Triterpenoid total synthesis. Part 6. Synthesis of testudinariols A and B, triterpene metabolites of the marine mollusc Pleurobrancus testudinarius

Article abstract of DOI:10.1039/b100777g

Testudinariols A (1) and B (1′) are ichthyotoxic and structurally unusual triterpene alcohols isolated from the skin and the mucus of the marine mollusc Pleurobrancus testudinarius. The first synthesis of (+)-1 and (+)-1′ was achieved by starting from (R)-glycidol.

Full text of DOI:10.1039/b100777g

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Triterpenoid total synthesis. Part 6.1 Synthesis of testudinariols A
and B, triterpene metabolites of the marine mollusc Pleurobrancus
testudinarius
1
Masao Yoshida, Hirosato Takikawa and Kenji Mori*
Department of Chemistry, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku,
Tokyo 162-8601, Japan
Received (in Cambridge, UK) 23rd January 2001, Accepted 1st March 2001
First published as an Advance Article on the web 3rd April 2001
Testudinariols A (1) and B (1Ј) are ichthyotoxic and structurally unusual triterpene alcohols isolated from the
skin and the mucus of the marine mollusc Pleurobrancus testudinarius. The first synthesis of (ϩ)-1 and (ϩ)-1Ј
was achieved by starting from (R)-glycidol.
Introduction
Results and discussion
In 1997, Spinella et al. isolated testudinariol A (1) and its
C-10Ј epimer, testudinariol B (1Ј) (Fig. 1) as metabolites of the
marine mollusc Pleurobrancus testudinarius.2 These compounds
are structurally unique triterpene alcohols and thought to be
defensive allomones of P. testudinarius, because 1 was ichthyo-
toxic against Gambusia affinis. The partially cyclized squalene
skeleton present in 1 and 1Ј is biosynthetically unusual, since
the general biosynthetic pathway for polycyclic triterpenoid via
squalene 2,3-oxide does not provide such a carbon skeleton.
Only two similar skeletons have been reported, in the cases of
limatulones [2 and 2Ј, defensive metabolites of the limpet
Achmeia (Collisella) limatula]3 and naurols (3 and 3Ј, metabol-
ites of the marine sponges with cytotoxicity to murine leukemia
cells P388).4 All of these natural products are C2-symmetric
triterpene alcohols or their diastereomers. We became inter-
ested in the unique structures of these marine triterpenoids and
have studied their synthesis. Up to the present, synthesis of 2,
2Ј5 and 31 has been accomplished and reported by us. Very
recently, we achieved the first synthesis of (ϩ)-1 and reported
it as a preliminary communication.6 Herein the synthesis of
testudinariols A (1) and B (1Ј) will be described in detail.
Synthetic plan
Scheme 1 shows our synthetic plan for testudinariol A (1).
Because a structural feature of target compound 1 is its C2-
symmetry, 1 can be obtained by dimerization or its equivalent
operation of A. The intermediate A may be prepared from B by
(Z)-selective installation of the two-carbon appendage. For the
stereoselective construction of the cyclopentane portion of B,
an intramolecular ene reaction is appropriate employing C as
the substrate. The intramolecular oxy-Michael-type cyclization
of D has been adopted to prepare the tetrahydropyran ring of
C. The intermediate D can be synthesized from F [(R)-glycidol]
via the known diol E.7 This synthetic plan is also applicable to
the synthesis of testudinariol B (1Ј).
Synthesis of testudinariol A
The starting (R)-glycidol (4, = F) was converted to the known
diol 5 (= E) (Scheme 2).7 Selective TBDMS protection of the
primary hydroxy group of 5 was followed by treatment with
4-methoxybenzyl trichloroacetimidate8 to give 6b (77% yield, 2
steps). The enantiomeric purity of 6b was determined by HPLC
Fig. 1 Structures of testudinariols A (1), B (1Ј) and related metabolites.
DOI: 10.1039/b100777g
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
This journal is © The Royal Society of Chemistry 2001
1007

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Table 1 Intramolecular oxy-Michael-type cyclization (10b→11a–d)
Run
10b E : Z
Basea
Solvent
Temp./ЊC
Time/h
Yieldb (%)
Ratioc 11a : 11b : 11cd
1
2
3
4
3 : 2
4 : 1
5 : 1
5 : 1
5 : 1
1 : 10
1 : 10
NaH
THF
THF
THF
MeCN
THF
THF
THF
0 to rt
0 to rt
Ϫ10 to 4
60
40
Ϫ10 to 0
rt
4
18
20
24
24
2
98
97
93
93
1 : 2 : 3.5
1 : 2 : 2
1 : 1 : 0.8
1 : 1.3 : 1.2
—
ca. 1 : 1 : 1
ca. 1 : 2 : 3
NaH
ButOK
LiH
5
Cs2CO3
ButOK
NaH
No reaction
90
90
6d
7d
6
a One eq. of 10b and 1.3~1.5 eq. of base were used in all runs except for run 3 (0.1 eq.) and 6 (~0.5 eq.). b Isolated yield. c Determined by 1H-NMR
analysis. d The corresponding Me ester was used as the substrate.
Fig. 2 Stereochemical assignment of 11a and 11b.
in 93% yield (E : Z = 5 : 1). Although these conditions resulted
in the best (E)-selectivity, it turned out that (E)-geometry was
not important for the diastereoselectivity in the later Michael-
type cyclization. After removal of the TBDMS protective group
(99%), the resulting 10b (= D) was exposed to one of the key
steps, intramolecular Michael-type cyclization.
Table 1 summarizes the results of our studies on diastereo-
selective cyclization. Our first attempt to obtain the desired
diastereomer 11a as the predominant product under kinetic
Scheme 1 Synthetic plan for 1.
control was unfortunately problematic. Although a wide
range of bases, NaH, LiH, K2CO3, Cs2CO3, TBAF, etc., and
Lewis acids, ZnCl2, Sc(OTf)3, TiCl4, etc., were examined under
various conditions, appropriate conditions to furnish 11a
diastereoselectively could not be established. We then tried
to obtain a mixture of all of the possible diastereomers under
thermodynamic control. Thus, 10b was treated with ButOK
(0.1 eq.) in THF at Ϫ10 to 4 ЊC to give, in 93% yield, a mixture
of 11a–d (11a : 11b : 11c : 11d = 5 : 5 : 2 : 2, as determined by
1H-NMR analysis). Under these conditions, the geometry of
the conjugated double bond did not play any role in deter-
mining diastereoselectivity, and the ratio of the products
reflected the thermodynamic equilibrium.
Stereochemical assignment of 11a–d was achieved as follows.
At first, trans- or cis-2,5-substitution on the tetrahydropyran
ring could easily be deduced based on the 1H-NMR analysis of
11a–d. However, the orientation of the homoprenyl group was
difficult to deduce. Therefore, 11a and 11b, whose stereostruc-
tures were uncertain at the time, were reduced with DIBAL-H
to afford 14a and 14b, respectively. The observed 1H-NMR
Scheme 2 Synthesis of testudinariol A (1)—1. Reagents and condi-
tions: (a) TBDMSCl, Et3N, DMAP, CH2Cl2 (85%); (b) 4-methoxy-
data including NOE correlation depicted in Fig. 2 suggested
benzyl trichloroacetimidate, TfOH, Et2O (90%); (c) OsO4, NMO,
that the stereostructures of 14a and 14b (hence 11a and 11b)
were as illustrated therein. In the same manner, the stereo-
structures of 11c and 11d were also elucidated. Although the
desired 11a was not predominant, chromatographic separation
of diastereomers was possible, and the undesired three isomers
(11b–d) could be recycled to the initial mixture by treatment
with ButOK at 4 ЊC. By repeating this process three times, 11a
was obtained in 68% overall yield.
ButOH, acetone, H2O (93%); (d) aq. NaIO4, SiO2, CH2Cl2 (98%); (e)
ethyl 2-diethoxyphosphoryl-6-methylhept-5-enoate, ButOK, toluene,
Ϫ20 ЊC (93%, E : Z = 5 : 1); (f) PPTS, MeOH (99%).
analysis to be 97.6% ee. This ether 6b was subjected to OsO4
mediated dihydroxylation and subsequently treated with NaIO4
to furnish 8 (91%, 2 steps). The aldehyde 8 was then employed
for the Horner–Wadsworth–Emmons (HWE) reaction with
ethyl 2-diethoxyphosphoryl-6-methylhept-5-enoate9 (9) under
several different conditions, and the use of ButOK in toluene
as the base at Ϫ20 ЊC provided the best result, furnishing 10a
The next challenge was the stereoselective construction of the
cyclopentane fragment. As mentioned in the synthetic plan, an
ene reaction was thought to be appropriate, and the aldehyde
1008
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017

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Table 2 Diastereoselective ene reaction (12→13a–c)
Run
Lewis acida
Solvent
Temp./ЊC
Time/min
Yieldb (%)
Ratioc 13a : 13b : 13c
1
2
3
4
5
Me2AlCl
Et2AlCl
SnCl4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
0
30
60
15
15
60
>95
>95
Decomp.
80
Decomp.
6 : 3 : 1
6 : 3 : 1
—
3 : 0 : 7
—
SnCl4
Ϫ78
Ϫ78
(PriO)2TiCl4
a 1.0 eq. of Lewis acid was used. b Isolated yield. c Determined by 1H-NMR analysis.
Scheme 3 Synthesis of testudinariol A (1)—2. Reagents and conditions: (a) ButOK (0.1 eq.), THF, Ϫ10 to 4 ЊC (93% for a mixture of 11a–d); (b) SiO2
chromatography (overall 68% for 11a); (c) DIBAL-H, toluene, Ϫ78 ЊC (98%); (d) 1.0 eq. Me2AlCl, CH2Cl2, 0 ЊC (59%).
12 (= C), which was prepared by DIBAL-H reduction of 11a
dimerize 19a by a metal mediated homo-coupling of allylic
halide,18 and found that the following conditions gave no
successful result: Na-naphthalenide in THF at Ϫ78 ЊC;
K-naphthalenide in THF at Ϫ95 ЊC; BaI2, Li-biphenylide in
THF at Ϫ78 ЊC,18 etc. However, the methodology employed
for the synthesis of limatulones,5 “sulfone coupling”, could be
applied successfully to overcome the difficulty. Accordingly, the
carbanion derived from 19b by treatment with KHMDS was
alkylated with 19a in the presence of 18-crown-6 at Ϫ78 ЊC to
give the coupling product 20a in 84% yield. It was noteworthy
that the conventional conditions, BunLi in THF–HMPA, did
not work at all, and the corresponding chloride (X = Cl) did not
react with 19b completely even under our successful conditions.
The coupling product 20a was desulfonylated by reduction with
Na–Hg to afford 20b. Although a small amount of inseparable
impurity(ies), which was not the (E,Z)-isomer, was found to be
present, the final deprotection of TBDMS groups made
purification possible to give pure (ϩ)-testudinariol A (1) (47%
yield, 2 steps), [α]D26 = ϩ13 (c = 0.17, CHCl3) {ref. 2 [α]D25 = ϩ15.2
(c = 0.3, CHCl3)}. Other physical and spectral data of synthetic
(ϩ)-1 were in good accord with those reported for the naturally
occurring 1. The overall yield was 5.2% based on 5 in 19 steps.
(98%), was submitted to it (Scheme 3). As shown in Table 2,
10
when aldehyde 12 was treated with Me2AlCl in CH2Cl2 at
0 ЊC, the desired 13a (= B) was generated as the major isomer
in a moderate selectivity (13a : 13b : 13c = 6 : 3 : 1). This selec-
tivity was not so high but acceptable for our synthesis of 1. In
addition, the conditions as listed in entry 411 provided 13c as
the major isomer, and this reversal of selectivity was exactly
what we desired for the synthesis of testudinariol B (1Ј). Struc-
ture elucidation of 13a–c was mainly established by NOE
experiments, and 1H-NMR data of 13a and 13c concerning the
cyclopentane portion were in good accord with those reported
for natural 1 and 1Ј, respectively.
The remaining tasks were the preparation of the key inter-
mediate A and its dimerization or its equivalent operation,
which were realized as follows. The hydroxy group of 13a was
protected as TBDMS ether (99%), and the resulting 15a was
treated with DDQ12 to give 15b in 97% yield (Scheme 4). Oxid-
ation of 15b with the Dess–Martin periodinane13 afforded 16
in 94% yield. The ketone 16 was employed for the next (Z)-
selective HWE reaction. As shown in Table 3, treatment with
a chiral phosphonoacetate (S)-17 developed by Fuji and
co-workers14 in the presence of NaHMDS15 realized the best
(Z)-selectivity (E : Z = ca. 1 : 5), while other commercially avail-
Synthesis of testudinariol B (1Ј)
able HWE reagents developed by Still [(CF CH O) P(᎐O)CH -
᎐
3
2
2
2
CO2Me]16 and Ando [(PhO) P(᎐O)CH CO Et]17 were less
It was obvious that the synthesis of testudinariol B (1Ј) could
be accomplished by just substituting the intermediate 13a by
13c. Thus, the intermediate 13c was converted into 16Ј in 3 steps
(90% yield) (Scheme 5). However, treatment of 16Ј with (S)-17
in the presence of NaHMDS, the successful combination, gave
a roughly 1 : 1 mixture of (E)- and (Z)-18aЈ. This unpredictable
decrease in (Z)-selectivity led us to examine other (Z)-selective
HWE reagents again, but only a slight improvement was
observed (E : Z = ca. 4 : 6), when Still’s phosphonoacetate16
was used. The resulting E–Z-mixture of 18aЈ was reduced and
the product was purified to give pure (Z)-18bЈ (49%, 2 steps).
