Stereocontrolled synthesis of the oxabicyclo[2.2.1]heptane segment of solanoeclepin A

Article abstract of DOI:10.1055/s-2005-865291

An asymmetric synthesis of the oxabicyclo[2.2.1]heptane segment of Solanoeclepin A, which shows significant hatch-stimulating activity for the potato cyst nematode, is described. The oxabicyclo framework was constructed by iodoetherification with bis(collidine)iodine(I) hexafluorophosphate in acetonitrile. The oxabicyclo segment was further synthesized by the following stereoselective dihydroxylation and dimethyl group introduction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865291

PAPER
1237
Stereocontrolled Synthesis of the Oxabicyclo[2.2.1]heptane Segment of
Solanoeclepin A
P
artial Synthe
h
S
olano
i
e
clepin
n
A
go Tojo, Minoru Isobe*
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Fax +81(52)7894111; E-mail: isobem@agr.nagoya-u.ac.jp
Received 22 December 2004; revised 17 January 2005
Our retrosynthetic analysis of 1 is shown in Sheme 1. The
Abstract: An asymmetric synthesis of the oxabicyclo[2.2.1]hep-
six-membered ring would be closed through an equivalent
tane segment of Solanoeclepin A, which shows significant hatch-
stimulating activity for the potato cyst nematode, is described. The
oxabicyclo framework was constructed by iodoetherification with
of the enolate 3 in the last step. Nicholas reaction5 of the
acetylene dicobalthexacarbonyl complex 4 may construct
bis(collidine)iodine(I) hexafluorophosphate in acetonitrile. The the seven-membered ring as a key step to 3. The precursor
oxabicyclo segment was further synthesized by the following ste-
reoselective dihydroxylation and dimethyl group introduction.
4 should be prepared by coupling between the oxabicyclo
segment 5 and the bicyclo[2.1.1]hexanone segment 6.
This segment 5 would be converted from the vinyl ether 7
via stereoselective dihydroxylation and the dimethylation.
The oxabicyclo framework of 7 should be constructed
through iodoetherification3a,b of the alcohol 8, and the lat-
Key words: solanoeclepin A, hatch-stimulating activity, oxabicy-
clo[2.2.1]heptane, iodoetherification
Potato is one of the most important agricultural products ter would be obtained from the known enone 9 prepared
in the world. Potato cyst nematode is well known as an in- from (–)-quinic acid. Herein, we describe in detail the
sect that causes significant damage to potatoes, and is ex- synthesis of the oxabicyclo segment 5.
tremely difficult to exterminate using the existing
agricultural chemicals or the rotation of crops. Solanoecl-
epin A (1), which was isolated from a large quantity of po-
The oxabicyclo[2.2.1]heptane moiety was constructed by
the following steps (Scheme 2). The enone 9, which was
easily prepared from the commercially available (–)-qui-
tato cultivation, shows significant hatch-stimulating
nic acid in four steps,6 was regioselectively reduced by
activity toward the potato cyst nematode.1a Therefore, 1
treating with Wilkinson’s catalyst and triethylsilane7 to
has received much attention regarding the relationship of
its structure and activity, and is expected to be a new ag-
afford the vinyl silyl ether 11 in 86% yield.8 Another at-
tempt using Birch reduction condition (Li, NH3, THF)
was unsuccessful, because 9 was immediately decom-
ricultural chemical. The related configuration was charac-
terized by X-ray crystallography,1b however, the absolute
posed under the basic condition. The Mukaiyama aldol
configuration has not yet been determined. The absolute
configuration was only assumed, as shown in Figure 1, on
reaction9 of 11 was successful with acetaldehyde and
ZnCl2 in CH2Cl2–Et2O to obtain the aldol products as a
the basis of the similarity of the oxabicyclo[2.2.1]heptane
mixture of diastereomers in a ratio of ca. 1:1 in 71% yield.
moiety to glycinoeclepin A (2), another hatching stimu-
Mesylation of the alcohol and subsequent treatment with
lant toward the soybean cyst nematode.2,3 The structure of
DBU in one-pot afforded the E-enone 12 in 74% yield.
1 contains a heptacyclic compound consisting of five dif-
ferent ring sizes ranging from three to seven, and includ-
ing an oxabicyclo[2.2.1]heptane unit and a highly strained
The reduction of 12 under Luche condition10 at –20 °C
provided largely the alcohol 13 together with a minor a-
isomer in a ratio of ca. 15:1, which was purified by silica
bicyclo[2.1.1]hexanone unit. Although Hiemstra’s group
gel flash column chromatography. It was protected with
has already reported some synthetic studies of 1,4 its total
benzoyl chloride to give 14. The acetonide group was re-
moved with aqueous AcOH in THF at 25 °C to afford the
synthesis has not yet been achieved.
diol 15 in 85% yield in 3 steps. The stereochemistry of the
OH
H
O
CO2H
CO2H
alcohol and the geometry of the alkene were confirmed by
the NOESY spectra of 15 as shown in Figure 2. Formation
of the oxabicyclo system was accomplished by
iodoetherification3a,b with bis(collidine)iodine(I) hexa-
fluorophosphate [I(collidine)2PF6]11 in acetonitrile to give
the iodide 16 in 96% yield. When N-iodosuccinimide
(NIS) was employed as the I+ source, this reaction was
very slow at room temperature to give 16 in lower yields.
Elimination of the iodine was facilitated by heating 16
with DBU in toluene to afford the alcohol 17, which was
further protected with TBDPSCl to obtain the silyl ether
18 in 86% yield in two steps.
HO
O
H
O
O
CO2H
O
HO
O
O
Solanoeclepin A (1)
Glycinoeclepin A (2)
Figure 1 Hatch-stimulating agents
SYNTHESIS 2005, No. 8, pp 1237–1244
Advanced online publication: 07.04.2005
x
x
.
x
x
.2
0
0
5
DOI: 10.1055/s-2005-865291; Art ID: F18604SS
© Georg Thieme Verlag Stuttgart · New York

1238
S. Tojo, M. Isobe
PAPER
X
OR
OH
OR
RO
R
RO
RO
OR
OR
O
X
O
1
OR
OR
OR
OM
O
(OC)6Co2
OR
3
4
RO
OR
O
OR
OR
RO
RO
SPh
O
RO
+
RO
5
6
RO
HO
O
O
OR
OR
O
O
7
8
9
Scheme 1 Retrosynthesis of 1
OH
HO
HO
O
O
O
ref. 6
a
CO2H
O
O
OTES
OH
(–)-quinic acid (10)
9
11
O
O
b, c
d
f
O
O
O
OR
e
13, R = H
14, R = Bz
12
RO
HO
HO
HO
g
I
h
O
O
OBz
OBz
OBz
17, R = H
18, R = TBDPS
15
16
i
Scheme 2 Reagents and conditions: a) Et3SiH, RhCl(PPh3)3, 60 °C, 50 min (86%); b) MeCHO, ZnCl2, CH2Cl2–Et2O (10:1), –20 °C → 0 °C,
2.5 h (71%); c) MsCl, Et3N, CH2Cl2, 0 °C → 27 °C, 1.5 h, then DBU, 27 °C, 14.5 h (74%); d) NaBH4, CeCl3·7H2O, MeOH, –20 °C, 15 min;
e) BzCl, DMAP, CH2Cl2, 26 °C, 23 h; f) AcOH–THF–H2O (3:1:1), 25 °C, 9.5 h (3 steps, 93%); g) I(collidine)2PF6, MeCN, 0 → 20 °C, 4 h
(96%); h) DBU, toluene, 105 °C, 18 h; i) TBDPSCl, imidazole, CH2Cl2, 21 °C, 45 min (2 steps 86%)
OH
HO OBz
because of the major products were mixtures of the mi-
grated benzoyl group (entry 2). The attempted reagent
: NOE
4
1
HO
HO
H
control turned out to be a mismatched pair due to the ex-
isting functional groups in 18. Therefore, the substrate
control conditions were examined with OsO4 (cat.) and
NMO in various solvents. All the reactions smoothly pro-
ceeded and gave the diols with moderate selectivity but in
high yields, and the major product was proved to have the
desired stereochemistry (entries 3, 4, and 5). After several
4
6
H
1
H
6
H
H
OBz
15
JH1-H6 = 5.2, 5.6 Hz
Figure 2 NOE correlations and coupling constants of 15
Next, in order to introduce the secondary hydroxyl group, trials, we found that the treatment of 18 with a mixture of
we examined the stereoselective dihydroxylation of 18 OsO4 (cat.), (DHQ)2PHAL (cat.), and NMO in THF–H2O
under various conditions as listed in Scheme 3. We first at 0 °C afforded 19 in the ratio of ca. 7.1:1 in 99% yield
used AD-mix reagents12 as the reagent control conditions. without any migration of the benzoyl group (entry 7).
