The novel skeletal rearrangement of cyclopentanones into hydroazulenones via a radical process and its application to the formal synthesis of damsinic acid

Article abstract of DOI:10.1016/S0040-4020(00)00892-9

A new skeletal rearrangement of cyclopentanones with pentynyl side chains into hydroazulene compounds via a radical process was developed. The presence of a triethylsilyloxy group at the α-position of the cyclopentanone was found to increase the reactivity. Except for this, there was no limitation of the reaction: The reaction was also applied to synthetic studies of damsinic acid, which was isolated from Ambrosia ambrosioides (Cav.) Payne along with damsin. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00892-9

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9241±9257
The Novel Skeletal Rearrangement of Cyclopentanones into
Hydroazulenones via a Radical Process and its Application to the
Formal Synthesis of Damsinic Acid
Atsushi Nishida,a Irie Miyoshi,a Yukie Ogasawara,a Shinji Nagumo,a Norio Kawahara,a,
*
Mayumi Nishidab and Hiroaki Takayanagic
aHokkaido College of Pharmacy, Katuraoka 7-1, Otaru 047-0264, Japan
bFaculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
cSchool of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo 180-0072, Japan
Received 9 August 2000; accepted 25 September 2000
AbstractÐA new skeletal rearrangement of cyclopentanones with pentynyl side chains into hydroazulene compounds via a radical process
was developed. The presence of a triethylsilyloxy group at the a-position of the cyclopentanone was found to increase the reactivity. Except
for this, there was no limitation of the reaction. The reaction was also applied to synthetic studies of damsinic acid, which was isolated from
Ambrosia ambrosioides (Cav.) Payne along with damsin. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
cal process would be a more attractive method because of its
potential for the synthesis of medium and large rings.2 We
previously reported that treatment of cyclohexanones 1 with
triphenyltin hydride and azobisisobutyronitrile (AIBN) in
re¯uxing benzene gave bicyclo[6.3.0]undecanones 2 in
fairly good yield3 as shown in Scheme 1. In this transforma-
tion, the stannylvinyl radical A derived from 1 attacked the
carbonyl group on the proximate ring. The resulting oxy
radical B was then converted into a tertiary carbon-centered
radical C through a ring opening. The radical C was added
A radical process has been recognized as being a useful
method for the construction of a carbon±carbon bond. An
extension of this reaction to an intramolecular mode
increased its potency in organic synthesis. One of the
most important advantages is that a highly hindered
carbon±carbon bond and quaternary stereogenic center
can be easily constructed through a radical cyclization.1 A
skeletal rearrangement including ring expansion via a radi-
Scheme 1.
Keywords: radical skeletal rearrangement; cyclopentanone derivatives; hydroazulene compound; damsinic acid.
* Corresponding author. Tel.: 181-134-62-1835; fax: 181-134-62-5161; e-mail: kawahara@hokuyakudai.ac.jp
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00892-9

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A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
in a wide variety of natural sources. We report here the
radical skeletal rearrangement of cyclopentanones 3 to
hydroazulenone compounds 4.4 Furthermore, the formal
synthesis of damsinic acid based on the newly developed
method is also described.
Synthesis of substrates 3a±i (Scheme 2)
Cyclopentanones 3a±i were selected as substrates of the
radical skeletal rearrangement. Compound 3a (Scheme 5)
was prepared by the reported method5. Compound 3b was
prepared from cyclopentanone 5.6 Treatment of 5 with
5-trimethyl-4-pentynyllithium, derived from 5-iodo-1-
trimethylsilyl-1-pentyne7 and tert-BuLi, followed by
desilylation with tetrabutylammonium ¯uoride (TBAF)
and deacetalization gave 6 in 70% yield. Silylation of 6
with triethylsilyl tri¯uoromethanesulfonate (TESOTf) in
the presence of 2,6-di-tert-butylpyridine afforded 3b in
92% yield. Compound 3c was synthesized on the basis of
the coupling of 5 and a side chain moiety 9, which was
derived from ethyl 2-methylpropionate. Alkylation of
2-methylpropionate with trimethylsilylpropargyl bromide
gave 7 in 78% yield. Reduction of 7 with LiAlH4, followed
by the sequence of tosylation and iodination afforded 9.
Coupling of 5 with an alkyllithium reagent, derived from
9, followed by deacetalization gave 10, which was
converted into 11 on treatment with TBAF. Silylation of
11 with TESOTf afforded 3c in 96% yield (Scheme 3).
Scheme 2. Reagents: (a) (i) 5-iodo-1-trimethylsilyl-1-pentyne, tert-BuLi,
Et2O, 2708C; (ii) TBAF, THF, 08C; (iii) dil. H2SO4, AcOH, H2O, THF
708C; (b) 2,6-di-tert-butylpyridine, TESOTf, CH2Cl2, 2688C; (c) LDA,
3-bromo-1-trimethylsilyl-1-propyne, THF, 2788C; (d) LiAlH4, Et2O,
08C; (e) (i) TsCl, DMAP, pyridine, 08C; (ii) Nal, DMF, 1108C; (f) (i) 9,
tert-BuLi, Et2O, 2788C; (ii) dil. H2SO4, AcOH, H2O, THF, 708C; (g)
TBAF, THF, 08C; (h) 2,6-di-tert-butylpyridine, TESOTF, CH2Cl2, 2788C.
Next, we prepared ketones 3d±i (Scheme 4), which were
expected to be converted into hydroazulenone 4d±i with a
hydroxy group on the cyclopentane ring (Tables 1 and 2).
This hydroxy group in 4d±i would be important for the
synthesis of natural products. At ®rst, alcohols 18 and 19,
which were common intermediates of 3d±i, were prepared
from hydroxy ketal 12.6 Protection of 12 by the methoxy-
phenylmethyl (MPM) group followed by deacetalization
afforded the ketone 13. Treatment of 13 with an allyl
grignard reagent gave two isomeric alcohols, 14 and 15.
to the proximate stannylvinyl group, generating a secondary
carbon-centered radical D. Finally, the addition of the radi-
cal to the carbonyl group followed by ring-opening afforded
2. In the last step, Ph3Snz should be regenerated. This facile
ring transformation was considered to be applicable to the
construction of a hydroazulene skeleton, which is presented
Scheme 3. Reagents: (a) (i) MPMCl, NaH, DMSO, THF, rt; (ii) dil. H2SO4, AcOH, H2O, THF, 708C; (b) allyl bromide, Mg, 08C; (c) 2,6-di-tert-butylpyridine,
TESOTf, CH2Cl2, 2688C; (d) OsO4, NaIO4, tert-BuOH, H2O, rt; (e) propargyl bromide, Mg, HgCl2, Et2O, 08C; (f) TBAF, THF, 08C; (g) benzaldehyde, PPTS,
benzene, 458C.

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9243
yields by the sequence of protection of the hydroxy group
(TES, methoxymethyl (MOM) or silyloxyethoxymethyl
(SEM) group), deprotection of the MPM group, and oxida-
tion with tetrapropylammonium perruthenate (TPAP).
Alcohol 19 was also converted into 3g±i by the same
procedure.
Radical skeletal rearrangement
Radical skeletal rearrangement of 3 was carried out by
treatment with Ph3SnH (1.5±2 equiv.)8 and AIBN (1.1±
1.5 equiv.). The general procedure was that a toluene
solution of Ph3SnH and AIBN was added to a re¯uxing
solution of 3 in toluene using a syringe pump. Contrary to
our expectation, treatment of 3a under radical conditions
gave a complex mixture, while 3b with a silyloxy group
at the C-2 position was converted into hydroazulenone
compound 4b (39%) and vinyl stannane 36 (43%). An
electron-donating substituent such as a silyloxy group at
the C-2 position might be essential for smooth conversion
of the skeletal rearrangement.4 This group should stabilize
the radical intermediate C and facilitate the attack of the
radical on the exo ole®n. The substituents at the side chain in
substrates were also crucial for reactivity. Conversion of 3c
proceeded smoothly under the standard conditions to give
4c in 79% yield. This result might be explained by con-
sidering that geminal dimethyl substituents increased the
ground state strain energy of the radical intermediate A
(Scheme 5).9
The effect of substituents at the side chain was further
examined by using 3d±i (Tables 1 and 2). Compounds 3d
and 3g, having a TESO group at the side chain, were
successfully converted into the rearranged products in
good yield using either AIBN or azobis(cyclohexane)carbo-
nitrile (ACN)10 as an initiator. Except for 3e, the substrates
3f, 3h and 3i, which have acetal groups at the side chain,
were less reactive under the radical conditions using AIBN.
The acetal group may not be bulky enough to lower the
activation energy for the ®rst cyclization step. It is worth
mentioning that the rearrangements of 3f, 3h and 3i were
improved by using ACN instead of AIBN. Since compared
to AIBN, the more thermally stable compound ACN can
generate a suf®cient concentration of Ph3Snz continuously
at 1108C and move the equilibrium point of this reaction
toward cyclization.
Scheme 4. Reagents: (a) TESOTf, 2,6-lutidine, CH2Cl2, 2788C;
(b) MOMCl, (i-Pr)2NEt, DMAP, rt; (c) SEMCl, (i-Pr)2NEt, CH2Cl2, rt;
Ê
(d) DDQ, H2O, CH2Cl2, rt; (e) TPAP, NMO, MS4 A, CH2Cl2, rt.
After being separated, the major isomer 14 was converted
into aldehyde 17 by the sequence of silylation and oxidative
cleavage of ole®n. Treatment of 17 with a propargyl
grignard reagent provided two isomeric alcohols 18 and
19, which were separated by column chromatography on
silca gel. To determine the stereochemistry of these
compounds, 18 and 19 were converted into acetals, 22 and
23, respectively. These compounds exhibited NOE correla-
tions as shown in Scheme 3.
Compound 18 was converted into 3d, 3e and 3f in good
Table 1. Radical cyclization of 3d±f
Run
Substrate
R
Initiator
Yield of 4 (%)
Recovery of 3 (%)
Ratio of isomersa
1
2
3
4
5
6
3d
3d
3e
3e
3f
SiEt3
SiEt3
MOM
MOM
SEM
SEM
AIBN
ACN
AIBN
ACN
AIBN
ACN
60
68
51
74
19
55
8
±
24
±
61
14
4d:4gˆ2.3:1
4d:4gˆ2.2:1
4e:4hˆ1.8:1
4e:4hˆ1.2:1
4f:4iˆ1.2:1
4f:4iˆ2.1:1
3f
a Ratio was determined with 1H NMR.

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A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
Table 2. Radical cyclization of 3g±i
Run
Substrate
R
Initiator
Yield of 4 (%)
Recovery of 3 (%)
Ratio of isomersa
1
2
3
4
5
3g
3h
3h
3i
SiEt3
MOM
MOM
SEM
SEM
AIBN
AIBN
ACN
AIBN
ACN
64
11
57
13
45
±
66
±
55
27
4d:4gˆ1:3.4
4e:4hˆ1:3.5
4e:4hˆ1:6.2
4f:4iˆ1:3
3i
4f:4iˆ1:2.8
a Ratio was determined with 1H NMR.
It should be noted that the reaction of 3d±i was concomitant
with partial epimerization to give two isomeric hydro-
azulene compounds. The stereochemistries of 4d±f
(cis-isomers) and 4g±i (trans-isomers) were assigned on
the basis of 1H NMR. The C-2 proton peak of 4d±f appeared
at a higher magnetic ®eld (ca. 0.4 ppm) than that of 4g±i.
The relative con®guration of 4h was unequivocally deter-
mined by X-ray analysis of 37, which was prepared from 4h
by 3 steps (Scheme 6).
Synthetic studies of damsinic acid
We then applied this reaction to the synthesis of pseudo-
guaianolides,11 a group of non-isoprenoid hydroazulenic
sesquiterpenes.12 These compounds are different from
other hydroazulenic natural products in that they possess
an angular methyl group at the C-1 position. This means
that 1,2-methyl migration from C-10 to C-1 proceeds at
some stage in their biosynthesis.13 It has also been shown
that various members exhibit signi®cant antitumor or
co-carcinogenic activity.14 Damsinic acid,15 which was
The epimerization might be due to the interconversion
between conformation C-1 and C-2 in the 9-membered
radical intermediate, as shown in Scheme 7. The ratio of
isomeric products was dependent on the substrate structure.
That is, when 3d±f was subjected to radical conditions,
cis-isomers, 4d±f, were major products. On the other
hand, 3g±i afforded 4g±i as major products under the
same conditions. These ®ndings suggested that the cycliza-
tion of radical C followed by subsequent processes proceeds
to give hydroazulenic products before the equilibration
between C-1 and C-2 is established.
Scheme 6. Reagents: (a) DIBAH, toluene, 2788C; (b) p-bromobenzoyl
chloride, DMAP, Pyr, rt; (c) TBAF, THF, 08C.
Scheme 5. Reagents: (a) Ph3SnH, AIBN, toluene, re¯ux.
Scheme 7.

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9245
Scheme 8.
isolated from Ambrosia ambrosioides (Cav.) Payne along
with damsin, has the same relative con®guration as other
pseudoguaianolides at C-1, 3, 6 and 10. We describe here
synthetic studies of damsinic acid based on a newly
developed radical skeletal rearrangement.
skeletal rearrangement of 41 by using ACN afforded an
inseparable mixture of 42 and 43 (50%, 42:43ˆ8:1) and
vinyl stannane 44 (21%). Fortunately, reduction of the
mixture with diisobutylaluminum hydride (DIBAH)
followed by column chromatography with silica gel gave
the desired alcohol 45 (73%) as a single compound and a
mixture of 46 and 47 (17%) (Scheme 9).
Our retrosynthetic strategy is shown in Scheme 8. Damsinic
acid has already been prepared from diketone a by
Lansbury's group.16 The diketone a was expected to be
easily prepared from b, which might be obtained by carrying
out cyclopropanation and hydroxylation at the C-10 position
of the enone d. The enone d could be prepared by the radical
skeletal rearrangement of the cyclopentanone derivative e.
Furthermore, the installation of a pentynyl side chain to
enamine f followed by hydrolysis was expected to give e.
The alcohol 45 was further acetylated to give 48 in 97%
yield. Hydroxylation of 48 at the C-10 position has been
achieved by SeO2 oxidation, and the desired allyl alcohol
49 was obtained in 88% yield. In this oxidation reaction, the
presence of pyridine was essential for obtaining an excellent
yield.18 The hydroxy group was stereoselectively introduced
from the a-side, which was later proved by X-ray analysis.
After protection of the hydroxy gruop in 49 by the MOM
group, the acetyl group of 50 was hydrolyzed with
potassium carbonate to give 51. Stereoselective cyclo-
propanation of 51 by Simmons±Smith's method19 followed
by oxidation with TPAP afforded 53 in 60% yield (2 steps).
Coupling of enamine 3817 with 5-trimethylsilyloxy-4-
pentynyl lithium followed by the sequence of removal of
the trimethylsilyl (TMS) group and silylation of the tertiary
alcohol group gave ketone 41 in good yield. The radical
Scheme 9. Reagents: (a) 4-iodo-1-trimethylsilyl-1-pentyne, tert-BuLi, Et2O, 2708C; (b) TBAF, THF, 08C; (c) 2,6-di-tert-butylpyridine, TESOTf, CH2Cl2,
2758C; (d) Ph3SnH, ACN, toluene, re¯ux; (e) DIBAH, toluene, 758C.

