.2 (q), 27.3 (t),
26.8 (t), 21.8 (q), 20.8 (q), 0.2 (q).
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