Enantioselective total synthesis of both diastereomers of preclavulone-A methyl ester

Article abstract of DOI:10.1016/j.tet.2006.08.068

The enantioselective total synthesis of preclavulone-A methyl ester and its diastereomer was achieved from enantiomerically pure 5 in a stereocontrolled manner. The absolute stereochemistry of naturally occurring preclavulone-A methyl esters was determine

Full text of DOI:10.1016/j.tet.2006.08.068

Tetrahedron 62 (2006) 10425–10433
Enantioselective total synthesis of both diastereomers of
preclavulone-A methyl ester
*
Hisanaka Ito, Tsutomu Momose, Masami Konishi, Eriko Yamada,
*
Kinzo Watanabe and Kazuo Iguchi
School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 3 August 2005; accepted 12 August 2006
Available online 7 September 2006
Abstract—The enantioselective total synthesis of preclavulone-A methyl ester and its diastereomer was achieved from enantiomerically pure
5 in a stereocontrolled manner. The absolute stereochemistry of naturally occurring preclavulone-A methyl esters was determined by com-
parison of the [a]D value.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
Very recently, a trace amount of preclavulone-A methyl ester
(4) and its diastereomer 3 was isolated from the methanol
extract of C. viridis by our group (Fig. 1).5 Interestingly,
both compounds 4 and 3 were found to be an enantiomeric
mixture (4: 8% ee, 3: 46% ee) from the HPLC analysis using
a chiral column. Preclavulone-A derivatives 3 and 4 were
previously synthesized by Corey and Xiang (4: enantiomeri-
cally pure form)6 and Traverso et al. (3: racemic form).7
Although the determination of absolute stereochemistry of
4 was achieved by the comparison of [a]D value reported
by Corey et al., the absolute stereochemistry of trans isomer
3 could not be determined. Therefore, stereocontrolled syn-
thesis of 3 as an enantiomerically pure form was required to
establish the stereochemistry of the natural compounds and
to clarify the detailed stereochemical course of the biosyn-
thesis of clavulones. We have recently developed a novel
stereocontrolled synthetic method for (ꢀ)-3 and (ꢀ)-4 in a
highly stereoselective manner via the common intermediate
5.8 Now, both compounds 3 and 4 were prepared from an
enantiomerically pure 5 and the predominant enantiomer
of natural 3 and 4 was determined.
Clavulones1 (claviridenones2) and related marine prosta-
noids,3 isolated from the Okinawan soft coral, Clavularia
viridis, have received much attention owing to their struc-
tural features, significant biological activities, and unique
biosynthesis. Corey et al. proposed a biosynthetic pathway
of clavulones starting from oxidation of arachidonic acid
by lipoxygenase (LOX) through (8R)-HPETE, allene oxide,
and preclavulone-A (2) as shown in Scheme 1.4
OOH
O
CO2H
CO2H
arachidonic
acid
8R-HPETE
allene oxide
OAc
O
O
CO2Me
CO2H
OAc
preclavulone-A (2)
clavulone I (1)
Scheme 1. Biosynthetic pathway of calvulones proposed by Corey et al.
O
O
CO2Me
This biosynthesis was based on experimental results show-
ing that 2 was obtained by treating labeled arachidonic
acid as well as labeled (8R)-HPETE with the cell-free extract
or acetone powder prepared from C. viridis, although the
absolute configuration of 2 could not be determined due to
its small amount. The trans diastereomer of preclavulone-
A was also obtained in this biosynthetic experiment, but its
absolute configuration was not determined.
CO2Me
3
4
Figure 1.
2. Results and discussions
2.1. Retrosynthetic analysis
Our synthetic plan of compounds 3 and 4 each in enantio-
merically pure form was the same as that for our previously
* Corresponding authors. Tel.: +81 426 76 5473; fax: +81 426 76 7282;
e-mail addresses: itohisa@ls.toyaku.ac.jp; onocerin@ls.toyaku.ac.jp
0040–4020/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.08.068

10426
H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
OH
O
O
O
O
O
MPMO
BzO
H
H
H
H2N
Ph
N
H
Ph
N
H
Ph
OH
CHO
OTBDPS
O
O
3
+
THF, 50 °C
OH
O
(quant)
H
( )-5
10
11
O
6
7
O
O
1) 1M H2SO4, dioxane/H2O
reflux
N
H
Ph
O
5
H
H
H
2) camphorsulfonic acid, benzene
1
O
CHO
OTBDPS
OH
reflux
94%
4
2
3
(+)-5
[α]D +29.4
10
5
4
H
9
8
Scheme 2. Synthesis of enantiomerically pure 5.
Figure 2. Retrosynthetic pathway of compounds 3 and 4.
compounds 10 and 11 were obtained as a diastereomeric
mixture (Scheme 2). After separation of each diastereomer
by HPLC, compound 10 was converted to (+)-5 ([a]D
+29.4) by acid hydrolysis and following lactonization
using an acid catalyst in 91% yield. Compound (ꢁ)-5
([a]D ꢁ29.2) was also prepared from compound 11 in the
same manner. Absolute stereochemistry of compound 5
was determined by comparing optical rotation value of the
literature after conversion of 5 to 4-ethyltetrahydropyran-
2-one.10
reported synthesis of racemic 3 and 4 as shown in Figure 2.8
The a- and u-chains of compounds 3 and 4 could be con-
structed from the corresponding aldehyde by Wittig reaction
with high Z-selectivity. So, it was important to prepare com-
pounds 6 and 8 in a highly stereocontrolled manner. For the
construction of the cyclopentene ring of 6 and 8, ring-closing
olefin metathesis was employed. Compound 7 having a
trans-relationship between the a- and b-substituents on the
lactone was prepared from 5 through diastereoselective
Mukaiyama aldol reaction using boron enolate. On the other
hand, compound 9 could be prepared by the trans-selective
a-alkylation of compound 5. The 3-methyl-2-butenyl group
was chosen as an alkylating agent because tri-substituted
carbon–carbon double bond should not be reacted during
the ring-closing olefin metathesis and is possible for the site-
selectiveepoxidation. Introduction of vinyl group tocarbonyl
moiety and following ring-closing olefin metathesis could
be obtained cis-disubstituted cyclopentene derivative 8.
2.3. Enantioselective and stereocontrolled total synthesis
of 3
The total synthesis of (+)-3 from (R)-(+)-5 is shown in
Scheme 3. The construction of 7 having two trans-related
substituents on the lactone was achieved by Mukaiyama
aldol reaction through boron enolate using dibutylboron
triflate and diisopropylethylamine in a highly diastereo-
selective manner (80% yield, minor isomer could not be
detected by crude 1H NMR).11 Although other metals (lith-
ium, zinc, and magnesium) for the enolate were examined,
the control of the stereochemistry of the newly formed chiral
centers could not be achieved. After the conversion of com-
pound 7 to 12 by protection of hydroxyl group and reduction
of lactone moiety, the ring-closing olefin metathesis of 12
by the use of first generation Grubbs catalyst12 proceeded
to give compound 13 in 76% yield. One carbon elongation
of the a-chain was achieved as follows. Mono-protection of
the hydroxyl groups to obtain compound 14, oxidation of
another hydroxyl group, Wittig reaction by the use of meth-
oxymethyltriphenylphosphonium chloridewith butyllithium,
and following acid hydrolysis of the resulting enol ether
2.2. Synthesis of the common key intermediate 5
The preparation of optically pure compound 5 was essential
for the enantioselective synthesis of 3 and 4. Our main pur-
pose in the synthesis of compounds 3 and 4 as enantiomeri-
cally pure form is for the determination of the absolute
stereochemistry of natural 3 and 4. So, both enantiomers of
5 could be applied for the synthesis of 3 and 4. Additionally,
racemic 5 was easily obtained by the 1,4-addition of
vinylmagnesium chloride to 5,6-dihydro-2H-pyran-2-one.9
Therefore, optical resolutionofracemic5wasselectedforthe
preparation of enantiomerically pure 5 as shown in Scheme 2.
Racemic 5 was reacted with (S)-1-phenylethylamine and
O
OH
MPMO
O
MPMO
MPMO
MPMO
H
H
H
H
H
H
H
H
H
a
O
e
f-h
b,c
d
OH
OH
OH
OH
OH
CHO
OTBDPS
O
OTBDPS
H
H
(R)-5
7
12
13
14
6
MPMO
MPMO
k-m
O
H
H
H
H
i,j
n,o
CO2Me
CO2Me
CO2Me
OTBDPS
synthetic: >98% ee
H
H
[α]D +105.7 (c 0.73, CHCl3)
natural: 46% ee
16
15
(8R,12S)-(+)-3
[α]D –51.0 (c 0.08, CHCl3)
Scheme 3. Reagents and conditions: (a) Bu2BOTf, EtNiPr2, CH2Cl2, ꢁ78 ꢂC, then acrolein, ꢁ78 ꢂC to 0 ꢂC, 80%; (b) p-methoxybenzyl trichloroacetimidate,
camphorsulfonic acid, CH2Cl2, 0 ꢂC to rt; (c) LiAlH4, ether, rt, two steps 50%; (d) first Grubbs catalyst, toluene, 50 ꢂC, 78%; (e) TBDPSCl, imidazole, DMF, rt,
53%; (f) Dess–Martin periodinane, CH2Cl2, rt, 95%; (g) Ph3P+ClꢁCH2OMe, n-BuLi, THF, rt; (h) TsOH, acetone, rt, two steps, 50%; (i) Ph3P+Brꢁ(CH2)4CO2H,
NaHMDS, THF, rt, 78%; (j) CH2N2, ether, 0 ꢂC, 90%; (k) TBAF, THF, rt, 99%; (l) Dess–Martin periodinane, CH2Cl2, rt, 89%; (m) Ph3P+Brꢁ(CH2)5CH3,
NaHMDS, THF, rt, 87%; (n) DDQ, CH2Cl2/H2O, rt, 95%; and (o) Dess–Martin periodinane, CH2Cl2, rt, 98%.