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A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
Scheme 10. Reagents: (a) Ac2O, DMAP, pyridin, rt; (b) SeO2, pyr, toluene, re¯ux; (c) MOMCl, (i-Pr)2NEt, CH2Cl2, rt; (d) K2CO3, MeOH, rt; (e) Zn±Cu,
CH2l2, DME, Et2O, re¯ux; (f) TPAP, NMO, CH2Cl2, rt; (g) H2, Pd(OH)2±C, EtOH, rt; (h) TBAF, THF, 08C; (i) MsCl, Et3N, CH2C2, rt; (j) HCl, THF, rt;
(k) TPAP, NMO, CH2Cl2, rt.
Catalytic hydrogenation of 53 led to the cyclopropane ring-
opening to give 54 in 92% yield. When 54 was desilylated
on treatment with TBAF, crystal alcohol 55 was obtained in
94% yield. The relative con®guration of 55 was unequivo-
cally determined to be (1b, 6b, 7b, 10a) by X-ray crystal-
lography. Treatment of 55 with methanesulfonyl chloride
(MsCl) in the presence of triethyamine caused dehydration,
giving the desired product 56 and its ole®nic isomer 57 in
the ratio of 1:2.3. These were separated by column chroma-
tography on silica gel. A number of attempts at isomeriza-
tion from 57 to 56 were made,20 but the reaction did not
proceed. Finally, compound 56 was treated with HCl in THF
to afford the secondary alcohol 58, which was successfully
converted into diketone 59 by oxidation with TPAP.
Spectroscopic data of 59 were in agreement with those of
59, which was prepared by our group using Lansbury's
method (Scheme 10).
based on the radical skeletal rearrangement of cyclo-
alkanone 41. This novel reaction is expected to be
applicable to other pseudoguaianolides.
Experimental
Melting points were measured using a Yanaco micro point
apparatus and are uncorrected.1H NMR spectra were
recorded on a JEOL JNM-GX270 (270 MHz) spectrometer
in CDCl3 unless otherwise speci®ed, and chemical shift
values are expressed in d (ppm) with tetramethylsilane as
an internal standard. 13C NMR spectra (68 MHz) were also
recorded in CDCl3 unless otherwise speci®ed, and chemical
shift values are expressed in d(ppm) with CDCl3 as an
internal standard. Coupling constants (J) are expressed in
hertz (Hz). Abbreviations are as follows: sˆsinglet,
dˆdoublet, tˆtriplet, qˆqualted, quint. ˆquinted, mˆ
multiplet, and brˆbroad. The secondary ion mass spectra
(SI-MS) and electron impact mass spectra (EI-MS) were
measured using a Hitachi-M-2000 mass spectrometer, and
IR spectra were measured using a JASCO FT-IR7000.
Reactions were followed by thin-layer chromatography
(TLC) on Silica gel 60 F254-precoated TLC plates. Solvents
were dried according to the established procedure by
distillation under an argon atmosphere from the appropriate
drying agent. Column chromatography was carried out
Conclusions
We developed a new method for the construction of a hydro-
azulene ring by a radical skeletal rearrangement. The
triethylsilyloxy group at the C-2 position in substrates was
found to increase the yield of this reaction. Substituents at
other positions did not disturb the skeletal rearrangement.
We also achieved the formal total synthesis of damsinic acid

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9247
using silica gel (Silica gel 60, Merck, 70±230 or 230±400
mesh).
(20 ml) under an argon atmosphere at 2788C. A solution of
ethyl 2-methylpropanate (2.0 g, 17.2 mmol) in THF (7.5 ml)
was added to the LDA solution. After being stirred for
35 min, a solution of 3-bromo-1-trimethylsilyl-1-propyne
(3.2 ml, 22 mmol) in THF (6.5 ml) was added to the
reaction mixture. After being stirred for an additional
1.5 h at 2788C, the reaction mixture was quenched with
saturated aqueous NH4Cl at 08C and extracted with ether.
Combined extracts were washed with brine and dried
(MgSO4). The solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (20/1) as an eluent to give 7 (3.04 g,
2-Hydroxy-2-pent-4-ynylcyclopentan-1-one (6). To a
solution of 5-iodo-1-trimethylsilyl-1-pentyne (1.56 g,
7.1 mmol) in ether (30 ml) was added dropwisely tert-
BuLi (1.57 M in n-pentane solution, 8.0 ml, 12.6 mmol)
under an argon atmosphere, and the reaction mixture was
stirred at 2708C for 35 min. At the same temperature, a
solution of 5 (625 mg, 4.4 mmol) in ether (20 ml) was
added. After being stirred for 30 min, the reaction mixture
was quenched with saturated aqueous NH4Cl and extracted
with ether. Combined extracts were washed with brine and
dried (MgSO4). The solvent was removed under reduced
pressure. The residue was puri®ed by column chromato-
graphy with hexane±AcOEt (5/1) as an eluent to give
alcohol material (2.32 g). This obtained alcohol was
dissolved in THF (40 ml), and TBAF (1.0 M in THF,
10.0 ml, 10.0 mmol) was added at 08C. After being stirred
for 40 min, the reaction mixture was quenched with satu-
rated aqueous NH4Cl, extracted with ether. Combined
extracts were washed with brine, and dried (MgSO4). The
solvent was removed under reduced pressure. The residue
was puri®ed by column chromatography with hexane±
AcOEt (3/1) as an eluent to give desilylated compound
(1.69 g). To a solution of the desilylated compound in
AcOH (11 ml), H2O (11 ml) and THF (11 ml) was added
conc. H2SO4 (0.45 ml) at room temperature. After being
stirred for 2 h at 708C, the reaction mixture was quenched
with saturated aqueous NaHCO3 and extracted with ether.
Combined extracts were washed with brine and dried
(MgSO4). The solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (5/2) as an eluent to give 6 (1.27 g, 70%
from 5) as a colorless oil. 1H NMR (CDCl3) d: 2.63 (1H, s),
2.35±2.27 (2H, m), 2.24±2.15 (2H, m), 2.09±1.73 (4H, m),
1.93 (1H, t, Jˆ2.7 Hz), 1.67±1.50 (4H, m). 13C NMR
(CDCl3) d: 219.6, 83.7, 78.7, 68.8, 34.6, 34.5, 34.2, 22.0,
18.5, 17.0. IR (neat) cm21: 3450, 3300, 2110, 1740. EI-MS
m/z: 166 (M1), 149, 138, 127, 110. HIMS m/z: 166.0965
(Calcd for C10H14O2: 166.0993).
1
13.5 mmol, 78%) as a colorless oil. H NMR (CDCl3) d:
4.14 (2H, q, Jˆ7.1 Hz), 2.46 (2H, s), 1.23 (3H, t, Jˆ7.1 Hz),
1.23 (6H, s), 0.14 (9H, s). 13C NMR (CDCl3) d: 103.7, 87.3,
60.5, 42.1, 30.9, 24.4, 14.1, 0.1. IR (neat) cm21: 2180, 1730.
EI-MS m/z: 226 (M1), 212, 153, 84. HIMS m/z: 226.1404
(Calcd for C12H22O2Si: 226.1388).
7-Iodo-2,2,6,6-tetramethyl-2-silahept-3-yne (9). Under an
argon atmosphere, to an ice-cooling suspension of LiAlH4
(779 mg, 20.5 mmol) in ether (200 ml) was added
dropwisely a solution of 7 (3.04 g, 13.4 mmol) in ether
(22 ml) for 45 min. After 15 min, the mixture was warmed
to room temperature and stirred for 2 h. The reaction
mixture was quenched with 4% NaOH (2.7 ml), diluted
with ether and ®ltered through a Celite pad. The ®ltrate
was evaporated under reduced pressure to give a crude
alcohol 8 (2.22 g). To a solution of 8 in pyridine (10 ml)
were added DMAP (146 mg, 1.2 mmol) and p-toluene-
sulfonyl chloride (3.12 g, 16.4 mmol) at 08C. After 5 min,
the mixture was warmed to room temperature and stirred for
18 h. Then the reaction mixture was partitioned between
ether (10 ml) and H2O (10 ml). The separated aqueous
layer was extracted with ether. Combined organic layers
were washed with cold 1% HCl, saturated aqueous
NaHCO3 and brine. The dried (MgSO4) solvent was
removed under reduced pressure. The residue was puri®ed
by column chromatography with hexane±AcOEt (10/1) as
an eluent to give a crude p-toluenesulfonate (1.73 g). A
mixture of NaI (1.56 g, 10 mmol) and the crude p-toluene-
sulfonate in DMF (7 ml) was heated at 1108C for 18 h. Then
the mixture was partitioned between n-pentane and H2O.
The separated aqueous layer was extracted with n-pentane.
Combined organic layers were washed with 5% Na2S2O3,
H2O and brine, and dried (MgSO4). The solvent was
removed under reduced pressure. The residue was puri®ed
by distillation under reduced pressure (508C / 0.5 mmHg) to
2-(1,1-Diethyl-1-silapropoxy)-2-pent-4-ynylcyclopentan-
1-one (3b). To a solution of 6 (176.7 mg, 1.1 mmol) and
2,6-di-tert-butylpyridine (0.74 ml, 3.3 mmol) in CH2Cl2
(5 ml) was added TESOTf (0.38 ml, 1.7 mmol) at 2688C
under an argon atmosphere. After being stirred for 5 h, the
reaction mixture was quenched with saturated aqueous
NaHCO3 extracted with ether. Combined extracts were
washed with brine and dried (MgSO4). The solvent was
removed under reduced pressure. The residue was puri®ed
by column chromatography with hexane±AcOEt (20/1) as
1
give 9 (1.0 g, 23% from 7) as a colorless oil. H NMR
(CDCl3) d: 3.26 (3H, s), 2.28 (2H, s), 1.13 (6H, s), 0.16
(9H, s). 13C NMR (CDCl3) d: 103.9, 34.0, 32.4, 26.4,
24.6, 22.3, 0.1. IR (neat) cm21: 2902, 2178. EI-MS m/z:
294 (M1), 238, 209, 167, 78. HIMS m/z: 294.0302 (Calcd
for C10H19ISi: 294.0300).
1
an eluent to give 3b (274.5 mg, 92%) as a colorless oil. H
NMR (CDCl3) d: 2.33±2.15 (4H, m), 2.05±1.48 (9H, m),
0.92 (9H, t, Jˆ7.8 Hz), 0.59 (6H, q, Jˆ7.8 Hz). 13C NMR
(CDCl3) d: 217.8, 84.0, 80.6, 68.6, 36.7, 35.2, 34.8, 22.4,
18.7, 17.5, 6.9, 6.2. IR (neat) cm21: 3300, 2110, 1740. EI-
MS m/z: 251 (M12C2H5), 224, 213, 195. HIMS m/z:
251.1483 (Calcd for C14H23O2Si: 251.1467).
2-Hydroxy-2-(2,2,6,6-tetramethyl-6-silahept-4-ynyl)cyclo-
pentan-1-one (10). To a solution of 9 (1.43 g, 4.9 mol) in
ether (30 ml) was added tert-BuLi (1.7 M in n-pentane,
6.0 ml, 10.2 mmol) under an argon atmosphere at 2788C,
and the reaction mixture was stirred for 2.5 h. At the same
temperature, a solution of 5 (666 mg, 4.7 mmol) in ether
(15 ml) was added. After being stirred for 1.5 h, the reaction
mixture was quenched with saturated aqueous NH4Cl and
Ethyl 2,2,6,6-tetramethyl-6-silahept-4-ynoate (7). LDA
was prepared from diisopropylamine (3.1 ml, 22.1 mmol)
and n-BuLi (1.68 M in hexane, 13 ml, 21.8 mmol) in THF

9248
A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
extracted with ether. Combined extracts were washed with
brine and dried (MgSO4). The solvent was removed under
reduced pressure to give a crude material (435 mg). In a
similar manner as the preparation of 6, the crude material
was converted into 10 (311.0 mg, 40% from 5) as a colorless
d, Jˆ11.6 Hz), 4.62 (1H, d, Jˆ11.6 Hz), 3.80 (3H, s), 3.78
(1H, m), 2.28±1.97 (4H, m), 1.89±1.65 (2H, m). 13C NMR
(CDCl3) d: 216.4, 159.3, 129.7, 129.6, 113.8, 79.7, 71.6,
55.2, 35.4, 29.6, 17.3. IR (neat) cm21: 1740. EI-MS m/z:
220 (M1), 181, 137, 122, 77. HIMS m/z: 220.1109 (Calcd
for C13H16O3: 220.1099).
1
oil. H NMR (CDCl3) d: 2.31 (1H, d, Jˆ16.9 Hz), 2.40±
1.88 (7H, m), 2.17 (1H, d, Jˆ16.9 Hz), 1.91 (1H, d,
Jˆ15.3 Hz), 1.51 (1H, d, Jˆ15.3 Hz), 1.09 (3H, s), 1.08
(3H, s), 0.16 (9H, s). 13C NMR (CDCl3) d: 210.9, 103.1,
79.5, 44.4, 37.0, 34.4, 34.0, 33.7, 29.2, 28.3, 17.3, 0.1. IR
(neat) cm21: 3460, 2170, 1745. EI-MS m/z: 266 (M1), 265,
251, 238, 223, 137, 119, 86. HIMS m/z: 266.1673 (Calcd for
C15H26O2Si: 266.1701).
(1Rp,2Rp)-2-[(4-Methoxyphenyl)methoxy]-1-prop-2-enyl-
cyclopentan-1-ol (14), (1Rp,2Sp)-2-[(4-methoxyphenyl)-
methoxy]-1-prop-2-enylcyclopentan-1-ol (15). Under a
nitrogen atmosphere, to a suspension of Mg (turnings,
188.2 mg, 7.7 mmol) in ether (0.6 ml) was added
dropwisely a solution of allylbromide (0.7 ml, 8.1 mmol)
in ether (7.5 ml) at room temperature. To the reaction
mixture, a solution of 13 (238.8 mg, 1.09 mmol) in ether
(2.8 ml) was added at 08C. After being stirred for 30 min,
the reaction mixture was quenched with saturated aqueous
NH4Cl and extracted with ether. Combined extracts were
washed with brine (3 ml) and dried (MgSO4). The solvent
was removed under reduced pressure. The residue was puri-
®ed by column chromatography with hexane±AcOEt (10/1)
as an eluent to give 14 (203.8 mg, 72%) as a colorless oil
2-(2,2-Dimethyl-4-ynyl)-2-hydroxycyclopentan-1-one (11).
To a solution of 10 (311 mg, 1.2 mmol) in THF (3 ml) was
added TBAF (1.0 M in THF, 1.5 ml, 1.5 mmol) at 08C.
After being stirred for 1 h, the reaction mixture was
quenched with saturated aqueous NH4Cl and extracted
with ether. Combined extracts were washed with brine
and dried (MgSO4). The solvent was removed under
reduced pressure. The residue was puri®ed by column chro-
matography with hexane±AcOEt (5/1) as an eluent to give
1
and 15 (26.9 mg, 9%) as a colorless oil. 14: H NMR
1
11 (163 mg, 72%) as a colorless oil. H NMR (CDCl3) d:
(CDCl3) d: 7.26 (2H, d, Jˆ8.8 Hz), 6.89 (2H, d,
Jˆ8.8 Hz), 5.88 (1H, m), 5.09±5.01 (2H, m), 4.57 (1H, d,
Jˆ11.4 Hz), 4.43 (1H, d, Jˆ11.4 Hz), 3.81 (3H, s), 3.54
(1H, t, Jˆ5.8 Hz), 2.72 (1H, s), 2.33 (1H, ddt, Jˆ14.0,
7.0, 1.3 Hz), 2.21 (1H, ddt, Jˆ14.0, 7.7, 1.3 Hz), 1.96±
1.40 (6H, m). 13C NMR (CDCl3) d: 159.3, 134.5, 130.3,
129.3, 117.4, 113.8, 82.8, 79.8, 71.4, 55.3, 43.7, 35.2,
28.7, 19.5. IR (neat) cm21: 3550, 3060, 1640. EI-MS m/z:
262 (M1), 235, 141, 122, 99. HIMS m/z: 262.1542 (Calcd
for C16H22O3: 262.1568). 15: 1H NMR (CDCl3) d: 7.25 (2H,
d, Jˆ8.5 Hz), 6.89 (2H, d, Jˆ8.5 Hz), 5.86 (1H, m), 5.22±
5.13 (2H, m), 4.52 (1H, d, Jˆ11.6 Hz), 4.35 (1H, d,
Jˆ11.6 Hz), 3.80 (3H, s), 3.58 (1H, m), 2.56 (1H, dd,
Jˆ13.8, 7.0 Hz), 2.36 (1H, dd, Jˆ13.8, 7.9 Hz), 1.82±
1.59 (7H, m). 13C NMR (CDCl3) d: 159.1, 134.5, 130.9,
129.1, 119.0, 113.7, 85.8, 82.4, 70.6, 55.3, 40.1, 36.1,
28.6, 20.3. IR (neat) cm21: 3460, 3076, 1640, 1610. EI-
MS m/z: 262 (M1), 181, 148, 121, 99. HIMS m/z:
262.1545 (Calcd for C16H22O3: 262.1568).
2.38±1.88 (8H, m), 2.04 (1H, t, Jˆ2.6 Hz), 1.88 (1H, d,
Jˆ15.2 Hz), 1.55 (1H, brs), 1.54 (1H, d, Jˆ15.2 Hz), 1.10
(3H, s), 1.09 (3H, s). 13C NMR (CDCl3) d: 215.3, 83.2,
80.1, 71.4, 45.0, 37.5, 34.8, 33.3, 29.5, 29.0, 18.1. IR
(neat) cm21: 3450, 3300, 2110, 1740. EI-MS m/z: 194
(M1), 179, 151, 61. HIMS m/z: 194.1307 (Calcd for
C12H18O2: 194.1306).
2-(1,1-Diethyl-1-silapropoxy)-2-(2,2-dimethyl-4-ynyl)cy-
clopentan-1-one (3c). In the similar manner as the prepara-
tion of 3b, 11 (163 mg, 0.84 mmol) was converted into 3c
(248 mg, 96%) as a colorless oil. 1H NMR (CDCl3) d: 2.29±
1.82 (8H, m), 1.98 (1H, t, Jˆ2.7 Hz), 1.77 (1H, d,
Jˆ14.8 Hz), 1.57 (1H, d, Jˆ14.8 Hz), 1.08 (3H, s), 1.07
(3H, s), 0.93 (9H, t, Jˆ7.8 Hz), 0.58 (6H, q, Jˆ7.8 Hz).
13C NMR (CDCl3) d: 218.3, 82.8, 81.7, 70.2, 45.2, 38.1,
34.6, 34.2, 33.0, 28.3, 28.3, 17.5, 7.03, 6.30. IR (neat)
cm21: 3300, 2110, 1750. EI-MS m/z: 308 (M1), 279, 269,
252, 118, 82. HIMS m/z: 308.2182 (Calcd for C18H32O2Si:
308.2170).
(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-methoxy-
phenyl)methoxy]-1-prop-2-enylcyclopentane (16). In a
similar manner as the preparation of 3b, 14 (524.2 mg,
2.0 mmol) was converted into 16 (747.1 mg, 99%) as a
colorless oil after column chromatography with hexane±
2-[(4-Methoxyphenyl)methoxy]-cyclopentan-1-one (13).
Under a nitrogen atmosphere, to a mixture of NaH (60%
dispersion in mineral oil, 9.5 g, 237.5 mmol) and DMSO
(200 ml) was added dropwisely a solution of 12 (19 g,
131.8 mmol) in THF (100 ml). Then the mixture was treated
with a solution of 4-methoxybenzyl chloride (25 g, ca
159.7 mmol) in THF (100 ml), and the whole mixture was
stirred at room temperature for 1 h. The reaction mixture
was quenched with Et2NH (10 ml). To the ice-cooling
mixture was added saturated aqueous NH4Cl. The resulting
mixture was extracted with ether. Combined extracts were
washed with brine and dried (MgSO4). The solvent was
removed under reduced pressure to give a crude material
(32.7 g). In a similar manner as the preparation of 6, the
crude material was converted into 13 (19.5 g, 68% from
12) as a colorless oil after column chromatography with
1
AcOEt (50/1) as an eluent. H NMR (CDCl3) d: 7.62 (2H,
d, Jˆ8.8 Hz), 6.86 (2H, d, Jˆ8.8 Hz), 5.84 (1H, m), 5.06±
4.95 (2H, m), 4.53 (1H, d, Jˆ11.9 Hz), 4.47 (1H, d,
Jˆ11.9 Hz), 3.81 (3H, s), 3.44 (1H, t, Jˆ6.2 Hz), 2.35±
2.20 (2H, m), 1.85±1.34 (6H, m), 0.93 (9H, t, Jˆ7.8 Hz),
0.61 (6H, q, Jˆ7.8 Hz). 13C NMR (CDCl3) d: 165.2, 136.2,
134.9, 129.1, 117.0, 113.5, 83.6, 82.4, 71.2, 55.3, 43.3, 35.5,
27.8, 19.0, 7.2, 6.9. IR (neat) cm21: 1640, 1610. EI-MS m/z:
376 (M1), 347, 255, 171, 122, 87. HIMS m/z: 376.2449
(Calcd for C22H36O3Si: 376.2449).
2-[(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-methoxy-
phenyl)methoxy]-cyclopentyl]ethanal (17). A mixture of
16 (9.5 g, 25.3 mmol) in ether (70 ml) and H2O (70 ml) was
treated with OsO4 (3.9 mg/ml in tert-BuOH, 70 ml,
1
hexane±AcOEt (3/1) as an eluent. H NMR (CDCl3) d:
7.30 (2H, d, Jˆ8.7 Hz), 6.88 (2H, d, Jˆ8.7 Hz), 4.76 (1H,