The olefin 18 was initially treated with AD-mix-b, expect- (DHQ)2PHAL was added for the purpose of increasing the
ing the desired diol with an S configuration, however, the steric hindrance of OsO4. It was important that the combi-
reaction was extremely slow and afforded a mixture of the nation of OsO4 and NMO was effective for avoiding the
diols 19 and 20 in only trace yields (entry 1). On the other benzoate migration, because this migration was observed
hand, the treatment with AD-mix-a gave the desired diol under the basic conditions with K2OsO2(OH)4 and NMO
19 as the major isomer. However, the yield was very low in THF–H2O.
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

PAPER
Partial Synthesis of Solanoeclepin A
1239
OH
OH
TBDPSO
Entry
TBDPSO
OH TBDPSO
OH
conditons
O
+
O
O
OBz
OBz
OBz
18
19
20
Yield (%)a
trace
Ratio (19:20)b
Conditions
1
2
-
AD-mix-β, t-BuOH–THF–H2O (1:1:0.7), 22 °C, 4 d
AD-mix-α, t-BuOH–THF–H2O (1:1:0.7), 22 °C, 4 d
12
6.0:1
OsO4 (0.1 equiv), NMO, t-BuOH–THF–H2O (1:1:0.7),
20 °C, 36.5 h
3
92
4.3:1
OsO4 (0.1 equiv), NMO, THF-H2O (2:1), 22 °C, 18.5 h
OsO4 (0.1 equiv), NMO, acetone–H2O (2:1), 22 °C, 11.5 h
OsO4 (0.1 equiv), (DHQ)2PHAL (0.16 eq),c NMO,
THF-H2O (2:1), 19 °C, 13 h
OsO4 (0.02 equiv), (DHQ)2PHAL (0.03 equiv),c NMO,
THF–H2O (2:1), 0 °C, 38 h
4
5
99
96
4.5:1
3.7:1
99
99
6
7
5.8:1
7.1:1
a Combined yields of 19 and 20.
b The ratios were determined from the 1H NMR data (270 MHz).
c (DHQ)2PHAL ligand is contained in AD-mix-α.
Scheme 3 Dihydroxylation of 18
Selective protection of 19 with benzoyl chloride in the reaction of the remaining amount of 24 provided the E-es-
presence of pyridine 0 °C produced the primary benzoate ter 26 in 99% yield, which was reduced with DIBAL-H in
21, followed by protection of the secondary alcohol with toluene–THF (5:1) at –78 °C to give the allyl alcohol 27
TESOTf to obtain 22. Both benzoyl groups were then re- in 97% yield. The primary alcohol group of 27 was selec-
moved with DIBAL-H to afford the diol 23 in 85% yield tively converted to the phenyl sulfide 28 with N-(phe-
in 3 steps (Scheme 4). At this step, the mixture of the dia- nylthio)phthalimide and Bu3P15 in CH2Cl2 at –20 °C in
stereomers could be easily separated by silica gel column 99% yield. The ring alcohol was then oxidized to the ke-
chromatography.
tone 29 by Swern oxidation16 in 92% yield. Finally, intro-
duction of the gem-dimethyl groups to the ketone 29 was
achieved with MeI and t-BuOK in THF at –78 °C to af-
ford the dimethyl compound 30 in 94% yield.
Selective oxidation of the primary alcohol of 23 smoothly
proceeded with IBX (2-iodoxybenzoic acid)13 under neu-
tral condition to afford the lactol 24 as a mixture in a ratio
of ca. 1:1 in 86% yield. In order to confirm the configura- In conclusion, we have achieved the efficient synthesis of
tion of the secondary alcohol (introduced at the dihydrox- the oxabicylco segment 30 in 19 steps from the enone 9.
ylation step of 18), a part of 24 was oxidized with TPAP14 The oxabicyclo framework was constructed by iodoether-
to produce the lactone 25. The stereochemistry was deter- ification with I(collidine)2PF6, and the introduction of the
mined from the NOESY spectra (Scheme 5). The Wittig hydroxyl group was accomplished by the diastereoselec-
OH
OR2
OTES
OH
TBDPSO
OR1
TBDPSO
TBDPSO
OH
a
d
O
O
O
O
OBz
OH
19
21, R1 = Bz, R2 = H
22, R1 = Bz, R2 = TES
23, R1 = H, R2 = TES
24
b
c
OTES
TESO
TBDPSO
R
TBDPSO
e
f
h
CO2Et
O
O
OH
OH
26
27, R = OH
28, R = SPh
g
OTES
OTES
TBDPSO
SPh
TBDPSO
SPh
i
O
O
O
O
29
30
Scheme 4 Reagents and conditions: a) BzCl, Py–CH2Cl2 (20:1), 0 °C, 2 h; b) TESOTf, 2,6-lutidine, CH2Cl2, 21 °C, 1 h; c) DIBAL, CH2Cl2,
–78 °C, 20 min, then separation (3 steps 85%); d) IBX, NaHCO3, THF–DMSO (1:1), 16 °C, 11 h (86%); e) Ph3P=CHCO2Et, toluene, 80 °C,
6.5 h (99%); f) DIBAL, toluene–THF, (5:1), –78 °C, 20 min (97%); g) N-(phenylthio)phthalimide, Bu3P, CH2Cl2, –20 °C, 10 min (99%); h)
(COCl)2, DMSO, CH2Cl2, –78 °C, 80 min, then Et3N, –78 → 0 °C, 40 min (92%); i) MeI, t-BuOK, THF, –78 °C, 7 h (94%)
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

1240
S. Tojo, M. Isobe
PAPER
J = 3.6, 4.9, 6.9 Hz, H-4), 2.40 (1 H, dd, J = 3.3, 16.5 Hz, H-6),
2.35–2.25 (1 H, m, H-3), 2.16 (1 H, ddd, J = 1.3, 5.6, 16.5 Hz, H-6),
2.03–1.93 (1 H, m, H-3), 1.49 (3 H, s, CH3, acetonide), 1.25 (3 H, s,
CH3, acetonide), 1.00 [9 H, t, J = 7.9 Hz, CH3, TES), 0.67 [6 H, q,
J = 7.9 Hz, CH2, TES).
13C NMR (CDCl3, 67.8 MHz): d = 149.9, 107.9, 98.4, 74.5, 73.2,
34.5, 28.0, 27.5, 25.0, 7.1, 5.5.
O
OTBDPS
OTES
O
TBDPSO
H
a
OTES
O
24
O
O
H
H
O
H
25
: NOE
FAB-HRMS: m/z calcd for C15H28O3Si (M + Na)+: 307.1705;
found: 307.1696.