H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
10427
gave compound 6. Construction of the a- and u-chains by
Wittig reaction proceeded with high Z-selectivity (minor
isomer could not be detected by 1H NMR) to give compound
16. Total synthesis of enantiomerically pure (8R,12S)-3
(>98% ee, determined by HPLC using chiralcel OD-H)
was achieved by deprotection of MPM group by treating
with DDQ and following oxidation of resulting allylic alco-
hol moiety using Dess–Martin periodinane. Comparison
of the optical rotation values of the synthetic and natural
compounds indicated that the synthetic (8R,12S)-3 was a
minor enantiomer of natural 3 and a major enantiomer was
(8S,12R)-3.
reaction, and(8R,12R)-4wasobtainedasanenantiomerically
pure form (>98% ee, determined by HPLC using chiralcel
OD-H). Comparison of the optical rotation values of the
synthetic and natural compounds indicated that (8R,12R)-4
is a major enantiomer of the natural 4 and was in good
accordance with the reported value of synthetic 4.6
3. Conclusion
The enantioselective total syntheses of preclavulone-A
methyl ester and its diastereomer were achieved from enan-
tiomerically pure common intermediate 5 and the absolute
stereochemistries of the predominant enantiomers of natu-
rally occurring 3 and 4 were determined as shown in
Figure 1. These results are an important information for the
elucidation of the biosynthetic pathway of clavulones.
2.4. Enantioselective and stereocontrolled total synthesis
of 4
Although the enantioselective total synthesis of 4 was
achieved by Corey and Xiang,6 an alternative total synthesis
of 4 as an enantiomerically pure form was established by our
developed synthetic route from (S)-(ꢁ)-5 as shown in
Scheme 4. Two chiral centers of 4 were constructed dia-
stereoselectively through the a-alkylation of 5 by employing
1-bromo-3-methyl-2-butene. The reaction proceeded to give
compound 9 as a single diastereomer in 94% yield. Com-
pound 9 was converted to the precursor of the ring-closing
olefin metathesis by half-reduction of the lactone moiety
and following addition of vinylmagnesium chloride. The
ring-closing metathesis of 17 was examined by the use of
second generation Grubbs catalyst13 and compound 18 was
obtained as a diastereomeric mixture in 80% yield. If first
generation of Grubbs catalyst was employed in this step,
the reaction did not proceed. After the protection of two
hydroxyl groups, the site-selective oxidative cleavage of
the tri-substituted carbon–carbon double bond was achieved
to give compound 8. Stereoselective construction of both
side chains was achieved in the same manner as mentioned
for the synthesis of the trans isomer 3 through the Wittig
4. Experimental
4.1. General
All reactions were carried out under an argon atmosphere.
Unless otherwise noted, materials were obtained from com-
mercial suppliers and used without further purification. H
1
and 13C NMR spectra were measured on a Bruker AV-300
and the chemical shifts are given in parts per million using
CHCl3 (7.26 ppm) in CDCl3 for 1H NMR and CDCl3
(77.0 ppm) for 13C NMR as an internal standard. IR spectra
were taken with a Perkin–Elmer PARAGON 1000 FT-IR and
only noteworthy absorptions were listed. Mass spectra were
measured on a Micromass LCT.
4.1.1. 3-(2-Hydroxyethyl)-4-pentenoic acid (1-phenyl-
ethyl) amide (10, 11). To a solution of racemic 5 (6.9 g,
54.7 mmol) in THF (20 mL) was added (S)-phenylethyl-
amine (9 mL, 71.1 mmol) at ambient temperature and the
mixture was stirred at 50 ꢂC for 2 days. The mixture was
concentrated under vacuum and the resulting residue was
purified by silica gel column chromatography (AcOEt) and
the compounds 10 and 11 were obtained as a diastereomeric
mixture (13.5 g, 54.6 mmol, 99%). The resulting diastereo-
meric mixture was separated by HPLC (AcOEt/IPA, 10:1).
Compound 10: colorless oil. [a]2D4 ꢁ66.0 (c 0.65, CHCl3).
IR (neat) n cmꢁ1: 699, 915, 995, 1050, 1548, 1643, 2930,
3284. 1H NMR (300 MHz, CDCl3) d: 1.47 (3H, d,
J¼7.1 Hz), 1.63 (2H, q, J¼6.4 Hz), 2.00 (1H, br s), 2.22
(1H, dd, J¼7.3, 14.4 Hz), 2.28 (1H, dd, J¼6.8, 14.4 Hz),
2.74 (1H, sext, J¼7.2 Hz), 3.63 (2H, t, J¼5.7 Hz), 5.04
(1H, dd, J¼1.2, 10.2 Hz), 5.08 (1H, dd, J¼1.2, 17.2 Hz),
5.13 (1H, quint, J¼7.1 Hz), 5.68 (1H, ddd, J¼8.3, 10.2,
17.2 Hz), 5.80 (1H, br d, J¼7.2 Hz), 7.23–7.38 (5H, m).
13C NMR (75 MHz, CDCl3) d: 21.6, 37.1, 37.5, 42.0, 48.8,
60.5, 115.5, 126.2, 127.4, 128.7, 141.0, 143.0, 170.8.
HREIMS calcd for C15H22NO2: 248.1651 (M+H)+, found:
248.1663. Compound 11: colorless oil. [a]2D4 ꢁ96.0 (c
0.65, CHCl3). IR (neat) n cmꢁ1: 699, 916, 994, 1050,
1449, 1548, 1643, 2930, 3284. 1H NMR (300 MHz,
CDCl3) d: 1.47 (3H, d, J¼6.9 Hz), 1.62 (2H, q, J¼6.4 Hz),
2.20 (1H, dd, J¼7.5, 14.3 Hz), 2.29 (1H, dd, J¼6.7,
14.3 Hz), 2.73 (1H, sext, J¼7.3 Hz), 3.57–3.72 (2H, m),
5.01 (1H, d, J¼10.2 Hz), 5.05 (1H, d, J¼17.2 Hz), 5.11
O
OH
O
H
H
H
a
O
d
b,c
O
OH
H
H
H
(S)-5
9
17
HO
BzO
H
BzO
H
g,h
OTBDPS
e,f
CHO
OTBDPS
OH
H
H
H
18
19
8
synthetic: >98% ee
O
H
H
[α]D –135.3 (c 0.13, CHCl3)
lit.6 [α]D –131.8 (c 1.14, THF)
natural: 8% ee
i-o
CO2Me
(8R,12R)-(-)-4
[α]D –17.9 (c 0.05, CHCl3)
Scheme 4. Reagents and conditions: (a) LiHMDS, THF, ꢁ78 ꢂC, then
1-bromo-3-methyl-2-butene, ꢁ78 ꢂC to 0 ꢂC, 94%; (b) DIBALH, ether,
ꢁ78 ꢂC to ꢁ20 ꢂC, 98%; (c) vinylmagnesium chloride, THF, 0 ꢂC to rt,
94%; (d) second Grubbs catalyst, CH2Cl2, rt, 80%; (e) TBDPSCl, triethyl-
amine, DMAP, CH2Cl2, 0 ꢂC, 98%; (f) benzoyl chloride, pyridine, DMAP,
CH2Cl2, 0 ꢂC, 78%; (g) m-CPBA, CH2Cl2, 0 ꢂC, 80%; (h) HIO4, H2O,
t-BuOH, rt, 99%; (i) Ph3P+Brꢁ(CH2)4CO2H, NaHMDS, THF, ꢁ78 ꢂC to
rt, 76%; (j) CH2N2, ether, 0 ꢂC, 90%; (k) TBAF, THF, rt, 98%; (l) Dess–
Martin periodinane, CH2Cl2, rt, 99%; (m) Ph3P+Brꢁ(CH2)5CH3, NaHMDS,
THF, ꢁ78 ꢂC to 0 ꢂC, 98%; (n) NaOMe, MeOH, 50 ꢂC, 88%; and (o) MnO2,
CH2Cl2, rt, 95%.

10428
H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
(1H, quint, J¼7.1 Hz), 5.65 (1H, ddd, J¼8.4, 10.2, 17.2 Hz),
6.01 (1H, br s), 7.21–7.37 (5H, m). 13C NMR (75 MHz,
CDCl3) d: 21.6, 36.9, 37.4, 41.9, 48.8, 60.2, 115.5, 126.2,
127.4, 128.6, 140.9, 142.9, 171.2.
m), 2.51 (1H, dd, J¼3.1, 9.4 Hz), 2.77 (1H, quint, J¼
7.6 Hz), 3.06(1H, br s), 4.23–4.35 (2H, m), 4.35 (1H, br d, J¼
4.2 Hz), 5.13 (1H, d, J¼10.3 Hz), 5.14 (1H, d, J¼17.2 Hz),
5.15 (1H, d, J¼10.3 Hz), 5.24 (1H, d, J¼17.2 Hz), 5.74
(1H, ddd, J¼8.1, 10.3, 17.2 Hz), 6.08 (1H, ddd, J¼6.2,
10.3, 17.2 Hz). 13C NMR (75 MHz, CDCl3) d: 29.0, 37.7,
50.3, 67.0, 72.2, 116.0, 116.5, 138.8, 139.5, 172.3. Anal.
Calcd for C10H14O3: C, 65.92; H, 7.74. Found: C, 65.60; H,
8.03. HREIMS calcd for C10H15O3: 183.1021 (M+H)+,
found: 183.1012.