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9249
1.4 mmol) and NaIO4 (16 g, 76 mmol) at room temperature.
After being stirred for 1 h, the reaction mixture was
extracted with ether. Combined extracts were washed with
saturated aqueous NaHCO3 and brine (5 ml). The dried
(Na2SO4) solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (8/1) as an eluent to give 17 (6.7 g, 70%) as
a colorless oil. 1H NMR (CDCl3) d: 9.87 (1H, t, Jˆ3.2 Hz),
7.24 (2H, d, Jˆ8.6 Hz), 6.86 (2H, d, Jˆ8.6 Hz), 4.55 (1H, d,
Jˆ11.7 Hz), 4.43 (1H, d, Jˆ11.7 Hz), 3.80 (3H, s), 3.50
(1H, t, Jˆ3.0 Hz), 2.56 (1H, dd, Jˆ15.2, 3.2 Hz), 2.43
(1H, dd, Jˆ15.2, 3.2 Hz), 1.98±1.40 (6H, m), 0.92 (9H, t,
Jˆ7.9 Hz), 0.62 (6H, q, Jˆ7.9 Hz). 13C NMR (CDCl3) d:
203.0, 134.7, 130.8, 129.3, 113.7, 83.6, 82.0, 71.3, 55.3,
52.5, 36.4, 27.0, 19.0, 7.12, 6.74. IR (neat) cm21: 2860,
1725. EI-MS m/z: 378 (M1), 377, 363, 331, 258, 125.
HIMS m/z: 378.2220 (Calcd for C21H34O4Si: 378.2225).
manner as the preparation of 11, 18 (180 mg, 0.43 mmol)
was converted into 20 (110.1 mg, 84%). Recrystallization
from toluene±hexane (1/5) afforded 20 as a colorless cubic,
mp 618C. 1H NMR (CDCl3) d: 7.25 (2H, d, Jˆ8.7 Hz), 6.89
(2H, d, Jˆ8.7 Hz), 4.60 (1H, d, Jˆ11.4 Hz), 4.45 (1H, d,
Jˆ11.4 Hz), 4.10 (1H, m), 3.81 (3H, s), 3.55 (1H, t,
Jˆ5.2 Hz), 2.44 (1H, ddd, Jˆ16.5, 5.3, 2.6 Hz), 2.31 (1H,
ddd, Jˆ16.5, 7.3, 2.6 Hz), 2.02 (1H, t, Jˆ2.6 Hz), 1.99±
1.48 (8H, m). 13C NMR (CDCl3) d: 159.4, 129.7, 129.5,
113.9, 84.3, 81.4, 81.3, 71.5, 70.1, 68.2, 55.3, 43.8, 35.0,
28.4, 27.3, 19.4. IR (neat) cm21: 3446, 2120. EI-MS m/z:
304 (M1), 286, 218, 165, 93. HIMS m/z: 304.1701 (Calcd
for C18H24O4: 304.1673).
(1Rp,5Rp,7Sp,9Rp)-1-[(4-Methoxyphenyl)methoxy]-6,8-
dioxa-7-phenyl-9-prop-2-ynylspiro[4.5]decane (22). A
mixture of 20 (38.7 mg, 0.13 mmol), benzaldehyde
(0.04 ml, 0.57 mmol) and pyridinium p-toluenesulfonate
(3 mg, 0.01 mmol) in benzene (1 ml) was stirred at 40±
458C for 2 days. The reaction mixture was quenched with
saturated aqueous NaHCO3 and extracted with ether.
Combined extracts were washed with brine and dried
(MgSO4). The solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (10/1) as an eluent to give 22 (32.1 mg,
(2Rp)-1-{(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-
methoxyphenyl)methoxy]cyclopentyl}pent-4-yn-2-ol
(18), (2Sp)-1-{(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-
[(4-methoxyphenyl)methoxy]cyclopentyl}pent-4-yn-2-ol
(19). Under a nitrogen atmosphere, to a mixture of Mg (turn-
ings, 56.1 mg, 2.3 mmol) in ether (0.5 ml) was added a
solution of propargyl bromide (0.05 ml) in ether (5 ml)
and HgCl2 (1 mg) at room temperature. Additional pro-
pargyl bromide (total 0.2 ml, 2.2 mmol) was added again
to the reaction mixture, and the mixture was stirred until
the reaction started. The whole mixture was then cooled to
08C. A solution of 17 (172.4 mg, 0.46 mmol) in ether (2 ml)
was added to the reaction mixture. After being stirred for
10 min, the reaction mixture was quenched with saturated
aqueous NH4Cl and extracted with ether. Combined extracts
were washed with brine (3 ml) and dried (MgSO4). The
solvent was removed under reduced pressure. The residue
was puri®ed by column chromatography with hexane±
AcOEt (8/1) as an eluent to give more-polar 18 (65.7 mg,
34%) as a colorless oil and less-polar 19 (94.1 mg, 49%) as a
colorless oil. 18: 1H NMR (CDCl3) d: 7.25 (2H, d,
Jˆ8.7 Hz), 6.84 (2H, d, Jˆ8.7 Hz), 4.68 (1H, d, Jˆ
1.2 Hz), 4.56 (1H, d, Jˆ11.0 Hz), 4.40 (1H, d, Jˆ
11.0 Hz), 4.09 (1H, m), 3.80 (3H, s), 3.56 (1H, dd, Jˆ7.8,
6.8 Hz), 2.43 (1H, ddd, Jˆ16.6, 5.3, 2.6 Hz), 2.30 (1H, ddd,
Jˆ16.6, 7.4, 2.6 Hz), 2.00 (1H, t, Jˆ2.6 Hz), 1.97±1.40
(8H, m), 0.95 (9H, t, Jˆ7.8 Hz), 0.64 (6H, q, Jˆ7.8 Hz).
13C NMR (CDCl3) d: 159.2, 129.9, 129.4, 113.7, 84.9, 82.8,
81.6, 70.7, 70.0, 66.4, 55.2, 46.2, 37.2, 27.5, 27.0, 18.4,
7.14, 6.68. IR (neat) cm21: 3400, 2122. EI-MS m/z: 418
(M1), 403, 379, 297, 199. HIMS m/z: 418.2560 (Calcd for
C24H38O4Si: 418.2537). 19: 1H NMR (CDCl3) d: 7.27 (2H,
d, Jˆ8.7 Hz), 6.87 (2H, d, Jˆ8.7 Hz), 4.60 (1H, d,
Jˆ11.2 Hz), 4.43 (1H, d, Jˆ11.2 Hz), 4.13±4.05 (2H, m),
3.80 (3H, s), 3.65 (1H, t, Jˆ5.1 Hz), 2.40 (1H, ddd, Jˆ16.7,
5.4, 2.6 Hz), 2.27 (1H, ddd, Jˆ16.7, 7.1, 2.6 Hz), 2.00 (1H,
t, Jˆ2.6 Hz), 2.04±1.42 (8H, m), 0.94 (9H, t, Jˆ7.8 Hz),
0.64 (6H, q, Jˆ7.8 Hz). 13C NMR (CDCl3) d: 159.0, 130.9,
129.1, 113.6, 84.9, 82.5, 81.2, 71.3, 70.1, 67.7, 55.2, 44.8,
37.6, 28.1, 27.5, 19.2, 7.09, 6.72. IR (neat) cm21: 3475,
2110. EI-MS m/z: 418 (M1), 359, 297, 267, 199. HIMS
m/z: 418.2542 (Calcd for C24H38O4Si: 418.2537).
1
64%) as a colorless oil. H NMR (500 MHz, C6D6) d:
7.68 (2H, brd, Jˆ6.8 Hz), 7.26 (2H, dd, Jˆ8.6, 1.9 Hz),
7.21±7.17 (2H, m), 7.12 (1H, t, Jˆ7.3 Hz), 6.77 (2H, d,
Jˆ8.4 Hz), 5.58 (1H, s), 4.65 (1H, dd, Jˆ11.8, 1.7 Hz),
4.56 (1H, d, Jˆ11.8 Hz), 3.78 (1H, m), 3.33 (1H, t,
Jˆ5.7 Hz), 3.32 (3H, s), 2.47 (1H, ddd, Jˆ16.6, 5.5,
2.8 Hz), 2.25 (1H, ddd, Jˆ16.6, 7.6, 2.8 Hz), 2.00 (1H,
m), 1.85±1.72 (4H, m), 1.65 (1H, m), 1.41 (1H, ddd,
Jˆ13.7, 9.2, 4.7 Hz), 1.34±1.24 (2H, m). 13C NMR
(CDCl3) d: 159.0, 138.9, 131.2, 129.2, 128.5, 128.1,
126.3, 113.6, 96.2, 84.9, 83.1, 80.0, 72.2, 71.9, 70.4, 55.3,
36.9, 29.7, 27.8, 25.9, 19.1. IR (neat) cm21: 3294, 2124.
EI-MS m/z: 392 (M1), 271, 121, 99. HIMS m/z: 392.1963
(Calcd for C25H28O4: 392.1986).
(1Rp,2Rp)-1-((2Sp)-2-Hydroxypent-4-ynyl)-2-[(4-methoxy-
phenyl)methoxy]-cyclopentan-1-ol (21). In the similar
manner as preparation of 11, 19 (90 mg, 0.21 mmol) was
converted into 21 (61.1 mg, 93%). Recrystallization from
toluene±hexane (1/5) afforded 21 as colorless needles, mp
1
658C. H NMR (CDCl3) d: 7.26 (2H, d, Jˆ8.4 Hz), 6.89
(2H, d, Jˆ8.4 Hz), 4.60 (1H, d, Jˆ11.4 Hz), 4.43 (1H, d,
Jˆ11.4 Hz), 4.05 (1H, m), 3.81 (3H, s), 3.73 (1H, brs), 3.65
(1H, t, Jˆ5.2 Hz), 3.29 (1H, brs), 2.41 (1H, ddd, Jˆ17.0,
5.9, 2.6 Hz), 2.34 (1H, ddd, Jˆ17.0, 6.8, 2.6 Hz), 2.02 (1H,
t, Jˆ2.6 Hz), 1.89±1.45 (8H, m). 13C NMR (CDCl3) d:
159.6, 130.1, 129.6, 114.1, 83.1, 81.4, 81.2, 71.6, 70.5,
68.1, 55.5, 43.8, 38.6, 28.7, 27.8, 20.0. IR (neat) cm21
:
3440, 2110. EI-MS m/z: 304 (M1), 286, 265, 218, 78.
HIMS m/z: 304.1702 (Calcd for C18H24O4: 304.1673).
(1Rp,5Rp,7Rp,9Rp)-1-[(4-Methoxyphenyl)methoxy]-6,8-
dioxa-7-phenyl-9-prop-2-ynylspiro[4.5]decane (23). In
the same manner as the preparation of 22, 21 (68.7 mg,
0.23 mmol) was converted into 23 (67.0 mg, 76%) as a
1
colorless oil. H NMR (500 MHz, C6D6) d: 7.76 (2H, d,
Jˆ8.0 Hz), 7.22±7.18 (4H, m), 7.11 (1H, t, Jˆ7.2 Hz),
(1Rp,2Rp)-1-((2Rp)-2-Hydroxypent-4-ynyl)-2-[(4-methoxy-
phenyl)methoxy]-cyclopentan-1-ol (20). In the similar
6.79 (2H, d, Jˆ8.6 Hz), 6.25 (1H, s), 4.45 (1H, d,