Scheme 5 Reagents and conditions: a) TPAP, NMO, MS 4Å,
CH2Cl2, 20 °C, 2.5 h (86%)
(2E,4S,5R)-2-Ethylidene-4,5-(dimethylmethylenedioxy)cyclo-
hexan-1-one (12)
To a solution of 11 (55.9 mg, 0.197 mmol) and MeCHO (ca. 220
mL, 3.92 mmol) in CH2Cl2 (2.4 mL) at –20 °C was added ZnCl2 (1.0
tive dihydroxylation of the vinyl ether 18. The diol 19 was
converted into the oxabicyclo[2.2.1]heptane segment 30
via the extension of the side chain and the dimethylation.
An additional synthetic study, including the investigation M solution in Et2O, 240 mL, 240 mmol). After stirring for 2.5 h, the
mixture was allowed to warm to 0 °C. The reaction was quenched
of the seven-membered ring on solanoeclepin A, is now
by sat. aq NaHCO3 (2 mL), and extracted with Et2O (4 × 3 mL). The
combined extracts were dried (MgSO4) and concentrated, and the
residue was purified by flash chromatography (SiO2, hexane–
EtOAc, 5:2, 2:1, 1) to furnish a mixture of the aldol products (ca.
1:1) (31.7 mg, 71%) as white solids. To a solution of the aldol com-
pounds (19.7 mg, 92.4 mmol) and Et3N (65 mL, 0.466 mmol) in
CH2Cl2 (0.5 mL) was added dropwise a solution of MsCl (9 mL,
0.114 mmol) in CH2Cl2 over 10 min at 0 °C. After stirring at 27 °C
for 1.5 h, an additional amount of DBU (20 mL, 0.134 mmol) was
added, and the mixture was stirred at the same temperature for 12.5
h. Again DBU (5 mL, 33.5 mmol) was added, and the stirring was
continued for an additional 2 h. The reaction was quenched with sat.
aq NH4Cl (2 mL) at 0 °C, and the mixture was extracted with Et2O
(3 × 2 mL). Drying (MgSO4), concentration, and flash chromatog-
raphy (SiO2, hexane–EtOAc, 7:1, 6:1, 5:1, 4:1) gave the enone 12
(13.4 g, 74%) as a colorless liquid; [a]D23 +4.2 (c = 0.98, CHCl3).
under way in our laboratory.
Solvents and reagents were dried and distilled before use. THF was
distilled from sodium benzophenone ketyl. CH2Cl2, MeCN, pyri-
dine, and Et3N were distilled from CaH2. Normal reagent-grade sol-
vents were used for the flash chromatography and extraction.
I(collidine)2PF6, and IBX were prepared by literature methods.11c,13c
All other reagents were commercially available and used without
further purification. All reactions were monitored by TLC analysis
using precoated SiO2 plates (Merck, silica gel 60 F254 Art. 5715).
Visualization was achieved via UV light and the appropriate spray
reagent, followed by heating. Selected spray reagents were as fol-
lows: a 2.5% ethanolic p-anisaldehyde solution containing 1%
AcOH acid and 3.4% conc. H2SO4, a 10% ethanolic phosphomolyb-
dic acid solution, and I2 on SiO2. SiO2 (Merck, silica gel 60, 230–
400 mesh ASTM and NACALAI TESQUE, silica gel 60, spherical,
neutrality, 105–210 mm) was used for the flash chromatography.
Melting points were measured using a Yanagimoto MP-S3 micro-
melting point apparatus and are uncorrected. IR spectra were ob-
IR (neat): 2988, 2936, 2915, 1704, 1636, 1437, 1411, 1381, 1268,
1211, 1165, 1088, 1043, 893, 848, 700, 545, 513 cm–1.
1H NMR (CDCl3, 270 MHz): d = 6.90 (1 H, dq, J = 2.0, 7.3 Hz,
=CH, ethylidene), 4.68–4.57 (2 H, m, H-4, H-5), 2.98 (1 H, dd,
J = 2.8, 15.5 Hz, H-3), 2.73 (1 H, dd, J = 3.0, 15.8 Hz, H-6), 2.53 (1
H, dd, J = 3.5, 15.8 Hz, H-6), 2.37 (1 H, dddd, J = 2.0, 2.6, 2.8, 15.5
Hz, H-3), 1.80 (3 H, dd, J = 2.6, 7.3 Hz, =CHCH3, ethylidene), 1.32
(3 H, s, CH3, acetonide), 1.32 (3 H, s, CH3, acetonide).
13C NMR (CDCl3, 100 MHz): d = 197.3, 135.8, 132.5, 108.0, 72.9,
72.8, 42.1, 28.7, 26.1, 24.2, 13.6.
EI-HRMS: m/z calcd for C11H17O3 (M + H)+: 197.1178; found:
197.1183.
1
tained using a JASCO FT/IR-8300 spectrophotometer. H NMR
spectra were recorded on JEOL GSX-270 (270 MHz), JNM-a-400
(400 MHz), and JNM-a-600 (600 MHz) NMR spectrometers.
Chemical shifts (d) were reported with tetramethylsilane (d = 0.00)
or C6H6 (d = 7.15) as the internal standard. 13C NMR spectra were
measured on JEOL GSX-270 (67.8 MHz), JNM-a-400 (100 MHz),
JNM-LA-500 (125 MHz) and JNM-a-600 (150 MHz) NMR spec-
trometers. Chemical shifts (d) were reported with CHCl3 (d = 77.0)
or C6H6 (d = 128) as the internal standard. Optical rotations were re-
corded using a JASCO P-1010-GT digital polarimeter with CHCl3
as the solvent. High-resolution mass spectra (HRMS) were obtained
using a JEOL JMS-700 mass spectrometer. Elemental analyses
were performed by Mr. Kitamura in the analytical laboratory of
Nagoya university. All reactions were carried out under anhydrous
conditions in argon, unless otherwise noted.
(1S,2E,4S,5R)-2-Ethylidene-4,5-(dimethylmethylenedioxy)cy-
clohexan-1-ol (13)
To a solution of 12 (3.17 g, 16.2 mmol) and CeCl3·7H2O (8.13 g,
21.8 mmol) in MeOH (100 mL) was added NaBH4 (795 mg, 21.0
mmol) at –78 °C, and the reaction mixure was stirred at the same
temperature for 50 min. Brine (100 mL) was added and the mixure
was extracted with Et2O (3 × 200 mL). Drying (MgSO4), concentra-
tion, and flash chromatography (SiO2, hexane–EtOAc, 6:1, 5:1,
(1E,4S,5R)-1-Triethylsilyloxy-4,5-(dimethylmethylenedioxy)cy-
clohex-1-ene (11)
To a suspension of 9 (251 mg, 1.49 mmol) and RhCl(PPh3)3 (1.4
mg, 1.50 mmol) was added Et3SiH (350 mL, 2.19 mmol) at 60 °C.
After stirring at the same temperature for 45 min, the reaction mix-
ture was filtered through a Celite pad, which was washed with hex-
ane. The filtrate was concentrated and the residue was purified by
flash chromatography (SiO2, hexane–EtOAc, 50:1, 40:1, trace
Et3N) to give a mixture of the silyl vinyl ether 11 (359 mg, 84%) and
the 1,2-product (ca. 30:1) as a colorless liquid.
23
4:3) afforded the alcohol 13 (2.97 g, 93%) as a white solid; [a]D
–21.6 (c = 1.00, CHCl3).
IR (neat): 3447, 2985, 2935, 1456, 1381, 1217, 1155, 1046, 843,
590, 514 cm–1.