4.1.2. (4R)-4-Vinyltetrahydropyran-2-one ((D)-5). The
mixture of 10 (1.07 g, 8.46 mmol) and H2SO4 (1 M in water,
10.2 mL, 10.2 mmol) in dioxane (10 mL) and water (10 mL)
was heated under reflux for 1 h. Aftercoolingatambienttem-
perature, the mixture was extracted with AcOEt three times
and the resulting organic layer was washed with brine, dried
over MgSO4, and concentrated under vacuum. The mixture
was diluted with benzene (10 mL) and camphorsulfonic
acid (213 mg, 0.85 mmol) was added to the mixture. The
mixture was refluxed with removal of water for 15 h. Then,
saturated aqueous NaHCO3 was added to the mixture and
the mixture was extracted with AcOEt. The organic layer
was washed with brine, dried over MgSO4, and concentrated
under vacuum. The residue was purified by silica gel column
chromatography(hexane/AcOEt,2:1)toaffordthecompound
(+)-5 as an enantiomerically pure form (1.54 g, 7.91 mmol,
94%). Colorless oil. [a]D24 +29.4 (c 0.52, CHCl3). IR (neat)
n cmꢁ1: 921, 996, 1737, 2977. 1H NMR (300 MHz, CDCl3)
d: 1.56–1.73 (1H, m), 1.88–2.02 (1H, m), 2.28 (1H, dd,
J¼11.2, 18.8 Hz), 2.54–2.69 (2H, m), 4.22 (1H, ddd, J¼3.9,
9.8, 11.4 Hz), 4.35 (1H, td, J¼4.8, 11.4 Hz), 5.01 (1H, dd,
J¼1.0, 17.4 Hz), 5.02 (1H, dd, J¼1.0, 10.1 Hz), 5.71 (1H,
ddd, J¼6.1, 10.1, 17.4 Hz). 13C NMR (75 MHz, CDCl3) d:
28.9, 35.5, 35.9, 68.7, 115.4, 140.0, 171.0.
4.1.5. 4-Hydroxymethyl-5-(4-methoxybenzyloxy)-3-
vinyl-6-hepten-1-ol (12). To a solution of 7 (1.0 g,
5.48 mmol) in CH2Cl2 (5 mL) was added a solution of
MPM imidate (10 mmol) in cyclohexane (5 mL) and cam-
phorsulfonic acid (125.2 mg, 0.5 mmol) and the mixture
was stirred at ambient temperature for 24 h. The resulting
mixture was filtered through Celite and concentrated under
vacuum. To the residue, which was diluted with ether
(20 mL) was added LiAlH4 (249.6 mg, 6.58 mmol) at ambi-
ent temperature. After being stirred for 2 h, saturated aque-
ous Rochelle salt was added to the mixture and stirred for
1 h. The mixture was extracted with AcOEt and the organic
layer was washed with brine and dried over MgSO4. Filtra-
tion and concentration of the mixture under reduced pressure
gave crude material, which was purified by silica gel column
chromatography(hexane/AcOEt, 1:1)toafford12(839.5 mg,
2.74 mmol) in 50% yield. Colorless oil. [a]2D4 ꢁ15.8 (c 1.06,
CHCl3). 1H NMR (300 MHz, CDCl3) d: 1.33–1.49 (2H, m),
1.81–1.96 (1H, m), 1.94 (1H, br s), 2.53–2.66 (1H, m),
3.49–3.75 (3H, m), 3.80 (3H, s), 3.94 (1H, dd, J¼1.8,
11.8 Hz), 4.07–4.16 (1H, m), 4.18 (1H, d, J¼11.0 Hz), 4.51
(1H, d, J¼10.0 Hz), 4.96 (1H, dd, J¼1.8, 17.0 Hz), 5.06
(1H, dd, J¼1.8, 10.2 Hz), 5.28 (1H, d, J¼17.0 Hz), 5.33
(1H, d, J¼9.8 Hz), 5.60 (1H, dt, J¼9.8, 17.0 Hz), 5.84 (1H,
ddd, J¼7.0, 10.2, 17.0 Hz), 6.86 (2H, d, J¼8.5 Hz), 7.21
(2H, d, J¼8.5 Hz). 13C NMR (75 MHz, CDCl3) d: 33.7,
39.1, 48.3, 55.2, 60.2, 61.3, 70.7, 82.1, 113.8, 116.7, 117.8,
129.5, 129.9, 137.4, 141.0, 159.3. HREIMS calcd for
C18H26O4Na: 329.1729 (M+Na)+, found: 329.1749.
4.1.3. (D)-4-Ethyltetrahydropyran-2-one. The mixture of
(+)-5 (20 mg, 0.16 mmol) and catalytic amount of 5% Pd/C
in MeOH (2 mL) was stirred at ambient temperature under
hydrogen atmosphere for 2 h. The reaction mixture was fil-
tered and the filtrate was concentrated under vacuum and
the resulting residue was purified by silica gel column chro-
matography (hexane/AcOEt, 3:1) to afford 4-ethyltetra-
hydropyran-2-one (9.1 mg, 0.071 mmol) in 44% yield.
[a]D24 +17.9 (c 0.52, CHCl3). Colorless oil. [a]2D4 +27.8
(c 8.1, CHCl3).10 The spectral data was same as reported
value.10
4.1.6. 2-[5-Hydroxymethyl-4-(4-methoxybenzyloxy)-2-
cyclopentenyl]ethanol (13). To a solution of 12 (227 mg,
0.74 mmol) in toluene (7 mL) was added benzylidene-
bis(tricyclohexylphosphine)dichlororuthenium (60.9 mg,
0.07 mmol) at 50 ꢂC. After being stirred for 1.5 h at the
same temperature, water was added to the mixture and the
mixture was extracted with AcOEt. The organic layer was
washed with brine and dried over MgSO4. Filtration and con-
centration of the mixture under reduced pressure gave crude
material, which was purified by silica gel column chromato-
graphy (hexane/AcOEt, 1:1) to afford 13 (161.5 mg,
0.58 mmol) in 78% yield. Colorless oil. [a]2D4 ꢁ46.0 (c
1.51, CHCl3). IR (neat) n cmꢁ1: 1060, 1248, 1585, 1612,
2931, 3361. 1H NMR (300 MHz, CDCl3) d: 1.52–1.65 (2H,
m), 1.80–1.93 (1H, m), 2.18–2.28 (1H, m), 2.52–2.62
(1H, m), 3.53 (1H, t, J¼9.4 Hz), 3.68–3.78 (3H, m), 3.80
(3H, s), 4.26 (1H, br s), 4.49 (2H, s), 5.81 (1H, td, J¼1.9,
5.6 Hz), 5.88 (1H, dd, J¼1.5, 5.6 Hz), 6.87 (2H, d,
J¼8.6 Hz), 7.27 (2H, d, J¼8.6 Hz). 13C NMR (75 MHz,
CDCl3) d: 37.7, 45.1, 51.5, 55.3, 60.8, 65.4, 70.5, 86.6,
113.8, 129.1, 129.4, 130.4, 138.9, 159.2. HREIMS calcd
for C16H23O4: 279.1596 (M+H)+, found: 279.1624.
4.1.4. 3-(1-Hydroxy-2-propenyl)-4-vinyltetrahydro-
pyran-2-one (7). To a solution of (R)-5 (550 mg,
4.35 mmol) in CH2Cl2 (10 mL) was added dibutylboron
trifluoromethanesulfonate (1 M in dichloromethane,
8.7 mL, 8.7 mmol) and diisopropylethylamine (1.86 mL,
10.9 mmol) was added at ꢁ78 ꢂC. After being stirred for
2 h at the same temperature, acrolein (0.58 mL, 8.7 mmol)
was added to the mixture and the resulting mixture was
stirred at the same temperature for 1 h. After being stirred
for further 2 h at 0 ꢂC, phosphate buffer (pH 6.86, 10 mL),
methanol (20 mL), and H2O2 (10 mL) were added to the mix-
ture and the resulting mixture was stirred at ambient temper-
ature for 16 h. The mixture was concentrated under reduced
pressure and extracted with CH2Cl2. The organic layer was
washed with brine and dried over MgSO4. Filtration and con-
centration of the mixture under reduced pressure gave crude
material, which was purified by silica gel column chromato-
graphy (hexane/AcOEt, 2:1) to afford 7 (630 mg, 3.46 mmol)
in 80% yield. Colorless oil. [a]2D4 +43.1 (c 1.37, CHCl3). IR
(neat) n cmꢁ1 1122, 1727, 2918, 3432. 1H NMR
:
(300 MHz, CDCl3) d: 1.68–1.82 (1H, m), 1.95–2.08 (1H,

H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
10429
4.1.7. [5-[2-(tert-Butyldiphenylsilanyloxy)ethyl]-2-(4-
methoxybenzyloxy)-3-cyclopentenyl]methanol (14). To a
solution of 13 (155 mg, 0.558 mmol) in DMF (2 mL) were
added imidazole (83.6 mg, 1.228 mmol) and TBDPSCl
(0.16 mL, 0.614 mmol) at 0 ꢂC. After being stirred for 1 h,
water was added to the reaction mixture. The mixture was
extracted with AcOEt and the organic layer was washed
with brine and dried over MgSO4. Filtration and concentra-
tion of the mixture under reduced pressure gave crude
material, which was purified by silica gel column chromato-
graphy (hexane/AcOEt, 5:1) to afford 14 (150 mg,
0.29 mmol) in 53% yield. Colorless oil. [a]2D4 ꢁ48.8 (c
1.15, CHCl3). IR (neat) n cmꢁ1: 702, 1036, 1111, 1247,
J¼3.0 Hz), 4.46 (2H, s), 5.79 (1H, td, J¼1.8, 5.8 Hz), 5.87
(1H, br d, J¼5.8 Hz), 6.86 (2H, d, J¼8.7 Hz), 7.23 (2H, d,
J¼8.7 Hz), 7.33–7.47 (6H, m), 7.65 (4H, d, J¼7.7 Hz),
9.73 (1H, t, J¼2.6 Hz). Anal. Calcd for C33H40O4Si: C,
74.68; H, 7.98. Found: C, 74.58; H, 7.70.
