SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

Article abstract of DOI:10.1016/j.tet.2009.10.082

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.

Full text of DOI:10.1016/j.tet.2009.10.082

Tetrahedron 65 (2009) 10893–10900
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
SmI2-induced cyclization of optically active (E)- and (Z)-
b-alkoxyvinyl
sulfoxides with aldehydes
*
Tomohiro Kimura, Mayumi Hagiwara, Tadashi Nakata
Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2009
Received in revised form 2 October 2009
Accepted 22 October 2009
Available online 27 October 2009
SmI2-induced reaction of (E)-
b
-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly
stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-
3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-
opened product, and that of (Z)-(S)-isomer yielded many products.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Furthermore, synthetic methods for not only 2,6-syn-2,3-trans-
tetrahydropyran-3-ol, but also the stereoisomers, have also been
Since the first isolation of brevetoxin-B as a red tide toxin,
a number of marine polycyclic ethers, exemplified by ciguatoxins,
gambierol, and maitotoxin, have been reported.1 The most char-
acteristic structural feature of these natural products is a trans-
fused polycyclic ether ring system. Their synthetically challenging,
complex structures and potent bioactivities have attracted the at-
tention of numerous synthetic organic chemists. Thus, various
synthetic methods have been extensively studied and total syn-
thesis of many polycyclic ethers has been achieved.2 We have
already developed an efficient method for the construction of
trans-fused polycyclic ether based on the SmI2-induced reductive
required for the synthesis of several marine polycyclic ethers. In
order to solve this problem, we have recently developed SmI2-in-
5
duced reductive cyclizations of
b
b
-alkoxyvinyl sulfones A2 and
-alkoxyvinyl sulfoxides A36,7 with aldehydes. Herein, we describe
in detail the SmI2-induced cyclization of optically active (E)- and
(Z)- -alkoxyvinyl sulfoxides A3 with aldehydes.
b
2. Results and discussion
In the reaction of -alkoxyvinyl sulfoxide A3 with SmI2, we
b
expected that the (R/S)-chirality of sulfoxide and the (E/Z)-stereo-
chemistry of the olefin in the substrates would influence the
transition state to give several stereoisomers as products, stereo-
selectively. Therefore, we investigated the SmI2-induced reductive
cyclization using four stereoisomers, 5, 8, 13, and 17, as the
substrates.
cyclization of b-alkoxyacrylate A1 with a carbonyl group, affording
2,6-syn-2,3-trans-tetrahydropyran-3-ol B1 with complete stereo-
selectivity (Fig. 1).3 This method has been successfully applied to
the synthesis of polycyclic ethers.4 The product B1 is a cyclic ether
having an acetic acid moiety, that is, a two-carbon unit, as the C2-
side chain. A functional one-carbon unit as the C2-side chain is
often required and is useful for the synthesis of polycyclic ethers.
First, we examined the reaction of (E)-b-alkoxyvinyl (R)- and (S)-
sulfoxides, 5 and 8, with aldehydes (Scheme 1). The substrate 5 was
synthesized from the known alcohol 1,4g which was prepared by
SmI2-induced cyclization as the key reaction. Treatment of 1 with
(R)-ethynyl p-tolylsulfoxide 28 in the presence of N-methyl-
H
H
H
H
O
O
OH
SmI2
CHO
3
morpholine (NMM) stereoselectively afforded (E)-b-alkoxyvinyl
6
2
R
R
MeOH
THF
(R)-sulfoxide 4 in 96% yield,9 and this was reduced with DIBAH to
give the aldehyde 5 in 85% yield. Upon treatment of (E)-(R)-5 with
O
O
H
H
10
2.6 equiv of SmI2 in the presence of MeOH (2.5 equiv) in THF,
A1: R = CO2Et
A2: R = SO2Ph
A3: R = S(O)-p-Tol
B1: R = CO2Et
B2: R = SO2Ph
B3: R = S(O)-p-Tol
reductive cyclization took place smoothly at 0 ꢀC to give 2,6-anti-
2,3-cis-tetrahydropyran-3-ol 6a as a single product, which was
acetylated with Ac2O in pyridine to give the acetate 6b in 64% yield
(two steps). Use of CF3CH2OH instead of MeOH as a proton source
slightly improved the yield of 6b (71%).11 The 2,6-anti-2,3-cis-con-
figuration of 6b was confirmed by the coupling constants of C3-H;
Figure 1. SmI2-induced reductive cyclizations.
* Corresponding author.