᎐
2
2
2
selective. It was also noteworthy that the reaction with (R)-17
proceeded with the opposite selectivity (E : Z = 16 : 1). It was,
to the best of our knowledge, the first example in which Fuji’s
phosphonoacetate (17) afforded the (E)-isomer as major
product. The resulting inseparable mixture of (Z)- and (E)-18a
was reduced with DIBAL-H and purified by SiO2 chrom-
atography to give geometrically pure (Z)-18b in 78% yield. The
alcohol 18b was then converted to the corresponding bromide
19a (93%) and sulfone 19b (87%) in the conventional manner.
The final challenge was “dimerization”. We first attempted to
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
1009

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Table 3 (Z)-Selective Horner–Wadsworth–Emmons reaction (16→18a)
Run
Reagenta
Base
Additive
Solvent
Temp./ЊC
Time/h
Yieldb (%)
>90
>90
93
>90
91
94
18ac E : Z
1d
2
A
NaHMDS
KHMDS
KHMDS
KHMDS
NaHMDS
NaHMDs
—
THF
THF
Toluene
THF
THF
THF
Ϫ40
Ϫ40
Ϫ40
Ϫ40
Ϫ20
Ϫ20
24
6
10
6
24
24
3 : 2
1 : 2
1 : 2
1 : 1.3
1 : 5
16 : 1
B
18-C-6e
18-C-6e
18-C-6e
—
3
B
4d
5
C
(S)-D
(R)-D
6
—
a Reagents: A. (EtO)2P(O)CH2CO2Et, B. (CF3CH2O)2P(O)CH2CO2Me (Still), C. (PhO)2P(O)CH2CO2Et (Ando), D. chiral phosphonoacetate (= 17)
(Fuji). b Isolated yield. c Determined by 1H-NMR analysis. d The corresponding Et ester was obtained as the product. e 18-crown-6.
Scheme 5 Synthesis of testudinariol B (1Ј). Reagents and conditions:
(a) TBDMSOTf, 2,6-lutidine, CH2Cl2 (98%); (b) DDQ, aq. CH2Cl2
(97%); (c) Dess–Martin periodinane, pyridine, CH2Cl2 (95%); (d)
(CF3CH2O)2P(O)CH2CO2Me,
KHMDS,
18-crown-6,
toluene,
Ϫ78 to Ϫ40 ЊC (91%, E : Z = 4 : 6); (e) DIBAL-H, CH2Cl2 (54%);
(f) Ms2O, LiBr, DMAP, s-collidine, DMF (64%); (g) 19b, KHMDS,
18-crown-6, THF then 19aЈ (78%); (h) Na–Hg, Na2HPO4, MeOH;
(i) TBAF, THF (36%, 2 steps).
Conclusion
In conclusion, the first synthesis of testudinariols A (1) and
B (1Ј), structurally and biosynthetically unusual triterpene
alcohols isolated from the marine mollusc Pleurobrancus
testudinarius, has been achieved by starting from (R)-glycidol.
As a result, the proposed unique structures for 1 and 1Ј were
proved to be correct.
Scheme 4 Synthesis of testudinariol A (1)—3. Reagents and con-
ditions: (a) TBDMSOTf, 2,6-lutidine, CH2Cl2 (99%); (b) DDQ, aq.
CH2Cl2 (97%); (c) Dess–Martin periodinane, pyridine, CH2Cl2 (94%);
(d) (S)-17, NaHMDS, THF, Ϫ78 to Ϫ20 ЊC (91%, E : Z = 1 : 5); (e)
DIBAL-H, CH2Cl2 (78%); (f) Ms2O, LiBr, DMAP, s-collidine, DMF
(93%); (g) PhSO2Na, DMF (87%); (h) KHMDS, 18-crown-6, THF
then 19a (84%); (i) Na–Hg, Na2HPO4, MeOH; (j) TBAF, THF (47%,
2 steps).
Experimental
The remaining steps were fortunately straightforward, and we
could accomplish the synthesis of (ϩ)-1Ј (18%, 4 steps), [α]D25
=
Mps are uncorrected. IR spectra were measured on a JASCO
A-102 spectrometer or a JASCO FT/IR-460 spectrometer.
1H-NMR spectra were recorded at 90 MHz on a JEOL JNM-
EX 90A spectrometer, at 400 MHz on a JEOL JNM-LA400
spectrometer and at 500 MHz on a JEOL JNM-LA500 spec-
ϩ19 (c = 0.16, CHCl3) {ref. 2 [α]D25 = ϩ15.0 (c = 0.05, CHCl3)}.
Other physical and spectral data of synthetic (ϩ)-1Ј were in
good accord with those reported for the naturally occurring 1Ј.
The overall yield was 3.7% based on 5 in 19 steps.
1010
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017

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trometer. The peak for TMS, or CHCl3 in CDCl3 (at δ 7.26) was
used as the internal standard. Chemical shifts are reported in
ppm on the δ scale and J-values are given in Hz. 13C-NMR
spectra were recorded at 100 MHz on a JEOL JNM-LA400
spectrometer and at 126 MHz on a JEOL JNM-LA500 spec-
trometer. The peak for CDCl3 (at δ 77.0) was used as the
internal standard. Optical rotations were taken with a JASCO
DIP-1000 polarimeter or a JASCO P-1010 polarimeter. [α]D
added N-methylmorpholine N-oxide (50% water; 4.0 cm3, 19.4
mmol) and osmium() oxide (1 g/100 cm3 solution in tert-
butyl alcohol; 7.0 cm3, 0.28 mmol) at room temperature. After
having been stirred at room temperature for 40 h, the reaction
mixture was quenched with sodium sulfite heptahydrate, diluted
with water and extracted with EtOAc. The extract was washed
with water and brine, dried (MgSO4), and concentrated under
reduced pressure. The residue was chromatographed on SiO2 to
23
values are given in 10Ϫ1 deg cm2
g
Ϫ1. Mass spectra were
give 7 (4.59 g, 93%) as a colourless oil, nD 1.4970 (Found: C,
measured with a JEOL JMS-SX102A spectrometer. Column
chromatography was carried out on Merck Kieselgel 60 Art
1.07734 unless otherwise stated. TLC analyses were performed
on Merck silica gel plates 60 F-254.
62.25; H, 9.29. C20H36O5Si requires C, 62.46; H, 9.44%); [α]D26
Ϫ24.3 (c 1.04 in CHCl3); νmax(film)/cmϪ1 3400s (OH), 1610m
(Ar), 1585w (Ar), 1515s (Ar), 1245s (Si–CH3); δH(90 MHz;
CDCl3) 0.06 (6H, s, SiMe2), 0.90 (9H, s, SiBut), 1.36–1.82 (4H,
m, 3-H2 and 4-H2), 2.41 (2H, s, 2 × OH), 3.30–3.96 (6H, m,
1-H2, 2-H, 5-H and 6-H2), 3.80 (3H, s, OMe), 4.52 (1H, d,
J 11.3, Ar-CHH), 4.67 (1H, d, J 11.3, Ar-CHH), 6.76–6.98
(2H, d like, J 8.8, m-aromatic-H), 7.15–7.36 (2H, d like, J 8.8,
o-aromatic-H).
(S)-1-(tert-Butyldimethylsilyloxy)hex-5-en-2-ol 6a
The known (S)-hex-5-ene-1,2-diol (5) was prepared from (R)-
glycidol (4).7 To a stirred solution of 5 (8.87 g, 76.4 mmol) in
dry CH2Cl2 (90 cm3) were added TBDMSCl (12.7 g, 84.3
mmol), NEt3 (13.8 cm3, 99.0 mmol) and DMAP (930 mg, 7.61
mmol) at room temperature. After having been stirred at room
temperature overnight, the reaction mixture was quenched with
water and extracted with CH2Cl2. The extract was washed
with water, saturated aq. NH4Cl and brine, dried (Na2SO4), and
concentrated under reduced pressure. The residue was chrom-
atographed on SiO2 to give 6a (15.0 g, 85%) as a colourless oil,
nD22 1.4431 (Found: C, 62.26; H, 11.55. C12H26O2Si requires C,
62.55; H, 11.37%); [α]D23 ϩ8.33 (c 1.00 in CHCl3); νmax(film)/cmϪ1
(S)-5-(tert-Butyldimethylsilyloxy)-4-(4-methoxybenzyloxy)-
pentanal 8
To a stirred mixture of SiO2 (30 g) in CH2Cl2 (180 cm3) was
added a solution of NaIO4 (4.92 g, 23.0 mmol) in water (30
cm3) at room temperature. The mixture was stirred at room
temperature for 10 min and then treated with a solution of 7
(8.84 g, 23.0 mmol) in CH2Cl2 (90 cm3). After having been
stirred at room temperature for 6 h, the reaction mixture was
filtered through Celite and the Celite was washed with CH2Cl2.
After the filtrate and the washings were concentrated under
reduced pressure, the residue was chromatographed on SiO2 to
3450m (OH), 1640m (C᎐C), 1255s (Si–CH ); δ (90 MHz;
᎐
3
H
CDCl3) 0.07 (6H, s, SiMe2), 0.91 (9H, s, SiBut), 1.35–1.65 (2H,
m, 3-H2), 2.01–2.38 (2H, m, 4-H2), 2.40 (1H, d like, J 2.4, OH),
3.26–3.81 (3H, m, 1-H2 and 2-H), 4.88–5.19 (2H, m, 6-H2),
5.60–6.08 (1H, m, 5-H).
23
give 8 (7.92 g, 98%) as a colourless oil, nD 1.4896 (Found: C,
64.82; H, 9.02. C19H32O4Si requires C, 64.73; H, 9.15%); [α]D27
Ϫ35.4 (c 1.03 in CHCl3); νmax(film)/cmϪ1 2730w (CHO), 1725s
(S)-6-(tert-Butyldimethylsilyloxy)-5-(4-methoxybenzyloxy)hex-
1-ene 6b
(C᎐O), 1615m (Ar), 1590w (Ar), 1520s (Ar), 1250s (Si–CH );
᎐
3
δH(90 MHz; CDCl3) 0.03 (6H, s, SiMe2), 0.90 (9H, s, SiBut),
1.56–2.10 (2H, m, 3-H2), 2.49 (2H, dt like, J 7.2 and 1.8, 2-H2),
3.30–3.88 (3H, m, 4-H and 5-H2), 3.80 (3H, s, OMe), 4.41 (1H,
d, J 11.3, Ar-CHH), 4.61 (1H, d, J 11.3, Ar-CHH), 6.76–7.00
(2H, d like, J 8.8, m-aromatic-H), 7.14–7.39 (2H, d like, J 8.8,
o-aromatic-H), 9.71 (1H, t, J 1.8, CHO).
To a stirred solution of 6a (1.00 g, 4.34 mmol) and 4-methoxy-
benzyl trichloroacetimidate (1.84 g, 6.51 mmol) in dry Et2O (20
cm3) was added CF3SO3H (3.8 mm3, 43 µmol) at room temper-
ature under Ar. After having been stirred at room temperature
for 30 min, the reaction mixture was quenched with saturated
aq. NaHCO3 and extracted with Et2O. The extract was washed
with water, saturated aq. NaHCO3 and brine, dried (MgSO4),
and concentrated under reduced pressure. The residue was
chromatographed on SiO2 to give recovered 6a (126 mg, 13%)
and 6b (1.19 g, 90% based on consumed 6a) as a colourless oil,
Ethyl (S,E)-7-(tert-butyldimethylsilyloxy)-6-(4-methoxybenzyl-
oxy)-2-(4Ј-methylpent-3Ј-enyl)hept-2-enoate 10a
To a stirred solution of ethyl 2-diethoxyphosphoryl-6-methyl-
hept-5-enoate (9) (452 mg, 1.48 mmol) in dry toluene (5.0 cm3)
was added ButOK (166 mg, 1.48 mmol) at Ϫ20 ЊC under Ar.
After the mixture was stirred at Ϫ20 ЊC for 30 min, a solution
of 8 (378 mg, 1.07 mmol) in dry toluene (4.0 cm3) was added
dropwise. After having been stirred at Ϫ20 ЊC for 5 h, the result-
ing solution was quenched with saturated aq. NH4Cl and
extracted with EtOAc. The extract was washed with water and
brine, dried (MgSO4), and concentrated under reduced pres-
sure. The residue was chromatographed on SiO2 to give 10a
(503 mg, 93%, E : Z = 5 : 1 as determined by 1H-NMR analysis)
23
nD 1.4860 (Found: C, 68.53; H, 9.61. C20H34O3Si requires C,
68.52; H, 9.78%); [α]D25 Ϫ22.9 (c 1.00 in CHCl3); νmax(film)/cmϪ1
1640w (C᎐C), 1610m (Ar), 1585w (Ar), 1510s (Ar), 1245s
᎐
(Si–CH3); δH(90 MHz; CDCl3) 0.06 (6H, s, SiMe2), 0.91 (9H,
s, SiBut), 1.48–1.76 (2H, m, 4-H2), 2.00–2.34 (2H, m, 3-H2),
3.30–3.88 (3H, m, 5-H and 6-H2), 3.80 (3H, s, OMe), 4.47
(1H, d, J 11.2, Ar-CHH), 4.65 (1H, d, J 11.2, Ar-CHH), 4.85–
5.14 (2H, m, 1-H2), 5.59–6.06 (1H, m, 2-H), 6.78–6.97 (2H,
d like, J 8.8, m-aromatic-H), 7.19–7.37 (2H, d like, J 8.8,
o-aromatic-H).
24
as a colourless oil, nD 1.4924 (Found: C, 69.16; H, 9.58.