4.1.9. 7-[2-[2-(tert-Butyldiphenylsilanyloxy)ethyl]-5-(4-
methoxybenzyloxy)-3-cyclopentenyl]-5-heptenoic acid
methyl ester (15). To a suspension of 4-hydroxycarbonyl-
butyltriphenylphosphonium bromide(45.3 mg, 0.102 mmol)
in THF (1.2 mL) was added a solution of NaHMDS (1 M in
THF, 0.2 mL, 0.2 mmol) at 0 ꢂC and the mixture was stirred
at ambient temperature for 1 h. A solution of 6 (18 mg,
0.034 mmol) in THF (0.3 mL) was added to the mixture at
0 ꢂC and the mixture was stirred at ambient temperature for
1 h. Saturated aqueous ammonium chloride was added to
the reaction mixture and the resulting mixture was extracted
with CHCl3. The organic layer was washed with brine and
dried over MgSO4. Filtration and concentration of the
mixture under reduced pressure gave crude material, which
was purified by silica gel column chromatography (hexane/
AcOEt, 2:1) to afford carboxylic acid (16 mg, 0.026 mmol)
in 76% yield. Colorless oil. [a]2D4 ꢁ16.1 (c 0.58, CHCl3).
1
1513, 1612, 2929, 3450. H NMR (300 MHz, CDCl3) d:
1.05 (9H, s), 1.53–1.67 (2H, m), 1.67–1.81 (1H, m), 2.03–
2.14 (1H, m), 2.49–2.60 (1H, m), 3.65 (2H, d, J¼7.0 Hz),
3.70–3.80 (2H, m), 3.82 (3H, s), 4.35 (1H, br s), 4.50 (2H,
s), 5.78 (1H, dt, J¼1.9, 5.7 Hz), 5.83 (1H, d, J¼5.7 Hz),
6.87 (2H, d, J¼8.6 Hz), 7.27 (2H, d, J¼8.6 Hz), 7.34–7.47
(6H, m), 7.67 (4H, dd, J¼1.5, 7.5 Hz). 13C NMR (75 MHz,
CDCl3) d: 19.2, 38.2, 44.3, 52.8, 55.3, 62.5, 65.3, 70.5,
86.8, 113.8, 127.7, 129.3, 129.4, 129.7, 130.8, 133.5,
133.6, 135.5, 138.3. HREIMS calcd for C32H40O4NaSi:
539.2594 (M+Na)+, found: 539.2580.
1
IR (neat) n cmꢁ1: 702, 1247, 1587, 1707, 3069. H NMR
(300 MHz, CDCl3) d: 1.06 (9H, s), 1.60–1.82 (4H, m),
1.83–1.92 (1H, m), 2.00–2.21 (4H, m), 2.32 (2H, t,
J¼7.5 Hz), 2.35–2.45 (1H, m), 3.73 (2H, t, J¼6.4 Hz), 3.80
(3H, s), 4.17 (1H, br s), 4.46 (2H, s), 5.30–5.54 (2H, m),
5.76 (1H, td, J¼1.9, 5.7 Hz), 5.58 (1H, dd, J¼1.3, 5.7 Hz),
6.86 (2H, d, J¼8.7 Hz), 7.26 (2H, d, J¼8.7 Hz), 7.34–7.47
(6H, m), 7.68 (4H, d, J¼7.3 Hz). 13C NMR (75 MHz,
CDCl3) d: 19.2, 24.5, 26.6, 26.8, 31.3, 33.4, 38.7, 46.9,
49.9, 55.2, 62.5, 70.4, 88.8, 113.6, 127.6, 128.9, 129.3,
129.5, 130.9, 133.9, 135.5, 138.6, 159.0, 179.5. Anal. Calcd
for C38H48O5Si: C, 74.47; H, 7.89. Found: C, 74.44; H, 7.82.
To a solution of carboxylic acid (16 mg, 0.026 mmol) in ether
(2 mL) was added a solution of diazomethane in ether at 0 ꢂC
and the mixture was stirred for 15 min at the same tempera-
ture. After concentration under the reduced pressure, crude
material was purified by silica gel column chromatography
(hexane/AcOEt, 3:1) to afford 15 (14.7 mg, 0.023 mmol) in
90% yield. Colorless oil. [a]2D4 ꢁ10.0 (c 1.62, CHCl3). IR
(neat) n cmꢁ1: 702, 1111, 1247, 1737, 2930. 1H NMR
(300 MHz, CDCl3) d: 1.06 (9H, s), 1.59–1.79 (4H, m),
1.79–1.92 (1H, m), 1.96–2.21 (4H, m), 2.29 (2H, t,
J¼7.5 Hz), 2.35–2.44 (1H, m), 3.66 (3H, s), 3.73 (2H, t,
J¼6.5 Hz), 3.80 (3H, s), 4.17 (1H, br s), 4.45 (2H, s), 5.34–
5.52 (2H, m), 5.76 (1H, td, J¼1.9, 5.8 Hz), 5.87 (1H, dd,
J¼1.3, 5.8 Hz), 6.86 (2H, d, J¼8.6 Hz), 7.25 (2H, d,
J¼8.6 Hz), 7.34–7.48 (6H, m), 7.67 (4H, d, J¼7.4 Hz). 13C
NMR (75 MHz, CDCl3) d: 19.2, 24.8, 26.5, 26.7, 26.8,
31.3, 33.4, 38.7, 46.9, 49.9, 51.4, 55.2, 62.5, 70.4, 88.8,
113.7, 127.6, 127.7, 128.8, 129.2, 129.3, 129.5, 129.7,
131.0, 133.9, 134.8, 135.5, 138.5, 159.0, 174.0. Anal. Calcd
for C39H50O5Si: C, 74.72; H, 8.04. Found: C, 74.53; H, 8.06.
4.1.8. [5-[2-(tert-Butyldiphenylsilanyloxy)ethyl]-2-(4-
methoxybenzyloxy)-3-cyclopentenyl]acetaldehyde (6).
To a solution of 14 (265 mg, 0.512 mmol) in CH2Cl2
(5 mL) was added Dess–Martin periodinane (239 mg,
0.564 mmol) at ambient temperature. After being stirred
for 30 min, the mixture was diluted with ether and washed
with saturated aqueous NaHCO3. The organic layer was
washed with brine and dried over MgSO4. Filtration and
concentration of the mixture under reduced pressure gave
crude material, which was purified by silica gel column
chromatography (hexane/AcOEt, 5:1) to afford aldehyde
(251 mg, 0.487 mmol) in 95% yield. A solution of n-butyl-
lithium (1.58 M in hexane, 1.74 mL, 2.7 mmol) was added
to a suspension of methoxymethyltriphenylphosphonium
chloride (858 mg, 2.5 mmol) in THF (15 mL) at ꢁ40 ꢂC
and the mixture was stirred at the same temperature for
1 h. A solution of aldehyde (247 mg, 0.481 mmol) in THF
(5 mL) was added to the reaction mixture at the same tem-
perature and the mixture was stirred at ambient temperature
for 2 h. Saturated aqueous ammonium chloride was added to
the reaction mixture and the mixture was extracted with
ether. The organic layer was washed with brine and dried
over MgSO4. Filtration and concentration of the mixture
under reduced pressure gave crude material, which was
used for next step without further purification. To a solution
of crude material in acetone (5 mL) was added a catalytic
amount of p-toluenesulfonic acid (20 mg) and the mixture
was stirred at ambient temperature for 1 h. Water was added
to the mixture and the resulting mixture was extracted with
CH2Cl2. The organic layer was washed with brine and dried
over MgSO4. Filtration and concentration of the mixture
under reduced pressure gave crude material, which was pu-
rified by silica gel column chromatography (hexane/AcOEt,
5:1) to afford 6 (127 mg, 0.24 mmol) in 50% yield. Colorless
oil. [a]2D4 ꢁ20.4 (c 1.11, CHCl3). IR (neat) n cmꢁ1: 702,
4.1.10. 7-[2-(4-Methoxybenzyloxy)-5-(2-octenyl)cyclo-
pent-3-enyl]-5-heptenoic acid methyl ester (16). To a solu-
tion of 15 (74.6 mg, 0.119 mmol) in THF (2 mL) was added
a solution of tetrabutylammonium fluoride (1 M in THF,
0.14 mL, 0.14 mmol) at ambient temperature. After being
stirred for 2 h at the same temperature, the mixture was
poured onto water and the mixture was extracted with
1
1111, 1248, 1722. H NMR (300 MHz, CDCl3) d: 1.04
(9H, s), 1.58–1.83 (2H, m), 2.21–2.33 (1H, m), 2.38–2.58
(3H, m), 3.73 (2H, t, J¼6.3 Hz), 3.79 (3H, s), 4.21 (1H, d,

10430
H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
AcOEt. The organic layer was washed with brine and dried
over MgSO4. Filtration and concentration of the mixture
under reduced pressure gave crude material, which was pu-
rified by silica gel column chromatography (hexane/AcOEt,
2:1) to afford the alcohol (45.7 mg, 0.118 mmol) in 99%
yield. Colorless oil. [a]2D4 ꢁ29.2 (c 1.17, CHCl3). IR (neat)
n cmꢁ1: 1057, 1247, 1513, 1736, 2930, 3441. 1H NMR
(300 MHz, CDCl3) d: 1.61–1.78 (4H, m), 1.94–2.16 (5H,
m), 2.30 (2H, t, J¼7.5 Hz), 2.29–2.42 (1H, m), 3.65 (3H,
s), 3.62–3.72 (2H, m), 3.78 (3H, s), 4.15 (1H, br s), 4.45
(1H, d, J¼11.4 Hz), 4.47 (1H, d, J¼11.4 Hz), 5.35–5.51
(2H, m), 5.81 (1H, td, J¼1.9, 5.7 Hz), 5.90 (1H, dd,
J¼2.0, 5.7 Hz), 6.85 (2H, J¼8.7 Hz), 7.24 (2H,
J¼8.7 Hz). 13C NMR (75 MHz, CDCl3) d: 24.7, 26.6,
31.8, 33.4, 37.8, 47.3, 49.0, 51.5, 55.2, 60.8, 70.5, 88.8,
113.7, 128.6, 129.3, 129.6, 130.1, 130.6, 138.6, 159.1,
174.1. Anal. Calcd for C23H32O5: C, 71.11; H, 8.30. Found:
C, 70.73; H, 8.26. To a solution of alcohol (39 mg,
0.10 mmol) in CH2Cl2 (2 mL) was added Dess–Martin peri-
odinane (55.1 mg, 0.13 mmol) at ambient temperature. After
being stirred for 30 min, the mixture was diluted with ether
and washed with saturated aqueous NaHCO3. The organic
layer was washed with brine and dried over MgSO4.