E-mail address: nakata@rs.kagu.tus.ac.jp (T. Nakata).
d
5.16 (ddd, J¼11.3, 5.5, 5.5 Hz). On the other hand, the reaction of 1
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.082

10894
T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
O
(R)-2
S
p-Tol
H
H
H
H
H
H
H
H
H
H
H
H
R
R
Ph
O
O
Ph
O
OH
CO2Et
Ph
O
O
O
NMM
DIBAH
S(O)-p-Tol
CO2Et
S(O)-p-Tol
O
O
O
H
CHO
CH2Cl2, rt
96%
CH2Cl2, –78 °C
85%
O
O
O
1
4
5
Ac2O
H
H
H
H
H
a) SmI2, MeOH
THF, 0 °C
R
R
Ph
O
Ph
O
O
O
pyridine, rt
S(O)-p-Tol
OAc
S(O)-p-Tol
OH
6
2
6
2
3
3
O
64% (2 steps via a)
71% (2 steps via b)
b) SmI2, CF3CH2OH
THF, 0 °C
O
O
H
H
H
H
H
H
6a
6b
O
(S)-3
S
p-Tol
H
H
H
H
H
H
H
H
H
H
S
S
Ph
O
O
Ph
O
OH
Ph
O
O
NMM
DIBAH
S(O)-p-Tol
CO2Et
S(O)-p-Tol
O
O
CO2Et
O
H
CHO
CH2Cl2, rt
96%
CH2Cl2, –78 °C
92%
O
O
H
O
H
7
8
1
H
H
H
H
H
S
S
Ph
O
O
Ph
O
O
O
SmI2, MeOH
THF, 0 °C
Ac2O
S(O)-p-Tol
OAc
S(O)-p-Tol
OH
6
2
6
2
3
3
O
pyridine, rt
O
O
85% (2 steps)
H
H
H
H
H
H
9a
9b
Scheme 1.
and (S)-ethynyl p-tolylsulfoxide 3 in the presence of NMM, fol-
lowed by DIBAH reduction, afforded the aldehyde 8 in 88% yield
(two steps). The SmI2-induced cyclization of (E)-(S)-8 in the pres-
ence of MeOH afforded 2,6-syn-2,3-trans-tetrahydropyran-3-ol 9a,
which was acetylated with Ac2O to give the acetate 9b in 85% yield
(two steps). The 2,6-syn-2,3-trans-configuration of 9b was also
confirmed by the coupling constants of C3-H;
9.8, 4.6 Hz).
d
4.67 (ddd, J¼11.0,
These results can be explained as follows (Fig. 2). In the SmI2-
induced cyclization, the first single-electron reduction of aldehyde
Ph
H
O
O
O
Ph
H
H
O
O
O
H
H
O
O
H
O
O
R
S
(E)-(R)-5
Sm
O
I2Sm
R
I2
O
S
axial
ii
i
Me
equatorial
Me
H
H
H
H
H
H
6
H
R
R
Ph
Ph
O
O
Ph
O
O
S(O)-p-Tol
OH
S(O)-p-Tol
6
2
2
3
3
O
O
O
O
OH
H
H
H
H
H
2,6-syn-2,3-trans-10a
2,6-anti-2,3-cis-6a
H
O
H
O
H
Ph
O
O
H
H
O
O
H
O
O
Me
equatorial
S
(E)-(S)-8
O
S
I2Sm
Sm
S
O
O
I2
O
S
Me
axial
iv
iii
H
H
H
H
H
H
H
6
H
S
S
Ph
O
O
Ph
O
O
S(O)-p-Tol
OH
S(O)-p-Tol
OH
2
6
2
3
3
O
O
O
O
H
H
H
H
2,6-anti-2,3-cis-11a
2,6-syn-2,3-trans-9a
Figure 2. Plausible transition states for the SmI2-induced cyclization of 5 and 8.