C29H48O5Si requires C, 69.00; H, 9.58%); [α]D26 Ϫ22.8 (c 1.02 in
Determination of the enantiomeric purity of 6b
CHCl3); νmax(film)/cmϪ1 1710s (C᎐O), 1645w (C᎐C), 1615m
᎐
᎐
(Ar), 1585w (Ar), 1520s (Ar), 1250s (Si–CH3); (E)-10a: δH(500
MHz; CDCl3) 0.06 (6H, s, SiMe2), 0.90 (9H, s, SiBut), 1.29 (3H,
t, J 7.1, CO2CH2CH3), 1.51–1.73 (2H, m, 5-H2), 1.58 (3H, s,
The enantiomeric purity of the synthesized 6b was estimated
by HPLC analysis. HPLC analysis [column, Chiralcel OD
(4.6 mm × 25 cm); solvent, hexane–propan-2-ol = 10000 : 1;
flow rate, 0.5 cm3 minϪ1; detection at 254 nm]: 6b tR/min 23.3
[98.8%, (S)-6b], 27.4 [1.2%, (R)-6b]. The enantiomeric purity
of 6b was estimated to be 97.6% ee.
Me–C᎐Ccis), 1.67 (3H, s, Me–C᎐Ctrans), 2.07 (2H, m, 2Ј-H2),
᎐
᎐
2.16–2.35 (4H, m, 4-H2 and 1Ј-H2), 3.45 (1H, m, 6-H), 3.57 (1H,
dd, J 10.4 and 5.5, 7-Ha), 3.70 (1H, dd, J 10.4 and 5.8, 7-Hb),
3.80 (3H, s, OMe), 4.18 (2H, q, J 7.1, CO2CH2CH3), 4.47 (1H,
d, J 11.2, Ar-CHH), 4.63 (1H, d, J 11.2, Ar-CHH), 5.12 (1H,
tdd, J 7.4, 1.5 and 1.2, 3Ј-H), 6.72 (1H, t, J 7.3, 3-H), 6.84–
6.88 (2H, d like, J 8.9, m-aromatic-H), 7.23–7.28 (2H, d like,
J 8.9, o-aromatic-H); (Z)-10a: δH(500 MHz; CDCl3) 0.06 (6H,
s, SiMe2), 0.90 (9H, s, SiBut), 1.28 (3H, t, J 7.1, CO2CH2CH3),
(2RS,5S)-6-(tert-Butyldimethylsilyloxy)-5-(4-methoxybenzyl-
oxy)hexane-1,2-diol 7
To a stirred solution of 6b (4.53 g, 12.9 mmol) in tert-butyl
alcohol (9.0 cm3), acetone (27 cm3) and water (9.0 cm3) were
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
1011

View Article Online
1.51–1.73 (2H, m, 5-H ), 1.58 (3H, s, Me–C᎐C ), 1.67 (3H, s,
6Ј-Heq), 4.17 (2H, m, CO2CH2CH3), 4.44 (1H, d, J 11.6, Ar-
᎐
2
cis
Me–C᎐Ctrans), 2.07 (2H, m, 2Ј-H2), 2.16–2.35 (3H, m, 4-Ha and
CHH), 4.49 (1H, d, J 11.6, Ar-CHH), 5.05 (1H, tdd, J 5.8, 1.5
and 1.2, 5-H), 6.82–6.89 (2H, d like, J 8.6, m-aromatic-H), 7.19–
7.26 (2H, d like, J 8.6, o-aromatic-H); δC(100 MHz; CDCl3)
14.2, 17.6, 25.6, 25.7, 27.9, 28.6, 29.9, 51.1, 55.2, 60.2, 70.4,
70.8, 72.3, 78.5, 113.7, 123.3, 129.1, 130.5, 132.4, 159.1, 174.3.
᎐
1Ј-H2), 2.50 (1H, m, 4-Hb), 3.45 (1H, m, 6-H), 3.57 (1H, dd,
J 10.4 and 5.5, 7-Ha), 3.70 (1H, dd, J 10.4 and 5.8, 7-Hb), 3.80
(3H, s, OMe), 4.18 (2H, q, J 7.1, CO2CH2CH3), 4.47 (1H, d,
J 11.2, Ar-CHH), 4.63 (1H, d, J 11.2, Ar-CHH), 5.08 (1H, tdd,
J 7.4, 1.5 and 1.2, 3Ј-H), 5.80 (1H, t, J 7.3, 3-H), 6.84–6.88
(2H, d like, J 8.9, m-aromatic-H), 7.23–7.28 (2H, d like, J 8.9,
o-aromatic-H).
23
Compound 11b: a colourless oil, nD 1.5028 (Found: C,
70.87; H, 9.02. C23H34O5 requires C, 70.74; H, 8.78%); [α]D24
ϩ5.64 (c 1.01 in CHCl3); νmax(film)/cmϪ1 1730s (C᎐O), 1615m
᎐
(Ar), 1585w (Ar), 1515s (Ar), 1250m (C–O), 1100m (C–O);
δH(400 MHz; CDCl3) 1.26 (3H, t, J 7.1, CO2CH2CH3), 1.34–
Ethyl (S,E)-7-hydroxy-6-(4-methoxybenzyloxy)-2-(4Ј-methyl-
pent-3Ј-enyl)hept-2-enoate 10b
1.48 (2H, m, 3Ј-Hax and 4Ј-H ), 1.57 (3H, s, Me–C᎐C ), 1.61–
᎐
ax
cis
1.78 (3H, m, 3-H and 3Ј-H ), 1.66 (3H, s, Me–C᎐Ctrans), 1.95
᎐
2
eq
To a solution of 10a (2.47 g, 4.89 mmol, E : Z = 5 : 1) in dry
MeOH (26 cm3) was added PPTS (127 mg, 0.511 mmol) at
room temperature under Ar. After having been stirred at 40 ЊC
for 14 h, the resulting solution was quenched with saturated aq.
NaHCO3 and extracted with EtOAc. The extract was washed
with water and brine, dried (MgSO4), and concentrated under
reduced pressure. The residue was chromatographed on SiO2 to
(2H, m, 4-H2), 2.16 (1H, m, 4Ј-Heq), 2.41 (1H, ddd, J 10.0, 8.1
and 4.2, 2-H), 3.13 (1H, dd, J 11.0 and 10.5, 6Ј-Hax), 3.33 (1H,
ddd, J 10.0, 8.1 and 2.0, 2Ј-H), 3.40 (1H, m, 5Ј-H), 3.79 (3H, s,
OMe), 4.06 (1H, ddd, J 11.0, 4.6 and 2.2, 6Ј-Heq), 4.14 (2H, q,
J 7.1, CO2CH2CH3), 4.44 (1H, d, J 11.6, Ar-CHH), 4.50 (1H, d,
J 11.5, Ar-CHH), 5.07 (1H, tdd, J 7.2, 5.8 and 1.3, 5-H), 6.83–
6.89 (2H, d like, J 8.6, m-aromatic-H), 7.21–7.26 (2H, d like,
J 8.6, o-aromatic-H); δC(100 MHz; CDCl3) 14.2, 17.6, 25.7,
25.9, 28.0, 29.1, 29.8, 50.7, 55.2, 60.3, 70.4, 70.9, 72.5, 77.9,
113.8, 123.5, 129.2, 130.5, 132.2, 159.2, 173.9.
15
give 10b (1.90 g, 99%, E : Z = 5 : 1) as a colourless oil, nD
1.5156 (Found: C, 70.79; H, 8.87. C23H34O5 requires C, 70.74;
H, 8.78%); [α]D24 Ϫ2.15 (c 1.04 in CHCl3); νmax(film)/cmϪ1 3470m
(OH), 1710s (C᎐O), 1640w (C᎐C), 1615m (Ar), 1585w (Ar),
᎐
᎐
24
Compound 11c: a colourless oil, nD 1.5064 (Found: C,
1520s (Ar); (E)-10b: δH(90 MHz; CDCl3) 1.29 (3H, t, J 7.1,
CO2CH2CH3), 1.44–2.58 (8H, m, 4-H2, 5-H2, 1Ј-H2 and 2Ј-H2),
70.91; H, 9.08. C23H34O5 requires C, 70.74; H, 8.78%); [α]D26
Ϫ1.48 (c 1.03 in CHCl3); νmax(film)/cmϪ1 1725s (C᎐O), 1610m
᎐
1.58 (3H, br s, Me–C᎐C ), 1.67 (3H, s, Me–C᎐Ctrans), 3.33–3.85
᎐
᎐
cis
(Ar), 1585w (Ar), 1515s (Ar), 1245m (C–O), 1120m (C–O);
δH(400 MHz; CDCl3) 1.26 (3H, t, J 7.0, CO2CH2CH3), 1.34–
1.42 (1H, m, 4Ј-Hax), 1.51–2.07 (7H, m, 3-H2, 4-H2, 3Ј-H2 and
(3H, m, 6-H and 7-H2), 3.81 (3H, s, OMe), 4.19 (2H, q, J 7.1,
CO2CH2CH3), 4.52 (2H, br s, Ar-CH2), 5.12 (1H, m, 3Ј-H), 6.72
(1H, t, J 7.5, 3-H), 6.78–6.98 (2H, d like, J 8.6, m-aromatic-H),
7.19–7.38 (2H, d like, J 8.6, o-aromatic-H); (Z)-10b: δH(90
MHz; CDCl3) 1.29 (3H, t, J 7.1, CO2CH2CH3), 1.44–2.58 (8H,
4Ј-H ), 1.57 (3H, s, Me–C᎐C ), 1.66 (3H, s, Me–C᎐Ctrans), 2.52
᎐
᎐
eq
cis
(1H, ddd, J 10.6, 8.6 and 3.2, 2-H), 3.37 (1H, br s, 5Ј-H), 3.41
(1H, m, 2Ј-H), 3.46 (1H, dd, J 12.0 and 1.6, 6Ј-Hax), 3.80 (3H, s,
OMe), 4.04 (1H, br d, J 12.0, 6Ј-Heq), 4.15 (2H, m,
CO2CH2CH3), 4.49 (2H, s, Ar-CH2), 5.08 (1H, t like, J 7.0,
5-H), 6.83–6.89 (2H, d like, J 8.4, m-aromatic-H), 7.24–7.30
(2H, d like, J 8.4, o-aromatic-H); δC(100 MHz; CDCl3) 14.3,
17.6, 24.7, 25.7, 25.8, 26.7, 29.0, 51.2, 55.2, 60.2, 69.5, 69.8,
70.0, 77.9, 113.7, 123.8, 129.1, 130.7, 131.9, 159.0, 174.2.
m, 4-H , 5-H , 1Ј-H and 2Ј-H ), 1.58 (3H, br s, Me–C᎐C ),
᎐
cis
2
2
2
2
1.67 (3H, s, Me–C᎐Ctrans), 3.33–3.85 (3H, m, 6-H and 7-H2),
᎐
3.81 (3H, s, OMe), 4.19 (2H, q, J 7.1, CO2CH2CH3), 4.52 (2H,
br s, Ar-CH2), 5.12 (1H, m, 3Ј-H), 5.82 (1H, t, J 7.5, 3-H), 6.78–
6.98 (2H, d like, J 8.6, m-aromatic-H), 7.19–7.38 (2H, d like,
J 8.6, o-aromatic-H).
24
Compound 11d: a colourless oil, nD 1.5085 (Found: C,
Ethyl (R)-2-[(2ЈR,5ЈS)-5Ј-(4-methoxybenzyloxy)tetrahydro-
pyran-2Ј-yl]-6-methylhept-5-enoate 11a
70.81; H, 9.06. C23H34O5 requires C, 70.74; H, 8.78%); [α]D28
Ϫ26.9 (c 1.04 in CHCl3); νmax(film)/cmϪ1 1730s (C᎐O), 1610m
᎐
To a stirred solution of 10b (7.02 g, 18.0 mmol, E : Z = 5 : 1) in
dry THF (120 cm3) was added ButOK (202 mg, 1.80 mmol) at
Ϫ10 ЊC under Ar. After having been stirred at 4 ЊC for 18 h, the
resulting solution was quenched with saturated aq. NH4Cl and
extracted with EtOAc. The extract was washed with water
and brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was chromatographed on SiO2 to give a
mixture of all of the possible diastereomers, 11a–d (6.53 g, 93%,
11a : 11b : 11c : 11d = 5 : 5 : 2 : 2 as determined by 1H-NMR
analysis) as a colourless oil. The diastereomers were rechromato-
graphed on spherical SiO2 [Silica Gel 60 N (spherical, neutral),
40–50 µm, Kanto Chemical Co., Inc.] to give the desired 11a
(2.26 g, 32%) and the undesired isomers 11b–11d (4.21 g, 60%).
11b–11d were converted to the initial mixture by treatment with
ButOK (0.1 eq.) at 4 ЊC for 18 h. By repeating this process three
times, 11a (4.80 g, 68%) was obtained as a colourless oil.
Analytical samples of 11b–11d were obtained by chromato-
graphic separation of the diastereomers.
(Ar), 1585w (Ar), 1515s (Ar), 1250m (C–O), 1120m (C–O);
δH(400 MHz; CDCl3) 1.25 (3H, t, J 7.0, CO2CH2CH3),
1.44–1.78 (5H, m, 3-H2, 3Ј-H2 and 4Ј-Hax), 1.57 (3H, s, Me–
C᎐C ), 1.67 (3H, s, Me–C᎐Ctrans), 1.95 (2H, dt like, J 8.4 and
᎐
᎐
cis
7.2, 4-H2), 2.04 (1H, m, 4Ј-Heq), 2.53 (1H, ddd, J 10.4, 8.8
and 4.1, 2-H), 3.36 (1H, br s, 5Ј-H), 3.44 (1H, dd, J 12.8 and
1.6, 6Ј-Hax), 3.52 (1H, ddd, J 10.4, 8.8 and 1.6, 2Ј-H), 3.80 (3H,
s, OMe), 4.02 (1H, br d, J 12.8, 6Ј-Heq), 4.16 (2H, m,
CO2CH2CH3), 4.46 (1H, d, J 11.8, Ar-CHH), 4.51 (1H, d,
J 11.8, Ar-CHH), 5.07 (1H, t like, J 7.6, 5-H), 6.82–6.89 (2H,
d like, J 8.4, m-aromatic-H), 7.23–7.29 (2H, d like, J 8.4,
o-aromatic-H); δC(100 MHz; CDCl3) 14.2, 17.6, 23.7, 25.65,
25.73, 27.0, 28.2, 51.0, 55.2, 60.1, 69.4, 69.5, 70.1, 78.6, 113.6,
123.5, 129.1, 130.7, 132.3, 159.0, 174.7.