1H NMR (CDCl3, 600 MHz): d = 5.70 (1 H, br q, J = 6.6 Hz, =CH,
ethylidene), 4.38–4.35 (1 H, m, H-5), 4.25–4.22 (1 H, m, H-4),
4.16–4.13 (1 H, m, H-1), 2.79 (1 H, d, J = 9.6 Hz, OH), 2.57 (1 H,
dd, J = 6.6, 14.4 Hz, H-3), 2.40 (1 H, dd, J = 6.0, 14.4 Hz, H-3),
2.27 (1 H, td, J = 3.6, 15.6 Hz, H-6), 1.93 (1 H, ddd, J = 3.6, 4.2,
15.6 Hz, H-6), 1.65 (3 H, d, J = 6.6 Hz, =CHCH3, ethylidene), 1.51
(3 H, s, CH3, acetonide), 1.34 (3 H, s, CH3, acetonide).
IR (neat): 2956, 2913, 2878, 1663, 1560, 1457, 1379, 1242, 1188,
1054, 892, 746 cm–1.
1H NMR (C6D6, 270 MHz): d = 4.79 (1 H, ddd, J = 1.3, 4.0, 5.6 Hz,
H-2), 4.14 (1 H, ddd, J = 3.3, 5.6, 6.9 Hz, H 5), 4.04 (1 H, ddd,
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

PAPER
Partial Synthesis of Solanoeclepin A
1241
13C NMR (CDCl3, 67.8 MHz): d = 136.2, 121.6, 108.3, 74.3, 73.6,
by dilution with THF (10 mL) and sat. aq CuSO4 (50 mL) was add-
ed. After stirring vigorously at 20 °C for 15 min, the mixture was
extracted with EtOAc (3 × 30 mL), dried (MgSO4), and concentrat-
ed. The residue was purified by flash chromatography (SiO2, hex-
ane–EtOAc, 3:1, 2:1, 3:2) to furnish the iodide 16 (751 mg, 96%) as
white needles; mp 181.0–181.5 °C; [a]D28 +86.1 (c = 1.11, CHCl3).
70.6, 34.3, 28.0, 27.6, 25.5, 13.0.
EI-HRMS: m/z calcd for C11H18O3 (M)+: 198.1256; found:
198.1251.
(1S,2E,4S,5R)-1-Benzoyloxy-2-ethylidene-4,5-(dimethylmethyl-
enedioxy)cyclohexane (14)
IR (KBr): 3490, 2970, 2932, 1717, 1266, 1110, 1024, 990, 948, 710,
636 cm–1.
To a solution of 13 (513mg, 2.59 mmol) in CH2Cl2 (20 mL) were
added DMAP (794 mg, 6.50 mmol) and BzCl (360 mL, 3.10 mmol)
at 0 °C, and the mixture was stirred at 24 °C for 2 h. The reaction
was quenched with sat. aq NaHCO3 (15 mL), and extracted with
Et2O (3 × 20 ml). The combined extracts were dried (MgSO4) and
concentrated, and the residue was purified by flash chromatography
(SiO2 hexane–EtOAc, 20:1, 10:1, 8:1) to give the benzoate 14 (781
mg, ca.100%) as a colorless oil; [a]D22 +58.4 (c = 1.19, CHCl3).
1H NMR (C6D6, 400 MHz): d = 8.24–8.14 (2 Harom, m, Bz), 7.20–
6.98 (6 Harom, m, Bz), 5.13 (1 H, dd, J = 2.4, 6.8 Hz, H-2), 4.75 (1
H, q, J = 6.8 Hz, H-1¢), 4.08 (1 H, br d, J = 5.6 Hz, H-4), 3.30–3.24
(1 H, m, H-5), 1.84 (1 H, d, J = 6.8 Hz, H-2¢), 1.60 (1 H, dd, J = 6.4,
14.0 Hz, H-6), 1.53 (1 H, dd, J = 6.8, 14.0 Hz, H-3), 1.47 (1 H, ddd,
J = 1.6, 2.4, 14.0 Hz, H-6), 1.43 (1 H, ddd, J = 2.4, 5.6 14.0 Hz, H-
3), 1.07 (1 H, d, J = 8.0 Hz, OH).
IR (neat): 3065, 3033, 2985, 2936, 2875, 1717, 1603, 1452, 1368,
1272, 1216, 1158, 1113, 1059, 865, 840, 713, 513 cm–1.
13C NMR (CDCl3, 67.8 MHz): d = 165.5, 133.2, 129.8, 129.5,
128.4, 89.4, 83.5, 76.8, 74.5, 39.3, 36.6, 22.5, 18.7.
1H NMR (CDCl3, 270 MHz): d = 8.12–8.06 (2 Harom, m, Bz), 7.58–
7.51 (1 Harom, m, Bz), 7.46–7.38 (2 Harom, m, Bz), 5.74 (1 H, dq,
J = 1.0, 6.9 Hz, =CH, ethylidene), 5.46 (1 H, dd, J = 4.9, 5.6 Hz, H-
1), 4.29 (1 H, dd, J = 5.3, 10.6 Hz, H-5), 4.18 (1 H, dd, J = 6.3, 7.3
Hz, H-4), 2.64–2.57 (2 H, m, H-3), 2.33 (1 H, ddd, J = 5.3, 5.6, 14.5
Hz, H-6), 2.16 (1 H, ddd, J = 4.9, 10.6, 14.5 Hz, H-6), 1.67 (3 H, dd,
J = 0.5, 6.9 Hz, =CHCH3, ethylidene), 1.57 (3 H, s, CH3, acetonide),
1.37 (3 H, s, CH3, acetonide).
13C NMR (CDCl3, 150 MHz): d = 165.8, 132.8, 132.0, 130.6, 129.7,
128.3, 123.3, 108.5, 74.3, 72.5, 72.5, 33.4, 28.4, 27.7, 25.9, 12.9.
EI-HRMS: m/z calcd for C18H22O4 (M)+: 302.1518; found:
302.1519.
Anal. Calcd for C15H17O4I: C, 46.41; H, 4.41. Found: C, 46.45; H,
4.47.
FAB-HRMS: m/z calcd for C15H18O4I (M + H)+: 389.0250; found:
389.0257.
(1S,2S,4R,5S)-2-Benzoyloxy-1-vinyl-7-oxabicyclo[2.2.1]heptan-
5-ol (17)
To a suspension of 16 (744 mg, 1.92 mmol) in toluene (15 mL) was
added DBU (1.45 mL, 9.70 mmol). After stirring at 105 °C for 18
h, the reaction was quenched by with sat. aq NH4Cl (20 mL), and
the aqueous layer was extracted with Et2O (3 × 50 ml). Drying
(MgSO4), concentration, and flash chromatography (SiO2, hexane–
EtOAc, 2:1, 3:2, 1:1, 2:3) gave the vinyl ether 17 (478 mg, 96%) as
a colorless oil; [a]D22 +40.8 (c = 1.20, CHCl3).
(1S,2E,4S,5R)-1-Benzoyloxy-2-ethylidene-4,5-cyclohexanediol
(15)
IR (neat): 3448, 2993, 2950, 1717, 1451, 1316, 1276, 1110, 1073,
994, 950, 713, 468, 456, 451 cm–1.
To a solution of 14 (98.9 mg, 0.327 mmol) in THF (0.3 mL) and
H2O (0.3 mL) was added AcOH (0.9 mL) at 0 °C, and the mixture
was stirred at 25 °C for 9.5 h. The reaction mixture was neutralized
by sat. aq NaHCO3, and extracted with EtOAc (3 × 20 mL). The
combined extracts were dried (MgSO4) and concentrated. The resi-
due was purified by flash chromatography (SiO2, hexane–EtOAc,
1:1, 1:2) to give the diol 15 (85.5 mg, ca. 100%) as a colorless amor-
phous powder; [a]D22 +46.9 (c = 1.10, CHCl3).