T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
10895
R
R
S(O)-p-Tol
S(O)-p-Tol
H
H
H
H
H
H
H
H
H
H
H
H
Ph
O
OH
CO2Et
LHMDS
Ph
O
O
Ph
O
O
THF, 0 °C;
DIBAH
O
O
CO2Et
O
CHO
O
then (R)-2
–78 to –20 °C
88%
O
CH2Cl2, –78 °C
45%
O
1
12
13
R
a) 1) SmI2, MeOH
THF, 0 °C
S(O)-p-Tol
H
H
H
H
R
H
H
H
H
Ph
O
O
2) Ac2O, pyridine
rt
Ph
O
OR
3
S(O)-p-Tol
OR
6
2
3
O
O
+
O
O
OR
b) 1) SmI2, CF3CH2OH
THF, 0 °C
H
H
H
2) Ac2O, pyridine
rt
14a: R =H
15a: R = H
15b: R = Ac
14b: R = Ac
27% (2 steps via a)
45% (2 steps via b)
26% (2 steps via a)
27% (2 steps via b)
S
S
S(O)-p-Tol
S(O)-p-Tol
H
H
H
H
H
H
H
H
Ph
O
OH
LHMDS
Ph
O
O
Ph
Ph
O
O
THF, 0 °C;
DIBAH
O
CO2Et
O
CO2Et
O
O
CHO
O
then (S)-3
O
CH2Cl2, –78 °C
73%
O
H
H
H
H
–78 to –20 °C
91%
1
16
17
S
S(O)-p-Tol
H
H
H
H
H
H
H
H
H
H
H
H
1) SmI2, MeOH
THF, 0 °C
S
S
Ph
O
O
Ph
O
O
O
OR
3
S(O)-p-Tol
S(O)-p-Tol
6
2
6
2
3
3
+
+
O
O
2) Ac2O, pyridine
rt
O
OR
O
OR
O
OR
H
H
H
H
H
9a: R = H
18a: R =H
18b: R = Ac (19%, 2 steps)
19a: R = H
19b: R = Ac (7%, 2 steps)
9b: R = Ac (16%, 2 steps)
Scheme 2.
with SmI2 gives a ketyl radical and then C–C bond formation occurs
in the chelated intermediate to give the cyclized product.3 From the
result of reaction of (E)-(R)-5 to give 6a, the reaction is considered
to proceed through transition state i, involving chelation by Sm(III)
and sulfoxide. The intermediate i has an equatorial p-tolyl group in
the chair-like conformation. If the reaction proceeded through the
other chelated transition state ii having an axial p-tolyl group, the
2,6-syn-2,3-trans-isomer 10a must be produced. Namely, in this
cyclization, equatorial configuration of the p-tolyl group in the
transition state should be most important to control the stereo-
chemistry of the product. Furthermore, the result of the reaction of
(E)-(S)-8 giving 9a also supports the above conclusion, that is, the
Me
I2
H
H
H
H
Ph
H
R
Ph
O
O
O
O
O
Sm
O
H
S(O)-p-Tol
S
6
2
O
R
3
equatorial
(Z)-(R)-13
O
O
H
O
OH
H
H
v
2,6-syn-2,3-cis-14a
Me
I2
axial
Ph
Ph
H
S
I2Sm
S
H
O
O
O
O
O
Ph
S(O)-p-Tol
S(O)-p-Tol
H
H
H
H
O
O
O
O
Sm
O
H
S
O
O
H
O
O
(Z)-(S)-17
O
S
OSmI2
H
vi
vii
viii
2,6-syn-2,3-trans-9a
2,6-syn-2,3-cis-18a
I2
Sm
Ph
O
H
O
O
H
v
O
O
15a
19a
(Z)-(R)-13
(Z)-(S)-17
Me
S
viii
H
O
R or S
ix
Figure 3. Plausible transition states for the SmI2-induced cyclization of 13 and 17.

10896
T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
H
H
H
H
H
TBSCl
(CF3CO)2O, pyridine
MeCN, 0 °C;
H
H
H
H
H
H
H
H
H
S
S
Ph
O
O
Ph
O
O
CHO
Ph
O
O
imidazole
S(O)-p-Tol
S(O)-p-Tol
O
O
O
DMF, rt
90%
(2 steps from 8)
K2CO3, H2O, 0 °C
72%
O
OH
O
OTBS
O
OTBS
H
H
H
H
22
21
Scheme 3.
9a
reaction of 8 would proceed through the chelated transition state iii
having an equatorial p-tolyl group to give 9a. In this case, the other
transition state iv having an axial p-tolyl group must produce the
2,6-anti-2,3-cis-isomer 11a.
derivatives. The desired stereoisomers of tetrahydropyran-3-ols
could be obtained by selecting the appropriate combination of
substrate and reagent, (R)-2 or (S)-3.