Stereochemical assignment of 11a and 11b
Stereochemical assignment of the separated diastereomers 11a
23
1
Compound 11a: a colourless oil, nD 1.5081 (Found: C,
and 11b was established by H-NMR analysis at the stage of
70.75; H, 8.67. C23H34O5 requires C, 70.74; H, 8.78%); [α]D24
alcohol 14 after reduction of ester 11.
ϩ19.6 (c 1.02 in CHCl3); νmax(film)/cmϪ1 1735s (C᎐O), 1615m
To a stirred solution of 11a (11 mg, 28 µmol) in hexane (0.5
cm3) was added DIBAL-H (0.95 mol dmϪ3 in hexane; 0.20 cm3,
0.19 mmol) at Ϫ5 ЊC under Ar. After having been stirred at
Ϫ5 ЊC for 30 min, the resulting solution was quenched with
MeOH. The mixture was filtered through Celite, and the filtrate
was concentrated under reduced pressure. The residue was
purified by PTLC to give 14a (7.6 mg, 78%) as a colourless oil.
In the same manner as described above, 11b was converted to
14b as a colourless oil.
᎐
(Ar), 1590w (Ar), 1520s (Ar), 1250m (C–O), 1100m (C–O);
δH(500 MHz; CDCl3) 1.26 (3H, t, J 7.0, CO2CH2CH3), 1.30
(1H, m, 3Ј-Hax or 4Ј-Hax), 1.37–1.47 (2H, m, 3-Ha, 4Ј-Hax or
3Ј-H ), 1.53–1.70 (1H, m, 3-H ), 1.57 (3H, s, Me–C᎐C ), 1.67
᎐
cis
ax
b
(3H, s, Me–C᎐Ctrans), 1.82 (1H, m, 3Ј-Heq), 1.93 (2H, m, 4-H2),
᎐
2.17 (1H, m, 4Ј-Heq), 2.38 (1H, ddd, J 12.2, 8.4 and 3.8, 2-H),
3.12 (1H, dd, J 10.7 and 10.4, 6Ј-Hax), 3.36–3.46 (2H, m, 2Ј-H,
5Ј-H), 3.80 (3H, s, OMe), 4.04 (1H, ddd, J 10.7, 4.7 and 2.3,
1012
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017

View Article Online
Compound 14a: δH(400 MHz; CDCl3) 1.31–1.54 (5H, m,
2-H, 3-H2, 3Ј-Hax and 4Ј-H ), 1.59 (3H, s, Me–C᎐C ), 1.67
solid. An analytical sample of 13b was obtained by recrystal-
lization from hexane as colourless plates.
Compound 13a: a colourless oil, nD 1.4505 (Found: C,
72.69; H, 8.59. C21H30O4 requires C, 72.80; H, 8.73%); [α]D27
ϩ7.16 (c 1.00 in CHCl3); νmax(film)/cmϪ1 3500m (OH), 1650w
᎐
ax
cis
25
(3H, br s, Me–C᎐Ctrans), 1.76–1.84 (1H, m, 3Ј-Heq), 2.00 (2H, m,
᎐
4-H2), 2.16–2.23 (1H, m, 4Ј-Heq), 3.12 (1H, dd, J 10.5 and 10.5,
6Ј-Hax), 3.28 (1H, ddd, J 10.8, 6.4 and 2.0, 2Ј-H), 3.43 (1H, m,
5Ј-H), 3.58 (1H, dd, J 11.2 and 6.4, 1-Ha), 3.77 (1H, dd, J 11.2
and 2.7, 1-Hb), 3.80 (3H, s, OMe), 4.08 (1H, ddd, J 10.5, 4.6 and
2.2, 6Ј-Heq), 4.45 (1H, d, J 11.3, Ar-CHH), 4.52 (1H, d, J 11.3,
Ar-CHH), 5.07 (1H, tdd, J 7.1, 1.5 and 1.2, 5-H), 6.84–6.91
(2H, d like, J 8.5, m-aromatic-H), 7.21–7.27 (2H, d like, J 8.5,
o-aromatic-H).
(C᎐C), 1615m (Ar), 1590w (Ar), 1520s (Ar), 1250s (C–O),
᎐
1095m (C–O); δH(500 MHz; CDCl3) 1.14–1.23 (1H, m, 3-Ha),
1.29–1.46 (2H, m, 3Ј-Hax and 4Ј-Hax), 1.63–1.72 (2H, m, 4-Ha
and OH), 1.74–1.80 (2H, m, 4-Hb and 3Ј-Heq), 1.83 (3H, s,
CH ᎐C–CH ), 1.83–1.94 (2H, m, 2-H and 3-H ), 2.18 (1H, m,
᎐
2
3
b
4Ј-Heq), 2.37 (1H, ddd, J 11.6, 5.8 and 5.5, 5-H), 3.02 (1H, ddd,
J 10.7, 8.6 and 1.9, 2Ј-H), 3.14 (1H, dd, J 10.5 and 10.5, 6Ј-Hax),
3.46 (1H, m, 5Ј-H), 3.80 (3H, s, OMe), 4.09 (1H, ddd, J 10.5, 4.7
and 2.3, 6Ј-Heq), 4.14 (1H, dd, J 5.5 and 2.3, 1-H), 4.46 (1H,
d, J 11.6, Ar-CHH), 4.51 (1H, d, J 11.6, Ar-CHH), 4.81 (1H, s,
Compound 14b: δH(500 MHz; CDCl3) 1.20–1.63 (5H, m,
3-H , 3Ј-H and 4Ј-H ), 1.60 (3H, s, Me–C᎐C ), 1.68 (3H, s,
᎐
cis
2
2
ax
Me–C᎐Ctrans), 1.78 (1H, m, 2-H), 1.96 (1H, m, 4-Ha), 2.04 (1H,
᎐
m, 4-Hb), 2.18–2.26 (1H, m, 4Ј-Heq), 3.15 (1H, dd, J 10.4 and
10.4, 6Ј-Hax), 3.41 (1H, m, 5Ј-H), 3.48 (1H, dt like, J 11.0
and 3.0, 2Ј-H), 3.61 (1H, m, 1-Ha), 3.70 (1H, m, 1-Hb), 3.80
(3H, s, OMe), 4.07 (1H, ddd, J 10.4, 4.8 and 2.4, 6Ј-Heq), 4.46
(1H, d, J 11.3, Ar-CHH), 4.51 (1H, d, J 11.3, Ar-CHH),
5.08 (1H, tdd, J 7.0, 1.5 and 1.2, 5-H), 6.85–6.90 (2H,
d like, J 8.5, m-aromatic-H), 7.21–7.29 (2H, d like, J 8.5,
o-aromatic-H).
CHH᎐C–CH ), 4.97 (1H, s, CHH᎐C–CH ), 6.85–6.89 (2H,
᎐
᎐
3
3
d like, J 8.6, m-aromatic-H), 7.22–7.28 (2H, d like, J 8.6,
o-aromatic-H); δC(126 MHz; CDCl3) 23.3, 26.8, 27.1, 29.1, 30.1,
52.0, 52.9, 55.2, 70.4, 70.7, 72.8, 74.6, 80.2, 112.2, 113.8, 129.2,
130.6, 144.2, 159.2.
Compound 13b: colourless plates, mp 70.5–72.0 ЊC (Found:
C, 72.77; H, 8.95. C21H30O4 requires C, 72.80; H, 8.73%); [α]D25
Ϫ0.98 (c 1.02 in CHCl3); νmax(KBr)/cmϪ1 3410s (OH), 1630m
(C᎐C), 1610s (Ar), 1585m (Ar), 1510s (Ar), 1245s (C–O);
δH(500 MHz; CDCl3) 1.35 (1H, m, 3Ј-Hax), 1.45 (1H, m, 4Ј-Hax),
1.54 (1H, m, 3-Ha), 1.67–1.83 (3H, m, 3-Hb, 4-Ha and 3Ј-Heq),
᎐
(R)-2-[(2ЈR,5ЈS)-5Ј-(4-Methoxybenzyloxy)tetrahydropyran-2Ј-
yl]-6-methylhept-5-enal 12
To a stirred solution of 11a (1.60 g, 4.10 mmol) in dry toluene
(20 cm3) was added DIBAL-H (1.00 mol dmϪ3 in toluene; 10.0
cm3, 10.0 mmol) dropwise at Ϫ78 ЊC under Ar. After having
been stirred at Ϫ78 ЊC for 3 h, the solution was quenched with
MeOH at Ϫ78 ЊC. After having been warmed to room temper-
ature with vigorous stirring, the mixture was filtered through
Celite and the Celite was washed with Et2O. After the filtrate
and the washings were concentrated under reduced pressure,
the residue was chromatographed on SiO2 to give 12 (1.40 g,
98%) as a colourless oil, nD23 1.5169 (Found: C, 72.51; H, 8.49.
C21H30O4 requires C, 72.80; H, 8.73%); [α]D24 ϩ1.70 (c 1.02 in
1.82 (3H, s, CH ᎐C–CH ), 1.85–1.96 (2H, m, 2-H and 4-H ),
᎐
2 3 b
2.14–2.22 (1H, m, 4Ј-Heq), 2.42 (1H, dd, J 8.3 and 8.3, 5-H),
3.19 (1H, dd, J 10.4 and 10.4, 6Ј-Hax), 3.39 (1H, ddd, J 10.7, 8.9
and 1.8, 2Ј-H), 3.44 (1H, m, 5Ј-H), 3.80 (3H, s, OMe), 4.07
(1H, ddd, J 10.7, 4.7 and 2.4, 6Ј-Heq), 4.25 (1H, dd, J 3.4
and 3.4, 1-H), 4.46 (1H, d, J 11.3, Ar-CHH), 4.52 (1H, d,
J 11.3, Ar-CHH), 4.82 (1H, s, CHH᎐C–CH ), 4.96 (1H, br s,
᎐
3
CHH᎐C–CH ), 6.85–6.89 (2H, d like, J 8.8, m-aromatic-H),
᎐
3
7.22–7.28 (2H, d like, J 8.8, o-aromatic-H); δC(126 MHz;
CDCl3) 23.3, 24.7, 24.8, 29.6, 30.1, 50.1, 52.4, 55.2, 70.4, 70.6,
72.5, 72.9, 77.7, 111.4, 113.8, 129.2, 130.6, 144.2, 159.2.
CHCl3); νmax(film)/cmϪ1 2730w (CHO), 1725s (C᎐O), 1615m
᎐
(Ar), 1585w (Ar), 1515s (Ar), 1250m (C–O), 1090m (C–O);
δH(400 MHz; CDCl3) 1.36–1.46 (2H, m, 3Ј-Hax and 4Ј-Hax),
(1S,2S,5S)-2-[(2ЈR,5ЈS)-5Ј-(4-Methoxybenzyloxy)tetrahydro-
pyran-2Ј-yl]-5-(1-methylethenyl)cyclopentanol 13c
1.45–1.59 (1H, m, 3-H ), 1.56 (3H, s, Me–C᎐C ), 1.67 (3H, s,
᎐
a
cis
Me–C᎐Ctrans), 1.73 (1H, m, 3-Hb), 1.78 (1H, m, 3Ј-Heq), 1.97
To a stirred solution of 12 (1.40 g, 4.04 mmol) in dry CH2Cl2
(90 cm3) was added SnCl4 (1.0 mol dmϪ3 in CH2Cl2; 4.0 cm3, 4.0
mmol) dropwise at Ϫ78 ЊC under Ar. After having been stirred
at Ϫ78 ЊC for 15 min, the resulting solution was quenched
with dil. aq. HCl (1.0 mol dmϪ3) and extracted with CH2Cl2.
The extract was washed with water, saturated aq. NaHCO3
and brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was chromatographed on SiO2 to give a
mixture of 13a and 13c (1.11 g, 80%, 13a : 13c = 3 : 7, as deter-
᎐
(2H, m, 4-H2), 2.17–2.29 (2H, m, 2-H and 4Ј-Heq), 3.11 (1H,
dd, J 10.6 and 10.6, 6Ј-Hax), 3.40 (1H, m, 5Ј-H), 3.45–3.51 (1H,
m, 2Ј-H), 3.79 (3H, s, OMe), 4.04 (1H, ddd, J 10.6, 4.8 and 2.3,
6Ј-Heq), 4.42 (1H, d, J 11.5, Ar-CHH), 4.50 (1H, d, J 11.5,
Ar-CHH), 5.04 (1H, tdd, J 5.9, 1.5 and 1.2, 5-H), 6.84–6.89
(2H, d like, J 8.7, m-aromatic-H), 7.21–7.26 (2H, d like, J 8.7,
o-aromatic-H), 9.62 (1H, d, J 3.9, CHO); δC(100 MHz; CDCl3)
17.7, 25.4, 25.6, 26.4, 28.3, 29.9, 55.2, 56.1, 70.4, 70.9, 72.3,
77.4, 113.8, 123.2, 129.2, 130.4, 132.8, 159.2, 204.3.