9250
A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
Ê
Jˆ11.5 Hz), 4.26 (1H, m), 4.14 (1H, d, Jˆ11.5 Hz), 3.68
(1H, t, Jˆ5.8 Hz), 3.30 (3H, s), 2.49 (1H, ddd, Jˆ16.5, 5.0,
2.7 Hz), 2.26 (1H, ddd, Jˆ16.5, 7.6, 2.7 Hz), 2.04 (1H, ddd,
Jˆ13.2, 9.4, 5.8 Hz), 1.89 (1H, m), 1.82 (1H, t, Jˆ2.7 Hz),
1.76 (1H, m), 1.66±1.60 (2H, m), 1.55 (1H, dd, Jˆ13.3,
2.5 Hz), 1.40 (1H, ddd, Jˆ13.2, 9.4, 5.6 Hz), 1.25 (1H,
m). 13C NMR (CDCl3) d: 159.2, 139.1, 130.4, 129.4,
128.5, 128.1, 126.3, 113.8, 97.4, 82.2, 81.7, 80.1, 71.9,
70.6, 70.5, 55.3, 38.4, 38.2, 28.3, 26.0, 18.3. IR (neat)
cm21: 3294, 2124. EI-MS m/z: 392 (M1), 271, 121, 99.
HIMS m/z: 392.1975 (Calcd for C25H28O4: 392.1986).
sieves 4 A (145.5 mg) in CH2Cl2 (3 ml) was added
N-methylmorpholine-N-oxide (NMO, 146.4 mg, 1.2
mmol) and TPAP (15.5 mg, 0.04 mmol). After being stirred
for 1.5 h at room temperature, the reaction mixture was
diluted with ether. The mixture was ®ltered through ¯orisil.
The ®ltrate was evaporated in vacuo. The residue was puri-
®ed by column chromatography with hexane±AcOEt (20/1)
as an eluent to give 3d (168.5 mg, 77%) as a colorless oil. 1H
NMR (CDCl3) d: 4.04 (1H, quint., Jˆ5.4 Hz), 2.45±2.42
(2H, m), 2.29±2.19 (2H, m), 2.07±1.80 (7H, m), 0.97±0.90
(18H, m), 0.68±0.53 (12H, m). 13C NMR (CDCl3) d: 216.9,
81.4, 80.2, 70.2, 66.8, 43.5, 37.6, 34.2, 28.4, 16.9, 7.0, 6.9,
6.3, 4.9. IR (neat) cm21: 3316, 2124, 1752. EI-MS m/z: 410
(M1), 381, 343, 299, 249, 155, 115, 87. HIMS m/z:
410.2688 (Calcd for C22H42O3Si2: 410.2670).
1-[(1Rp)-1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-
[(4-methoxyphenyl)-methoxy]cyclopentyl}methyl)but-3-
ynyloxy]-1,1-diethyl-1-silapropane (24). To a solution of
18 (315.6 mg, 0.75 mmol) and 2,6-lutidine (0.5 ml,
2.2 mmol) in CH2Cl2 (7 ml) was added TESOTf (0.25 ml,
1.1 mmol) at 2788C. After being stirred for 2 h, the reaction
mixture was quenched with saturated aqueous NaHCO3 and
extracted with ether. Combined extracts were washed with
brine and dried (MgSO4). The solvent was removed under
reduced pressure. The residue was puri®ed by column
chromatography with hexane±AcOEt (10/1) as an eluent
(1Rp)-1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-
methoxyphenyl)-methoxy]cyclopentyl}methyl)-1-(meth-
oxymethoxy)but-3-yne (26). Under an argon atmosphere, a
mixture of 18 (1.01 g, 2.4 mmol), (i-Pr)2NEt (10 ml,
57.4 mmol), methoxymethyl chloride (3 ml, 39.5 mmol)
and N,N-dimethylaminopyridine (66.7 mg, 0.55 mmol) in
CH2Cl2 (10 ml) was stirred at room temperature for 19 h.
The reaction mixture was quenched with 10 ml of saturated
aqueous NaHCO3 and extracted with ether. Combined
extracts were washed with H2O and brine, and dried
(MgSO4). The solvent was removed in vacuo. The residue
was puri®ed by column chromatography with hexane±
AcOEt (7/1) as an eluent to give 26 (922.0 mg, 82%) as a
1
to give 24 (371.0 mg, 92%) as a colorless oil. H NMR
(CDCl3) d: 7.27 (2H, d, Jˆ8.7 Hz), 6.86 (2H, d, Jˆ
8.7 Hz), 4.56 (1H, d, Jˆ12.0 Hz), 4.49 (1H, d, Jˆ
12.0 Hz), 4.06 (1H, m), 3.80 (3H, s), 3.66 (1H, t,
Jˆ4.8 Hz), 2.44 (1H, ddd, Jˆ16.4, 6.0, 2.7 Hz), 2.35 (1H,
ddd, Jˆ16.4, 5.0, 2.7 Hz), 1.98 (1H, t, Jˆ2.7 Hz), 1.93±
1.44 (6H, m), 1.88 (1H, dd, Jˆ14.3, 5.0 Hz), 1.74 (1H,
dd, Jˆ14.3, 5.0 Hz), 0.99±0.85 (18H, m), 0.67±0.55
(12H, m). 13C NMR (CDCl3) d: 158.9, 131.5, 128.9,
113.5, 83.5, 82.2, 81.7, 71.0, 70.2, 67.8, 55.2, 45.9, 36.8,
28.6, 27.3, 19.2, 7.3, 6.9, 6.9, 5.2. IR (neat) cm21: 3314,
2124. EI-MS m/z: 532 (M1), 494, 381, 235, 132, 115. HIMS
m/z: 532.3426 (Calcd for C30H52O4Si: 532.3401).
1
colorless oil. H NMR (CDCl3) d: 7.26 (2H, d, Jˆ8.7 Hz),
6.86 (2H, d, Jˆ8.7 Hz), 4.62 (1H, d, Jˆ6.9 Hz), 4.56 (1H, d,
Jˆ6.9 Hz), 4.55 (1H, d, Jˆ12.0 Hz), 4.48 (1H, d,
Jˆ12.0 Hz), 3.91 (1H, m), 3.80 (3H, s), 3.65 (1H, dd,
Jˆ5.8, 4.1 Hz), 3.34 (3H, s), 2.60 (1H, ddd, Jˆ16.8, 5.8,
2.6 Hz), 2.43 (1H, ddd, Jˆ16.8, 4.3, 2.6 Hz), 1.98 (1H, t,
Jˆ2.6 Hz), 1.88 (1H, dd, Jˆ14.8, 6.7 Hz), 1.78 (1H, dd,
Jˆ14.8, 4.9 Hz), 2.00±1.42 (6H, m), 0.97±0.90 (9H, m),
0.67±0.58 (6H, m). 13C NMR (CDCl3) d: 158.9, 131.3,
129.1, 113.6, 96.4, 83.3, 82.1, 81.2, 73.6, 71.1, 70.0, 55.7,
(1Rp,2Rp)-2-[(2Rp)-2-(1,1-Diethyl-1-silapropoxy)pent-4-
ynyl]-2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol (25).
To a mixture of 24 (328.0 mg, 0.62 mmol) and H2O
(0.34 ml) in CH2Cl2 (6 ml) was added 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) (192.5 mg, 0.85 mmol)
at room temperature. After 15 min, saturated aqueous
NaHCO3 was added. The reaction mixture was extracted
with CH2Cl2. Combined extracts were washed with satu-
rated aqueous NaHCO3 and brine, and dried (MgSO4).
The solvent was removed under reduced pressure. The
residue was puri®ed by column chromatography with
hexane±AcOEt (30/1) as an eluent to give 25 (220.7 mg,
55.2, 43.5, 37.1, 27.5, 26.0, 19.2, 7.3, 6.9. IR (neat) cm21
:
3300, 2110, 1610. EI-MS m/z: 462 (M1), 423, 341, 279,
122. HIMS m/z: 462.2775 (Calcd for C26H42O5Si:
462.2799).
(1Rp,2Rp)-2-[(2Rp)-2-(Methoxymethoxy)pent-4-ynyl]-2-
(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol (27). In the
similar manner as the preparation of 25, 26 (1.0 mg,
2.17 mmol) was converted into 27 (534.4 mg, 72%) as a
1
colorless oil. H NMR (CDCl3) d: 4.72 (1H, d, Jˆ7.1 Hz),
1
0.53 mmol, 87%) as a colorless oil. H NMR (CDCl3) d:
4.69 (1H, d, Jˆ7.1 Hz), 3.98±3.89 (2H, m), 3.41 (3H, s),
2.60 (1H, ddd, Jˆ16.8, 6.3, 2.6 Hz), 2.45 (1H, ddd, Jˆ16.8,
4.0, 2.8 Hz), 2.01 (1H, t, Jˆ2.7 Hz), 2.02±1.40 (7H, m),
1.96 (1H, dd, Jˆ14.9, 3.4 Hz), 1.86 (1H, dd, Jˆ14.9,
7.8 Hz), 1.02±0.96 (9H, m), 0.72±0.63 (6H, m). 13C NMR
(CDCl3) d: 96.7, 83.0, 80.9, 75.6, 73.2, 70.3, 55.9, 43.8,
37.7, 31.3, 26.0, 19.6, 7.1, 6.6. IR (neat) cm21: 3540,
2110. EI-MS m/z: 343 (M1), 304, 284, 229, 115. HIMS
m/z: 342.2249 (Calcd for C18H34O4Si: 342.2225).
4.13 (1H, m), 4.00 (1H, q, Jˆ5.0 Hz), 2.54 (1H, d,
Jˆ5.0 Hz), 2.40±2.37 (2H, m), 2.01 (1H, t, Jˆ2.7 Hz),
2.05±1.42 (7H, m), 1.73 (1H, dd, Jˆ14.7, 7.8 Hz), 0.98
(9H, t, Jˆ7.9 Hz), 0.97 (9H, t, Jˆ7.9 Hz), 0.69±0.59
(12H, m). 13C NMR (CDCl3) d: 83.6, 81.2, 75.2, 70.5,
67.5, 45.4, 37.2, 30.7, 28.9, 19.6, 7.1, 6.9, 6.6, 5.2. IR
(neat) cm21: 3550, 2120. EI-MS m/z: 412 (M1), 383, 280,
251, 115. HIMS m/z: 412.2848 (Calcd for C22H44O3Si:
412.2827).
(2Rp)-2-[(2Rp)-2-(Methoxymethoxy)pent-4-ynyl]-2-(1,1-
diethyl-1-silapropoxy)cyclopentan-1-one (3e). In the
similar manner as the preparation of 3d, 27 (144.5 mg,
0.42 mmol) was converted into 3e (85 mg, 58%) as a
(2Rp)-2-[(2Rp)-2-(1,1-Diethyl-1-silapropoxy)pent-4-ynyl]-
2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-one (3d). To
a mixture of 25 (220.7 mg, 0.53 mmol) and molecular