Next, the reactions of (Z)-b-alkoxyvinyl (R)- and (S)-sulfoxides,
4. Experimental
13 and 17, with SmI2 were examined (Scheme 2). Treatment of 1
with LHMDS followed by addition of (R)-sulfoxide 2 stereo-
4.1. General
selectively afforded (Z)-b
-alkoxyvinyl (R)-sulfoxide 12 in 88% yield,9
and DIBAH reduction gave the aldehyde 13 in 45% yield. Treatment
of (Z)-(R)-13 with SmI2 in the presence of MeOH in THF at 0 ꢀC,
followed by acetylation, afforded two products; 2,6-syn-2,3-cis-3-
Flash column chromatography was performed on Silica gel 60 N
(spherical neutral, 40–100 mm, Kanto Kagaku). Melting points were
measured on a Yanaco MP-S9 and are uncorrected. Optical rotations
were measured on a JASCO P-1010 polarimeter. IR spectra were
recorded on a JASCO FT/IR-460. 1H and 13C NMR spectra were
recorded on JEOL JNM-EX 300, JEOL JNM-EX 500, BRUKER Biospin
ADVANCE 400 M, and BRUKER 600 UltraShield . Mass spectra were
recorded on JEOL JMS-SX102A.
acetoxy-tetrahydropyran 14b (27%) and (E)-g-acetoxyvinyl sulfox-
ide 15b (26%). Use of CF3CH2OH instead of MeOH in the present
reaction slightly increased the yield to give 14b (45%) and 15b
(27%). The 2,6-syn-2,3-cis-configuration of 14b was confirmed by
the coupling constant of C3-H;
d
5.11 (br s, W1/2¼5.6 Hz) and ob-
served NOE between C2-H and C6-H. The structure of the (E)-olefin
15b was determined by characteristic 1H NMR signals of vinyl
4.1.1. (E)-b-Alkoxyvinyl (R)-sulfoxide-ester 4. To a solution of 1
protons;
C1-H).12 Moreover, addition of 1 and (S)-sulfoxide 3 in the presence
of LHMDS gave the (Z)- -alkoxyvinyl (S)-sulfoxide 16 in 91% yield,
d
6.53 (dd, J¼15.3, 5.5 Hz, C2-H), 6.38 (dd, J¼15.3, 1.2 Hz,
(51.2 mg, 0.159 mmol) in CH2Cl2 (1.5 mL) were added N-methyl-
morpholine (18.4 mg, 0.180 mmol) and (R)-2 (41.0 mg, 0.250 mmol)
at 0 ꢀC. After stirring at room temperature for 16 h, the reaction
mixture was quenched with 1 N-HCl and extracted with EtOAc. The
combined organic layer was washed with brine, dried over MgSO4,
and evaporated in vacuo. The residue was purified by flash column
b
and this was reduced with DIBAH to give the aldehyde 17 in 73%
yield. The reaction of (Z)-(S)-17 with SmI2, followed by acetylation,
gave many products, which contain 2,6-syn-2,3-trans-9b (ca. 16%),
2,6-syn-2,3-cis-18b (ca. 19%), (E)-g-acetoxyvinyl sulfoxide 19b
chromatography (n-hexane/EtOAc, 2:1) to give vinyl sulfoxide 4
(ca. 7%), etc.13 Use of CF3CH2OH did not improve the yield of
23
(74.2 mg, 96%) as a yellow oil. [
a
]
¼ꢁ55.2 (c 1.04, CHCl3); IR
D
the cyclized products. The 2,6-syn-2,3-cis-configuration of 18b
(neat) 2980, 2933, 2867, 1733, 1622, 1599, 1496, 1456, 1393, 1369,
1327, 1299, 1278, 1180, 1099, 1038, 1013 cmꢁ1 1H NMR (500 MHz,
CDCl3)
7.49 (d, J¼7.9 Hz, 2H), 7.45 (dd, J¼7.6, 2.1 Hz, 1H), 7.37–7.34
was confirmed by the coupling constant of C3-H;
d 5.05 (br s,
;
W1/2¼7.0 Hz, 1H) and observed NOE between C2-H and C6-H. The
d
structure of the (E)-olefin 19b was also determined by character-
(m, 3H), 7.30 (d, J¼8.2 Hz, 2H), 7.15 (d, J¼12.5 Hz, 1H), 5.81 (d,
J¼12.5 Hz, 1H), 5.48 (s, 1H), 4.28 (dd, J¼10.4, 4.6 Hz, 1H), 4.15 (br q,
J¼7.0 Hz, 2H), 3.96 (ddd, J¼10.1, 10.1, 4.6 Hz, 1H), 3.89 (ddd, J¼8.5,
8.5, 2.7 Hz, 1H), 3.64 (dd, J¼10.4, 10.4 Hz, 1H), 3.51 (ddd, J¼12.2,
12.2, 3.4 Hz, 1H), 3.42 (ddd, J¼9.5, 9.5, 4.6 Hz, 1H), 2.69 (dd, J¼15.3,
3.1 Hz, 1H), 2.55 (ddd, J¼11.0, 3.7, 3.7 Hz, 1H), 2.45 (dd, J¼15.6,
7.9 Hz, 1H), 2.39 (s, 3H), 1.76 (ddd, J¼11.0, 11.0, 11.0 Hz, 1H), 1.25 (br
istic 1H NMR signals;
d
6.49 (dd, J¼15.2, 5.8 Hz, C2-H), 6.41 (d,
J¼15.2 Hz, C1-H).14
The reaction of (Z)-(R)-13 would also proceed through the
chelated transition state v to give 14a (Fig. 3). In the case of (Z)-(S)-
17, the corresponding chelated transition state vi would be un-
favorable, because of the axial p-tolyl group; thus, the reaction
would proceed via the non-chelated transition states, vii and viii, to
give 9a and 18a, respectively. The olefinic by-products 15a and 19a
might be produced by ring opening subsequent to the cyclization;
the participation of the axial-O-Sm(III) to the ring-O atom in the
intermediate ix, generated through v or viii via C–C bond formation
followed by the second reduction with SmI2, might assist the ring
opening.