Filtration and concentration of the mixture under reduced
pressure gave crude material, which was purified by silica
gel column chromatography (hexane/AcOEt, 3:1) to afford
aldehyde (34.4 mg, 0.089 mmol) in 89% yield. To a suspen-
sion of hexyltriphenylphosphonium bromide (119.2 mg,
0.279 mmol) in THF (2 mL) was added a solution of
NaHMDS (1 M in THF, 0.28 mL, 0.28 mmol) at 0 ꢂC and
the mixture was stirred at ambient temperature for 1 h. A so-
lution of aldehyde (36 mg, 0.093 mmol) in THF (1 mL) was
added to the mixture at 0 ꢂC and the mixture was stirred at
ambient temperature for 2 h. Saturated aqueous ammonium
chloride was added to the reaction mixture and the resulting
mixture was extracted with CHCl3. The organic layer was
washed with brine and dried over MgSO4. Filtration and
concentration of the mixture under reduced pressure gave
crude material, which was purified by silica gel column
chromatography (hexane/AcOEt, 7:1) to afford 16
(36.8 mg, 0.081 mmol) in 87% yield. Colorless oil. [a]D24
+5.6 (c 1.55, CHCl3). IR (neat) n cmꢁ1: 1247, 1513, 1613,
concentration of the mixture under reduced pressure gave
crude material, which was purified by silica gel column chro-
matography (hexane/AcOEt, 5:1) to afford an alcohol
(22.2 mg, 0.067 mmol) in 95% yield. Colorless oil. [a]D24
ꢁ20.3 (c 0.51, CHCl3). IR (neat) n cmꢁ1: 1260, 1731, 2924,
3446. 1H NMR (300 MHz, CDCl3) d: 0.88 (3H, t,
J¼6.8 Hz), 1.17–1.39 (6H, m), 1.60–1.70 (2H, m), 1.70
(2H, quint, J¼7.4 Hz), 2.01 (2H, q, J¼6.8 Hz), 2.10 (2H, q,
J¼7.2 Hz), 2.15–2.34 (5H, m), 2.33 (2H, t, J¼7.4 Hz), 3.67
(3H, s), 4.43 (1H, d, J¼1.9 Hz), 5.28–5.57 (4H, m), 5.72
(1H, td, J¼1.9, 5.7 Hz), 5.80 (1H, td, J¼1.5, 5.7 Hz). 13C
NMR (75 MHz, CDCl3) d: 14.1, 22.6, 24.8, 26.7, 27.3,
29.3, 30.6, 31.5, 32.8, 33.4, 50.2, 51.5, 53.7, 82.7, 127.1,
128.7, 130.0, 131.5, 132.4, 137.3, 166.9. HREIMS calcd for
C21H33O2: 317.2481 (MꢁH2O+H)+, found: 317.2471. To a
solution of the alcohol (22.0 mg, 0.066 mmol) in CH2Cl2
(1 mL) was added Dess–Martin periodinane (42.4 mg,
0.1 mmol) at ambient temperature. After being stirred for
30 min, the mixture was diluted with ether and washed with
saturated aqueous NaHCO3. The organic layer was washed
with brine and dried over MgSO4. Filtration and concentra-
tion of the mixture under reduced pressure gave crude mate-
rial, which was purified by silica gel column chromatography
(hexane/AcOEt, 7:1) to afford 35 (21.5 mg, 0.0647 mmol) in
98% yield. Colorless oil. [a]2D4 +105.4 (c 0.74, CHCl3).
4.1.12. (3R,4R)-3-(3-Methyl-2-butenyl)-4-vinyltetra-
hydropyran-2-one (9). To a solution of (S)-5 (1.07 g,
8.46 mmol) in THF (20 mL) was added a solution of
LiHMDS (1 M in THF, 10.2 mL, 10.2 mmol) at ꢁ78 ꢂC
and the mixture was stirred at the same temperature for
1 h. 1-Bromo-3-methyl-2-butene (1.51 g, 10.2 mmol) was
added to the reaction mixture at the same temperature and
the resulting mixture was stirred for 3 h. Then, saturated
aqueous ammonium chloride was added to the reaction
mixture and the resulting mixture was extracted with AcOEt.
The organic layer was washed with brine and dried over
MgSO4. Filtration and concentration of the mixture under
reduced pressure gave crude material, which was purified
by silica gel column chromatography (hexane/AcOEt,
10:1) to afford 9 (1.54 g, 7.91 mmol) in 94% yield. Colorless
oil. [a]2D4 ꢁ24.0 (c 2.25, CHCl3). IR (neat) n cmꢁ1: 1190,
1
1
1739, 2926. H NMR (300 MHz, CDCl3) d: 0.88 (3H, t,
1732, 2922. H NMR (300 MHz, CDCl3) d: 1.61 (3H, s),
J¼6.8 Hz), 1.19–1.39 (6H, m), 1.68 (2H, quint, J¼7.4 Hz),
1.84–1.92 (1H, m), 1.97–2.26 (9H, m), 2.31 (2H, t,
J¼7.5 Hz), 3.66 (3H, s), 3.80 (3H, s), 4.18 (1H, br s), 4.47
(2H, s), 5.32–5.52 (4H, m), 5.77 (1H, td, J¼1.6, 5.7 Hz),
5.86 (1H, d, J¼5.7 Hz), 6.86 (2H, d, J¼8.6 Hz), 7.27 (2H,
d, J¼8.6 Hz). 13C NMR (75 MHz, CDCl3) d: 14.1, 22.6,
24.8, 26.7, 27.3, 29.4, 31.3, 31.5, 33.4, 33.5, 49.5, 50.3,
51.5, 55.3, 70.5, 89.0, 113.7, 127.5, 128.8, 129.3, 129.6,
129.7, 131.0, 131.2, 138.3, 159.0. HREIMS calcd for
C29H42O4Na: 477.2981 (M+Na)+, found: 477.2955. Anal.
Calcd for C29H42O4: C, 76.61; H, 9.31. Found: C, 76.78;
H, 9.19.
1.70 (3H, s), 1.70–1.82 (1H, m), 1.88–1.97 (1H, m), 2.26–
2.58 (4H, m), 4.24 (1H, ddd, J¼3.7, 9.1, 11.2 Hz), 4.35
(1H, ddd, J¼4.4, 5.3, 11.2 Hz), 5.05–5.15 (3H, m), 5.70
(1H, ddd, J¼6.4, 10.5, 16.8 Hz). 13C NMR (75 MHz,
CDCl3) d: 18.6, 26.4, 28.3, 29.7, 40.3, 46.2, 68.0, 116.6,
121.0, 134.9, 140.4, 173.7.
4.1.13. 4-(3-Methyl-2-butenyl)-3-vinyl-6-heptene-1,5-
diol (17). To a solution of 9 (1.26 g, 6.41 mmol) in THF
(20 mL) was added a solution of DIBAL (0.93 M in hexane,
8.15 mL, 7.58 mmol) at ꢁ78 ꢂC. After being stirred at
ꢁ20 ꢂC for 4 h, saturated aqueous potassium sodium tartrate
was added to the reaction mixture and the mixture was
stirred at ambient temperature for 1 h. The mixture was ex-
tracted with AcOEt and the organic layer was washed with
brine and dried over MgSO4. Filtration and concentration
of the mixture under reduced pressure gave crude material,
which was purified by silica gel column chromatography
(hexane/AcOEt, 5:1) to afford lactol (1.32 g, 6.73 mmol)
4.1.11. trans-Preclavulone-A methyl ester (3). To a
solution of 16 (32 mg, 0.07 mmol) in CH2Cl2 (2 mL) was
added2,3-dichloro-5,6-dicyano-1,4-benzoquinone(58.5 mg,
0.21 mmol) at ambient temperature. After being stirred for
1 h, water was added to the reaction mixture and the resulting
mixture was extracted with AcOEt. The organic layer was
washed with brine and dried over MgSO4. Filtration and
1
in 98% yield. Colorless oil. H NMR (300 MHz, CDCl3)

H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
10431
d: 1.20–2.41 (6H, m), 1.59 (3H, s), {1.67 (s), 1.68 (s), 3H},
{2.84 (dd, J¼1.0, 3.2 Hz), 3.35 (d, J¼6.2 Hz), 1H}, 3.45–
3.62 (1H, m), 3.92–4.13 (1H, m), 4.49 (0.4H, dd, J¼6.0,
8.2 Hz), 4.97–5.23 (3.6H, m), {5.58 (ddd, J¼8.7, 10.0,
17.1 Hz), 5.64 (ddd, J¼8.5, 10.2, 17.2 Hz), 1H}. To a solu-
tion of lactol (1.26 g, 6.41 mmol) in THF (20 mL) was added
a solution of vinylmagnesium chloride (1.38 M in THF,
18.6 mL, 25.7 mmol) at 0 ꢂC. After being stirred for 1 h, sat-
urated aqueous ammonium chloride was added to the reac-
tion mixture and the resulting mixture was extracted with
AcOEt. The organic layer was washed with brine and dried
over MgSO4. Filtration and concentration of the mixture
under reduced pressure gave crude material, which was pu-
rified by silica gel column chromatography (hexane/AcOEt,
1:1) to afford 17 (1.36 g, 6.06 mmol) in 94% yield. Com-
pound 17a: colorless oil. IR (neat) n cmꢁ1: 916, 994, 1044,
1.97–2.28 (3H, m), 2.83–2.93 (1H, m), 3.59–3.76 (2H, m),
4.51 (1H, br d, J¼4.8 Hz), 5.18–5.26 (1H, m), 5.80 (1H,
td, J¼1.6, 5.8 Hz), 6.00 (1H, ddd, J¼1.3, 2.4, 5.8 Hz). 13C
NMR (75 MHz, CDCl3) d: 18.0, 25.8, 26.9, 33.8, 42.8,
51.8, 61.9, 81.8, 123.1, 133.0, 133.6, 137.7.