1
mined by H-NMR analysis) as a colourless oil. The mixture
was rechromatographed on spherical SiO2 [Silica Gel 60 N
(spherical, neutral), 40–50 µm, Kanto Chemical Co., Inc.] to
give 13a (337 mg, 24%) and the desired 13c (774 mg, 55%) as a
colourless oil, nD23 1.5171 (Found: C, 72.66; H, 8.48. C21H30O4
requires C, 72.80; H, 8.73%); [α]D27 ϩ6.88 (c 1.03 in CHCl3);
(1S,2S,5R)-2-[(2ЈR,5ЈS)-5Ј-(4-Methoxybenzyloxy)tetrahydro-
pyran-2Ј-yl]-5-(1-methylethenyl)cyclopentanol 13a
To a stirred solution of 12 (820 mg, 2.37 mmol) in dry CH2Cl2
(50 cm3) was added Me2AlCl (0.98 mol dmϪ3 in hexane; 2.45
cm3, 2.40 mmol) dropwise at 0 ЊC under Ar. After having been
stirred at 0 ЊC for 30 min, the resulting solution was quenched
with dil. aq. HCl (1.0 mol dmϪ3) and extracted with Et2O. The
extract was washed with water, saturated aq. NaHCO3 and
brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was chromatographed on SiO2 to give a
mixture of all of the possible diastereomers, 13a–c (807 mg,
98%, 13a : 13b : 13c = 6 : 3 : 1 as determined by 1H-NMR
analysis) as a colourless oil. The diastereomers were rechrom-
atographed on spherical SiO2 [Silica Gel 60 N (spherical,
neutral), 40–50 µm, Kanto Chemical Co., Inc.] to give the
desired 13a (484 mg, 59%) as a colourless oil and other isomers,
13b and 13c (inseparable mixtures; 313 mg, 38%) as a colourless
νmax(film)/cmϪ1 3550s (OH), 1650m (C᎐C), 1610s (Ar), 1585m
᎐
(Ar), 1510s (Ar), 1240m (C–O), 1090m (C–O); δH(400 MHz;
CDCl3) 1.16–1.55 (4H, m, 3-Ha, 4-Ha, 3Ј-Hax and 4Ј-Hax), 1.72–
1.91 (4H, m, 2-H, 3-H , 4-H and 3Ј-H ), 1.75 (3H, s, CH ᎐
᎐
b
b
eq
2
C–CH3), 2.12–2.20 (1H, m, 4Ј-Heq), 2.46 (1H, dt, J 9.5 and 9.5,
5-H), 3.18 (1H, dd, J 10.5 and 10.5, 6Ј-Hax), 3.14–3.22 (1H, m,
2Ј-H), 3.44 (1H, m, 5Ј-H), 3.80 (3H, s, OMe), 3.83 (1H, dd, J 9.5
and 8.1, 1-H), 4.09 (1H, ddd, J 10.5, 4.6 and 2.2, 6Ј-Heq), 4.46
(1H, d, J 11.3, Ar-CHH), 4.52 (1H, d, J 11.3, Ar-CHH), 4.79
(1H, s, CHH᎐C–CH ), 4.86 (1H, s, CHH᎐C–CH ), 6.84–6.91
᎐
᎐
3
3
(2H, d like, J 8.8, m-aromatic-H), 7.22–7.28 (2H, d like, J 8.8,
o-aromatic-H); δC(100 MHz; CDCl3) 20.1, 24.0, 26.6, 29.8, 29.9,
50.7, 53.2, 55.3, 70.5, 70.6, 72.6, 80.0, 83.4, 110.5, 113.9, 129.2,
130.5, 145.8, 159.3.
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
1013

View Article Online
(1S,2R,5R)-2-[(2ЈR,5ЈS)-5Ј-(4-Methoxybenzyloxy)tetrahydro-
pyran-2Ј-yl]-1-(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)-
cyclopentane 15a
1.81–1.93 (3H, m, 2Ј-H, 3Ј-Hb and 4Ј-Hb), 2.09–2.18 (2H, m,
4-Heq and 5Ј-H), 2.89 (1H, ddd, J 10.4, 8.6 and 1.9, 2-H), 3.05
(1H, dd, J 10.5 and 10.1, 6-Hax), 3.69 (1H, m, 5-H), 3.99 (1H,
ddd, J 10.5, 4.9 and 2.5, 6-Heq), 4.21 (1H, d, J 4.6, 1Ј-H), 4.69
To a stirred solution of 13a (916 mg, 2.64 mmol) in dry CH2Cl2
(15 cm3) were added 2,6-lutidine (2,6-dimethylpyridine) (0.62
cm3, 5.3 mmol) and TBDMSOTf (0.91 cm3, 4.0 mmol) at 0 ЊC.
After having been stirred at 0 ЊC for 15 min, the resulting
solution was added to water and extracted with CH2Cl2. The
extract was washed with water and brine, dried (MgSO4), and
concentrated under reduced pressure. The residue was chrom-
atographed on SiO2 to give 15a (1.20 g, 99%) as a colourless oil,
(1H, s, CHH᎐C–CH3), 4.77 (1H, br s, CHH᎐C–CH3); δC(126
᎐
᎐
MHz; CDCl3) Ϫ5.1, Ϫ4.2, 18.1, 23.1, 25.8, 26.5, 27.1, 28.7,
33.1, 52.2, 53.6, 66.6, 72.7, 76.0, 79.8, 110.9, 144.5.
(2R,5S)-2-[(1ЈS,2ЈR,5ЈS)-1Ј-(tert-Butyldimethylsilyloxy)-5Ј-
(1-methylethenyl)-2Ј-cyclopentyl]tetrahydropyran-5-ol 15bЈ
In the same manner as described above, 15aЈ (753 mg, 1.63
mmol) was converted to 15bЈ (541 mg, 97%) as a colourless oil,
nD23 1.4811 (Found: C, 66.89; H, 10.59. C19H36O3Si requires C,
67.01; H, 10.65%); [α]D26 ϩ25.6 (c 1.04 in CHCl3); νmax(film)/cmϪ1
25
nD 1.5031 (Found: C, 70.31; H, 9.70. C27H44O4Si requires C,
70.39; H, 9.63%); [α]D26 ϩ4.67 (c 1.03 in CHCl3); νmax(film)/cmϪ1
1640w (C᎐C), 1610m (Ar), 1585w (Ar), 1515s (Ar), 1250s
᎐
(Si–CH3); δH(400 MHz; CDCl3) 0.01, 0.03 (6H, each s, SiMe2),
0.82 (9H, s, SiBut), 1.05–1.16 (1H, m, 3-Ha), 1.23 (1H, m, 3Ј-
Hax ), 1.38 (1H, m, 4Ј-Hax), 1.53–1.63 (1H, m, 4-Ha), 1.70–1.79
3400s (OH), 1640w (C᎐C), 1250m (Si–CH ); δ (500 MHz;
᎐
3
H
CDCl3) 0.00, 0.02 (6H, each s, SiMe2), 0.85 (9H, s, SiBut), 1.31–
1.50 (4H, m, 3-Hax, 4-Hax, 3Ј-Ha and 4Ј-Ha), 1.54 (1H, s, OH),
(1H, m, 3Ј-H ), 1.75 (3H, s, CH ᎐C–CH ), 1.79–1.92 (3H, m,
᎐
eq
2
3
1.65–1.83 (3H, m, 3-H , 3Ј-H and 4Ј-H ), 1.70 (3H, s, CH ᎐
᎐
eq b b 2
2-H, 3-Hb and 4-Hb), 2.10–2.22 (2H, m, 5-H and 4Ј-Heq), 2.89
(1H, ddd, J 10.6, 8.5 and 1.9, 2Ј-H), 3.11 (1H, dd, J 10.5 and
10.5, 6Ј-Hax), 3.44 (1H, m, 5Ј-H), 3.81 (3H, s, OMe), 4.08 (1H,
ddd, J 10.5, 4.8 and 2.3, 6Ј-Heq), 4.20 (1H, d, J 4.6, 1-H), 4.48
(1H, d, J 11.5, Ar-CHH), 4.52 (1H, d, J 11.5, Ar-CHH), 4.69
C–CH3), 1.97 (1H, m, 2Ј-H), 2.10–2.18 (1H, m, 4-Heq), 2.44
(1H, dt like, J 8.3 and 6.5, 5Ј-H), 3.06 (1H, dd, J 10.7 and 10.4,
6Ј-Hax), 3.16 (1H, m, 2-H), 3.68 (1H, m, 5-H), 3.96 (1H, dd,
J 6.5 and 6.1, 1Ј-H), 3.99 (1H, ddd, J 10.7, 4.8 and 2.3, 6-Heq),
4.74 (1H, br s, CHH᎐C–CH ), 4.75 (1H, br s, CHH᎐C–CH );
᎐
᎐
3
3
(1H, s, CHH᎐C–CH ), 4.77 (1H, s, CHH᎐C–CH ), 6.84–6.91
᎐
᎐
3
3
δC(126 MHz; CDCl3) Ϫ4.4, Ϫ4.2, 18.0, 20.4, 25.2, 25.9, 27.4,
(2H, d like, J 8.8, m-aromatic-H), 7.22–7.30 (2H, d like, J 8.6,
o-aromatic-H); δC(100 MHz; CDCl3) Ϫ5.1, Ϫ4.1, 18.1, 23.1,
25.8, 26.4, 27.0, 28.7, 30.3, 52.2, 53.7, 55.2, 70.3, 70.6, 73.1,
75.9, 80.1, 110.8, 113.8, 129.1, 130.7, 144.6, 159.1.
28.5, 33.0, 52.3, 56.4, 66.5, 72.8, 78.7, 78.9, 111.0, 146.2.
(R)-2-[(1ЈS,2ЈR,5ЈR)-1Ј-(tert-Butyldimethylsilyloxy)-5Ј-
(1-methylethenyl)-2Ј-cyclopentyl]tetrahydropyran-5-one 16
To a stirred solution of 15b (127 mg, 0.373 mmol) in CH2Cl2
(4.5 cm3) were added the Dess–Martin periodinane (209 mg,
0.496 mmol) and three drops of pyridine at 0 ЊC. After having
been stirred at room temperature for 40 min, the resulting
mixture was diluted with Et2O and then were added saturated
aq. NaHCO3 and saturated aq. Na2S2O3 with vigorous stirring.
The mixture was extracted with Et2O. The extract was then
washed with water and brine, dried (MgSO4), and concentrated
under reduced pressure. The residue was chromatographed on
(1S,2R,5S)-2-[(2ЈR,5ЈS)-5Ј-(4-Methoxybenzyloxy)tetrahydro-
pyran-2Ј-yl]-1-(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)-
cyclopentane 15aЈ
In the same manner as described above, 13c (641 mg, 1.85
mmol) was converted to 15aЈ (832 mg, 98%) as a colourless oil,
25
nD 1.5041 (Found: C, 70.23; H, 9.74. C27H44O4Si requires C,
70.39; H, 9.63%); [α]D24 ϩ28.9 (c 1.04 in CHCl3); νmax(film)/cmϪ1
1650w (C᎐C), 1620m (Ar), 1595w (Ar), 1525s (Ar), 1260s
᎐
24
(Si–CH3); δH(500 MHz; CDCl3) 0.00, 0.02 (6H, each s, SiMe2),
0.85 (9H, s, SiBut), 1.29–1.49 (4H, m, 3-Ha, 4-Ha, 3-Hax and
4Ј-Hax), 1.67–1.81 (3H, m, 3-Hb, 4-Hb and 3Ј-Heq), 1.70 (3H, s,
SiO2 to give 16 (118 mg, 94%) as a colourless oil, nD 1.4785
(Found: C, 67.25; H, 10.09. C19H34O3Si requires C, 67.40; H,
10.12%); [α]D29 ϩ19.5 (c 1.03 in CHCl3); νmax(film)/cmϪ1 1725s
(C᎐O), 1645w (C᎐C), 1255m (Si–CH ); δ (500 MHz; CDCl )
CH ᎐C–CH ), 1.97 (1H, m, 2-H), 2.17–2.23 (1H, m, 4Ј-H ),
᎐
2
3
eq
᎐
᎐
3
H
3
Ϫ0.01, 0.03 (6H, each s, SiMe2), 0.82 (9H, s, SiBut), 1.09–1.20
2.44 (1H, dt like, J 8.3 and 6.4, 5-H), 3.13 (1H, dd, J 10.7 and
10.4, 6Ј-Hax), 3.18 (1H, ddd, J 10.7, 6.7 and 1.8, 2Ј-H), 3.45 (1H,
m, 5Ј-H), 3.80 (3H, s, OMe), 3.94 (1H, dd, J 6.4 and 6.1, 1-H),
4.07 (1H, ddd, J 10.7, 4.7 and 2.3, 6Ј-Heq), 4.47 (1H, d, J 11.4,
Ar-CHH), 4.52 (1H, d, J 11.4, Ar-CHH), 4.74 (1H, br s,
CHH᎐C–CH ), 4.75 (1H, br s, CHH᎐C–CH ), 6.85–6.89 (2H,
(1H, m, 3Ј-H ), 1.58–1.68 (1H, m, 4Ј-H ), 1.76 (3H, s, CH ᎐
᎐
2
a
a
C–CH3), 1.76–1.86 (1H, m, 3-Hax), 1.86–1.98 (2H, m, 3Ј-Hb and
4Ј-Hb), 1.98–2.06 (1H, m, 2Ј-H), 2.06–2.13 (1H, m, 3-Heq), 2.18
(1H, ddd, J 10.9, 5.8 and 4.9, 5Ј-H), 2.41 (1H, ddd, J 16.8, 11.3
and 6.8, 4-Ha), 2.58 (1H, dddd, J 16.8, 4.0, 4.0 and 1.5, 4-Hb),
3.32 (1H, ddd, J 12.2, 9.8 and 3.0, 2-H), 3.93 (1H, d, J 16.4,
6-Ha), 4.14 (1H, dd, J 16.4 and 1.5, 6-Hb), 4.26 (1H, d, J 4.9,
᎐
᎐
3
3
d like, J 8.9, m-aromatic-H), 7.23–7.27 (2H, d like, J 8.9,
o-aromatic-H); δC(126 MHz; CDCl3) Ϫ4.4, Ϫ4.1, 18.1, 20.3,
25.0, 26.0, 27.3, 28.5, 30.2, 52.3, 55.3, 56.3, 70.4, 70.8, 73.0,
78.7, 79.2, 111.1, 113.8, 129.2, 130.7, 146.2, 159.2.