1H NMR (CDCl3, 400 MHz): d = 8.04–8.00 (2 Harom, m, Bz), 7.58–
7.53 (1 Harom, m, Bz), 7.45–7.40 (2 Harom, m, Bz), 6.18 (1 H, dd,
J = 11.2, 17.6 Hz, CH=CH2), 5.46 (1 H, dd, J = 1.6, 17.6 Hz,
CH=CH2), 5.29 (1 H, dd, J = 1.6, 11.2 Hz, CH=CH2), 5.06 (1 H, br
dd, J = 2.4, 7.2 Hz, H-4), 4.50 (1 H, dd, J = 6.4, 7.2 Hz, H-2), 4.06–
4.00 (1 H, m, H-5), 2.20 (1 H, dd, J = 6.8, 14.0 Hz, H-6), 2.10 (1 H,
dd, J = 7.2, 14.0 Hz, H-3), 2.07 (1 H, br d, J = 9.6 Hz, OH), 1.91 (1
H, dd, J = 2.4, 6.4, 14.0 Hz, H-3), 1.59 (1 H, ddd, J = 1.6, 2.0, 14.0
Hz, H-3).
13C NMR (CDCl3, 67.8 MHz): d = 165.9, 133.0, 132.4, 129.9,
129.5, 128.2, 117.4, 87.4, 81.3, 76.3, 74.5, 43.1, 35.7.
FAB-HRMS: m/z calcd for C15H17O4 (M + H)+: 261.1127; found:
261.1121.
IR (neat): 3446, 3064, 2918, 1717, 1601, 1452, 1316, 1275, 1178,
1118, 1070, 1027, 993, 711 cm–1.
1H NMR {CDCl3 + D2O (trace), 400 MHz}: d = 8.05–8.01 (2 Harom
,
m, Bz), 7.61–7.55 (1 Harom, m, Bz), 7.48–7.43 (2 Harom, m, Bz), 5.76
(1 H, br q, J = 6.8 Hz, =CH, ethylidene), 5.51 (1 H, dd, J = 5.2, 5.6
Hz, H-1), 4.00 (1 H, ddd, J = 3.2, 4.0, 6.4 Hz, H-5), 3.78 (1 H, ddd,
J = 3.2, 3.6, 8.4 Hz, H-4), 2.63 (1 H, br dd, J = 8.4, 13.6 Hz, H-3),
2.44 (1 H, br dd, J = 3.6, 13.6 Hz, H-3), 2.19 (1 H, ddd, J = 5.6, 6.4,
13.6 Hz, H-6), 2.06 (1 H, ddd, J = 4.0, 5.2, 13.6 Hz, H-6), 1.69 (3
H, d, J = 6.8 Hz, =CHCH3, ethylidene).
(1S,2S,4R,5S)-2-Benzoyloxy-5-(tert-butyldiphenylsilyloxy)-1-vi-
nyl-7-oxabicyclo[2.2.1]heptane (18)
To a solution of 17 (1.90 g, 7.30 mmol) in CH2Cl2 (15 ml) at 0 °C
were added imidazole (994 mg, 14.63 mmol) and TBDPSCl (2.01
g, 7.31 mmol). After stirring at 22 °C for 1.5 h, additional amount
of TBDPSCl (99.3 g, 0.361 mmol) was added, and the mixture was
stirred for 1.5 h. The mixture was poured into sat. aq NH4Cl (50 mL)
and the aqueous layer was extracted with Et2O (3 × 100 mL). Dry-
ing (MgSO4), concentration, and flash chromatography (SiO2, hex-
ane–EtOAc, 10:1, 5:1) gave the silyl ether 18 (3.49 g, 96%) as a
colorless amorphous powder; [a]D23 +25.8 (c = 0.85, CHCl3).
13C NMR (CDCl3, 67.8 MHz): d = 165.1, 133.0, 131.6, 130.0,
129.4, 128.4, 123.0, 73.7, 70.5, 69.6, 35.8, 29.1, 12.9.
EI-HRMS: m/z calcd for C15H18O4 (M)+: 262.1205; found:
262.1209.
(1R,2S,4R,5S)-2-Benzoyloxy-1-[(1¢S)-1¢-iodoethyl]-7-oxabicy-
clo[2.2.1]heptan-5-ol (16)
To a solution of 15 (529 mg, 2.02 mmol) in MeCN (20 mL) at 0 °C
was added I(collidine)2PF6 (1.66 g, 3.23 mmol). After stirring at
20 °C in the dark for 2 h, additional amount of I(collidine)2PF6 (334
mg, 0.649 mmol) was added and the mixture was stirred at same
temperature for 2 h. The reaction was quenched with sat. aq
Na2S2O3 (20 mL), which was followed by extraction with Et2O
(3 × 50 mL). The combined extracts were concentrated, followed
IR (neat): 2931, 2858, 1718, 1274, 1111, 1001, 864, 823, 703, 612,
508 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.99–7.97 (2 Harom, m), 7.70–7.64
(4 Harom, m), 7.55–7.51 (1 Harom, m), 7.45–7.37 (8 Harom, m), 6.16 (1
H, dd, J = 10.8, 17.4 Hz, CH=CH2), 5.45 (1 H, dd, J = 1.2, 17.4 Hz,
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

1242
S. Tojo, M. Isobe
PAPER
(1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S,2¢E)-4¢-
CH=CH2), 5.27 (1 H, dd, J = 1.8, 10.8 Hz, CH=CH2), 4.92 (1 H, dd,
J = 2.4, 7.2 Hz, H-2), 4.38 (1 H, br d, J = 6.0 Hz, H-4), 3.99 (1 H,
dd, J = 2.4, 6.6 Hz, H-5), 1.94 (1 H, dd, J = 6.6, 13.2 Hz, H-6), 1.80
(1 H, dd, J = 7.2, 13.8 Hz, H-3), 1.75–1.72 (1 H, m, H-6), 1.68 (1 H,
ddd, J = 2.4, 6.0, 13.8 Hz, H-3), 1.07 [9 H, s, SiC(CH3)3].
13C NMR (CDCl3, 67.8 MHz): d = 165.8, 135.6, 135.6, 133.8,
133.6, 132.9, 132.7, 130.0, 129.7, 129.6, 129.5, 128.2, 127.6, 127.6,
117.2, 87.3, 81.2, 76.6, 75.9, 43.1, 36.1, 26.9, 19.1.
(ethoxycarbonyl)-1¢-(triethylsilyloxy)prop-2¢-enyl]-7-oxabicy-
clo[2.2.1]heptan-2-ol (26)
To a solution of 23 (226 mg, 0.417 mmol) in THF (3 mL) and
DMSO (3 mL) was added IBX (349 mg, 1.25 mmol), and the mix-
ture was stirred at 16 °C for 11 h. The mixture was diluted with H2O
(4 mL), and stirred at 0 °C for 10 min. The resulting suspension was
filtered through a Celite pad, which was washed with EtOAc. The
filtrate was diluted with brine (5 mL), followed by extraction with
Et2O (3 × 15 mL). The combined extracts were dried (MgSO4) and
concentrated. The residue was purified by flash chromatography
(SiO2, hexane–EtOAc, 6:1, 4:1) to provide a mixture of the lactols
24 (ca. 1:1) (193 mg, 86%) as a colorless oil. To a solution of 24
(29.0 mg, 53.6 mmol) in toluene (1 mL) at 22 °C was added ethyl
(triphenylphosphoranylidene)acetate (58.9 mg, 0.161 mmol). After
stirring at 80 °C for 6.5 h, the mixture was diluted with sat. aq
NaHCO3 (1 mL), followed by extraction with Et2O (3 × 2 mL). Dry-
ing (MgSO4), concentration, and flash chromatography (SiO2, hex-
ane–EtOAc, 10:1, 7:1) afforded the ethyl ester 26 (32.4 mg, 99%)
as white needles; mp 101.8–102.6 °C; [a]D21 –0.7 (c = 0.93, CHCl3).