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9251
1
colorless oil. H NMR (CDCl3) d: 4.61 (1H, d, Jˆ7.1 Hz),
351, 279, 199, 115. HIMS m/z: 427.2690 (Calcd for
C22H43O4Si2: 427.2697).
4.48 (1H, d, Jˆ7.1 Hz), 3.86 (1H, m), 3.36 (3H, s), 2.60
(1H, ddd, Jˆ16.8, 6.3, 2.6 Hz), 2.48 (1H, ddd, Jˆ16.8, 4.0,
2.8 Hz), 2.36 (1H, m), 2.23±1.80 (5H, m), 2.11 (1H, dd,
Jˆ14.8, 7.6 Hz), 2.00 (1H, t, Jˆ2.6 Hz), 1.88 (1H, dd,
Jˆ14.8, 3.3 Hz), 0.96±0.91 (9H, m), 0.63±0.53 (6H, m).
13C NMR (CDCl3) d: 216.9, 97.5, 80.9, 80.3, 73.3, 70.1,
1-[(1Sp)-1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-
[(4-methoxyphenyl)-methoxy]cyclopentyl}methyl)but-3-
ynyloxy]-1,1-diethyl-1-silapropane (30). In the similar
manner as the preparation of 24, 19 (176.7 mg, 1.1 mmol)
was converted into 30 (312.4 mg, 83%) as a colorless oil. 1H
NMR (CDCl3) d: 7.26 (2H, d, Jˆ8.7 Hz), 6.86 (2H, d,
Jˆ8.7 Hz), 4.53 (1H, d, Jˆ11.6 Hz), 4.40 (1H, d,
Jˆ11.6 Hz), 4.12 (1H, m), 3.81 (3H, s), 3.46 (1H, t,
Jˆ7.0 Hz), 2.46 (1H, ddd, Jˆ16.8, 6.0, 2.6 Hz), 2.35 (1H,
ddd, Jˆ16.8, 4.6, 2.6 Hz), 2.02 (1H, m), 1.99 (1H, t,
Jˆ2.6 Hz), 1.84±1.42 (7H, m), 0.99±0.85 (18H, m),
0.67±0.55 (12H, m). 13C NMR (CDCl3) d: 159.0, 131.0,
129.4, 113.5, 84.7, 83.0, 81.7, 71.0, 70.2, 68.1, 55.2, 45.6,
55.7, 42.6, 37.6, 33.8, 26.3, 16.5, 7.0, 6.3. IR (neat) cm21
:
2110, 1750. EI-MS m/z: 340 (M1), 279, 249, 222. HIMS
m/z: 340.2093 (Calcd for C18H32O4Si: 340.2067).
(1Rp)-1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-
methoxyphenyl)-methoxy]cyclopentyl}methyl)-1-[(3,3-
dimethyl-3-silabutoxy)methoxy]but-3-yne (28). Under an
argon atmosphere, a mixture of 18 (470.5 mg, 1.12 mmol),
(i-Pr)2NEt (1.0 ml, 5.7 mmol), and 2-(trimethylsilyl)ethoxy-
methyl chloride (0.6 ml, 3.4 mmol) in CH2Cl2 (0.6 ml) was
stirred at room temperature for 1 h. The reaction was
quenched with saturated aqueous NaHCO3 (3 ml) and
extracted with ether. Combined extracts were washed with
H2O and brine, and dried (MgSO4). The solvent was
evaporated in vacuo. The residue was puri®ed by column
chromatography with hexane±AcOEt (10/1) as an eluent to
give 28 (497.1 mg, 81%) as a colorless oil. 1H NMR
(CDCl3) d: 7.25 (2H, d, Jˆ8.1 Hz), 6.85 (2H, d,
Jˆ8.1 Hz), 4.98±4.44 (4H, m), 3.89 (1H, m), 3.80 (3H, s),
3.80±3.44 (3H, m), 2.63 (1H, m), 2.47±2.32 (2H, m), 2.17±
1.43 (8H, m), 0.98±0.86 (11H, m), 0.66±0.56 (6H, m),
0.01 (9H, s). 13C NMR (CDCl3) d: 129.1, 113.6, 94.8,
83.4, 82.2, 81.5, 73.7, 71.2, 70.0, 65.4, 55.3, 43.5, 37.1,
36.2, 28.7, 27.0, 19.2, 7.34, 7.01, 6.94, 5.23. IR (neat) cm21
:
3314, 2124, 1615. EI-MS m/z: 532 (M1), 493, 381, 235,
115. HIMS m/z: 532.3384 (Calcd for C30H52O4Si:
532.3401).
(1Rp,2Rp)-2-[(2Sp)-2-(1,1-Diethyl-1-silapropoxy)pent-4-
ynyl]-2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol (31).
In the similar manner as the preparation of 25, 30 (310 mg,
0.58 mmol) was converted into 31 (218.7 mg, 90%) as a
1
colorless oil. H NMR (CDCl3) d: 3.98 (1H, tt, Jˆ6.5,
4.9 Hz), 3.89 (1H, q, Jˆ8.1 Hz), 2.52±2.34 (3H, m), 2.01
(1H, t, Jˆ2.6 Hz), 1.98±1.89 (3H, m), 1.81±1.68 (2H, m),
1.64±1.40 (3H, m), 1.01±0.94 (18H, m), 0.71±0.58 (12H,
m). 13C NMR (CDCl3) d: 83.0, 81.2, 76.6, 70.6, 68.5, 44.3,
27.6, 26.1, 19.3, 18.2, 7.3, 6.9, 21.4. IR (neat) cm21
:
35.7, 31.5, 28.4, 19.3, 7.1, 6.8, 6.6, 5.2. IR (neat) cm21
:
3314, 2122, 1613. EI-MS m/z: 548 (M1), 509, 451, 281,
149, 122. HIMS m/z: 548.3353 (Calcd for C30H52O5Si2:
548.3351).
3550, 3300, 2120. EI-MS m/z: 412 (M1), 383, 280, 185,
118. HIMS m/z: 412.2843 (Calcd for C22H44O3Si:
412.2827).
(1Rp,2Rp)-2-{(2Rp)-2-[(3,3-Dimethyl-3-silabutoxy)methyl]-
pent-4-ynyl}-2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol
(29). In a similar manner as the preparation of 25, 28
(497.1 mg, 0.9 mmol) was converted into 29 (186.7 mg,
(2Rp)-2-[(2Sp)-2-(1,1-Diethyl-1-silapropoxy)pent-4-ynyl]-
2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-one (3g). In a
similar manner as the preparation of 3d, 31 (213.3 mg,
0.52 mmol) was converted into 3g (163.5 mg, 0.40 mmol,
77%) as a colorless oil. 1H NMR (CDCl3) d: 4.19 (1H, m),
2.44 (1H, ddd, Jˆ16.7, 6.4, 2.7 Hz), 2.36 (1H, ddd, Jˆ16.7,
5.0, 2.7 Hz), 2.29±2.16 (3H, m), 2.00±1.80 (4H, m), 1.98
(1H, t, Jˆ2.7 Hz), 1.65 (1H, dd, Jˆ14.4, 7.3 Hz), 1.01±0.90
(18H, m), 0.69±0.54 (12H, m). 13C NMR (CDCl3) d: 218.1,
81.1, 80.0, 70.4, 67.3, 42.1, 36.9, 35.1, 28.5, 17.6, 7.0, 6.9,
6.2, 5.2. IR (neat) cm21: 3300, 2110, 1745. EI-MS m/z: 410
(M1), 383, 353, 250, 115. HIMS m/z: 410.2678 (Calcd for
C22H42O3Si2: 410.2670).
1
48%) as a colorless oil. H NMR (CDCl3) d: 4.79±4.65
(2H, m), 3.98±3.88 (2H, m), 3.76 (1H, m), 3.55 (1H, m),
2.63 (1H, m), 2.45 (1H, m), 2.01±1.40 (10H, m), 1.01±0.91
(11H, m), 0.72±0.63 (6H, m), 0.02 (9H, s). 13C NMR
(CDCl3) d: 95.0, 83.1, 81.0, 75.6, 73.2, 70.3, 65.7, 43.9,
37.7, 31.4, 25.2, 19.7, 18.2, 7.2, 6.4, 21.4. IR (neat)
cm21: 3350, 2120. Positive SI-MS m/z: 429 (M1H)1,
311, 279, 251, 185, 103. HIMS m/z: 429.2852 (Calcd for
C22H45O4Si2: 429.2854).
(2Rp)-2-{(2Rp)-2-[(3,3-Dimethyl-3-silabutoxy)methyl]-
pent-4-ynyl}-2-(1,1-diethyl-1-silapropoxy)cyclopentan-
1-one (3f). In a similar manner as the preparation of 3d, 29
(394.5 mg, 0.92 mmol) was converted into 3f (321.2 mg,
(1Sp)-1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-[(4-
methoxyphenyl)-methoxy]cyclopentyl}methyl)-1-(meth-
oxymethoxy)but-3-yne (32). In the similar manner as the
preparation of 26, 19 (930.9 mg, 2.2 mmol) was converted
into 32 (958.3 mg, 93%) as a colorless oil. 1H NMR (CDCl3)
d: 7.26 (2H, d, Jˆ8.7 Hz), 6.86 (2H, d, Jˆ8.7 Hz), 4.73
(1H, d, Jˆ6.9 Hz), 4.67 (1H, d, Jˆ6.9 Hz), 4.54 (1H, d,
Jˆ11.6 Hz), 4.40 (1H, d, Jˆ11.6 Hz), 3.92 (1H, m), 3.81
(3H, s), 3.44 (1H, t, Jˆ7.4 Hz), 3.39 (3H, s), 2.63 (1H, ddd,
Jˆ16.8, 5.9, 2.7 Hz), 2.43 (1H, ddd, Jˆ16.8, 4.1, 2.7 Hz),
2.00 (1H, t, Jˆ2.7 Hz), 1.99 (1H, dd, Jˆ14.7, 3.5 Hz),
1.88±1.43 (6H, m), 1.67 (1H, dd, Jˆ14.7, 8.1 Hz), 0.92±
0.86 (9H, m), 0.65±0.54 (6H, m). 13C NMR (CDCl3) d:
159.0, 130.8, 129.4, 113.5, 96.6, 84.5, 82.8, 81.2, 73.8,
1
82%) as a colorless oil. H NMR (CDCl3) d: 4.61 (1H, d,
Jˆ7.3 Hz), 4.56 (1H, d, Jˆ7.3 Hz), 3.84 (1H, m), 3.76 (1H,
m), 3.44 (1H, m), 2.62 (1H, ddd, Jˆ16.8, 6.3, 2.6 Hz), 2.47
(1H, ddd, Jˆ16.8, 3.7, 2.6 Hz), 2.35 (1H, m), 2.23±1.82
(5H, m), 2.11 (1H, dd, Jˆ14.8, 7.7 Hz), 1.99 (1H, t,
Jˆ2.6 Hz), 1.87 (1H, dd, Jˆ14.8, 3.2 Hz), 0.98±0.85
(11H, m), 0.63±0.54 (6H, m), 0.01 (9H, s). 13C NMR
(CDCl3) d: 216.9, 95.8, 80.9, 80.3, 73.2, 70.1, 65.4, 42.7,
37.6, 33.8, 26.3, 18.1, 16.5, 7.0, 6.3, 21.5. IR (neat) cm21
3316, 2122, 1754. Positive SI-MS m/z: 427 (M1H)1, 409,
:

9252
A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
71.2, 70.0, 55.7, 55.2, 43.3, 36.5, 26.9, 26.2, 19.2, 7.29,
6.96. IR (neat) cm21: 3300, 2110, 1610. EI-MS m/z: 462
(M1), 423, 341, 279, 121. HIMS m/z: 462.2771 (Calcd for
C26H42O5Si: 462.2799).
36.2, 31.7, 25.7, 19.3, 18.1, 7.1, 6.6, 21.5. IR (neat)
cm21: 3350, 3300, 2120. Positive SI-MS m/z: 429
(M1H)1, 311, 281, 199, 185, 103. HIMS m/z: 429.2832
(Calcd for C22H45O4Si2: 429.2854).
(1Rp,2Rp)-2-[(2Sp)-2-(Methoxymethoxy)pent-4-ynyl]-2-
(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol (33). In the
similar manner as the preparation of 25, 32 (958.3 mg,
2.1 mmol) was converted into 33 (645.3 mg, 91%) as a
(2Rp)-2-{(2Sp)-2-[(3,3-Dimethyl-3-silabutoxy)methyl]-
pent-4-ynyl}-2-(1,1-diethyl-1-silapropoxy)cyclopentan-
1-one (3i). In the similar manner as the preparation of 3d, 35
(568.8 mg, 1.3 mmol) was converted into 3i (371.5 mg,
1
1
colorless oil. H NMR (CDCl3) d: 4.70 (2H, s), 3.86±3.76
66%) as a colorless oil. H NMR (CDCl3) d: 4.77 (1H, d,
(2H, m), 3.40 (3H, s), 2.66±2.48 (2H, m), 2.50 (1H, d,
Jˆ7.9 Hz), 2.07±1.88 (4H, m), 1.86±1.68 (3H, m), 1.66±
1.40 (2H, m), 0.98±0.95 (9H, m), 0.72±0.63 (6H, m). 13C
NMR (CDCl3) d: 96.1, 82.7, 80.9, 76.6, 73.5, 70.3, 55.8,
42.9, 36.3, 31.7, 25.7, 19.3, 7.1, 6.6. IR (neat) cm21: 3496,
3314, 2122. EI-MS m/z: 343, 342 (M1), 304, 229, 211, 131,
115. HIMS m/z: 342.2244 (Calcd for C18H34O4Si:
342.2225).
Jˆ7.1 Hz), 4.73 (1H, d, Jˆ7.1 Hz), 4.00 (1H, ddt, Jˆ7.8,
5.9, 4.0 Hz), 3.77 (1H, m), 3.54 (1H, m), 2.63 (1H, ddd,
Jˆ16.8, 5.9, 2.6 Hz), 2.45 (1H, ddd, Jˆ16.8, 4.1, 2.6 Hz),
2.30±2.15 (3H, m), 2.00±1.74 (3H, m), 1.98 (1H, t,
Jˆ2.6 Hz), 1.88 (1H, dd, Jˆ14.8, 4.0 Hz), 1.78 (1H, dd,
Jˆ14.8, 7.8 Hz), 0.97±0.88 (11H, m), 0.63±0.54 (6H, m),
0.02 (9H, s). 13C NMR (CDCl3) d: 218.0, 94.7, 80.8, 79.7,
72.9, 70.2, 65.5, 39.6, 36.8, 35.2, 25.9, 18.1, 17.7, 7.0, 6.2,
21.5. IR (neat) cm21: 3316, 2110, 1750. Positive SI-MS m/
z: 427 (M1H)1, 409, 351, 279, 199, 115. HIMS m/z:
427.2700 (Calcd for C22H43O4Si2: 427.2697).
(2Rp)-2-[(2Sp)-2-(Methoxymethoxy)pent-4-ynyl]-2-(1,1-
diethyl-1-silapropoxy)-cyclopentan-1-one (3h). In the
similar manner as the preparation of 3d, 33 (603.2 mg,
1.76 mmol) was converted into 3h (346.7 mg, 58%) as a
1
General procedure for radical skeletal rearrangement
colorless oil. H NMR (CDCl3) d: 4.73 (1H, d, Jˆ6.8 Hz),
4.70 (1H, d, Jˆ6.8 Hz), 4.00 (1H, ddt, Jˆ7.8, 5.9, 4.2 Hz),
3.40 (3H, s), 2.61 (1H, ddd, Jˆ16.8, 5.9, 2.6 Hz), 2.45 (1H,
ddd, Jˆ16.8, 4.2, 2.6 Hz), 2.30±2.15 (3H, m), 2.00 (1H, t,
Jˆ2.6 Hz), 1.91 (1H, dd, Jˆ14.7, 4.2 Hz), 1.78 (1H, dd,
Jˆ14.7, 7.8 Hz), 2.02±1.78 (3H, m), 0.96±0.90 (9H, m),
0.63±0.54 (6H, m). 13C NMR (CDCl3) d: 218.1, 96.4,
80.8, 79.7, 73.0, 70.3, 55.9, 39.7, 36.9, 35.3, 25.9, 17.8,
7.0, 6.2. IR (neat) cm21: 3300, 2100, 1745. EI-MS m/z:
340 (M1), 273, 222, 185, 119. HIMS m/z: 340.2319
(Calcd for C18H32O4Si: 340.2067).
Under an argon atmosphere, a solution of Ph3SnH
(113.9 mg, 0.32 mmol, 2.0 equiv.) and AIBN (41.3 mg,
0.25 mmol, 1.6 equiv.) or ACN (1,10-azobis cyclohexane-
carbonitrile, 61.1 mg, 0.25 mmol, 1.6 equiv.) in toluene
(4 ml) was added to a re¯uxing solution of substrate 3
(0.16 mmol) in toluene (4 ml, 40 mM) using a syringe
pump. The reaction mixture was stirred for 5 min to 7.5 h.
The reaction mixture was cooled to room temperature and
the solvent was evaporated in vacuo. The residue was puri-
®ed by ¯ash column chromatography with benzene±AcOEt
(30/1) as an eluent. In the case of using 3d±i, hydro-
azulenones were obtained as a diastereo mixture. The ratio
(1Sp)-1-{[1-({(1Rp,2Rp)-1-(1,1-Diethyl-1-silapropoxy)-2-
[(4-methoxyphenyl)-methoxy]cyclopentyl}methyl)-but-
3-ynyloxy]methoxy}-3,3-dimethyl-3-silabutane (34). In
the similar manner as the preparation of 28, 19 (657.7 mg,
1.57 mmol) was converted into 34 (836.3 mg, 97%) as a
1
of these diastereomers of enones was determined by H
NMR spectra, respectively. These diastereomers were
partially separated by repeated ¯ash column chromato-
graphy. Reaction conditions and yields are summarized in
Scheme 5 and Tables 1 and 2.
1
colorless oil. H NMR (CDCl3) d: 7.26 (2H, d, Jˆ8.6 Hz),
6.86 (2H, d, Jˆ8.6 Hz), 4.74 (2H, s), 4.53 (1H, d,
Jˆ11.6 Hz), 4.41 (1H, d, Jˆ11.6 Hz), 3.92 (1H, m), 3.81
(3H, s), 3.84±3.41 (3H, m), 2.66 (1H, ddd, Jˆ16.9, 5.4,
2.7 Hz), 2.42 (1H, ddd, Jˆ16.9, 4.1, 2.7 Hz), 1.99 (1H, t,
Jˆ2.7 Hz), 1.97 (1H, m), 1.85±1.40 (7H, m), 0.92±0.86
(11H, m), 0.68±0.54 (6H, m), 0.01 (9H, s). 13C NMR
(CDCl3) d: 132.3, 130.9, 115.0, 96.3, 86.1, 84.4, 82.8,
75.2, 72.6, 71.4, 66.9, 56.7, 44.8, 37.9, 28.4, 27.7, 20.7,
19.6, 8.8, 8.5, 0.0. IR (neat) cm21: 2878, 1613. EI-MS m/
z: 548 (M1), 509, 451, 122. HIMS m/z: 548.3321 (Calcd for
C30H52O5Si2: 548.3351).
8a-(1,1-Diethyl-1-silapropoxy)-1,2,3,6,7,8,8a-heptahydro-
azulen-5-one (4b). Colorless oil, 1H NMR (CDCl3) d: 5.88
(1H, dd, Jˆ3.9, 1.7 Hz), 3.02 (1H, ddd, Jˆ15.6, 10.5,
3.7 Hz), 2.77±2.63 (1H, m), 2.52±2.36 (2H,m), 2.21±1.54
(8H, m), 0.93 (9H, t, Jˆ8.0 Hz), 0.60 (6H, q, Jˆ8.0 Hz). 13C
NMR (CDCl3) d: 204.8, 164.8, 125.2, 82.6, 43.6, 42.0, 38.0,
34.2, 22.2, 19.6, 7.0, 6.5. IR (neat) cm21: 1665. EI-MS m/z:
280 (M1), 251, 131, 103. HIMS m/z: 280.1879 (Calcd for
C16H28O2Si: 280.1858).
(1Rp,2Rp)-2-{(2Sp)-2-[(3,3-Dimethyl-3-silabutoxy)methyl]-
pent-4-ynyl}-2-(1,1-diethyl-1-silapropoxy)cyclopentan-1-ol
(35). In the similar manner as the preparation of 25, 34
(826.3 mg, 1.5 mmol) was converted into 35 (568.8 mg,
2-(4EZ)-6,6,6-Triphenyl-6-stannahex-4-enyl)-2-(1,1-
diethyl-1-silapropoxy)cyclopentan-1-one (36). Colorless
oil, H NMR (CDCl3) d: 7.66±7.32 (15H, m), 6.80±6.03
1
(2H, m), 2.35±1.30 (12H, m), 0.92 (9H, t, Jˆ8.0 Hz), 0.57
(6H, q, Jˆ8.0 Hz). 13C NMR (CDCl3) d: 217.1, 152.8,
138.6, 137.3, 137.0, 136.9, 128.9, 128.5, 123.9, 81.5, 38.9,
1
87%) as a colorless oil. H NMR (CDCl3) d: 4.76 (1H, d,
Jˆ7.3 Hz), 4.71 (1H, d, Jˆ7.3 Hz), 3.84±3.51 (4H, m),
2.58±2.48 (3H, m), 1.99 (1H, t, Jˆ2.6 Hz), 2.06±1.90
(3H, m), 1.83±1.72 (2H, m), 1.62±1.46 (3H, m), 1.01±
0.90 (11H, m), 0.70±0.62 (6H, m), 0.02 (9H, s). 13C NMR
(CDCl3) d: 94.3, 82.7, 81.0, 76.7, 73.5, 70.3, 65.6, 43.4,
38.1, 35.5, 32.8, 26.2, 23.4, 12.5, 7.0, 6.3. IR (neat) cm21
:
1740. EI-MS m/z: 604 (M12C2H4), 555, 499, 423, 351, 253,
86. HIMS m/z: 604.1844 (Calcd for C32H40O2SiSn:
604.1818).