1Ј-H), 4.71 (1H, s, CHH᎐C–CH ), 4.79 (1H, br s, CHH᎐
᎐
᎐
3
C–CH3); δC(126 MHz; CDCl3) Ϫ5.1, Ϫ4.2, 18.0, 23.1, 25.8,
26.5, 27.0, 28.2, 37.0, 52.2, 53.5, 74.1, 75.9, 78.4, 111.1, 144.0,
208.6.
(2R,5S)-2-[(1ЈS,2ЈR,5ЈR)-1Ј-(tert-Butyldimethylsilyloxy)-5Ј-
(1-methylethenyl)-2Ј-cyclopentyl]tetrahydropyran-5-ol 15b
(R)-2-[(1ЈS,2ЈR,5ЈS)-1Ј-(tert-Butyldimethylsilyloxy)-5Ј-
(1-methylethenyl)-2Ј-cyclopentyl]tetrahydropyran-5-one 16Ј
To a stirred mixture of 15a (195 mg, 0.423 mmol) in CH2Cl2
(7.0 cm3) and water (0.7 cm3) was added DDQ (144 mg, 0.635
mmol) at 0 ЊC. After having been stirred at room temperature
for 2 h, the mixture was quenched with saturated aq. NaHCO3
and extracted with CH2Cl2. The extract was washed with water
and brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was chromatographed on SiO2 to give 15b
(140 mg, 97%) as a colourless oil, nD24 1.4812 (Found: C, 66.83;
H, 10.50. C19H36O3Si requires C, 67.01; H, 10.65%); [α]D29 Ϫ0.57
In the same manner as described above, 15bЈ (222 mg, 0.652
mmol) was converted to 16Ј (211 mg, 95%) as a colourless oil,
nD23 1.4780 (Found: C, 67.21; H, 10.07. C19H34O3Si requires C,
67.40; H, 10.12%); [α]D24 ϩ46.5 (c 1.02 in CHCl3); νmax(film)/cmϪ1
1725s (C᎐O), 1645w (C᎐C), 1250m (Si–CH ); δ (500 MHz;
᎐
᎐
3
H
CDCl3) 0.01, 0.02 (6H, each s, SiMe2), 0.85 (9H, s, SiBut), 1.39–
1.48 (1H, m, 3Ј-Ha), 1.48–1.57 (1H, m, 4Ј-Ha), 1.72 (3H, s,
(c 1.03 in CHCl3); νmax(film)/cmϪ1 3350s (OH), 1650m (C᎐C),
CH ᎐C–CH ), 1.79–1.94 (3H, m, 3-H , 3Ј-H and 4Ј-H ), 2.02–
᎐
᎐
2
3
ax
b
b
1255s (Si–CH3); δH(500 MHz; CDCl3) 0.00, 0.03 (6H, each s,
SiMe2), 0.82 (9H, s, SiBut), 1.06–1.16 (1H, m, 3Ј-Ha), 1.24–1.41
(2H, m, 3-Hax and 4-Hax), 1.52 (1H, br s, OH), 1.56–1.63 (1H,
2.12 (2H, m, 3-Heq and 2Ј-H), 2.38–2.50 (2H, m, 4-Ha and
5Ј-H), 2.60 (1H, dt like, J 16.8 and 4.3, 4-Hb), 3.55 (1H, ddd,
J 10.4, 7.3 and 3.1, 2-H), 3.91 (1H, d, J 16.5, 6-Hax), 4.07 (1H,
dd, J 5.8 and 5.5, 1Ј-H), 4.14 (1H, dd, J 16.5 and 1.7, 6-Heq),
m, 4Ј-H ), 1.72–1.78 (1H, m, 3-H ), 1.75 (3H, s, CH ᎐C–CH ),
᎐
a
eq
2
3
1014
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017

View Article Online
4.74–4.78 (2H, m, CH ᎐C–CH ); δ (126 MHz; CDCl ) Ϫ4.5,
Ϫ4.1, 18.0, 20.6, 25.6, 25.9, 27.6, 28.6, 37.1, 52.5, 56.4, 74.2,
77.6, 78.6, 111.0, 146.0, 208.6.
and 5Љ-H), 3.36 (1H, ddd, J 10.4, 7.3 and 3.1, 2Ј-H), 3.69 (3H,
s, CO2Me), 3.97–4.05 (2H, m, 6Ј-Ha and 1Љ-H), 4.74 (1H, m,
CHH᎐C–CH ), 4.76 (1H, br s, CHH᎐C–CH ), 5.46 (1H, d,
᎐
2
3
C
3
᎐
᎐
3
3
J 15.0, 6Ј-Hb), 5.66 (1H, s, 2-H); (E)-18aЈ: δH(500 MHz; CDCl3)
Methyl (Z)-2-{(R)-2Ј-[(1ЉS,2ЉR,5ЉR)-1Љ-(tert-butyldimethyl-
silyloxy)-5Љ-(1-methylethenyl)-2Љ-cyclopentyl]tetrahydropyran-
5Ј-ylidene}acetate 18a
0.01, 0.02 (6H, each s, SiMe2), 0.85 (9H, s, SiBut), 1.38–1.63
(3H, m, 3Ј-H , 3Љ-H and 4Љ-H ), 1.71 (3H, s, CH ᎐C–CH ),
᎐
ax
a
a
2
3
1.75–1.85 (3H, m, 3Ј-Heq, 3Љ-Hb and 4Љ-Hb), 2.01 (1H, m, 2Љ-H),
2.17 (1H, m, 4Ј-Ha), 2.41–2.50 (1H, m, 5Љ-H), 3.43 (1H, ddd,
J 11.0, 7.1 and 2.2, 2Ј-H), 3.70 (3H, s, CO2Me), 3.82 (1H, m,
4Ј-Hb), 3.97–4.05 (2H, m, 6Ј-Ha and 1Љ-H), 4.14 (1H, dd, J 13.1
To a stirred solution of (S)-17 (dried azeotropically with tolu-
ene; 136 mg, 0.337 mmol) in dry THF (2.0 cm3) was added
NaHMDS (1.0 mol dmϪ3 in THF; 310 mm3, 0.31 mmol) at
Ϫ78 ЊC under Ar. After the resulting solution was stirred at
Ϫ78 ЊC for 40 min, a solution of 16 (19 mg, 56 µmol) in dry
THF (1.0 cm3) was added dropwise. After having been stirred
at Ϫ20 ЊC for 24 h, the resulting solution was quenched with
saturated aq. NH4Cl and extracted with EtOAc. The extract
was washed with water and brine, dried (MgSO4), and concen-
trated under reduced pressure. The residue was chromato-
graphed on SiO2 to give 18a (20 mg, 91%, E : Z = ca. 1 : 5 as
and 1.8, 6Ј-H ), 4.74 (1H, m, CHH᎐C–CH ), 4.76 (1H, br s,
᎐
b
3
CHH᎐C–CH ), 5.68 (1H, s, 2-H); (Z)- and (E)-18aЈ: δ (126
᎐
3
C
MHz; CDCl3) Ϫ4.4, Ϫ4.2, Ϫ4.1, 18.0, 20.46, 20.51, 25.15,
25.19, 25.9, 26.5, 28.5, 28.6, 29.2, 29.3, 32.6, 51.08, 51.11, 52.6,
52.7, 56.40, 56.44, 67.1, 73.0, 78.2, 78.50, 78.54, 79.5, 110.97,
111.01, 113.97, 114.02, 146.13, 146.14, 156.0, 157.3, 166.3,
166.8.
(Z)-2-{(R)-2Ј-[(1ЉS,2ЉR,5ЉR)-1Љ-(tert-Butyldimethylsilyloxy)-5Љ-
(1-methylethenyl)-2Љ-cyclopentyl]tetrahydropyran-5Ј-ylidene}-
ethanol 18b
determined by 1H-NMR analysis) as a colourless oil, nD
24
1.4889 (Found: C, 67.07; H, 9.69. C22H38O4Si requires C, 66.96;
H, 9.71%); [α]D28 ϩ18.8 (c 1.00 in CHCl3); νmax(film)/cmϪ1 1720s
(C᎐O), 1660m (C᎐C), 1650m (C᎐C), 1255m (Si–CH ); (Z)-18a:
To a stirred solution of 18a (E : Z = ca. 1 : 5; 182 mg, 0.461
mmol) in CH2Cl2 (3.5 cm3) was added DIBAL-H (1.01 mol
dmϪ3 in toluene; 1.37 cm3, 1.38 mmol) dropwise at Ϫ78 ЊC
under Ar. After having been warmed to 0 ЊC with stirring for
3 h, the resulting solution was quenched with MeOH at 0 ЊC
and warmed to room temperature with vigorous stirring. The
mixture was filtered through Celite and the Celite was washed
with Et2O. The filtrate and the washings were concentrated
under reduced pressure, and the residue was chromatographed
on spherical SiO2 [Silica Gel 60 N (spherical, neutral), 40–50
µm, Kanto Chemical Co., Inc.] to give the desired 18b (131 mg,
78%) as a colourless solid and its (E)-isomer (25 mg, 15%) as
a colourless oil. An analytical sample of 18b was obtained by
recrystallization from hexane as colourless needles, mp 70.0–
72.0 ЊC (Found: C, 68.55; H, 10.63. C21H38O3Si requires C,
68.80; H, 10.45%); [α]D23 ϩ8.14 (c 1.00 in CHCl3); νmax(KBr)/cmϪ1
᎐
᎐
᎐
3
δH(400 MHz; CDCl3) 0.00, 0.03 (6H, each s, SiMe2), 0.82 (9H,
s, SiBut), 1.06–1.18 (1H, m, 3Љ-Ha), 1.48 (1H, m, 3Ј-Hax), 1.55–
1.65 (1H, m, 4Љ-H ), 1.76 (3H, s, CH ᎐C–CH ), 1.80–1.99 (4H,
᎐
a
2
3
m, 3Ј-Heq, 2Љ-H, 3Љ-Hb and 4Љ-Hb), 2.16 (1H, ddd, J 10.6, 5.6
and 4.9, 5Љ-H), 2.30–2.41 (1H, m, 4Ј-Ha), 2.46 (1H, dt like,
J 14.4 and 4.4, 4Ј-Hb), 3.11 (1H, ddd, J 10.9, 8.6 and 2.8, 2Ј-H),
3.69 (3H, s, CO2Me), 4.01 (1H, br d, J 15.1, 6Ј-Ha), 4.23 (1H,
d, J 4.9, 1Љ-H), 4.69 (1H, s, CHH᎐C–CH ), 4.78 (1H, br s,
᎐
3
CHH᎐C–CH ), 5.46 (1H, d, J 15.1, 6Ј-H ), 5.66 (1H, s, 2-H);
᎐
3
b
δC(100 MHz; CDCl3) Ϫ5.1, Ϫ4.1, 18.1, 23.1, 25.8, 26.1, 26.9,
30.1, 32.6, 51.1, 52.2, 53.7, 66.9, 75.9, 79.2, 110.9, 114.0, 144.4,
157.4, 166.3; (E)-18a: δH(500 MHz; CDCl3) Ϫ0.01, 0.02 (6H,
each s, SiMe2), 0.82 (9H, s, SiBut), 1.08–1.19 (1H, m, 3Љ-Ha),
1.40 (1H, m, 3Ј-Hax), 1.57–1.64 (1H, m, 4Љ-Ha), 1.75 (3H, s,
CH ᎐C–CH ), 1.82–1.96 (4H, m, 3Ј-H , 2Љ-H, 3Љ-H and
᎐
2
3
eq
b
4Љ-Hb), 2.12–2.21 (2H, m, 4Ј-Ha and 5Љ-H), 3.17 (1H, ddd,
J 10.6, 8.9 and 1.7, 2Ј-H), 3.70 (3H, s, CO2Me), 3.81 (1H, br d,
J 14.9, 4Ј-Hb), 4.02 (1H, d, J 13.1, 6Ј-Ha), 4.15 (1H, dd, J 13.1
3280m (OH), 1650m (C᎐C), 1250s (Si–CH ); δ (500 MHz;
᎐
3 H
CDCl3) 0.00, 0.03 (6H, each s, SiMe2), 0.82 (9H, s, SiBut), 1.09–
1.20 (1H, m, 3Љ-Ha), 1.37 (1H, m, 3Ј-Hax), 1.60 (1H, m, 4Љ-Ha),
1.67 (1H, br s, OH), 1.73–1.81 (1H, m, 3Ј-Heq), 1.75 (3H, s,
and 1.2, 6Ј-H ), 4.22 (1H, d, J 4.3, 1Љ-H), 4.70 (1H, s, CHH᎐
᎐
b
C–CH ), 4.78 (1H, s, CHH᎐C–CH ), 5.68 (1H, s, 2-H); δ (100
CH ᎐C–CH ), 1.82–1.96 (3H, m, 2Љ-H, 3Љ-H and 4Љ-H ), 2.16
᎐
2 3 b b
᎐
3
3
C
MHz; CDCl3) Ϫ5.1, Ϫ4.1, 18.1, 23.1, 25.8, 26.3, 26.6, 27.0,
30.2, 51.1, 52.2, 53.7, 72.9, 75.8, 80.4, 110.9, 113.9, 144.4, 156.1,
166.8.