t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 170.1, 154.9, 141.5,
140.9, 136.9, 129.8, 129.1, 128.2, 126.0, 124.1, 114.0, 101.6, 77.5, 76.3,
75.5, 73.1, 68.8, 60.7, 37.0, 34.3, 21.2, 14.1; HRMS (EI) calcd for
C26H30O7S [Mþ] 486.1712, found 486.1710.
4.1.2. (E)-b-Alkoxyvinyl (R)-sulfoxide-aldehyde 5. To a solution of 4
(282.3 mg, 0.580 mmol) in CH2Cl2 (5.8 mL) was added DIBAH
(1.20 mL, 0.97 M solution in n-hexane, 1.16 mmol) at ꢁ78 ꢀC. After
stirring for 20 min, i-PrOH (1.0 mL) and water (1.0 mL) were added
at the same temperature and silica gel was added at room tem-
perature. The mixture was diluted with EtOAc, stirred for 1 h, fil-
trated through a Celite pad, and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/EtOAc,
For application to the synthesis of polycyclic ethers, the p-
tolylsulfoxymethyl group of the product 9a was transformed to an
aldehyde group (Scheme 3). TBS protection of 9a afforded the TBS–
ether 21 in 90% yield (two steps from 8). Treatment of the sulfoxide
21 with (CF3CO)2O–pyridine followed by aqueous K2CO3 afforded
the aldehyde 22 in 72% yield. Thus, the SmI2-induced cyclization of
b-alkoxyvinyl sulfoxide should be useful for the construction of
1:1/1:2) to give aldehyde 5 (218.3 mg, 85%) as colorless crystals.
tetrahydropyran derivatives having a functional one-carbon unit as
the C2-side chain.
23
Mp 158.0–159.0 ꢀC (EtOAc); [
a
]
¼ꢁ74.2 (c 1.00, CHCl3); IR (KBr)
D
2941, 2880, 2743, 1723, 1622, 1491, 1451, 1401, 1390, 1372, 1338,
1290,1223,1207,1175, 1137, 1121,1100,1079,1050,1039,1011 cmꢁ1
1H NMR (500 MHz, CDCl3)
;
3. Conclusion
d
9.73 (t, J¼1.2 Hz, 1H), 7.49 (d, J¼7.9 Hz,
2H), 7.45 (dd, J¼7.6, 2.6 Hz, 2H), 7.37–7.35 (m, 3H), 7.30 (d, J¼7.9 Hz,
1H), 7.14 (d, J¼12.8 Hz, 1H), 5.82 (d, J¼12.8 Hz, 1H), 5.48 (s, 1H), 4.27
(dd, J¼10.7, 4.9 Hz, 1H), 3.97 (ddd, J¼9.7, 9.7, 3.1 Hz, 1H), 3.88 (ddd,
J¼10.7, 10.7, 4.6 Hz, 1H), 3.62 (dd, J¼10.4, 10.4 Hz, 1H), 3.51 (ddd,
In summary, SmI2-induced highly stereoselective cyclization of
b-alkoxyvinyl sulfoxides with aldehydes was developed for the
construction of several stereoisomers of tetrahydropyran-3-ol

T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
10897
J¼11.9, 9.5, 4.0 Hz, 1H), 3.43 (ddd, J¼9.5, 9.5, 4.9 Hz, 1H), 2.74 (dd,
J¼16.5, 1.5 Hz, 1H), 2.59–2.53 (m, 2H), 2.39 (3H, s), 1.76 (ddd, J¼11.3,
(dd, J¼15.6, 7.6 Hz, 1H), 2.41 (s, 3H), 1.80 (ddd, J¼11.6, 11.6, 11.6 Hz,
1H), 1.26 (t, J¼9.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 170.1, 155.0,
11.3, 11.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
199.0, 154.6, 141.4,
141.6, 141.1, 137.0, 129.9, 129.1, 128.3, 126.0, 124.2, 114.5, 101.6, 78.4,
76.4, 75.7, 73.2, 68.9, 60.8, 36.8, 34.7, 21.3, 14.1; HRMS (EI) calcd for
C26H30O7S [Mþ] 486.1712, found 486.1706.