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9253
1
8a-(1,1-Diethyl-1-silapropoxy)-2,2-dimethyl-1,2,3,6,7,8,
8a-heptahydroazulen-5-one (4c). Colorless oil, H NMR
Colorless oil, H NMR (CDCl3) d: 5.90 (1H, s), 4.62 (2H,
s), 4.33 (1H, tt, Jˆ5.9, 4.5 Hz), 3.35 (3H, s), 3.04±2.99 (1H,
m), 2.98 (1H, ddd, Jˆ15.4, 10.3, 4.2 Hz), 2.58 (1H, m), 2.44
(1H, ddd, Jˆ15.4, 7.4, 3.8 Hz), 2.30 (1H, dd, Jˆ13.8,
5.9 Hz), 2.15 (1H, m), 2.04±1.93 (3H, m), 1.75 (1H, m),
0.94 (9H, t, Jˆ7.9 Hz), 0.61 (6H, q, Jˆ7.9 Hz). 13C NMR
(CDCl3) d: 204.1, 161.8, 127.4, 95.4, 81.7, 74.4, 55.4, 49.8,
42.3, 41.1, 39.0, 19.3, 7.0, 6.4. IR (neat) cm21: 1665. EI-MS
m/z: 340 (M1), 311, 249, 222. HIMS m/z: 340.2061 (Calcd
for C18H32O4Si: 340.2067).
1
(CDCl3) d: 5.88 (1H, dd, Jˆ2.6, 1.3 Hz), 3.00 (1H, ddd,
Jˆ14.9, 10.9, 4.0 Hz), 2.71 (1H, dd, Jˆ15.7, 2.6 Hz), 2.43
(1H, dddd, Jˆ14.9, 6.4, 3.9, 2.0 Hz), 2.22±1.65 (7H, m),
1.15 (3H, s), 0.93 (3H, s), 0.93 (9H, t, Jˆ7.9 Hz), 0.60 (6H,
q, Jˆ7.9 Hz). 13C NMR (CDCl3) d: 204.5, 165.3, 126.2,
82.4, 58.3, 50.2, 41.6, 41.0, 35.9, 29.7, 28.2, 19.5, 7.0,
6.6. IR (neat) cm21: 1660. EI-MS m/z: 308 (M1), 279,
252, 177, 138. HIMS m/z: 308.2194 (Calcd for
C18H32O2Si: 308.2170).
(2Sp,8aRp)-8a-(1,1-Diethyl-1-silapropoxy)-2-[(3,3-di-
methyl-3-silabutoxy)methoxy]-1,2,3,6,7,8,8a-hepta-
hydroazulen-5-one (4i). Colorless oil, 1H NMR (CDCl3) d:
5.90 (1H, brs), 4.66 (2H, s), 4.35 (1H, tt, Jˆ5.6, 4.4 Hz),
3.62±3.56 (2H, m), 3.02 (1H, m), 2.98 (1H, m), 2.57 (1H,
m), 2.44 (1H, m), 2.29 (1H, m), 2.15 (1H, m), 2.07±1.89
(3H, m), 1.76 (1H, m), 0.96±0.90 (11H, m), 0.65±0.56 (6H,
m), 0.02 (9H, s). 13C NMR (CDCl3) d: 204.2, 161.9, 126.5,
93.7, 81.7, 74.4, 65.3, 49.8, 42.3, 41.1, 39.0, 19.4, 18.1, 7.1,
6.5, 21.4. IR (neat) cm21: 1673. EI-MS m/z: 426 (M1), 397,
339, 249, 147. HIMS m/z: 426.2618 (Calcd for C22H42O4Si2:
426.2619).
(2Rp,8aRp)-2,8a-bis(1,1-Diethyl-1-silapropoxy)-1,2,3,6,7,
8,8a-heptahydroazulen-5-one (4d). Colorless oil, 1H NMR
(CDCl3) d: 5.85 (1H, m), 4.00 (1H, tt, Jˆ9.3, 6.8 Hz), 3.05
(1H, ddd, Jˆ16.9, 11.5, 2.9 Hz), 2.81±2.65 (2H, m), 2.42±
2.32 (1H, m), 2.20±2.01 (3H, m), 1.91 (1H, m), 1.76±1.61
(2H, m), 0.99±0.90 (18H, m), 0.65±0.55 (12H, m). 13C
NMR (CDCl3) d: 205.8, 161.5, 126.0, 80.0, 69.0, 52.1,
44.1, 40.5, 39.1, 19.5, 7.0, 6.7, 6.4, 4.7. IR (neat) cm21
:
1670. EI-MS m/z: 410 (M1), 381, 354, 278, 249, 148.
HIMS m/z: 410.2684 (Calcd for C22H42O3Si2: 410.2670).
(2Rp,8aRp)-8a-(1,1-Diethyl-1-silapropoxy)-2-(methoxy-
methoxy)-1,2,3,6,7,8,8a-heptahydroazulen-5-one
(4e).
(3Rp,7Rp,9Sp)-7-Hydroxy-9-(methoxymethoxy)bicyclo-
[5.3.0]dec-1-en-3-yl 4-bromobenzoate (37). To a solution
of 4h (43.6 mg, 0.13 mmol) in toluene (0.5 ml) was added
DIBAH (1.02 M in toluene, 0.2 ml, 0.2 mmol) at 2788C
under an argon atmosphere. After being stirred for 35 min,
saturated aqueous NH4Cl (0.5 ml) was added. The reaction
mixture was allowed to warm up to room temperature and
was then diluted with ether. Anhydrous magnesium sulfate
was then added to the reaction mixture. After 1 h, the
mixture was ®ltered through a Celite pad and the pad was
washed with ether. The ®ltrate and washings were evapo-
rated under reduced pressure. The residue was puri®ed by
column chromatography with hexane±AcOEt (4/1) as an
eluent to give alcohol (25.3 mg) as a colorless oil. 1H
NMR (CDCl3) d: 6.02 (1H, dt, Jˆ7.3, 2.2 Hz), 4.63 (2H,
s), 4.19 (1H, quint., Jˆ6.4 Hz), 4.11±3.95 (2H,m), 3.36
(3H, s), 2.78 (1H, ddt, Jˆ16.2, 5.9, 1.7 Hz), 2.41±2.28
(3H, m), 2.01±1.93 (2H, m), 1.83 (1H, dd, Jˆ13.8,
7.2 Hz), 1.72 (1H, dd, Jˆ13.8, 2.8 Hz), 1.64±1.57 (2H,
m), 1.02±0.90 (9H, m), 0.74±0.58 (6H, m). IR (neat)
cm21: 3475.
1
Colorless oil, H NMR (CDCl3) d: 5.88 (1H, brs), 4.65
(2H, s), 3.93 (1H, tt, Jˆ9.5, 6.6 Hz), 3.38 (3H, s), 3.04
(1H, ddd, Jˆ16.7, 12.0, 3.0 Hz), 2.84 (1H, m), 2.78 (1H,
ddd, Jˆ16.4, 9.5, 3.0 Hz), 2.38 (1H, ddt, Jˆ16.7, 6.4,
2.1 Hz), 2.30 (1H, ddd, Jˆ12.7, 6.6, 1.6 Hz), 2.11 (1H,
dd, Jˆ12.8, 9.5 Hz), 2.10 (1H, m), 1.93 (1H, m), 1.73±
1.64 (2H, m), 0.93 (9H, t, Jˆ7.9 Hz), 0.61 (6H, q,
Jˆ7.9 Hz). 13C NMR (CDCl3) d: 206.4, 160.9, 126.5,
96.2, 80.3, 74.2, 55.8, 49.6, 41.6, 40.9, 39.2, 19.8, 7.3,
6.7. IR (neat) cm21: 1670. EI-MS m/z: 340 (M1), 311,
281, 249, 222, 147. HIMS m/z: 340.2052 (Calcd for
C18H32O4Si: 340.2067).
(2Rp,8aRp)-8a-(1,1-Diethyl-1-silapropoxy)-2-[(3,3-dimethyl-
3-silabutoxy)methoxy]-1,2,3,6,7,8,8a-heptahydroazulen-5-
one (4f). Colorless oil, 1H NMR (CDCl3) d: 5.87 (1H, brs),
4.70 (2H, s), 3.93 (1H, tt, Jˆ9.5, 6.7 Hz), 3.66±3.58 (2H,
m), 3.04 (1H, ddd, Jˆ16.7, 11.9, 3.1 Hz), 2.83 (1H, m), 2.78
(1H, m), 2.42±2.27 (2H, m), 2.17±1.82 (3H, m), 1.78±1.60
(2H, m), 0.97±0.90 (11H, m), 0.65±0.56 (6H, m), 0.03 (9H,
s). 13C NMR (CDCl3) d: 207.7, 160.7, 126.2, 94.3, 80.1,
73.9, 65.4, 49.5, 41.4, 40.6, 39.0, 19.5, 18.2, 7.0, 6.4,
21.5. IR (neat) cm21: 1671. EI-MS m/z: 426 (M1), 369,
278, 249, 219. HIMS m/z: 426.2608 (Calcd for
C22H42O4Si2: 426.2619).
To a solution of alcohol (25.3 mg) in pyridine (1 ml) was
added p-bromobenzoyl chloride (125 mg, 0.57 mmol) and
DMAP (2.4 mg, 0.02 mmol) at 08C under an argon
atmosphere. After being stirred for 13 h at room tempera-
ture, the reaction mixture was partitioned between ether and
H2O. The product was extracted with ether. The combined
organic layers were washed with brine and dried (MgSO4).
The solvent was evaporated in vacuo. The residue was puri-
®ed by column chromatography with hexane±AcOEt (10/1)
as an eluent to give the ester (36.5 mg) as a light-yellow oil.
1H NMR (CDCl3) d: 7.92 (2H, d, Jˆ8.7 Hz), 7.56 (2H, d,
Jˆ8.7 Hz), 5.64 (1H, brs), 5.51 (1H, m), 4.62 (2H, s), 4.34
(1H, m), 3.35 (3H, s), 3.00 (1H, m), 2.47±1.55 (9H, m), 0.95
(2Sp,8aRp)-2,8a-Bis(1,1-diethyl-1-silapropoxy)-1,2,3,6,7,
8,8a-heptahydroazulen-5-one (4g). Colorless oil, 1H NMR
(CDCl3) d: 5.87 (1H, m), 4.45 (1H, m), 3.04±2.91 (2H, m),
2.49±2.38 (2H, m), 2.24±1.67 (5H, m), 1.90 (1H, ddd,
Jˆ13.7, 5.6, 1.7 Hz), 0.98±0.90 (18H, m), 0.63±0.54
(12H, m). 13C NMR (CDCl3) d: 204.6, 162.7, 126.3, 82.0,
69.9, 52.7, 44.2, 42.1, 39.3, 19.4, 7.0, 6.7, 6.5, 4.7. IR (neat)
cm21: 1660. EI-MS m/z: 410 (M1), 381, 354, 278, 250, 147.
HIMS m/z: 410.2684 (Calcd for C22H42O3Si2: 410.2670).
(9H, t, Jˆ7.4 Hz), 0.64 (6H, q, Jˆ7.4 Hz). IR (neat) cm21
:
2858, 1712.
(2Sp,8aRp)-8a-(1,1-Diethyl-1-silapropoxy)-2-(methoxy-
methoxy)-1,2,3,6,7,8,8a-heptahydroazulen-5-one (4h).
To a solution of ester (36.5 mg) in THF (0.5 ml), TBAF