(1H, ddd, J 10.8, 5.8 and 5.2, 5Љ-H), 2.22–2.30 (1H, m, 4Ј-Ha),
2.32–2.38 (1H, m, 4Ј-Hb), 3.09 (1H, ddd, J 10.4, 8.6 and 1.9,
2Ј-H), 3.75 (1H, d, J 13.1, 6Ј-Ha), 4.07 (1H, ddd, J 12.4, 6.4 and
1.5, 1-Ha), 4.21 (1H, br d, J 5.8, 1Љ-H), 4.22 (1H, dd, J 12.4 and
Methyl (Z)-2-{(R)-2Ј-[(1ЉS,2ЉR,5ЉS)-1Љ-(tert-butyldimethyl-
silyloxy)-5Љ-(1-methylethenyl)-2Љ-cyclopentyl]tetrahydropyran-
5Ј-ylidene)}acetate 18aЈ
7.9, 1-H ), 4.60 (1H, br d, J 13.1, 6Ј-H ), 4.69 (1H, s, CHH᎐
᎐
b b
C–CH ), 4.77 (1H, br s, CHH᎐C–CH ), 5.44 (1H, dd, J 7.9 and
᎐
3
3
6.4, 2-H); δC(126 MHz; CDCl3) Ϫ5.0, Ϫ4.1, 18.0, 23.1, 25.8,
26.1, 26.9, 31.2, 33.0, 52.2, 53.7, 58.1, 66.2, 75.9, 80.4, 110.9,
122.6, 138.0, 144.5; (E)-isomer: δH(500 MHz; CDCl3) 0.00, 0.03
(6H, each s, SiMe2), 0.82 (9H, s, SiBut), 1.08–1.19 (1H, m, 3Љ-
Ha), 1.30 (1H, m, 3Ј-Hax), 1.56–1.64 (1H, m, 4Љ-Ha), 1.74–1.82
To a stirred mixture of (CF CH O) P(᎐O)CH CO Me (103 mg,
᎐
3
2
2
2
2
0.324 mmol) and 18-crown-6 (recrystallized MeCN complex;19
243 mg, 0.796 mmol) in dry toluene (4.0 cm3) was added
KHMDS (0.5 mol dmϪ3 in toluene; 0.64 cm3, 0.32 mmol) at
Ϫ78 ЊC under Ar. After the resulting mixture was stirred at
Ϫ78 ЊC for 30 min, a solution of 16Ј (54 mg, 0.16 mmol) in dry
toluene (2.0 cm3) was added dropwise. After having been stirred
at Ϫ40 ЊC for 20 h, the resulting solution was quenched with
saturated aq. NH4Cl and extracted with EtOAc. The extract
was washed with water and brine, dried (MgSO4), and concen-
trated under reduced pressure. The residue was chromato-
graphed on SiO2 to give 18aЈ (57 mg, 91%, E : Z = ca. 4 : 6 as
(1H, m, 3Ј-H ), 1.75 (3H, s, CH ᎐C–CH ), 1.82–1.96 (3H, m,
᎐
eq
2
3
2Љ-H, 3Љ-Hb and 4Љ-Hb), 2.01 (1H, dd like, J 14.3 and 14.3,
4Ј-Ha), 2.16 (1H, ddd, J 10.7, 5.8 and 4.9, 5Љ-H), 2.72 (1H, ddd
like, J 14.3, 2.1 and 1.9, 4Ј-Hb), 3.10 (1H, ddd, J 10.5, 8.7 and
2.0, 2Ј-H), 3.94 (1H, d, J 12.5, 6Ј-Ha), 4.12 (1H, dd, J 12.5 and
1.9, 6Ј-Hb), 4.15 (1H, dd, J 12.2 and 6.7, 1-Ha), 4.22 (1H, br d,
J 4.9, 1Љ-H), 4.22 (1H, dd, J 12.2 and 7.0, 1-Hb), 4.69 (1H, s,
CHH᎐C–CH ), 4.77 (1H, br s, CHH᎐C–CH ), 5.49 (1H, dd,
᎐
᎐
3
3
J 7.0 and 6.7, 2-H); δC(126 MHz; CDCl3) Ϫ5.1, Ϫ4.1, 18.1,
23.1, 25.7, 25.8, 26.3, 27.0, 30.6, 52.2, 53.8, 58.3, 73.5, 75.9,
80.5, 110.9, 122.3, 138.2, 144.6.
determined by 1H-NMR analysis) as a colourless oil, nD
23
1.4878 (Found: C, 66.99; H, 9.86. C22H38O4Si requires C, 66.96;
H, 9.71%); [α]D28 ϩ44.8 (c 1.03 in CHCl3); νmax(film)/cmϪ1 1720s
(C᎐O), 1660m (C᎐C), 1255m (Si–CH ); (Z)-18aЈ: δ (500 MHz;
᎐
᎐
3
H
(Z)-2-{(R)-2Ј-[(1ЉS,2ЉR,5ЉS)-1Љ-(tert-Butyldimethylsilyloxy)-5Љ-
(1-methylethenyl)-2Љ-cyclopentyl]tetrahydropyran-5Ј-ylidene}-
ethanol 18bЈ
CDCl3) 0.00, 0.03 (6H, each s, SiMe2), 0.85 (9H, s, SiBut),
1.38–1.63 (3H, m, 3Ј-Hax, 3Љ-Ha and 4Љ-Ha), 1.71 (3H, s,
CH ᎐C–CH ), 1.75–1.85 (3H, m, 3Ј-H , 3Љ-H and 4Љ-H ), 2.01
᎐
2
3
eq
b
b
(1H, m, 2Љ-H), 2.37 (1H, m, 4Ј-Ha), 2.41–2.50 (2H, m, 4Ј-Hb
In the same manner as described above, 18aЈ (E : Z = ca. 4 : 6;
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
1015

View Article Online
54 mg, 0.14 mmol) was converted to the desired 18bЈ (27 mg,
54%) as a colourless oil and its (E)-isomer (20 mg, 40%) as
(c 1.01 in CHCl3); νmax(film)/cmϪ1 1650w (C᎐C), 1585w (Ar),
1445m (Ar), 1310s (SO2), 1250s (Si–CH3), 1150s (SO2); δH(500
᎐
20
a colourless oil. 18bЈ: a colourless oil, nD 1.4949 (Found: C,
MHz; CDCl3) Ϫ0.03, Ϫ0.02 (6H, each s, SiMe2), 0.81 (9H, s,
68.52; H, 10.37. C21H38O3Si requires C, 68.80; H, 10.45%); [α]D23
ϩ40.9 (c 1.04 in CHCl3); νmax(film)/cmϪ1 3370m (OH), 1645m
SiBut), 1.03–1.14 (1H, m, 3-Ha), 1.26 (1H, m, 3Ј-Hax), 1.57 (1H,
m, 4-H ), 1.69–1.77 (1H, m, 3Ј-H ), 1.73 (3H, s, CH ᎐C–CH ),
᎐
a
eq
2
3
(C᎐C), 1250s (Si–CH ); δ (400 MHz; CDCl ) 0.00, 0.02 (6H,
1.78–1.90 (3H, m, 2-H, 3-Hb and 4-Hb), 2.11 (1H, ddd, J 10.7,
5.4 and 4.6, 5-H), 2.18–2.27 (1H, m, 4Ј-Ha), 2.34–2.41 (1H,
m, 4Ј-Hb), 2.98 (1H, dd like, J 8.6 and 8.6, 2Ј-H), 3.36 (1H, d,
J 13.4, 6Ј-Ha), 3.76 (1H, dd, J 14.3 and 7.0, 2Љ-Ha), 3.86 (1H, dd,
J 14.3 and 9.2, 1Љ-Hb), 4.13 (1H, d, J 4.6, 1-H), 4.19 (1H, d,
᎐
3
H
3
each s, SiMe2), 0.85 (9H, s, SiBut), 1.37–1.52 (3H, m, 3Ј-Hax,
3Љ-Ha and 4Љ-Ha), 1.62–1.83 (3H, m, 3Ј-Heq, 3Љ-Hb and 4Љ-Hb),
1.67 (1H, br s, OH), 1.70 (3H, s, CH ᎐C–CH ), 2.00 (1H, m, 2Љ-
᎐
2
3
H), 2.21–2.32 (1H, m, 4Ј-Ha), 2.33–2.40 (1H, m, 4Ј-Hb), 2.44
(1H, dt like, J 8.0 and 6.4, 5Љ-H), 3.37 (1H, ddd, J 11.0, 6.6 and
1.9, 2Ј-H), 3.75 (1H, d, J 13.0, 6Ј-Ha), 3.95 (1H, dd, J 6.4 and
6.4, 1Љ-H), 4.06 (1H, ddd, J 12.4, 6.3 and 1.4, 1-Ha), 4.21 (1H,
dd, J 12.4 and 7.6, 1-Hb), 4.60 (1H, dd, J 13.0 and 1.4, 6Ј-Hb),
J 13.4, 6Ј-H ), 4.68 (1H, s, CHH᎐C–CH ), 4.77 (1H, s,
᎐
b
3
CHH᎐C–CH ), 5.24 (1H, dd, J 9.2 and 7.0, 1Љ-H), 7.56 (2H, dd,
᎐
3
J 8.0 and 7.4, m-aromatic-H), 7.66 (1H, ddd, J 7.4, 7.4 and 1.2,
p-aromatic-H), 7.85 (2H, dd, J 8.0 and 1.2, o-aromatic-H);
δC(126 MHz; CDCl3) Ϫ5.0, Ϫ4.1, 18.0, 23.1, 25.8, 26.1, 26.9,
31.0, 33.1, 52.1, 53.6, 55.1, 65.8, 75.8, 80.2, 109.1, 111.0, 129.1,
133.7, 138.5, 144.4, 145.0.
4.74 (1H, d, J 1.4, CHH᎐C–CH ), 4.75 (1H, s, CHH᎐C–CH ),
᎐
᎐
3
3
5.45 (1H, dd, J 7.6 and 6.3, 2-H); δC(100 MHz; CDCl3) Ϫ4.3,
Ϫ4.1, 18.0, 20.4, 24.8, 25.9, 28.5, 30.0, 33.0, 52.5, 56.3, 58.1,
66.3, 78.5, 79.4, 111.1, 122.7, 138.0, 146.1; (E)-isomer: δH(400
MHz; CDCl3) 0.00, 0.02 (6H, each s, SiMe2), 0.85 (9H, s,
SiBut), 1.32–1.51 (3H, m, 3Ј-Hax, 3Љ-Ha and 4Љ-Ha), 1.66–1.83
(1S,1ЈS,2R,2ЈR,5R,5ЈR)-2,2Ј-{5,5Ј-[(RS)-2-Phenylsulfonyl-
butane-1,4-diylidene]bis[(2R,5Z)-tetrahydropyran-2-yl]}bis[1-
(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)cyclopentane]
20a
(3H, m, 3Ј-H , 3Љ-H and 4Љ-H ), 1.70 (3H, s, CH ᎐C–CH ),
᎐
eq
b
b
2
3
1.95–2.08 (2H, m, 4Ј-Ha and 2Љ-H), 2.44 (1H, dt like, J 7.6 and
6.3, 5Љ-H), 2.74 (1H, ddd like, J 14.2, 2.2 and 1.7, 4Ј-Hb), 3.38
(1H, ddd, J 11.0, 6.8 and 1.7, 2Ј-H), 3.95 (1H, d, J 12.4, 6Ј-Ha),
3.97 (1H, dd, J 6.3 and 6.3, 1Љ-H), 4.12 (1H, dd, J 12.4 and 1.7,
6Ј-Hb), 4.14 (1H, dd, J 12.4 and 6.8, 1-Ha), 4.22 (1H, dd, J 12.4
To a stirred solution of 19b (22 mg, 45 µmol) and 18-crown-6
(recrystallized MeCN complex;19 68 mg, 0.22 mmol) in dry
THF (2.0 cm3) was added KHMDS (0.5 mol dmϪ3 in toluene;
90 mm3, 45 µmol) at Ϫ78 ЊC under Ar. After the reaction mix-
ture had been stirred at Ϫ78 ЊC for 30 min to give a yellow
solution, a solution of 19a (crude; 12 mg, 28 µmol) in dry THF
(0.6 cm3) was added dropwise. After having been stirred at
Ϫ78 ЊC for 20 min, the resulting solution was quenched with
saturated aq. NH4Cl and extracted with Et2O. The extract was
washed with water and brine, dried (MgSO4), and concentrated
under reduced pressure. The residue was chromatographed on
SiO2 to give recovered 19b (8 mg, 36%) and 20a (20 mg, 84%
based on consumed 19b, 85% based on 19a) as a colourless oil.
It was found to be contaminated with ca. 20% of inseparable
impurities (checked by 1H-NMR analysis).
and 7.1, 1-H ), 4.74 (1H, d, J 1.4, CHH᎐C–CH ), 4.76 (1H, s,
᎐
b
3
CHH᎐C–CH ), 5.49 (1H, dd, J 7.1 and 6.8, 2-H); δ (100 MHz;
᎐
3
C
CDCl3) Ϫ4.3, Ϫ4.1, 18.0, 20.5, 25.1, 25.7, 26.0, 28.6, 29.5, 52.7,
56.4, 58.3, 73.6, 78.6, 79.5, 110.9, 122.5, 138.2, 146.3.
(1S,2R,5R)-2-[(2ЈR,5ЈZ)-5Ј-(2Љ-Bromoethylidene)-tetrahydro-
pyran-2Ј-yl]-1-(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)-
cyclopentane 19a
To a stirred solution of 18b (101 mg, 0.275 mmol) in DMF (6.0
cm3) were added LiBr (103 mg, 1.18 mmol), s-collidine (2,4,6-tri-
methylpyridine) (145 mm3, 1.10 mmol) and DMAP (ca. 3 mg)
at 0 ЊC under Ar. The mixture was stirred at 0 ЊC for 10 min and
then treated with Ms2O (recrystallized from dry Et2O; 192 mg,
1.10 mmol). After having been stirred at 4 ЊC for 24 h, saturated
aq. NaHCO3 was added to the mixture, then it was diluted
with water, and extracted with Et2O. The extract was washed
with water and brine, dried (MgSO4), and concentrated under
reduced pressure. The residue was chromatographed on SiO2 to
give recovered 18b (18 mg, 18%) and unstable 19a (90 mg, 93%
based on consumed 18b) as a pale yellow oil. This oil was
employed immediately for the next steps.