FAB-HRMS: m/z calcd for C31H35O4Si (M + H)+: 499.2305; found:
499.2310.
(1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S)-1¢-(trieth-
ylsilyloxy)-2¢-hydroxyethyl]-7-oxabicyclo[2.2.1]heptan-2-ol (23)
To a solution of 18 (2.65 g, 5.32 mmol) in THF (40 mL) and H2O
(20 mL) at 0 °C were added NMO (1.87 g, 16.0 mmol),
(DHQ)2PHAL (121 mg, 0.155 mmol) and OsO4 (0.15 M solution in
H2O, 660 mL, 0.100 mmol). After stirring at the same temperature
for 38 h, sat. aq Na2S2O3 (50 mL) was added. The mixture was
stirred at 23 °C for 20 min, and the aqueous layer was extracted with
Et2O (3 × 60 mL). The combined organic extracts were dried
(MgSO4) and concentrated. The residue was subjected to flash chro-
matography (SiO2, hexane–EtOAc, 3:1, 2:1, 3:2, 1) to furnish a
mixture of the diols 19 and 20 (ca. 7.1:1) (2.81 g, 99%) as a color-
less amorphous powder. To a solution of 19 and 20 (88.3 mg, 0.166
mmol) in CH2Cl2 (2 mL) and pyridine (0.1 mL) at 0 °C was added
BzCl (22 mL, 0.190 mmol). After stirring at the same temperature
for 2 h, the mixture was diluted with sat. aq NaHCO3 (3 mL), and
the aqueous layer was extracted with Et2O (3 × 4 mL). Drying
(MgSO4), concentration, and flash chromatography (SiO2, hexane–
EtOAc, 10:1, 5:1) gave a mixture of benzoate 21 (105 mg, ca.
100%) as a colorless amorphous powder. To a solution of 21 (640
mg, 1.01 mmol) in CH2Cl2 (15 mL) were added 2,6-lutidine (280
mL, 2.40 mmol) and TESOTf (280 mL, 1.24 mmol) at 0 °C, and the
mixture was stirred at 22 °C for 45 min. The reaction was quenched
with sat. aq NH4Cl (20 mL), and extracted with hexane (3 × 20 mL).
The combined extracts were dried (MgSO4) and concentrated: The
residue was purified by flash chromatography (SiO2, hexane/
EtOAc, 30:1, 2:1, 15:1) to furnish a mixture of the silyl ethers 22
(755 mg, ca. 100%) as a colorless amorphous. To a solution of 22
(755 mg, 1.00 mmol) in CH2Cl2 (15 mL) at –78 °C was added drop-
wise DIBAL-H (0.95 M solution in hexane, 4.8 mL, 4.56 mmol)
over 6 min. After stirring at the same temperature for 20 min, sat. aq
potassium sodium tartrate (15 mL) was added. The mixture was vig-
orously stirred at 23 °C for 2 h, and the aqueous layer was extracted
with Et2O (3 × 30 mL). The combined organic extracts were dried
(MgSO4) and concentrated. The residue was subjected to flash chro-
matography (SiO2, hexane–EtOAc, 8:1, 7:1, 5:1, 9:2) to afford the
pure diol 23 (462 mg, 85%) as white needles; mp 123.4–123.8 °C;
[a]D23 –0.2 (c = 1.04, CHCl3).
IR (KBr): 3459, 2958, 2878, 1725, 1659, 1429, 1369, 1276, 1158,
1112, 1031, 822, 739, 701, 692, 508 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.67–7.65 (2 Harom, m, TBDPS),
7.61–7.59 (2 Harom, m, TBDPS), 7.45–7.35 (6 Harom, m, TBDPS),
7.09 (1 H, dd, J = 4.5, 15.6 Hz, H-2¢), 6.16 (1 H, dd, J = 1.8, 15.6
Hz, H-3¢), 4.94 (1 H, dd, J = 1.8, 4.5 Hz, H-1¢), 4.26 (1 H, d, J = 6.6
Hz, H-4), 4.25–4.16 (2 H, m, OCH2CH3), 3.83 (1 H, dd, J = 1.8, 6.6
Hz, H-5), 3.74 (1 H, ddd, J = 1.2, 6.3, 7.2 Hz, H-2), 2.93 (1 H, d,
J = 7.2 Hz, OH), 1.53 (1 H, dd, J = 6.6, 13.8 Hz, H-3), 1.49 (1 H,
dd, J = 6.6, 14.4 Hz, H-6), 1.46 (1 H, br d, J = 14.4 Hz, H-6), 1.40
(1 H, ddd, J = 1.2, 6.3, 13.8 Hz, H-3), 1.30 (3 H, t, J = 7.2 Hz,
OCH2CH3), 1.02 (9 H, s, t-C4H9, TBDPS), 0.97 (9 H, t, J = 7.8 Hz,
CH3, TES), 0.68 (6 H, q, J = 7.8 Hz, CH2, TES).
13C NMR (CDCl3, 125 MHz): d = 166.2, 146.7, 135.7, 135.6, 134.0,
133.7, 129.7, 129.6, 127.7, 127.6, 122.3, 87.6, 80.7, 75.4, 73.3,
71.7, 60.4, 39.3, 38.3, 26.7, 19.0, 14.2, 6.7, 4.7.
Anal. Calcd for C34H50O6Si3: C, 66.84; H, 8.25, found: C, 66.85; H,
8.27.
FAB-HRMS: m/z calcd for C34H50O6Si2Na (M + Na)+: 633.3044;
found: 633.3052.
(1R,2R,4R,5S,7R,8S)-8-(tert-Butyldiphenylsilyloxy)-2-(triethyl-
silyloxy)-4,10-dioxatricyclo[5.2.1.01,5]decan-3-one (25)
To a suspension of 24 (4.4 mg, 8.1 mmol) and MS 4Å (10.0 mg) in
CH2Cl2 (1.0 mL) were added TPAP (1.2 mg, 3.4 mmol) and NMO
(4.1 mg, 35 mmol) at 20 °C. After stirring at the same temperature
for 2.5 h, the reaction mixture was filtered through a short column
of SiO2, and the filtrate was concentrated. The residue was purified
by PTLC (hexane–EtOAc, 5:1) to afford the lactone 25 (3.8 mg,
IR (KBr): 3344, 2955, 2876, 1112, 1001, 743, 702, 610, 506 cm–1.
23
86%) as white needles; mp 82.0–83.0 °C; [a]D –12.2 (c = 0.36,
1H NMR (CDCl3, 600 MHz): d = 7.67–7.62 (4 Harom, m, TBDPS),
7.45–7.36 (6 Harom, m, TBDPS), 4.37 (1 H, dd, J = 5.3, 5.6 Hz, H-
1¢), 4.25 (1 H, d, J = 6.2 Hz, H-4), 3.89–3.65 (3 H, m, H-2, H-1¢, H-
2¢), 2.81 (1 H, br d, J = 7.2 Hz, OH), 2.65 (1 H, br s, OH), 1.63–1.47
(3 H, m, H-3, H-6), 1.39 (1 H, ddd, J = 1.2, 6.6, 13.8 Hz, H-3eq),
1.05 (9 H, s, t-C4H9, TBDPS), 0.98 (9 H, t, J = 7.8 Hz, CH3, TES),
0.68 (6 H, q, J = 7.8 Hz, CH2, TES).
13C NMR (CDCl3, 125 MHz): d = 135.6, 133.9, 133.7, 129.7, 127.7,
88.2, 80.9, 75.3, 73.8, 71.5, 64.4, 39.2, 38.0, 26.8, 19.0, 6.8, 4.8.