141.0, 136.8, 129.9, 129.1, 128.2, 126.0, 124.1, 114.2, 101.6, 77.7, 75.4,
74.7, 73.1, 68.7, 45.4, 34.2, 21.2; HRMS (EI) calcd for C24H26O6S [Mþ]
442.1450, found 442.1451; Anal. Calcd for C24H26O6S: C, 65.14; H,
5.92, found C, 65.13; H, 6.17.
4.1.5. (E)-b-Alkoxyvinyl (S)-sulfoxide-aldehyde 8. To a solution of 7
(251.2 mg, 0.516 mmol) in CH2Cl2 (5.0 mL) was added DIBAH
(1.06 mL, 0.97 M solution in n-hexane, 1.028 mmol) at ꢁ78 ꢀC. After
stirring at ꢁ78 ꢀC for 20 min, i-PrOH (2.0 mL) and water (2.0 mL)
were added at the same temperature and silica gel was added at
room temperature. The mixture was diluted with EtOAc, stirred for
1 h, filtrated through a Celite pad, and concentrated in vacuo. The
residue was purified by flash column chromatography (n-hexane/
4.1.3. Reaction of (E)-(R)-5 with SmI2 followed by acetylation. (a) To
a
solution of 5 (65.0 mg, 0.147 mmol) and MeOH (11.9 mL,
0.368 mmol) in THF (1.5 mL) was added SmI2 (3.8 mL, 0.1 M solu-
tion in THF, 0.380 mmol) at 0 ꢀC. After stirring for 15 min, the
mixture was quenched with satd Na2S2O3 and satd NaHCO3, and
extracted with EtOAc. The combined organic layer was washed
with brine, dried over MgSO4, and evaporated in vacuo to give
crude alcohol 6a (63.4 mg). To a solution of 6a in pyridine (1.0 mL)
was added acetic anhydride (1.0 mL) at room temperature. After
stirring for 42 h, the mixture was evaporated azeotropically with
benzene in vacuo. The residue was purified by flash column chro-
EtOAc, 1:1/1:2) to give aldehyde 8 (210.0 mg, 92%) as colorless
21
crystals. Mp 136.0–137.0 ꢀC (EtOAc); [
a
]
¼ꢁ44.0 (c 1.06, CHCl3);
D
IR (KBr) 3045, 3014, 2974, 2932, 2875, 1733, 1729, 1616, 1602, 1493,
1456, 1394, 1373, 1338, 1303, 1287, 1212, 1186, 1151, 1102,
1007 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
9.75 (dd, J¼2.1, 1.5 Hz, 1H),
matography (n-hexane/EtOAc,1:1) to give acetate 6b (47.5 mg, 64%)
7.50–7.46 (m, 4H), 7.39–7.35 (m, 3H), 7.32 (d, J¼7.9 Hz, 2H), 7.12 (d,
J¼12.5 Hz, 1H), 5.85 (d, J¼12.5 Hz, 1H), 5.51 (s, 1H), 4.29 (dd, J¼10.4,
4.6 Hz, 1H), 3.98 (ddd, J¼9.2, 9.2, 3.4 Hz, 1H), 3.88 (ddd, J¼11.0, 11.0,
4.6 Hz, 1H), 3.64, (dd, J¼10.1, 10.1 Hz, 1H), 3.54 (ddd, J¼10.8, 8.9,
4.0 Hz, 1H), 3.44 (ddd, J¼9.8, 9.8, 4.9 Hz, 1H), 2.78 (ddd, J¼16.5, 3.4,
1.2 Hz, 1H), 2.67 (ddd, J¼11.6, 4.3, 4.3 Hz, 1H), 2.57 (ddd, J¼16.5, 8.2,
2.4 Hz,1H), 2.41 (s, 3H),1.81 (ddd, J¼11.3,11.3,11.3 Hz,1H); 13C NMR
21
as colorless crystals. Mp 200.0–201.0 ꢀC (EtOAc); [
a]
¼þ76.0 (c
D
1.02, CHCl3); IR (KBr) 3057, 3035, 2934, 2868, 1742, 1598, 1501, 1470,
1456,1418,1394,1378,1356,1332,1315,1293,1284,1190,1180,1175,
1157, 1105, 1100, 1048, 1027, 1014 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