4.1.15. Benzoic acid 4-[2-(tert-butyldiphenylsilanyloxy)-
ethyl]-5-(3-methyl-2-butenyl)-2-cyclopentenyl ester
(19). To a solution of 18 (647 mg, 3.29 mmol) in DMF
(10 mL) were added triethylamine (367 mg, 0.5 mL,
3.63 mmol),
tert-butyldiphenylchlorosilane
(998 mg,
0.85 mL, 3.63 mmol), and 4-dimethylaminopyridine
(22.2 mg, 0.18 mmol) at 0 ꢂC and the mixture was stirred
at same temperature for 1 h. Water was added to the reaction
mixture and the resulting mixture was extracted with AcOEt.
The organic layer was washed with brine and dried over
MgSO4. Filtration and concentration of the mixture under
reduced pressure gave crude material, which was purified
by silica gel column chromatography (hexane/AcOEt,
15:1) to afford silyl ether as a diastereomeric mixture
(1.4 g, 3.22 mmol) in 98% yield. a Isomer: colorless oil.
[a]D24 ꢁ39.1 (c 2.88, CHCl3). IR (neat) n cmꢁ1: 1111,
1
1436, 2915, 3345. H NMR (300 MHz, CDCl3) d: 1.55–
1.83 (3H, m), 1.60 (3H, s), 1.68 (3H, s), 2.01–2.20 (2H,
m), 2.46 (1H, sept, J¼4.7 Hz), 3.60 (1H, ddd, J¼6.2, 7.2,
10.7 Hz), 3.68 (1H, td, J¼6.1, 10.7 Hz), 4.23 (1H, t,
J¼5.4 Hz), 5.06 (1H, dd, J¼2.0, 17.2 Hz), 5.07 (1H, dd,
J¼2.0, 10.3 Hz), 5.14 (1H, d, J¼10.3 Hz), 5.15–5.22 (1H,
m), 5.22 (1H, d, J¼17.2 Hz), 5.73 (1H, ddd, J¼9.4, 10.3,
17.2 Hz), 5.90 (1H, ddd, J¼6.0, 10.3, 17.2 Hz). 13C NMR
(75 MHz, CDCl3) d: 18.0, 25.5, 25.9, 35.5, 41.6, 48.1,
61.2, 75.2, 115.4, 116.4, 124.0, 132.3, 139.8, 140.6. Anal.
Calcd for C14H24O2: C, 74.95; H, 10.78. Found: C, 74.72;
1
1427, 2930, 3331. H NMR (300 MHz, CDCl3) d: 1.06
(9H, s), 1.23–1.39 (1H, m), 1.68 (3H, s), 1.73 (3H, s),
1.87–2.00 (1H, m), 2.04–2.37 (3H, m), 2.63–2.73 (1H, m),
3.64–3.82 (2H, m), 4.50 (1H, dd, J¼2.6, 5.4 Hz), 5.21–
5.28 (1H, m), 5.93 (1H, ddd, J¼1.3, 2.5, 5.7 Hz), 6.13
(1H, dd, J¼2.8, 5.8 Hz), 7.35–7.48 (6H, m), 7.64–7.72
(4H, m). 13C NMR (75 MHz, CDCl3) d: 18.0, 19.2, 24.0,
25.8, 26.9, 36.0, 42.6, 45.9, 62.6, 123.2, 127.6, 129.6,
132.1, 132.2, 133.9, 135.6, 141.3. HREIMS calcd for
C28H38O2NaSi: 457.2539 (M+Na)+, found: 457.2532. b Iso-
mer: colorless oil. [a]D24 ꢁ102.2 (c 4.34, CHCl3). IR (neat)
n cmꢁ1: 1111, 1472, 2929, 3331. 1H NMR (300 MHz,
CDCl3) d: 1.06 (9H, s), 1.22–1.36 (1H, m), 1.65 (3H, s),
1.73 (3H s), 1.80–2.25 (4H, m), 2.86–2.97 (1H, m), 3.60–
3.76 (2H, m), 4.47 (1H, br s), 5.17–5.23 (1H, m), 5.73 (1H,
td, J¼1.6, 5.8 Hz), 5.92 (1H, ddd, J¼1.3, 2.5, 5.8 Hz),
7.35–7.48 (6H, m), 7.67 (4H, d, J¼7.6 Hz). 13C NMR
(75 MHz, CDCl3) d: 18.0, 19.2, 25.8, 26.8, 26.9, 33.6, 42.7,
51.8, 62.8, 81.9, 123.3, 127.6, 129.6, 132.7, 133.1,
133.9, 135.5, 138.2. HREIMS calcd for C28H38O2NaSi:
457.2539 (M+Na)+, found: 457.2565. To a solution of silyl
ether (1.38 g, 3.17 mmol) in CH2Cl2 (15 mL) were added
pyridine (377 mg, 0.38 mL, 4.76 mmol), benzoyl chloride
(669 mg, 0.55 mL, 4.76 mmol), and 4-dimethylaminopyri-
dine (38.7 mg, 0.32 mmol) at 0 ꢂC. After being stirred at
the same temperature for 2 h, methanol and saturated sodium
hydrogen carbonate were added to the reaction mixture. The
resulting mixture was extracted with AcOEt and the organic
layer was washed with brine and dried over MgSO4. Filtra-
tion and concentration of the mixture under reduced pressure
gave crude material, which was purified by silica gel column
chromatography (hexane/AcOEt, 15:1) to afford 19 as a
diastereomeric mixture (1.34 g, 2.49 mmol) in 78% yield.
Compound 19a: colorless oil. [a]2D4 ꢁ177.5 (c 2.51,
CHCl3). IR (neat) n cmꢁ1: 702, 1110, 1271, 1601, 1715,
H, 10.56. Compound 17b: colorless oil. IR (neat) n cmꢁ1
:
1
918, 995, 1440, 2926, 3346. H NMR (300 MHz, CDCl3)
d: 1.50–1.72 (3H, m), 1.61 (3H, s), 1.69 (3H, s), 1.86 (1H,
br s), 1.99–2.21 (2H, m), 2.55–2.67 (1H, m), 3.54–3.71
(2H, m), 4.13 (1H, br t, J¼7.1 Hz), 5.06–5.15 (3H, m),
5.18 (1H, td, J¼1.5, 10.5 Hz), 5.26 (1H, td, J¼1.6,
17.2 Hz), 5.76–5.87 (1H, m), 5.91 (1H, ddd, J¼5.3, 10.5,
17.2 Hz). 13C NMR (75 MHz, CDCl3) d: 17.9, 25.2, 25.8,
35.9, 40.4, 48.5, 61.1, 74.6, 115.0, 116.7, 123.6, 132.8,
140.6, 141.4. Anal. Calcd for C14H24O2: C, 74.95; H,
10.78. Found: C, 74.72; H, 10.56.
4.1.14. 4-(2-Hydroxyethyl)-5-(3-methyl-2-butenyl)-2-
cyclopenten-1-ol (18). To a solution of 17 (1.21 g,
5.39 mmol) in CH2Cl2 (50 mL) was added second genera-
tion of Grubbs catalyst (229 mg, 0.27 mmol) and the mixture
was stirred at ambient temperature for 1.5 h. Water was
added to the mixture and the resulting mixture was extracted
with AcOEt. The organic layer was washed with brine and
dried over MgSO4. Filtration and concentration of the
mixture under reduced pressure gave crude material, which
was purified by silica gel column chromatography (hexane/
AcOEt, 1:1) to afford 18 as a diastereomeric mixture
(846 mg, 4.31 mmol) in 80% yield. Compound 18a: color-
less oil. [a]2D4 ꢁ31.3 (c 0.46, CHCl3). IR (neat) n cmꢁ1
:
1
1117, 1275, 2918, 3418. H NMR (300 MHz, CDCl3) d:
1.45–1.59 (1H, m), 1.67 (3H, s), 1.72 (3H, s), 1.78–1.91
(3H, m), 2.08–2.23 (2H, m), 2.25–2.40 (1H, m), 2.63–2.73
(1H, m), 3.61–3.79 (2H, m), 4.53 (1H, dd, J¼2.8, 5.6 Hz),
5.19–5.24 (1H, m), 5.99 (1H, ddd, J¼1.5, 2.5, 5.8 Hz),
6.16 (1H, dd, J¼2.8, 5.8 Hz). 13C NMR (75 MHz, CDCl3)
d: 18.0, 24.1, 25.8, 35.0, 43.1, 45.7, 61.2, 76.5, 123.1,
132.4, 132.6, 140.4. Compound 18b: colorless oil. [a]D24
ꢁ191.4 (c 0.47, CHCl3). IR (neat) n cmꢁ1: 1117, 1275,
2918, 3418. 1H NMR (300 MHz, CDCl3) d: 1.25–1.43
(2H, m), 1.64 (3H, s), 1.72 (3H, s), 1.77–1.88 (1H, m),
1
2929. H NMR (300 MHz, CDCl3) d: 1.07 (9H, s), 1.30–
1.46 (1H, m), 1.61 (3H, s), 1.63 (3H, s), 1.85–1.98 (1H, m),
2.15 (2H, t, J¼7.4 Hz), 2.38–2.49 (1H, m), 2.99–3.10 (1H,
m), 3.65–3.81 (2H, m), 5.15 (1H, t, J¼6.3 Hz), 5.64 (1H,
br d, J¼5.7 Hz), 5.86 (1H, br d, J¼5.8 Hz), 6.06 (1H, td,
J¼1.0, 5.8 Hz), 7.36–7.48 (8H, m), 7.53 (1H, t, J¼7.4 Hz),

10432
H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
7.68 (4H, t, J¼7.4 Hz), 8.03 (2H,d, J¼7.1 Hz). 13C NMR
(75 MHz, CDCl3) d: 17.9, 19.2, 25.7, 26.7, 26.9, 33.4, 42.4,
47.5, 62.8, 84.6, 122.7, 127.6, 128.2, 129.4, 129.5, 129.6,
132.6, 132.7, 133.9, 135.5, 140.6, 166.5. Anal. Calcd for
C32H42O3Si: C, 78.02; H, 7.86. Found: C, 77.94; H, 7.90.