9254
A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
(1.0 M in THF, 0.1 ml, 0.1 mmol) was added at 08C. After
being stirred for 30 min, the reaction was quenched with
saturated aqueous NaHCO3 and extracted with AcOEt.
Combined extracts were washed with brine and dried
(MgSO4). The solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (5/1) as an eluent to give 37 (27.2 mg, 53%
from 4h) as a light-yellow crystal. Recrystallization from
(neat) cm21: 3550, 3300, 2100, 1740. EI-MS m/z: 180 (M1),
165, 137, 124, 113, 95. HIMS m/z: 180.1137 (Calcd for
C11H16O2: 180.1149).
(2Sp,3Sp)-2-(1,1-Diethyl-1-silapropoxy)-3-methyl-2-pent-
4-ynylcyclopentan-1-one (41). To a solution of 40
(288 mg, 1.6 mmol) and 2,6-di-tert-butylpyridine (0.7 ml,
3.1 mmol) in CH2Cl2 (3 ml) was added TESOTf (0.56 ml,
2.5 mmol) at 2758C. After being stirred for 3.3 h, the
reaction was quenched with saturated aqueous NaHCO3
and extracted with AcOEt. Combined extracts were washed
with brine and dried (MgSO4). The solvent was removed
under reduced pressure. The residue was puri®ed by column
chromatography with hexane±AcOEt (30/1) as an eluent to
give 41 (440 mg, 93%) as a colorless oil. 1H NMR (CDCl3)
d: 2.39 (1H, ddd, Jˆ19.0, 8.5, 2.1 Hz), 2.19 (2H, m), 2.08
(1H, dd, Jˆ19.0, 9.2 Hz), 1.99±1.63 (5H, m), 1.96 (1H, t,
Jˆ2.7 Hz), 1.51±1.23 (2H, m), 1.02 (3H, d, Jˆ6.4 Hz), 0.92
(9H, t, Jˆ7.9 Hz), 0.59 (6H, q, Jˆ7.9 Hz). 13C NMR
(CDCl3) d: 216.9, 83.7, 81.2, 68.6, 39.1, 35.2, 32.7, 26.1,
23.4, 18.9, 12.6, 6.9, 6.2. IR (neat) cm21: 3300, 2120, 1745.
EI-MS m/z: 265 (M12C2H5), 238, 227, 209. HIMS m/z:
265.1653 (Calcd for C15H25O2Si: 265.1623).
1
EtOH afforded 37 as a colorless prism, mp 958C. H NMR
(CDCl3) d: 7.85 (2H, d, Jˆ8.7 Hz), 7.59 (2H, d, Jˆ8.7 Hz),
5.93 (1H, dt, Jˆ7.4, 2.1 Hz), 5.55 (1H, t, Jˆ7.2 Hz), 4.65
(1H, d, Jˆ6.8 Hz), 4.63 (1H, d, Jˆ6.8 Hz), 4.29 (1H, tt,
Jˆ8.1, 6.2 Hz), 3.35 (3H, s), 2.89 (1H, ddt, Jˆ16.4, 6.4,
1.8 Hz), 2.67 (1H, d, Jˆ1.2 Hz), 2.46 (1H, ddd, Jˆ16.4,
7.9, 2.6 Hz), 2.34±2.04 (4H, m), 1.82±1.67 (4H, m). 13C
NMR (CDCl3) d: 228.4, 203.6, 164.6, 154.6, 132.0, 130.9,
122.1, 95.8, 78.5, 75.1, 71.3, 55.3, 49.0, 41.3, 38.6, 31.8,
19.0. IR (CHCl3) cm21: 3568, 1717. EI-MS m/z: 412 (M1),
411, 351, 350, 330, 185, 157, 148. HIMS m/z: 410.0750,
412.0698 (Calcd for C19H23O5Br: 410.0728, 412.0708).
Crystal data for 37: C19H23O5Br, Mˆ411.29;
Ê
47.7,2u,49.4; monoclinic; P21/n; aˆ10.118 (4) A,
Ê
Ê
bˆ6.402 (4) A, cˆ28.461 (3) A, bˆ90.54 (2)8; Vˆ1844
(1) A ; Zˆ4; Dcalcˆ1.482 g/cm3: m(CuKa)ˆ 32.67 cm21
;
Ê 3
F(000)ˆ848; full-matrix least-squares re®nement was
based on 2,708 observed re¯ections (I.3.00s(I)) and 298
variable parameters, Rˆ0.067, Rwˆ0.073.
(8Sp,8aSp)-8a-(1,1-Diethyl-1-silapropoxy)-8-methyl-1,2,3,
6,7,8,8a-hepta-hydroazulen-5-one (42). Radical skeletal
rearrangement of 41 (1.01 g, 3.4 mmol), according to the
general procedure, gave a mixture of 42 and 43 (401 mg,
50%, 42:43ˆ8:1) as a colorless oil and 44 (441 mg, 21%) as
a colorless oil. 42: 1H NMR (CDCl3) d: 5.86 (1H, dd, Jˆ2.0,
1.5 Hz), 3.03 (1H, dd, Jˆ16.3, 10.9 Hz), 2.74±2.29 (3H, m),
1.92±1.50 (7H, m), 1.08 (3H, d, Jˆ6.4 Hz), 0.92 (9H, t,
Jˆ7.9 Hz), 0.57 (6H, q, Jˆ7.9 Hz). 42: 13C NMR (CDCl3)
d: 205.6, 165.8, 125.3, 84.6, 41.6, 39.7, 39.0, 34.4, 28.4,
22.4, 16.5, 7.1, 6.5. IR (neat) cm21: 2950, 1665. EI-MS m/z:
294 (M1), 279, 265, 251, 209. HIMS m/z: 294.2018 (Calcd
for C17H30O2Si: 294.2014). 43 was presented from: 1H
NMR (CDCl3) d: 5.92 (brs), 3.04 (dd, Jˆ15.4, 10.9 Hz),
2.83 (m). 13C NMR (CDCl3) d: 40.5, 40.1, 34.9, 29.7,
27.9, 22.2, 17.2.
(2Sp,3Sp)-2-(6,6-Dimethyl-6-silahept-4-ynyl)-2-hydroxy-
3-methylcyclopentane-1-one (39). To a solution of 4-iodo-
1-trimethylsilyl-1-pentyne (1.89 g, 7.1 mol) in ether (30 ml)
was added tert-butyllithium (1.57 M in n-pentane, 9.8 ml,
15.4 mmol) dropwisely under an argon atmosphere at
2708C, and the reaction mixture was stirred for 35 min.
At the same temperature, a solution of 38 (778 mg,
4.7 mmol) in ether (5 ml) was added to the reaction mixture.
After being stirred for 15 min, the reaction mixture was
quenched with saturated aqueous NH4Cl and extracted
with ether. The combined extracts were washed with brine
and dried (MgSO4). The solvent was removed under
reduced pressure. The residue was puri®ed by column chro-
matography with hexane±AcOEt (5/1) as an eluent to give
(2Sp,3Sp)-2-(4ZE)-6,6,6-Triphenyl-6-stannahex-4-enyl)-2-
(1,1-diethyl-1-sila-propoxy)-3-methylcyclopentan-1-one
(44). Colorless oil, 1H NMR (CDCl3) d: 7.59±7.53 (6H, m),
7.40±7.33 (9H, m), 6.22±6.18 (2H, m), 2.39 (1H, ddd,
Jˆ19.3, 8.8, 2.2 Hz), 2.11±1.51 (10H, m), 1.37±1.12 (2H,
m), 1.00 (1H, d, Jˆ6.4 Hz), 0.89 (9H, t, Jˆ8.2 Hz), 0.56
(6H, q, Jˆ8.2 Hz). 13C NMR (CDCl3) d: 217.1, 152.8,
138.6, 137.3, 137.0, 136.9, 128.9, 128.5, 123.9, 81.5, 38.9,
1
39 (848 mg, 71%) as a colorless oil. H NMR (CDCl3) d:
2.34±2.01 (6H, m), 1.72±1.44 (6H, m), 0.96 (3H, d,
Jˆ7.1 Hz), 0.14 (9H, s). 13C NMR (CDCl3) d: 219.4,
106.6, 84.9, 80.6, 38.0, 34.4, 32.5, 25.1, 22.5, 19.9, 13.8,
0.04. IR (neat) cm21: 3470, 1740. EI-MS m/z: 252 (M1),
237, 196, 181, 167, 73. HIMS m/z: 252.1565 (Calcd for
C14H24O2Si: 252.1544).
38.1, 35.5, 32.8, 26.2, 23.4, 12.5, 7.0, 6.3. IR (neat) cm21
:
(2Sp,3Sp)-2-Hydroxy-3-methyl-2-pent-4-ynylcyclopentan-
1-one (40). To a solution of 39 (682 mg, 2.7 mmol) in THF
(6 ml) was added TBAF (1.0 M in THF, 4.0 ml, 4.0 mmol)
at 08C. After being stirred for 40 min, the reaction was
quenched with saturated aqueous NH4Cl, and extracted
with AcOEt. Combined extracts were washed with brine
and dried (MgSO4). The solvent was removed under
reduced pressure. The residue was puri®ed by column chro-
matography with hexane±AcOEt (5/1) as an eluent to give
1745. EI-MS m/z: 618 (M12C2H4), 569, 437, 351, 267, 86.
HIMS m/z: 618.1975 (Calcd for C33H42O2Si120Sn:
618.1974).
(3Rp,6Sp,7Sp)-7-(1,1-Diethyl-1-silapropoxy)-6-methyl-
bicyclo[5.3.0]dec-1-en-3-ol (45). Under an argon
atmosphere, to a solution of the mixture of 42 and 43
(845 mg, 2.87 mmol) in toluene (30 ml) was added
DIBAH (1.01 M in toluene, 4.3 ml, 4.3 mmol) at 2758C.
After being stirred for 1.5 h, the reaction was quenched with
saturated aqueous NH4Cl (1.2 ml) and diluted with ether,
and then anhydrous MgSO4 was added. After 1 h, the
mixture was ®ltered through a Celite pad and the pad was
1
40 (451 mg, 93%) as a colorless oil. H NMR (CDCl3) d:
2.35±2.02 (7H, m), 1.96 (1H, t, Jˆ2.6 Hz), 1.76±1.46 (5H,
m), 0.96 (3H, d, Jˆ6.8 Hz). 13C NMR (CDCl3) d: 219.5,
83.8, 80.6, 68.8, 38.1, 34.6, 32.5, 25.1, 22.3, 18.6, 13.9. IR

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9255
washed with ether. The ®ltrate and washings were evapo-
rated under reduced pressure. The residue was puri®ed by
column chromatography with hexane±AcOEt (20/1) as an
eluent to give 45 (631 mg, 73%) and a mixture of 46 and 47
at room temperature for 11 h. The reaction mixture was
quenched with saturated aqueous NaHCO3 (10 ml) and
extracted with CH2Cl2. Combined extracts were washed
with H2O and brine, and dried (MgSO4). The solvent was
evaporated in vacuo. The residue was puri®ed by column
chromatography with hexane±AcOEt (15/1) as an eluent to
give 50 (3.31 g, 90%) as a yellow oil. 1H NMR (CDCl3) d:
5.89 (1H, dt, Jˆ4.2, 1.2 Hz), 5.34 (1H, m), 4.72 (1H, d,
Jˆ7.0 Hz), 4.66 (1H, d, Jˆ7.0 Hz), 4.50 (1H, m), 3.39
(3H, s), 2.15 (1H, m), 2.05 (3H, s), 1.51±2.04 (8H, m),
0.97 (3H, d, Jˆ5.9 Hz), 0.95 (9H, t, Jˆ7.9 Hz), 0.60 (6H,
q, Jˆ7.9 Hz). 13C NMR (CDCl3) d: 170.8, 152.0, 129.2,
95.6, 84.0, 80.3, 71.7, 55.9, 42.0, 38.9, 31.8, 29.6, 29.0,
21.8, 18.1, 7.7, 7.3. IR (neat) cm21: 1738. EI-MS m/z: 398
(M1), 366, 353, 337, 293. HIMS m/z: 398.2456 (Calcd for
C21H38O5Si: 398.2486).
1
(149 mg) as a colorless oil. 45: H NMR (CDCl3) d: 6.00
(1H, dt, Jˆ7.3, 2.2 Hz), 4.02 (1H, m), 3.60 (1H, d,
Jˆ11.0 Hz), 2.48 (1H, m), 2.34±2.14 (2H, m), 2.05±1.90
(2H, m), 1.80±1.31 (6H, m), 0.99 (9H, t, Jˆ7.8 Hz), 0.96
(3H, d, Jˆ6.6 Hz), 0.70 (6H, q, Jˆ7.8 Hz). 13C NMR
(CDCl3) d: 152.4, 127.3, 86.0, 66.5, 42.2, 41.8, 34.9, 34.6,
28.2, 22.9, 18.5, 7.1, 6.9. IR (CHCl3) cm21: 3422, 2960. EI-
MS m/z: 296 (M1), 278, 267, 251, 225, 211, 83. HIMS m/z:
296.2144 (Calcd for C17H32O2Si: 269.2170). mixture of 46
and 47: 1H NMR (CDCl3) d: 5.60 (1H, brs), 4.58 (1H, brd,
Jˆ11.2 Hz), 2.46±1.16 (10H, m), 0.96 (9H, t, Jˆ7.8 Hz),
0.89 (3H, d, Jˆ6.6 Hz), 0.60 (6H, q, Jˆ7.8 Hz).
(3Rp,6Sp,7Sp)-7-(1,1-Diethyl-1-silapropoxy)-6-methyl-
bicyclo[5.3.0]dec-1-en-3-yl acetate (48). A mixture of 45
(2.11 g, 7.13 mmol), Ac2O (1 ml, 10.6 mmol), pyridine
(25 ml) and DMAP (90 mg, 0.73 mmol) was stirred at
room temperature for 15.5 h. The reaction mixture was
diluted with ether and water. The organic layer was
extracted with ether. Combined extracts were washed with
ice-cooled 1% HCl (5 ml£8) and brine, and dried (MgSO4).
The solvent was removed under reduced pressure. The
residue was puri®ed by column chromatography with
hexane±AcOEt (15/1) as an eluent to give 48 (2.28 g,
(3Rp,6Sp,7Sp,10Rp)-7-(1,1-Diethyl-1-silapropoxy)-10-
(methoxymethoxy)-6-methylbicyclo[5.3.0]dec-1-en-3-ol
(51). A solution of 50 (3.43 g, 8.62 mmol) in MeOH (40 ml)
was treated with K2CO3 (2.83 g 17.2 mmol) at room
temperature. After 1.8 h, the orange solution was diluted
with 20 ml of water and then evaporated in vacuo. The
aqueous layer was extracted with AcOEt. Combined
extracts were washed with H2O and brine, and dried
(MgSO4). The solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography with
hexane±AcOEt (10/1) as an eluent to give 51 (2.68 g, 87%)
as a colorless oil. 1H NMR (CDCl3) d: 6.27 (1H, dd, Jˆ8.1,
1.2 Hz), 4.69 (1H, d, Jˆ6.8 Hz), 4.60 (1H, d, Jˆ6.8 Hz),
4.37 (1H, brs), 4.14 (1H, m), 3.82 (1H, d, Jˆ11.2 Hz), 3.36
(3H, s), 2.23 (1H, m), 2.07±1.42 (8H, m), 0.98 (9H, t,
Jˆ7.8 Hz), 0.96 (3H, d, Jˆ7.3 Hz), 0.67 (6H, q,
Jˆ7.8 Hz). 13C NMR (CDCl3) d: 151.3, 133.0, 93.6, 85.2,
79.1, 66.2, 55.2, 42.2, 37.5, 34.4, 30.0, 28.1, 18.2, 7.0, 6.8.
IR (neat) cm21: 3440. EI-MS m/z: 356 (M1), 339, 295, 266,
224. HIMS m/z: 356.2354 (Calcd for C19H36O4Si:
356.2381).
1
97%) as a colorless oil. H NMR (CDCl3) d: 5.53 (2H, dt,
Jˆ3.7, 1.5 Hz), 5.26 (1H, dddd, Jˆ9.5, 3.7, 2.2, 1.5 Hz),
2.25 (1H, m), 2.35 (1H, m), 2.18 (1H, m), 2.04 (3H, s),
1.92±1.43 (7H, m), 0.96 (9H, t, Jˆ7.9 Hz), 0.96 (3H, d,
Jˆ6.4 Hz), 0.62 (6H, q, Jˆ7.9 Hz). 13C NMR (CDCl3) d:
170.6, 151.1, 124.4, 84.2, 71.7, 42.2, 41.2, 33.6, 31.9, 28.8,
21.6, 21.4, 17.9, 7.3, 6.8. IR (CHCl3) cm21: 1738. EI-MS
m/z: 338 (M1), 309, 278, 145, 131, 155, 86. HIMS m/z:
338.2274 (Calcd for C19H34O3Si: 338.2275).
(3Rp,6Sp,7Sp,10Rp)-7-(1,1-Diethyl-1-silapropoxy)-10-hy-
droxy-6-methyl-bicyclo[5.3.0]dec-1-en-3-yl acetate (49).
A solution of 48 (168 mg, 0.5 mmol), pyridine (0.08 ml)
and SeO2 (55 mg, 0.52 mmol) in toluene (5 ml) was re¯uxed
for 3 h. The mixture was diluted with AcOEt and ®ltered
through a Celite pad, and then the pad was washed with
AcOEt. The ®ltrate and washings were concentrated under
reduced pressure. The residue was puri®ed by column chro-
matography with hexane±AcOEt (4/1) as an eluent to give
(1Rp,3Sp,7Sp,8Sp,11Rp)-8-(1,1-Diethyl-1-silapropoxy)-11-
(methoxymethoxy)-7-methyltricyclo[6.3.0k1,3l]undecan-
4-one (53). In a 100-ml two-necked ¯ask, to a green solution
of Cu(OAc)2 (184 mg, 1.01 mmol) in acetic acid (8 ml) was
added Zn powder (2.2 g, 33.7 mmol) at 1108C. After 5 min,
a dark reddish-gray precipitate was formed, and the pre-
cipitate was then cooled to room temperature. The pre-
cipitate was washed with one portion of acetic acid (2 ml)
followed by three portions of ether (5 ml£3). Under an
argon atmosphere, to a dispersion of this amalgam in
ether (20 ml), with heating to re¯ux, was added dropwisely
a solution of 51 (600 mg, 1.69 mmol), CH2I2 (1.4 ml,
16.9 mmol) and 1,2-dimethoxyethane (1.76 ml, 16.9
mmol) in ether (35 ml) for 15 min. After being re¯uxed
for 1 h, the reaction mixture was cooled in an ice bath and
then quenched by addition of saturated aqueous NH4Cl and
ether. The mixture was stirred for 30 min at room tempera-
ture. The resultant brown and gray precipitates were
removed by ®ltration through a Celite pad, and the pad
was washed with ether. The combined ®ltrate and washings
were concentrated in vacuo. The yellow residue was diluted
with ether, and the separated aqueous layer was extracted
with ether. Combined extracts were washed with H2O, satu-
rated aqueous NaHCO3 and brine. The dried (Na2SO4)
1
49 (156 mg, 0.44 mmol, 88%) as a light-yellow oil. H
NMR (CDCl3) d: 5.90 (1H, dt, Jˆ3.9, 1.2 Hz), 5.31 (1H,
m), 4.60 (1H, m), 2.30±1.88 (2H, m), 2.06 (3H, s), 1.84±
1.49 (7H, m), 1.37 (1H, d, Jˆ4.9 Hz), 0.99 (3H, d,
Jˆ6.4 Hz), 0.95 (9H, t, Jˆ7.9 Hz), 0.60 (6H, q,
Jˆ7.9 Hz). 13C NMR (CDCl3) d: 170.5, 155.2, 127.8,
83.7, 75.5, 71.3, 41.9, 38.1, 31.9, 31.4, 28.5, 21.3, 17.7,
7.2, 6.8. IR (neat) cm21: 3424, 1738. EI-MS m/z: 354
(M1), 294, 279, 251, 237, 223. HIMS m/z: 354.2201
(Calcd for C19H34O4Si: 354.2225).
(3Rp,6Sp,7Sp,10Rp)-7-(1,1-Diethyl-1-silapropoxy)-10-
(methoxymethoxy)-6-methylbicyclo[5.3.0]dec-1-en-3-yl
acetate (50). Under an argon atmosphere, a mixture of 49
(3.27 g, 9.24 mmol), (i-Pr)2NEt (3.3 ml, 18.5 mmol) and
MOMCl (1.4 ml, 18.5 mmol) in CH2Cl2 (95 ml) was stirred