7.60 (d, J¼7.9 Hz, 2H), 7.48 (d, J¼6.4 Hz, 2H), 7.37 (d, J¼6.7 Hz, 5H),
5.52 (s, 1H), 5.16 (ddd, J¼11.3, 5.5, 5.5 Hz, 1H), 4.58 (ddd, J¼10.1, 5.5,
4.0 Hz, 1H), 4.31 (dd, J¼10.4, 4.9 Hz, 1H), 3.68 (dd, J¼10.4, 10.4 Hz,
1H), 3.58 (ddd, J¼12.5, 9.2, 4.0 Hz, 1H), 3.43 (ddd, J¼9.5, 9.5, 4.6 Hz,
1H), 3.31–3.26 (m, 2H), 3.22 (dd, J¼13.7, 10.7 Hz, 1H), 3.00 (dd,
J¼13.7, 3.4 Hz, 1H), 2.44 (s, 3H), 2.34–2.30 (m, 2H), 2.04 (s, 3H), 1.71
(ddd, J¼11.0, 11.0, 11.0 Hz, 1H), 1.55 (ddd, J¼11.3, 11.3, 11.3 Hz, 1H);
(75 MHz, CDCl3)
d 199.0, 154.5, 141.4, 141.2, 136.9, 129.9, 129.2,
128.3, 126.0, 124.2, 114.7, 101.6, 78.1, 75.6, 74.9, 73.3, 68.8, 45.3, 34.6,
21.3; HRMS (EI) calcd for C24H26O6S [Mþ] 442.1450, found 442.1448.
Anal. Calcd for C24H26O6S: C, 65.14; H, 5.92; S, 7.25, found C, 65.05;
H, 5.99; S, 7.18.
13C NMR (75 MHz, CDCl3)
d 169.4, 142.0, 140.7, 137.1, 130.1, 129.1,
128.3, 126.1, 124.2, 101.8, 77.1, 76.3, 73.7, 69.2, 69.0, 67.9, 67.4, 54.7,
34.5, 30.6, 21.4, 21.0; HRMS (EI) calcd for C26H30O7S [Mþ] 486.1712,
found 486.1707; Anal. Calcd for C26H30O7S: C, 64.18; H, 6.21; S, 6.59.
found C, 64.15; H, 6.24; S, 6.51.
(b) To a solution of 5 (128.1 mg, 0.289 mmol) and CF3CH2OH
(72.8 mL, 0.723 mmol) in THF (3.0 mL) was added SmI2 (7.2 mL,
0.1 M solution in THF, 0.720 mmol) at 0 ꢀC. After stirring at 0 ꢀC for
20 min, the mixture was quenched with satd Na2S2O3 and satd
NaHCO3, and extracted with EtOAc. The combined organic layer
was washed with brine, dried over MgSO4, and evaporated in vacuo
to give crude alcohol 6a (258.3 mg). To a solution of 6a in pyridine
(2.0 mL) was added acetic anhydride (2.0 mL) at room temperature.
After stirring for 12 h, the mixture was azeotropically evaporated
with benzene in vacuo. The residue was purified by flash column
chromatography (n-hexane/EtOAc, 1:1) to give an acetate 6b
(99.4 mg, 71%) as colorless crystals.
4.1.6. Reaction of (E)-(S)- 8 with SmI2 followed by acetylation. To
a
solution of 8 (55.9 mg, 0.126 mmol) and MeOH (10.3 mL,
0.315 mmol) in THF (1.2 mL) was added SmI2 (8.0 mL, 0.1 M solu-
tion in THF, 0.800 mmol) at 0 ꢀC. After stirring for 15 min, the
mixture was quenched with satd Na2S2O3 and satd NaHCO3 and
extracted with EtOAc. The combined organic layer was washed
with brine, dried over MgSO4 and evaporated in vacuo to give crude
alcohol 9a. To a solution of 9a in pyridine (1.0 mL) was added acetic
anhydride (1.0 mL) at room temperature. After stirring for 15 h, the
mixture was azeotropically evaporated with benzene in vacuo. The
residue was purified by flash column chromatography (n-hexane/
EtOAc, 2:1) to give acetate 9b (51.9 mg, 85%) as colorless crystals.