FAB-HRMS: m/z calcd for C30H46O5Si2Na (M + Na)+: 565.2782;
found: 565.2775.
CHCl3).
IR (KBr): 2960, 2881, 1801, 1139, 1107, 1019, 964, 824, 743, 705,
512 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.65–7.62 (4 Harom, m, TBDPS),
7.46–7.43 (2 Harom, m, TBDPS), 7.40–7.37 (4 Harom, m, TBDPS),
4.53 (1 H, s, H-2), 4.44 (1 H, d, J = 6.0 Hz, H-7), 4.12 (1 H, dd,
J = 2.1, 6.6 Hz, H-5), 3.99 (1 H, dd, J = 3.0, 6.6 Hz, H-8), 1.90 (1
H, br dd, J = 3.0, 12.0 Hz, H-9), 1.79 (1 H, ddd, J = 2.1, 6.0, 13.8
Hz, H-6), 1.73 (1 H, dd, J = 6.6, 12.0 Hz, H-9), 1.63 (1 H, dd,
J = 6.6, 13.8 Hz, H-6), 1.05 (9 H, s, t-C4H9, TBDPS), 1.04 (9 H, t,
J = 7.8 Hz, CH3, TES), 0.80–0.69 (6 H, m, CH2, TES).
13C NMR (CDCl3, 150 MHz): d = 173.5, 135.7, 135.6, 133.4, 133.4,
129.9, 129.8, 127.8, 127.7, 88.0, 83.9, 80.0, 76.0, 70.1, 37.5, 34.9,
26.7, 19.0, 6.6, 4.8.
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

PAPER
Partial Synthesis of Solanoeclepin A
1243
FAB-HRMS: m/z calcd for C30H42O5Si2Na (M + Na)+: 561.2469;
FAB-HRMS: m/z calcd for C38H52O4Si2Na (M + Na)+: 683.3023;
found: 561.2466.
found: 683.3040.
(1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S,2¢E)-1¢-
(triethylsilyloxy)-4¢-hydroxybut-2¢-enyl]-7-oxabicy-
clo[2.2.1]heptan-2-ol (27)
(1S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S,2¢E)-1¢-(tri-
ethylsilyloxy)-4¢-phenylsulfanylbut-2¢-enyl]-7-oxabicy-
clo[2.2.1]heptan-2-one (29)
To a solution of 26 (357 mg, 0.585 mmol) in toluene (7.4 mL) and
THF (2.0 mL) at –78 °C was added dropwise DIBAL-H (1.01 M so-
lution in toluene, 2.6 mL, 2.63 mmol) over 5 min. After stirring at
the same temperature for 20 min, sat. aq potassium sodium tartrate
(15 mL) was added. The mixture was vigorously stirred at 23 °C for
5 h, and the aqueous layer was extracted with Et2O (3 × 20 mL). The
combined organic extracts were dried (MgSO4) and concentrated.
The residue was subjected to flash chromatography (SiO2, hexane–
EtOAc, 3:1, 2:1) to furnish the diol 27 (321 mg, 97%) as white nee-
dles; mp 83.5–84.0 °C; [a]D20 +2.7 (c = 0.95, CHCl3).
To a solution of oxalyl chloride (190 mL, 2.18 mmol) in CH2Cl2 (8
mL) at –78 °C was added dropwise a solution of DMSO (305 mL,
4.30 mmol) in CH2Cl2 (1.5 mL). After stirring at the same temper-
ature for 20 min, a solution of 28 (357 mg, 0.540 mmol) in CH2Cl2
(3.5 mL) was added over 5 min. The resulting solution was stirred
at –78 °C for 80 min. After Et3N (1.2 mL, 8.61 mmol) was added,
the mixture was stirred at –78 °C for 10 min, and allowed to warm
to 0 °C for 30 min. Sat. aq NH4Cl (15 mL) was added and the mix-
ture was extracted with hexane (3 × 30 mL). Drying (MgSO4), con-
centration, and flash chromatography (SiO2, hexane–EtOAc, 35:1,
25:1, 20:1) afforded the ketone 29 (326 mg, 92%) as a colorless
amorphous powder; [a]D22 +27.1 (c = 1.26, CHCl3).
IR (neat): 3568, 3498, 2956, 2930, 2858, 1473, 1323, 1256, 1145,
1088, 837, 779, 703 cm–1.
IR (neat): 3072, 3051, 2955, 2876, 1768, 1473, 1428, 1238, 1113,
1046, 1009, 968, 879, 823, 740, 703, 691, 612, 508 cm–1.
1H NMR (CDCl3, 400 MHz): d = 7.68–7.61 (4 Harom, m, Bz), 7.45–
7.34 (6 Harom, m, Bz), 6.01–5.93 (1 H, m, H-3¢), 4.76 (1 H, dddd,
J = 1.2, 1.6, 6.0, 15.6 Hz, H-2¢), 4.76 (1 H, br d, J = 6.0 Hz, H-1¢),
4.26 (1 H, br d, J = 6.4 Hz, H-5), 4.23–4.17 (2 H, m, H-4¢), 3.85 (1
H, dd, J = 2.0, 6.4 Hz, H-4), 3.79 (1 H, ddd, J = 1.6, 6.0, 6.4 Hz, H-
2), 3.62 (1 H, d, J = 6.0 Hz, OH), 1.51 (1 H, dd, J = 6.4, 13.2 Hz, H-
3), 1.47–1.37 (4 H, m, H-3, H-6, and OH), 1.04 (9 H, s, t-C4H9, TB-
DPS), 0.98 (9 H, t, J = 8.0 Hz, CH3, TES), 0.67 (6 H, q, J = 8.0 Hz,
CH2, TES).
1H NMR (CDCl3, 600 MHz): d = 7.66–7.61 (4 Harom, m, TBDPS),
7.45–7.35 (6 Harom, m, TBDPS), 7.30–7.21 (4 Harom, m, SPh), 7.15–
7.11 (1 Harom, m, SPh), 5.78 (1 H, dd, J = 6.9, 15.6 Hz, H-2¢), 5.70
(1 H, ddd, J = 6.6, 7.8, 15.6 Hz, H-3¢), 4.49 (1 H, dd, J = 0.5, 6.0 Hz,
H-4), 4.42 (1 H, d, J = 6.9 Hz, H-1¢), 4.05 (1 H, dd, J = 2.7, 6.9 Hz,
H-5), 3.55 (1 H, dd, J = 7.8, 14.1 Hz, H-4¢), 3.51 (1 H, dd, J = 6.6,
14.1 Hz, H-4¢), 2.08 (1 H, dd, J = 6.0, 17.4 Hz, H-3eq), 1.93–1.89
(1 H, m, H-6eq), 1.61 (1 H, d, J = 17.4 Hz, H-3ax), 1.49 (1 H, dd,
J = 6.9, 13.2 Hz, H-6ax), 1.06 (9 H, s, t-C4H9, TBDPS), 0.91 (9 H, t,
J = 7.8 Hz, CH3, TES), 0.55 (6 H, q, J = 7.8 Hz, CH2, TES).
13C NMR (CDCl3, 125 MHz): d = 210.4, 135.9, 135.7, 135.6, 133.6,
133.3, 131.7, 129.9, 129.3, 128.7, 127.9, 127.8, 127.7, 125.9, 90.2,
81.2, 75.3, 70.2, 410.7, 37.7, 35.4, 26.8, 19.0, 6.8, 4.8.
FAB-HRMS: m/z calcd for C38H50O4Si2SNa (M + Na)+: 681.2866;
found: 681.2865.