HREIMS calcd for C32H42O3NaSi: 561.2801 (M+Na)+,
found: 561.2800. Compound 19b: colorless oil. [a]2D4 +72.5
(c 0.23, CHCl3). IR (neat) n cmꢁ1: 707, 1109, 1271, 1604,
4.1.17. cis-Preclavulone-A methyl ester (4). To a solution
of hydroxycarbonylbutyltriphenylphosphonium bromide
(1.17 g, 2.63 mmol) in THF (20 mL) was added a solution
of NaHMDS (1 M in THF, 4.82 mL, 4.82 mmol) at 0 ꢂC
and the mixture was stirred at ambient temperature for 1 h.
A solution of 8 in THF (5 mL) was added to the reaction
mixture at 0 ꢂC and the resulting mixture was stirred at
ambient temperature for 2 h. Saturated aqueous NH4Cl
was added to the reaction mixture and the resulting mixture
was extracted with AcOEt. The organic layer was washed
with brine and dried over MgSO4. Filtration and concentra-
tion of the mixture under reduced pressure gave crude
material, which was purified by silica gel column chromato-
graphy (hexane/AcOEt, 5:1) to give carboxylic acid as a
diastereomeric mixture (397 mg, 0.66 mmol) in 76% yield.
Colorless oil. IR (neat) n cmꢁ1: 707, 1111, 1272, 1713,
1
1715, 2929. H NMR (300 MHz, CDCl3) d: 1.06 (9H, s),
1.41–1.58 (1H, m), 1.47 (3H, s), 1.66 (3H, s), 1.98–2.40
(4H, m), 2.76–2.86 (1H, m), 3.68–3.84 (2H, m), 5.11–5.18
(1H, m), 5.68 (1H, dd, J¼2.6, 5.6 Hz), 6.02 (1H, ddd,
J¼1.0, 2.4, 5.8 Hz), 6.25 (1H, dd, J¼2.8, 5.8 Hz), 7.31–
7.46 (8H, m), 7.52 (1H, t, J¼7.4 Hz), 7.64–7.72 (4H, m),
7.98 (2H, d, J¼7.2 Hz). 13C NMR (75 MHz, CDCl3) d:
17.9, 19.2, 24.1, 25.8, 26.9, 35.4, 42.8, 45.4, 62.5, 77.2,
122.4, 127.6, 128.3, 129.1, 129.5, 129.6, 132.4, 132.7,
134.0, 135.5, 143.6. Anal. Calcd for C32H42O3Si: C, 78.02;
H, 7.86. Found: C, 77.94; H, 7.90. HREIMS calcd for
C32H42O3NaSi: 561.2801 (M+Na)+, found: 561.2813.
1
2930, 3069. H NMR (300 MHz, CDCl3) d: 1.06 (9H, s),
1.33–1.70 (3H, m), 1.79–2.48 (9H, m), {2.76–2.87 (m),
2.98–3.10 (m), 1H}, 3.63–3.85 (2H, m), 5.38–5.51 (2H,
m), 5.64–5.71 (1H, m), {5.85 (dt, J¼1.7, 5.8 Hz), 5.98–
6.06 (m), 6.24 (dd, J¼2.8, 5.8 Hz), 2H}, 7.30–7.47 (8H,
m), {7.47 (1H, t, J¼7.4 Hz), 7.97 (d, J¼6.9 Hz), 8.00 (d,
J¼7.1 Hz), 7H}. Anal. Calcd for C39H44O5Si: C, 74.72; H,
7.59. Found: C, 74.60; H, 7.56. A solution of carboxylic
acid (304 mg, 0.51 mmol) in ether (20 mL) was treated
with a solution of diazomethane to give methyl ester
4.1.16. Benzoic acid 4-[2-(tert-butyldiphenylsilanyloxy)-
ethyl]-5-(2-oxoethyl)-2-cyclopentenyl ester (8). To a solu-
tion of 19 (651 mg, 1.21 mmol) in CH2Cl2 (10 mL) was
added m-chloroperbenzoic acid (230 mg, 1.33 mmol) at
0 ꢂC. After being stirred at the same temperature for
30 min, saturated aqueous sodium thiosulfate and saturated
aqueous sodium hydrogen carbonate. The resulting mixture
was extracted with ether and the organic layer was washed
with brine and dried over MgSO4. Filtration and concentra-
tion of the mixture under reduced pressure gave crude
material, which was purified by silica gel column chromato-
graphy (hexane/AcOEt, 15:1) to give epoxide as a diastereo-
meric mixture (529 mg, 0.954 mmol) in 80% yield.
(280 mg, 0.458 mmol). Colorless oil. IR (neat) n cmꢁ1
:
1
702, 1109, 1270, 1713, 2931. H NMR (300 MHz, CDCl3)
d: 1.06 (9H, s), 1.44–1.75 (3H, m), 1.82–2.50 (8H, m),
{2.77–2.88 (m), 2.99–3.11 (m), 1H}, 3.64 (3H, s), 3.65–
3.85 (2H, m), 5.32–5.50 (2H, m), {5.64 (br d, J¼4.5 Hz),
5.68 (dd, J¼2.5, 5.5 Hz), 1H}, {5.85 (td, J¼1.7,
5.8 Hz), 6.02 (dd, J¼1.5, 5.5 Hz), 1H}, {6.06 (dd, J¼1.7,
5.8 Hz), 6.25 (dd, J¼2.8, 5.8 Hz), 1H}, 7.32–7.48 (8H, m),
7.54 (1H, t, J¼7.4 Hz), 7.63–7.70 (4H, m), {7.96 (d,
J¼8.6 Hz), 8.02 (d, J¼7.5 Hz), 2H}. Anal. Calcd for
C40H46O5Si: C, 74.72; H, 7.59. Found: C, 74.79; H, 7.76.
To a solution of methyl ester (25 mg, 0.04 mmol) in THF
(0.5 mL) was added a solution of TBAF (1 M in THF,
0.05 mL, 0.05 mmol) at ambient temperature. After being
stirred at the same temperature for 2 h, water was added to
the mixture and the resulting mixture was extracted with
AcOEt. The organic layer was washed with brine and dried
over MgSO4. Filtration and concentration of the mixture
under reduced pressure gave crude material, which was
purified by silica gel column chromatography (hexane/
AcOEt, 2:1) to give alcohol as a diastereomeric mixture
(16 mg, 0.04 mmol) in 98% yield. Colorless oil. IR (neat)
n cmꢁ1: 713, 1069, 1272, 1714, 1737, 2947, 3456.
1H NMR (300 MHz, CDCl3) d: 1.36–1.74 (4H, m), 1.82–
2.13 (3H, m), 2.14–2.55 (5H, m), {2.72–2.82 (m), 2.96–
3.07 (m), 1H}, {3.62 (s), 3.65 (s), 3H}, 3.58–3.85 (2H, m),
5.29–5.53 (2H, m), 5.66–5.74 (1H, m), {5.88–5.94 (m),
6.06–6.12 (m), 1H}, {6.15 (ddd, J¼0.8, 2.3, 5.8 Hz), 6.36
(dd, J¼2.8, 5.8 Hz), 1H}, 7.38–7.47 (2H, m), 7.55 (1H, t,
J¼7.4 Hz), 7.95–8.06 (2H, m). Anal. Calcd for C22H28O5:
C, 70.94; H, 7.58. Found: C, 70.91; H, 7.56. To a solution
of alcohol (14.3 mg, 0.038 mmol) was added Dess–Martin
periodinane (19.3 mg, 0.046 mmol) at ambient temperature
and the mixture was stirred at the same temperature for
30 min. The mixture was diluted with ether and poured
onto saturated aqueous sodium hydrogen carbonate. The
mixture was extracted with AcOEt and the organic layer
1
Colorless oil. IR (neat) n cmꢁ1: 702, 1110, 1271, 1714. H
NMR (300 MHz, CDCl3) d: 1.06 (9H, s), 1.16–1.32 (6H,
m), 1.34–2.13 (4H, m), {2.48–2.67 (m), 2.77–2.86 (m),
2H}, {2.80–2.94 (m), 3.02–3.16 (m), 1H}, 3.64–3.87 (2H,
m), 5.66–5.82 (1H, m), {5.83–5.90 (m), 6.02–6.12 (m),
6.27 (ddd, J¼2.8, 5.7, 8.2 Hz), 2H}, 7.31–7.48 (8H, m),
7.50–7.59 (1H, m), 7.62–7.71 (4H, m), 7.93–8.07 (2H, m).