9256
A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
solvent was evaporated in vacuo. The residue was puri®ed
by column chromatography using ¯orisil with hexane±
AcOEt (5/1) as an eluent to give an impure 52 (1.11 g) as
a colorless oil. This compound was used in the next step
without further puri®cation. 1H NMR (CDCl3) d: 4.60 (1H,
d, Jˆ6.6 Hz), 4.50 (1H, d, Jˆ6.6 Hz), 4.21 (1H, quint.,
Jˆ5.9 Hz), 3.49 (1H, dd, Jˆ7.2, 4.5 Hz), 3.32 (3H, s),
2.24±1.46 (11H, m), 1.00 (9H, t, Jˆ7.9 Hz), 0.89 (3H, d,
Jˆ6.8 Hz), 0.71 (6H, q, Jˆ7.9 Hz), 0.47 (1H, dd, Jˆ9.5,
4.6 Hz). IR (neat) cm21: 3364. To an ice-cooling solution of
52 (1.11 g) in CH2Cl2 (15 ml) was added NMO (317 mg,
2.7 mmol) and TPAP (23.7 mg, 0.07 mmol). The mixture
was stirred at room temperature for 1.25 h and then diluted
with ether. The mixture was ®ltered through ¯orisil, and the
¯orisil pad was washed with ether. The combined ®ltrate
was evaporated in vacuo to give a residue, which was puri-
®ed by column chromatography with hexane±AcOEt (5/1)
as an eluent to afford 53 (375.5 mg, 60%) as a colorless oil.
1H NMR (CDCl3) d: 4.60 (1H, d, Jˆ7.1 Hz), 4.50 (1H, d,
Jˆ7.1 Hz), 3.42 (1H, brt, Jˆ3.9 Hz), 3.35 (3H, s), 2.62 (1H,
dt, Jˆ11.1, 7.8 Hz), 2.39 (1H, ddd, Jˆ9.5, 8.8, 6.3 Hz), 2.25
(1H, ddd, Jˆ9.0, 6.4, 1.3 Hz), 2.13±1.44 (8H, m), 1.18 (1H,
dd, Jˆ9.0, 5.0 Hz), 1.00 (3H, d, Jˆ6.6 Hz), 1.02±0.93 (9H,
m), 0.72±0.63 (6H, m). 13C NMR (CDCl3) d: 210.5, 95.2,
85.7, 83.6, 55.5, 45.9, 40.7, 37.6, 35.6, 35.2, 29.7, 29.1,
21.7, 17.1, 7.3, 6.8. IR (neat) cm21: 1675. EI-MS m/z: 368
(M1), 323, 307, 236, 133. HIMS m/z: 368.2401 (Calcd for
C20H36O4Si: 368.2408).
Jˆ7.1 Hz), 1.06 (3H, s). 13C NMR (CDCl3) d: 213.5,
96.1, 85.8, 83.3, 55.4, 49.5, 44.8, 41.5, 41.5, 36.8, 26.7,
25.6, 20.1, 15.7. IR (CHCl3) cm21: 3417, 1678. EI-MS m/
z: 256 (M1), 238, 225, 194, 166. HIMS m/z: 256.1695
(Calcd for C14H24O4: 256.1673). Crystal data for 55:
C14H24O4, Mˆ256.34; 20.5,2u,29.6;monoclinic; P21/c;
Ê
Ê
Ê
aˆ8.382 (5) A, bˆ7.446 (3) A, cˆ22.899 (4) A, bˆ
Ê 3
100.01 (3)8; Vˆ1407 (1) A ; Zˆ4; Dcalcˆ1.210 g/cm3;
m(CuKa)ˆ6.72 cm21
;
F(000)ˆ560; full-matrix least-
squares re®nement was based on 1,852 observed re¯ections
(I.5.00s(I)) and 163 variable parameters, Rˆ0.062,
Rwˆ0.079.
(3aSp,3Rp)-3-(Methoxymethoxy)-8,3a-dimethyl-1,2,3,4,6,
7,3a-hepta-hydroazulen-5-one (56) and (3aSp,3Rp,8Sp)-3-
(methoxymethoxy)-8,3a-dimethyl-2,3,4,6a,7,8,3a-hepta-
hydroazulen-5-one (57). To a solution of 55 (27.7 mg,
0.11 mmol) in CH2Cl2 (0.7 ml) was added MsCl (0.2 ml,
1.2 mmol) and Et3N (0.2 ml, 1.4 mmol) at room tempera-
ture, and a light-yellow precipitate was formed. After 3 h, to
the ice-cooled mixture was added additional MsCl (0.2 ml,
1.2 mmol) and Et3N (0.2 ml, 1.4 mmol). After being stirred
for 50 min, the reaction was quenched with saturated
aqueous NaHCO3 and extracted with AcOEt. The combined
extracts were washed with brine and dried (MgSO4). The
solvent was removed under reduced pressure. The residue
was puri®ed by column chromatography with hexane±
AcOEt (10/1) as an eluent to give 56 (7.6 mg,
0.032 mmol, 29%) as a colorless oil and 57 (18.4 mg,
(1Rp,6Sp,7Sp,10Rp)-7-(1,1-Diethyl-1-silapropoxy)-10-
(methoxymethoxy)-1,6-dimethylbicyclo[5.3.0]undecan-
3-one (54). A solution of 53 (12 mg, 0.033mmol) in EtOH
(0.4 ml) was stirred at room temperature in the presence of
20% Pd(OH)2 on carbon (10 mg) under a hydrogen
atmosphere. When hydrogen consumption ceased, the
catalyst was ®ltered off. The ®ltrate was evaporated in
vacuo. The residue was puri®ed by column chromatography
with hexane±AcOEt (5/1) as an eluent to give 54 (11.1 mg,
71%) as a colorless oil. 56: H NMR (CDCl3) d: 4.67
1
(1H, d, Jˆ6.8 Hz), 4.56 (1H, d, Jˆ6.8 Hz), 3.64 (1H, m),
3.37 (3H, s), 3.10 (1H, d, Jˆ13.2 Hz), 2.61±2.34 (6H, m),
2.36 (1H, d, Jˆ13.2 Hz), 1.99±1.77 (2H, m), 1.73 (3H, s),
1.04 (3H, s). 13C NMR (CDCl3) d: 214.0, 140.9, 127.6, 95.0,
88.0, 55.7, 50.3, 47.4, 43.0, 30.3, 29.0, 27.4, 24.3, 23.2. IR
(neat) cm21: 1705. EI-MS m/z: 238 (M1), 206, 193, 175, 86.
HIMS m/z: 238.1557 (Calcd for C14H22O3: 238.1568). 57:
1H NMR (CDCl3) d: 5.45 (1H, t, Jˆ2.4 Hz), 4.67 (1H, d,
Jˆ6.7 Hz), 4.59 (1H, d, Jˆ6.7 Hz), 3.85 (1H, t, Jˆ6.0 Hz),
3.37 (3H, s), 2.86 (1H, m), 2.78 (1H, d, Jˆ12.4 Hz), 2.55
(1H, ddd, Jˆ16.1, 6.0, 2.4 Hz), 2.43 (1H, d, Jˆ12.4 Hz),
2.43±2.38 (2H, m), 2.22 (1H, ddd, Jˆ16.1, 6.0, 2.4 Hz),
1.98 (1H, m), 1.65 (1H, m), 1.18 (3H, s), 1.14 (3H, d,
Jˆ7.1 Hz). 13C NMR (CDCl3) d: 213.3, 152.0, 124.0,
95.8, 87.0, 55.5, 49.22, 49.17, 41.8, 36.8, 35.2, 29.4, 24.9,
22.2. IR (neat) cm21: 1700. EI-MS m/z: 238 (M1), 223, 206,
176, 83. HIMS m/z: 238.1542 (Calcd for C14H22O3:
238.1568).
1
92%) as a colorless oil. H NMR (CDCl3) d: 4.63 (1H, d,
Jˆ6.6 Hz), 4.56 (1H, d, Jˆ6.6 Hz), 3.93 (1H, t, Jˆ8.1 Hz),
3.34 (3H, s), 2.61±2.29 (4H, m), 2.14±2.02 (3H, m), 1.79±
1.53 (4H, m), 1.01 (3H, s), 1.01 (3H, d, Jˆ7.3 Hz), 0.98
(9H, t, Jˆ7.7 Hz), 0.66 (6H, q, Jˆ7.7 Hz). 13C NMR
(CDCl3) d: 214.3, 96.6, 87.2, 85.6, 55.3, 50.5, 43.9, 40.9,
39.5, 34.5, 26.6, 25.3, 19.1, 14.5, 7.3, 6.6. IR (neat) cm21
:
1696. EI-MS m/z: 370 (M1), 341, 309, 239, 131, 90. HIMS
m/z: 370.2532 (Calcd for C20H38O4Si: 370.2537).
(1Rp,6Sp,7Sp,10Rp)-7-Hydroxy-10-(methoxymethoxy)-
1,6-dimethylbicyclo-[5.3.0]undecan-3-one (55). To a solu-
tion of 54 (278 mg, 0.75 mmol) in THF (1 ml) was added
TBAF (1.0 M in THF, 2.3 ml, 2.3 mmol) at 0 8C. After
being stirred for 10 h, the reaction mixture was quenched
with saturated aqueous potassium sodium (1)-tartrate,
extracted with AcOEt. Combined extracts were washed
with brine and dried (MgSO4). The solvent was removed
under reduced pressure. The residue was puri®ed by column
chromatography with hexane±AcOEt (1/1) as an eluent to
give 55 (180.2 mg, 94%) as a colorless crystal. Recrystal-
lization from toluene afforded 55 as a colorless prism. mp.
(3aSp,3Rp)-3-hydroxy-8,3a-dimethyl-1,2,3,4,6,7,3a-hepta-
hydroazulen-5-one (58). To an ice-cooled solution of 56
(12.1 mg, 0.051 mmol) in THF (0.9 ml), conc. HCl
(0.04 ml) was added. The solution was stirred at room
temperature for 2.5 h, and then conc. HCl (0.02 ml) was
added again at 08C. After being stirred at room temperature
for 14 h, the reaction was quenched with saturated aqueous
NaHCO3 and extracted with AcOEt. Combined extracts
were washed with brine and dried (Na2SO4). The solvent
was removed under reduced pressure. The residue was puri-
®ed by column chromatography with hexane±AcOEt (2/1)
as an eluent to give 58 (9.7 mg, 98%) as a colorless oil. 1H
NMR (CDCl3) d: 3.77 (1H, brd, Jˆ3.7 Hz), 2.92 (1H, d,
Jˆ12.8 Hz), 2.57 (1H, d, Jˆ12.8 Hz), 2.56±2.24 (6H, m),
1
818C. H NMR (CDCl3) d: 4.63 (1H, d, Jˆ6.7 Hz), 4.56
(1H, d, Jˆ6.7 Hz), 3.90 (1H, t, Jˆ7.1 Hz), 3.34 (3H, s),
2.55±2.10 (6H, m), 1.89±1.40 (6H, m), 1.06 (3H, d,

A. Nishida et al. / Tetrahedron 56 (2000) 9241±9257
9257
2.09±1.95 (2H, m), 1.72 (3H, s), 1.05 (3H, s). 13C NMR
(CDCl3) d: 213.9, 140.1, 128.5, 83.7, 49.5, 48.5, 43.4,
30.6, 29.5, 28.3, 24.8, 22.8. IR (CHCl3) cm21: 3622, 1698.
EI-MS m/z: 194 (M1), 166, 149, 138, 84. HIMS m/z:
194.1331 (Calcd for C12H18O2: 194.1306). mp: 68±708C.
NOE correlation (10%) between C3±H and C3a-methyl±H
was observed.
4. Nishida, A.; Ogasawara, Y.; Kawahara, N.; Nishida, M.
Tetrahedron Lett. 1995, 36, 3015±3018.
5. Mandville, G.; Leyendecker, F.; Conia, J.-M. Bull. Soc. Chem.
Fr. 1973, 36, 963±971.
6. Vankar, Y. D.; Chaudhuri, N. C.; Rao, C. T. Tetrahedron Lett.
1987, 28, 551±554.
7. Smith, R.; Livinghouse, T. Tetrahedron 1985, 41, 3559±3568.
8. Actually, to complete this reaction, it needs more than an
equivalent amount of Ph3SnH.
(8aSp)-4,8-Dimethyl-2,3,5,6,8,8a-heptahydroazulene-1,7-
dione (59). To an ice-cooled solution of 58 (5 mg,
0.026 mmol) in CH2Cl2 (0.3 ml) was added NMO (5.4 mg,
0.05 mmol) and TPAP (1 mg, 0.03 mmol). The mixture was
stirred at room temperature for 5 min and then diluted with
ether. The reaction mixture was ®ltered through ¯orisil, and
the ¯orisil column was washed with ether. The solvent was
then evaporated in vacuo. The residue was puri®ed by
column chromatography with hexane±AcOEt (2/1) as an
9. RajanBabu, T. V.; Fukunaga, T. J. Am. Chem. Soc. 1989, 111,
296±300 (and references cited therein).
10. Keck, G. E.; Burnett, D. A. J. Org. Chem. 1987, 52, 2958±
2960.
11. Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds; Academic: New York, 1972; Vol. 2.
12. Romo, J.; deVivar, A. R. Prog. Chem. Org. Nat. Prod. 1967,
25, 90.
1
eluent to give 59 (2.4 mg, 48%) as a light-yellow oil. H
NMR (CDCl3) d: 2.83±2.26 (10H, m), 1.81 (3H, s), 1.14
13. (a) Romo, J.; deVivar, A. R. Fortshritte der Chemie
Organischen Naturstoffe 1973, 25, 190±230. (b) Yoshioka, H.,
Mabry, T. J., Yimmerman, B. N. Sesquiterpene Lactones;
University of Tokyo Press, 1973.
1
(3H, s). These H NMR data correspond to Lansbury's
synthetic intermediate 59. 13C NMR (CDCl3) d: 218.4,
210.3, 137.2, 131.0, 70.8, 48.7, 43.5, 35.5, 30.1, 24.2,
22.9, 21.9. IR (neat) cm21: 1744, 1707. EI-MS m/z: 192
(M1), 177, 164, 149, 121. HIMS m/z: 192.1138 (Calcd for
C12H16O2: 192.1149).
14. (a) Deskotch, R. W.; Hufford, C. D. J. Pharm. Sci. 1969, 58,
186±188. (b) Lee, K. H.; Huang, E.-S.; Pintadosi, C.; Pagano, J. S.;
Geissman, T. A. Cancer Res. 1971, 31, 1649±1654.
15. Doskotch, R. W.; Hufford, C. D. J. Org. Chem. 1970, 35, 486±
490.
X-Ray crystallography
16. Lansbury, P. T.; Serelis, A. K.; Hengeveld, J. E.; Hangauer,
D. G. Tetrahedron 1980, 36, 2701±2710.
Data for the crystal structure determinations were collected
on a Rigaku AFC5s diffractometer. The structure was solved
with MITHRIL and re®ned by the DIRDIF program.
17. Dahill Jr, R. T. J. Org. Chem. 1966, 31, 2694±2695.
18. (a) Danieli, N.; Marzur, Y.; Sondheimer, F. J. Am. Chem. Soc.
1962, 84, 875±876. (b) Camps, F.; Coll, J.; Parente, A. Synthesis
1978, 215±216.
References
19. (a) Simmons, H. E.; Blanchard, E. P.; Smith, R. D. J. Am.
Chem. Soc. 1964, 86, 1347±1356. (b) Simmons, H. E.; Cairus,
T. L.; Valduchick, S. A.; Hoiness, C. M. Org. React. 1972, 20,
1±131.
1. Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91,
1237±1286.
2. (a) Ellwood, C. W.; Pattenden, G. Tetrahedron Lett. 1991, 32,
1591±1594. (b) Dowd, P.; Zhang, W. Chem. Rev. 1993, 93, 2091±
2115. (c) Bowman, W. R.; Westlake, P. J. Tetrahedron Lett. 1992,
48, 1237±1286.
20. Examined conditions are as follows: PPTS in anhydrous THF
at re¯ux temperature, DBU in dichloromethane at room tempera-
ture and Wilkinson's cat. with addition of DABCO in re¯uxing
toluene.
3. Nishida, A.; Takahashi, H.; Takada, H.; Takada, N.; Yonemitsu,
O. J. Am. Chem. Soc. 1990, 112, 902±904.