(1S,1ЈS,2R,2ЈR,5R,5ЈS)-2,2Ј-{5,5Ј-[(RS)-2-Phenylsulfonyl-
butane-1,4-diylidene]bis[(2R,5Z)-tetrahydropyran-2-yl]}bis[1-
(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)cyclopentane]
20aЈ
In the same manner as described above, 19b (32 mg, 65 µmol)
and 19aЈ (crude; 12 mg, 28 µmol) were converted to 20aЈ (21
mg, 78% based on consumed 19b, 90% based on 19aЈ) as a
colourless oil and 19b (16 mg, 50%) was recovered. It was found
to be contaminated with ca. 20% of inseparable impurities
(checked by 1H-NMR analysis).
(1S,2R,5S)-2-[(2ЈR,5ЈZ)-5Ј-(2Љ-Bromoethylidene)-tetrahydro-
pyran-2Ј-yl]-1-(tert-butyldimethylsilyloxy)-5-(1-methylethenyl)-
cyclopentane 19aЈ
(1S,1ЈS,2R,2ЈR,5R,5ЈR)-2,2Ј-{5,5Ј-[Butane-1,4-diylidene]bis-
[(2R,5Z)-tetrahydropyran-2-yl]}bis[1-(tert-butyldimethylsilyl-
oxy)-5-(1-methylethenyl)cyclopentane] 20b
In the same manner as described above, 18bЈ (27 mg, 74 µmol)
was converted to unstable 19aЈ (12 mg, 64% based on consumed
18bЈ) as a pale yellow oil and 18bЈ (11 mg, 41%) was recovered.
This oil was employed immediately for the next steps.
To a mixture of 20a (20 mg, 24 µmol) and Na2HPO4 (34 mg,
0.24 mmol) in dry MeOH (2.0 cm3) was added 5% Na–Hg
(ca. 200 mg, excess) with vigorous stirring at 0 ЊC under Ar.
After having been stirred at room temperature for 26 h, the
resulting mixture was diluted with Et2O and then filtered
through Celite, and the Celite was washed with Et2O. After the
filtrate and the washings had been concentrated under reduced
pressure, the residue was chromatographed on SiO2 to give
recovered 20a (7 mg, 35%) and 20b (12 mg, quant. based on
consumed 20a) as a colourless oil. It was found to be con-
taminated with ca. 30% of inseparable impurities (checked
(1S,2R,5R)-2-[(2ЈR,5ЈZ)-5Ј-(2Љ-Phenylsulfonylethylidene)-tetra-
hydropyran-2Ј-yl]-1-(tert-butyldimethylsilyloxy)-5-(1-methyl-
ethenyl)cyclopentane 19b
To a solution of 19a (90 mg, 0.21 mmol) in DMF (2 cm3) was
added PhSO2Naؒ2H2O (84 mg, 0.42 mmol) at room temper-
ature. After the reaction mixture had been stirred at room tem-
perature for 16 h, water was added to the reaction mixture, and
it was extracted with Et2O. The extract was washed with water
and brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was chromatographed on SiO2 to give 19b
(89 mg, 87%) as a colourless oil, nD23 1.5174 (Found: C, 66.18;
H, 8.51. C27H42O4SSi requires C, 66.08; H, 8.63%); [α]D26 ϩ68.6
1
by H-NMR analysis). This oil was used in the next reaction
without further purification. 20b: δH(400 MHz; CDCl3) 0.01,
0.04 (12H, each s, 2 × SiMe2), 0.82 (18H, s, 2 × SiBut),
1.03–1.39 (4H, m, 5/5Ј-Hax and 8/8Ј-Ha), 1.51–1.79 (4H, m,
5/5Ј-Heq and 9/9Ј-Ha), 1.76 (6H, br s, 12/12Ј-H3), 1.79–1.97 (6H,
1016
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017

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m, 7/7Ј-H, 8/8Ј-Hb and 9/9Ј-Hb), 1.97–2.36 (10H, m, 1/1Ј-H2,
4/4Ј-H2 and 10/10Ј-H), 3.00–3.10 (2H, m, 6/6Ј-H), 3.69 (2H, d,
J 12.7, 15/15Ј-Ha), 4.22 (2H, br d, J 4.6, 14/14Ј-H), 4.54 (2H,
d, J 12.7, 15/15Ј-Hb), 4.69 (2H, s, 13/13Ј-Ha), 4.77 (2H, s, 13/
13Ј-Hb), 5.15 (2H, br t, J 6.3, 2/2Ј-H). The 1H-NMR spectrum
of this compound was assigned according to the numbering
system as illustrated in Fig. 1.
as a colourless oil, [α]D25 ϩ19 (c 0.16 in CHCl3); νmax(CHCl3)/cmϪ1
3525w (OH), 1645w (C᎐C), 1075s (C–O); δ (500 MHz; CDCl )
᎐
H
3
1.15–1.28 (2H, m, 8/8Ј-Ha), 1.39 (1H, m, 5Ј-Hax), 1.41 (1H, m,
5-Hax), 1.50 (1H, m, 9Ј-Ha), 1.65–1.92 (8H, m, 5/5Ј-Heq, 7Ј-H,
8/8Ј-Hb, 9-Ha and 9/9Ј-Hb), 1.75 (3H, s, 12Ј-H3), 1.83 (3H, s,
12-H3), 1.91–2.03 (3H, m, 1/1Ј-Ha and 7-H), 2.03–2.13 (2H, m,
1/1Ј-Hb), 2.17–2.33 (4H, m, 4/4Ј-H2), 2.40 (1H, ddd, J 11.5, 5.8
and 5.5, 10-H), 2.47 (1H, dt, J 9.5 and 9.5, 10Ј-H), 3.18 (1H,
ddd, J 10.4, 8.5 and 1.9, 6-H), 3.35 (1H, ddd, J 11.0, 9.2 and 1.9,
6Ј-H), 3.72 (1H, d, J 12.5, 15-Ha), 3.76 (1H, d, J 12.5, 15Ј-Ha),
3.85 (1H, dd, J 9.5 and 8.8, 14Ј-H), 4.15–4.20 (1H, m, 14-H),
4.59 (2H, br d, J 12.5, 15/15Ј-Hb), 4.80 (1H, br s, 13Ј-Ha), 4.82
(1H, s, 13-Ha), 4.87 (1H, br s, 13Ј-Hb), 4.97 (1H, s, 13-Hb), 5.17
(1H, m, 2-H), 5.18 (1H, m, 2Ј-H); δC(126 MHz; CDCl3) 20.2,
23.3, 23.7, 26.6, 26.7, 27.1, 27.2, 27.3, 32.0, 32.6, 32.7, 33.0,
50.9, 52.0, 53.06, 53.14, 66.62, 66.64, 74.8, 80.1, 80.7, 83.9,
110.4, 112.2, 123.3, 123.8, 133.8, 134.3, 144.4, 145.9; m/z (EI)
470 (15%)[Mϩ], 452 (21), 442 (2), 434 (7), 424 (3), 370 (6), 343
(11), 327 (14), 300 (11), 234 (39), 219 (18) [Found: (HREI-MS)
470.3409 [Mϩ]. C30H46O4 requires 470.3396]. The 1H-NMR
spectrum of this compound was assigned according to the
numbering system as illustrated in Fig. 1.
(1S,1ЈS,2R,2ЈR,5R,5ЈS)-2,2Ј-{5,5Ј-[Butane-1,4-diylidene]bis-
[(2R,5Z)-tetrahydropyran-2-yl]}bis[1-(tert-butyldimethylsilyl-
oxy)-5-(1-methylethenyl)cyclopentane] 20bЈ
In the same manner as described above, 20aЈ (21 mg, 25 µmol)
was converted to 20bЈ (inseparable mixtures; 12 mg, 91% based
on consumed 20aЈ) as a colourless oil and 20aЈ (5 mg, 24%) was
recovered. It was found to be contaminated with ca. 30% of
inseparable impurities (checked by 1H-NMR analysis). This oil
was used in the next reaction without further purification. 20bЈ
δH(500 MHz; CDCl3) 0.01, 0.04 (12H, each s, 2 × SiMe2), 0.82,
0.86 (18H, each s, 2 × SiBut), 1.03–1.51 (5H, m, 5/5Ј-Hax,
8/8Ј-Ha and 9Ј-Ha), 1.53–1.95 (8H, m, 5/5Ј-Heq, 7-H, 8/8Ј-Hb,
9-Ha and 9/9Ј-Hb), 1.71 (3H, s, 12Ј-H3), 1.76 (3H, br s, 12-H3),
1.95–2.37 (10H, m, 1/1Ј-H2, 4/4Ј-H2, 7Ј-H and 10-H), 2.45 (1H,
dt like, J 8.0 and 6.4, 10Ј-H), 3.00–3.09 (1H, m, 6-H), 3.31–3.39
(1H, m, 6Ј-H), 3.69 (1H, d, J 12.7, 15-Ha), 3.71 (1H, d, J 12.7,
15Ј-Ha), 3.97 (1H, dd, J 6.4 and 6.4, 14Ј-H), 4.22 (1H, br d,
J 4.6, 14-H), 4.54 (1H, d, J 12.7, 15-Hb), 4.55 (1H, d, J 12.7,
15Ј-Hb), 4.69 (1H, s, 13-Ha), 4.74 (1H, s, 13Ј-Ha), 4.77 (2H, s
like, 13/13Ј-Hb), 5.14 (1H, m, 2Ј-H), 5.15 (1H, m, 2-H). The
1H-NMR spectrum of this compound was assigned according
to the numbering system as illustrated in Fig. 1.
Acknowledgements
We thank Professor G. Cimino (Istituto per la Chimica di
Molecole di Interesse Biologico, Napoli, Italy) for sending
us the 1H-NMR spectrum of 1 prior to publication. We
acknowledge financial support by the Ministry of Education,
Science, Sports and Culture, Japan.
(1S,1ЈS,2S,2ЈS,5R,5ЈR)-2,2Ј-{5,5Ј-[Butane-1,4-diylidene]bis-
[(2R,5Z)-tetrahydropyran-2-yl]}bis[5-(1-methylethenyl)cyclo-
pentanol] (testudinariol A) 1
References
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To a stirred solution of 20b (inseparable mixture; 12 mg, 18
µmol) in dry THF (1.0 cm3) was added TBAF (1.0 mol dmϪ3
;
0.40 cm3, 0.40 mmol) at room temperature under Ar. After
having been stirred at room temperature for 20 h, the resulting
solution was quenched with water, and extracted with Et2O.
The extract was washed with brine, dried (MgSO4), and concen-
trated under reduced pressure. The residue was chromato-
graphed on spherical SiO2 [Silica Gel 60 N (spherical, neutral),
40–50 µm, Kanto Chemical Co., Inc.] to give 1 (3.4 mg, 2 steps,
47%) as a colourless oil, [α]D26 ϩ13 (c 0.17 in CHCl3);
νmax(CHCl3)/cmϪ1 3680w (OH), 1640w (C᎐C), 1075s (C–O);
᎐
δH(500 MHz; CDCl3) 1.15–1.28 (2H, m, 8/8Ј-Ha), 1.41 (2H, m,
5/5Ј-Hax), 1.65–1.92 (8H, m, 5/5Ј-Heq, 8/8Ј-Hb and 9/9Ј-H2), 1.83
(6H, s, 12/12Ј-H3), 1.91–2.03 (4H, m, 1/1Ј-Ha and 7/7Ј-H), 2.03–
2.13 (2H, m, 1/1Ј-Hb), 2.17–2.27 (2H, m, 4/4Ј-Ha), 2.27–2.33
(2H, m, 4/4Ј-Hb), 2.40 (2H, ddd, J 11.5, 5.8 and 5.5, 10/10Ј-H),
3.18 (2H, ddd, J 10.4, 8.5 and 1.9, 6/6Ј-H), 3.72 (2H, d, J 12.5,
15/15Ј-Ha), 4.15–4.20 (2H, m, 14/14Ј-H), 4.59 (2H, br d, J 12.5,
15/15Ј-Hb), 4.81 (2H, s, 13/13Ј-Ha), 4.97 (2H, s, 13/13Ј-Hb), 5.16
(2H, br t, J 5.8, 2/2Ј-H); δC(126 MHz; CDCl3) 23.3, 26.7, 27.1,
27.3, 32.0, 33.0, 52.0, 53.1, 66.7, 74.8, 80.7, 112.2, 123.4, 134.2,
144.4; m/z (EI) 470 (25%)[Mϩ], 452 (36), 442 (3), 434 (12), 424
(4), 370 (7), 343 (16), 327 (22), 300 (13), 234 (28), 219 (28)
[Found: (HREI-MS) 470.3400 [Mϩ]. C30H46O4 requires
470.3396]. The 1H-NMR spectrum of this compound was
assigned according to the numbering system as illustrated in
Fig. 1.
11 K. Mikami, T.-P. Loh and T. Nakai, J. Am. Chem. Soc., 1990, 112,
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(1S,1ЈS,2S,2ЈS,5R,5ЈS)-2,2Ј-{5,5Ј-[Butane-1,4-diylidene]bis-
[(2R,5Z)-tetrahydropyran-2-yl]}bis[5-(1-methylethenyl)cyclo-
pentanol] (testudinariol B) 1Ј
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In the same manner as described above, 20bЈ (inseparable mix-
ture; 12 mg, 18 µmol) was converted to 1Ј (3.2 mg, 2 steps, 36%)
19 G. W. Gokel and D. J. Cram, J. Org. Chem., 1974, 39, 2445.
J. Chem. Soc., Perkin Trans. 1, 2001, 1007–1017
1017