Anal. Calcd for C32H42O4Si: C, 75.77; H, 7.63. Found: C,
75.53; H, 7.56. To a solution of epoxide (504 mg,
0.909 mmol) in aqueous t-BuOH (5 mL) was added sodium
periodate (228 mg, 1.0 mmol). After being stirred at ambient
temperature for 2 h, saturated aqueous sodium hydrogen car-
bonate was added to the reaction mixture. The resulting
mixture was extracted with AcOEt and the organic layer
was washed with brine and dried over MgSO4. Filtration
and concentration of the mixture under reduced pressure
gave crude material, which was purified by silica gel column
chromatography (hexane/AcOEt, 10:1) to give 8 as a dia-
stereomeric mixture (466 mg, 0.906 mmol) in 99% yield.
Colorless oil. IR (neat) n cmꢁ1: 1109, 1270, 1715, 1731,
1
2932. H NMR (300 MHz, CDCl3) d: 1.08 (9H, s), 1.25–
1.53 (1H, m), 1.65–1.88 (1H, m), {2.52–2.77 (m), 2.87–
2.98 (m), 3.11–3.22 (m), 4H}, 3.62–3.83 (2H, m), {5.67
(dd, J¼1.3, 6.0 Hz), 5.80 (dd, J¼2.5, 5.8 Hz), 1H}, {5.86
(dt, J¼1.8, 5.9 Hz), 6.01 (dd, J¼1.7, 5.9 Hz), 1H}, {6.08
(dd, J¼2.3, 5.9 Hz), 6.23 (dd, J¼2.0, 5.9 Hz), 1H}, 7.33–
7.48 (8H, m), 7.52–7.59 (1H, m), 7.63–7.71 (4H, m),
7.92–8.06 (2H, m), 9.80 (1H, br s). HREIMS calcd for
C32H36O4NaSi: 535.2281 (M+Na)+, found: 535.2300.

H. Ito et al. / Tetrahedron 62 (2006) 10425–10433
10433
was washed with brine and dried over MgSO4. Filtration and
concentration of the mixture under reduced pressure gave
crude material, which was purified by silica gel column
chromatography (hexane/AcOEt, 5:1) to give aldehyde as
a diastereomeric mixture (14.0 mg, 0.038 mmol) in 99%
yield. Colorless oil. IR (neat) n cmꢁ1: 712, 1110, 1270,
1452, 1713, 1731, 1738, 2949. 1H NMR (300 MHz,
CDCl3) d: 1.50–1.74 (3H, m), 1.88–2.63 (7H, m), 2.66–
2.87 (1H, m), {3.13–3.24 (m), 3.39–3.52 (m), 1H}, {3.62
(s), 3.65 (s), 3H}, 5.30–5.49 (2H, m), {5.66 (dd, J¼1.0,
5.2 Hz), 5.68 (dd, J¼1.6, 5.8 Hz), 1H}, {5.93 (dt, J¼1.9,
5.8 Hz), 6.05–6.15 (m), 6.32 (dd, J¼2.8, 5.8 Hz), 2H},
7.39–7.49 (2H, m), 7.52–7.60 (1H, m), 7.95–8.06 (2H, m),
{9.84 (s), 9.87 (s), 1H}. Anal. Calcd for C22H26O5: C,
71.33; H, 7.07. Found: C, 71.02; H, 7.06. A solution of
NaHMDS (1 M in THF, 1.5 mL, 1.5 mmol) was added to
the suspension of hexyltriphenylphosphonium bromide
(641 mg, 1.5 mmol) in THF (10 mL) at 0 ꢂC and the mixture
was stirred at ambient temperature for 1 h. Then, a solution
of aldehyde (183.5 mg, 0.495 mmol) in THF (5 mL) was
added to the reaction mixture at 0 ꢂC and the mixture was
stirred at ambient temperature for 2 h. Saturated aqueous am-
monium chloride was added to the mixture and the mixture
was extracted with AcOEt. The organic layer was washed
with brine and dried over MgSO4. Filtration and concentra-
tion of the mixture under reduced pressure gave crude mate-
rial, which was purified by silica gel column chromatography
(hexane/AcOEt, 5:1) to give benzoic acid 5-(6-methoxy-
carbonyl-2-hexenyl)-4-(2-octenyl)-2-cyclopentenyl ester as
a diastereomeric mixture (212 mg, 0.483 mmol) in 98%
yield. Colorless oil. IR (neat) n cmꢁ1: 711, 1110, 1270,
(300 MHz, CDCl3) d: 0.88 (3H, t, J¼6.6 Hz), 1.11–1.79
(10H, m), 1.79–2.40 (10H, m), {2.54–2.65 (m), 2.75–2.86
(m), 1H}, 3.67 (3H, s), 4.47–4.52 (1H, m), 5.25–5.60 (4H,
m), {5.78 (dt, J¼1.5, 5.7 Hz), 5.97 (ddd, J¼1.3, 2.4,
5.8 Hz), 1H}, {5.95 (br d, J¼5.7 Hz), 6.12 (dd, J¼2.7,
5.8 Hz), 1H}. To a solution of alcohol (32 mg, 0.096 mmol)
in CH2Cl2 (2 mL) was added MnO2 (83.5 mg, 0.96 mmol)
at ambient temperature and the mixture was stirred at the
same temperature for 2 days. The mixture was filtered and
the filtrate was concentrated under vacuum. The residue was
purified by silica gel column chromatography (hexane/
AcOEt, 5:1) to give 45 (30 mg, 0.091 mmol) in 95% yield.
Colorless oil. [a]D24 ꢁ165.8 (c 0.13, CHCl3), [a]2D4 ꢁ135.3
(c 0.13, THF).
References and notes
1. (a) Kikuchi, H.; Tsukitani, Y.; Iguchi, K.; Yamada, Y.
Tetrahedron Lett. 1982, 23, 5171–5174; (b) Kikuchi, H.;
Tsukitani, Y.; Iguchi, K.; Yamada, Y. Tetrahedron Lett. 1983,
24, 1549–1552.
2. (a) Kobayashi, M.; Yasuzawa, T.; Yoshihara, M.; Akutsu, H.;
Kyogoku, Y.; Kitagawa, I. Tetrahedron Lett. 1982, 23, 5331–
5334; (b) Kitagawa, I.; Kobayashi, M.; Yasuzawa, T.; Son,
B. W.; Yoshihara, M.; Kyogoku, Y. Tetrahedron 1985, 41,
995–1005.
3. Watanabe, K.; Sekine, M.; Iguchi, K. J. Nat. Prod. 2003, 66,
1434–1440 and references cited therein.
4. (a) Corey, E. J.; Lansbury, P. T., Jr.; Yamada, Y. Tetrahedron
Lett. 1985, 26, 4171–4174; (b) Corey, E. J.; d’Alarcao, M.;
Matsuda, S. P. T.; Lansbury, P. T., Jr.; Yamada, Y. J. Am.
Chem. Soc. 1987, 109, 289–290; (c) Corey, E. J.; Nagata, R.;
Cleaver, B. M. Tetrahedron Lett. 1988, 29, 2555–2558.
5. Watanabe, K.; Sekine, M.; Iguchi, K. Chem. Pharm. Bull. 2003,
51, 909–913.
6. Corey, E. J.; Xiang, Y. B. Tetrahedron Lett. 1988, 29, 995–998.
7. Leggeri, P.; Di Giacomo, M.; Papeo, G.; Pirillo, D.; Traverso,
G. Farmaco 1993, 48, 117–126.
8. Ito, H.; Konishi, M.; Iguchi, K. Tetrahedron Lett. 2004, 45,
1941–1944.
9. Molander, G. A.; Harris, C. R. J. Am. Chem. Soc. 1995, 117,
3705–3716.
10. Kocienski, P. Tetrahedron 1991, 47, 9939–9946.
11. (a) Mukaiyama, T.; Inoue, T. Chem. Lett. 1976, 559–562; (b)
Kim, B. M.; Williams, S. F.; Masamune, S. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 2, Chapter 1.7.
12. Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1993,
115, 9856–9857; Grubbs, R. H.; Chang, S. Tetrahedron 1998,
54, 4413–4450.
1
1451, 1715, 1738, 2953. H NMR (300 MHz, CDCl3) d:
0.82–0.93 (3H, m), 1.15–1.38 (6H, m), 1.49–1.74 (2H, m),
1.92–2.53 (11H, m), {2.61–2.72 (m), 2.86–2.98 (m), 1H},
{3.62 (s), 3.65 (s), 3H}, 5.28–5.54 (4H, m), {5.70 (dd,
J¼1.1, 5.6 Hz), 5.72 (dd, J¼2.6, 5.4 Hz), 1H}, {5.89 (td,
J¼1.8, 5.8 Hz), 6.05 (dd, J¼1.3, 5.7 Hz), 1H}, {6.08 (ddd,
J¼1.0, 2.3, 5.8 Hz), 6.29 (dd, J¼2.8, 5.7 Hz), 1H}, 7.43
(2H, t, J¼7.5 Hz), 7.56 (1H, t, J¼7.4 Hz), 8.03 (2H, d,
J¼7.0 Hz). Anal. Calcd for C28H38O4: C, 76.68; H, 8.73.
Found: C, 76.65; H, 8.67. To a solution of benzoic acid 5-
(6-methoxycarbonyl-2-hexenyl)-4-(2-octenyl)-2-cyclopen-
tenyl ester (32 mg, 0.07 mmol) in MeOH (2 mL) was added
NaOMe (58.5 mg, 0.21 mmol) at ambient temperature and
the mixture was stirred at 50 ꢂC for 10 h. Water was added
to the mixture and the mixture was extracted with AcOEt.
The organic layer was washed with brine and dried over
MgSO4. Filtration and concentration of the mixture under
reduced pressure gave crude material, which was purified
by silica gel column chromatography (hexane/AcOEt, 5:1)
to give alcohol as a diastereomeric mixture (21.2 mg,
0.062 mmol) in 88% yield. Colorless oil. IR (neat) n cmꢁ1
702, 1109, 1270, 1715, 1736, 2930, 3404. 1H NMR
:
13. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953–956.