13C NMR (CDCl3, 125 MHz): d = 135.6, 135.6, 134.0, 133.9, 131.6,
129.8, 129.7, 127.6, 127.6, 87.6, 80.8, 75.7, 73.7, 73.5, 63.0, 40.4,
38.4, 26.8, 19.1, 6.8, 4.8.
Anal. Calcd for C32H48O5Si3: C, 67.56; H, 8.50. Found: C, 67.54; H,
8.69.
FAB-HRMS: m/z calcd for C32H48O5Si2Na (M + Na)+: 591.2938;
found: 591.2935.
(1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S,2¢E)-1¢-
(triethylsilyloxy)-4¢-phenylsulfanylbut-2¢-enyl]-7-oxabicy-
clo[2.2.1]heptan-2-ol (28)
(1S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-[(1¢S,2¢E)-1¢-(tri-
ethylsilyloxy)-4¢-phenylsulfanylbut-2¢-enyl]-3,3-dimethyl-7-
oxabicyclo[2.2.1]heptan-2-one (30)
To a solution of 27 (312 mg, 0.549 mmol) in CH2Cl2 (8 mL) at
–20 °C were added N-(phenylthio)phthalimide (351 mg, 1.37
mmol) and Bu3P (350 mL, 1.38 mmol). After stirring at the same
temperature for 10 min, the reaction was quenched with sat. aq
NaHCO3 (20 mL), and the aqueous layer was extracted with hexane
(3 × 30 mL). Drying (MgSO4), concentration, and flash chromatog-
raphy (SiO2, hexane–EtOAc, 25:1, 12:1, 11:1) gave the sulfide 28
To a solution of 29 (146 mg, 0.222 mmol) in THF (8 mL) at –78 °C
were added MeI (140 mL, 2.25 mmol) and t-BuOK (100 mg, 0.894
mmol), and the mixture was stirred at the same temperature for 7 h.
The reaction was quenched with sat. aq NH4Cl (4 mL), and the mix-
ture was extracted with Et2O (3 × 5 mL). The combined extracts
were dried (MgSO4) and concentrated. The residue was purified by
flash chromatography (SiO2, hexane–EtOAc, 50:1) to the ketone 30
(144 mg, 94%) as a colorless amorphous powder; [a]D23 +40.8 (c =
0.65, CHCl3).
22
(359 mg, 99%) as a colorless amorphous powder; [a]D –9.9 (c =
1.28, CHCl3).
IR (neat): 3448, 3073, 2955, 2876, 1589, 1473, 1428, 1112, 968,
823, 739, 702, 608, 508 cm–1.
IR (neat): 3071, 2956, 2875, 1762, 1717, 1559, 1473, 1112, 1070,
1023, 967, 740, 702, 612, 502, 484 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.67–7.61 (4 Harom, m, TBDPS),
7.45–7.36 (6 Harom, m, TBDPS), 7.32–7.29 (2 Harom, m, SPh), 7.24–
7.20 (2 Harom, m, SPh), 7.15–7.10 (1 Harom, m, SPh), 5.79 (1 H, ddd,
J = 6.6, 7.5, 15.6 Hz, H-3¢), 5.70 (1 H, dd, J = 6.3, 15.6 Hz, H-2¢),
4.62 (1 H, d, J = 6.3 Hz, H-1¢), 4.23 (1 H, br s, H-4), 3.96 (1 H, d,
J = 5.4 Hz, OH), 3.75 (1 H, br d, J = 6.3 Hz, H-5), 3.60 (1 H, dd,
J = 7.5, 14.1 Hz, H-4), 3.57–3.52 (2 H, m, H-2, H-4¢), 1.40–1.38 (2
H, m, H-3), 1.20 (1 H, br d, J = 13.5 Hz, H-6eq), 1.11 (1 H, dd,
J = 6.3, 13.5 Hz, H-6ax), 1.03 (9 H, s, t-C4H9, TBDPS), 0.94 (9 H, t,
J = 7.8 Hz, CH3, TES), 0.62 (3 H, q, J = 7.8 Hz, CH2, TES) 0.61
(3 H, q, J = 7.8 Hz, CH2, TES).
1H NMR (CDCl3, 400 MHz): d = 7.67–7.60 (4 Harom, m, TBDPS),
7.46–7.35 (6 Harom, m, TBDPS and SPh), 7.30–7.19 (4 Harom, m,
SPh), 7.14–7.09 (1 Harom, m, SPh), 5.86 (1 H, ddd, J = 1.2, 7.2, 15.6
Hz, H-2¢), 5.70 (1 H, dddd, J = 1.2, 6.8, 8.0, 15.6 Hz, H-3¢), 4.40 (1
H, br d, J = 7.2 Hz, H-1¢), 4.26 (1 H, dd, J = 2.4, 6.8 Hz, H-5), 3.91
(1 H, d, J = 1.6 Hz, H-4), 3.57–3.47 (2 H, m, H-4¢), 1.86 (1 H, ddd,
J = 1.6, 2.4, 13.6 Hz, H-6), 1.43 (1 H, dd, J = 6.8, 13.6 Hz, H-6),
1.06 (9 H, s, t-C4H9, TBDPS), 0.94 (3 H, s, CH3), 0.91 (9 H, t,
J = 7.6 Hz, CH3, TES), 0.56 (3 H, s, CH2), 0.55 (6 H, q, J = 7.6 Hz,
CH2, TES).
13C NMR (CDCl3, 125 MHz): d = 215.9, 136.0, 135.8, 135.7, 133.7,
133.5, 132.0, 129.8, 129.3, 128.8, 127.8, 127.7, 125.991.3, 90.1,
77.2, 71.7, 71.0, 46.8, 38.9, 35.4, 26.8, 22.1, 19.1, 18.5, 6.8, 4.9.
13C NMR (CDCl3, 125 MHz): d = 135.7, 135.6, 135.5, 134.1, 134.0,
132.0, 129.9, 129.7, 128.8, 127.9, 127.6, 127.6, 126.1, 87.1, 80.8,
75.8, 74.6, 73.5, 40.8, 38.5, 35.6, 26.8, 19.1, 6.7, 4.7.
Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York

1244
S. Tojo, M. Isobe
PAPER
van Maarseveen, J. H.; Rutjes, F. P. J. T.; Hiemstra, H. J.
FAB-HRMS: m/z calcd for C40H54O4Si2SNa (M + Na)+: 709.3179;
found: 709.3182.
Chem. Soc., Perkin Trans. 1 2002, 1693. (g) Benningshof,
J. C. J.; Ijsselstijn, M.; Wallner, S. R.; Koster, A. L.; Blaauw,
R. H.; van Ginkel, A. E.; Brière, J.-F.; van Maarseveen, J.
H.; Rutjes, F. P. J. T.; Hiemstra, H. J. Chem. Soc., Perkin
Trans. 1 2002, 1701. (h) Hue, B. T. B.; Dijkink, J.; Kuiper,
S.; Larson, K. K.; Guziec, F. S. Jr.; Goubitz, K.; Fraanje, J.;
Schenk, H.; van Maarseveen, J. H.; Hiemstra, H. Org.
Biomol. Chem. 2003, 1, 4364.
Acknowledgment
This study was supported by a Grant of the 21st Century COE Pro-
gram and Grant-in-Aid for Specially Promoted Research
(16002007) from the Ministry of Education, Culture, Sports, Sci-
ence and Technology (MEXT), Japan. We are grateful to Mr. S.
Kitamura at Nagoya University for the elemental analyses.
(5) For reviews, see: (a) Nicholas, K. M. Acc. Chem. Res. 1987,
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(7) This compund was obtained as a mixture of 11 and the
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5035. (b) Ojima, I.; Kogure, T. Organometallics 1982, 1,
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Synthesis 2005, No. 8, 1237–1244 © Thieme Stuttgart · New York