23
Mp 219.5–220.5 ꢀC (EtOAc); [
a
]
¼ꢁ11.7 (c 1.42, CHCl3); IR (KBr)
D
2925, 2878, 2857, 1748, 1494, 1456, 1424, 1387, 1376, 1340, 1329,
1312, 1289, 1220, 1190, 1106, 1092, 1074, 1048, 1039, 1029 cmꢁ1; 1H
NMR (500 MHz, CDCl3)
d
7.54 (d, J¼8.2 Hz, 2H), 7.50 (dd, J¼7.9,
1.8 Hz, 2H), 7.39–7.35 (m, 3H), 7.33 (d, J¼8.2 Hz, 2H), 5.55 (s, 1H),
4.67 (ddd, J¼11.0, 9.8, 4.6 Hz, 1H), 4.32 (dd, J¼10.4, 4.6 Hz, 1H), 3.98
(ddd, J¼11.6, 11.0, 1.8 Hz, 1H), 3.71 (dd, J¼10.4, 10.4 Hz, 1H), 3.62
(ddd, J¼11.6, 9.2, 4.0 Hz, 1H), 3.43 (ddd, J¼10.1, 10.1, 4.9 Hz, 1H),
3.35 (ddd, J¼11.0, 9.2, 4.0 Hz, 1H), 3.26 (ddd, J¼11.6, 9.2, 4.0 Hz, 1H),
2.91 (dd, J¼13.1, 1.8 Hz, 1H), 2.69 (dd, J¼13.1, 11.0 Hz, 1H), 2.54 (ddd,
J¼11.3, 4.3, 4.3 Hz, 1H), 2.50 (ddd, J¼11.0, 4.0, 4.0 Hz, 1H), 2.41 (3H,
s), 2.03 (3H, s), 1.75 (ddd, J¼11.3, 11.3, 11.3 Hz, 1H), 1.59 (ddd,
4.1.4. (E)-b-Alkoxyvinyl (S)-sulfoxide-ester 7. To a solution of 1
(100.0 mg, 0.310 mmol) in CH2Cl2 (3.0 mL) were added N-methyl-
morpholine (36.8 mg, 0.360 mmol) and (S)-3 (76.2 mg,
0.464 mmol) at 0 ꢀC. The mixture was stirring at room temperature
for 28 h, quenched with 1 N-HCl, and extracted with EtOAc. The
combined organic layer was washed with brine, dried over MgSO4,
and evaporated in vacuo. The residue was purified by flash column
chromatography (n-hexane/EtOAc, 2:1/1:1) to give vinyl sulfox-
J¼11.6, 11.6, 11.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 169.8,
20
ide 7 (145.2 mg, 96%) as a white solid. [
a
]
¼ꢁ26.1 (c 1.01, CHCl3);
141.6, 140.9, 137.2, 130.0, 129.1, 128.3, 126.1, 123.8, 101.8, 76.8,
76.6, 76.0, 73.7, 73.5, 69.6, 69.0, 61.0, 34.9, 34.5, 21.4, 21.0; HRMS
(EI) calcd for C26H30O7S [Mþ] 486.1712, found 486.1712.; Anal. Calcd
for C26H30O7S: C, 64.18; H, 6.21; S, 6.59. Found C, 64.18; H, 6.27;
S, 6.21.
D
IR (neat) 2982, 2935, 2876, 1739, 1733, 1622, 1602, 1493, 1456, 1389,
1369, 1330, 1306, 1287, 1195, 1180, 1100, 1031, 1015 cmꢁ1 1H NMR
(500 MHz, CDCl3)
7.48 (m, 4H), 7.34 (m, 5H), 7.14 (d, J¼12.5 Hz,
;
d
1H), 5.85 (d, J¼12.5 Hz, 1H), 5.50 (s, 1H), 4.30 (dd, J¼10.4, 4.9 Hz,
1H), 4.16 (qd, J¼7.0, 2.1 Hz, 2H), 3.98 (ddd, J¼10.7, 9.8, 4.6 Hz, 1H),
3.88 (ddd, J¼8.5, 7.9, 3.7 Hz, 1H), 3.65 (dd, J¼10.4, 10.4 Hz, 1H), 3.54
(ddd, J¼12.8, 8.8, 4.0 Hz, 1H), 3.43 (ddd, J¼10.0, 10.0, 4.9 Hz, 1H),
2.72 (dd, J¼15.9, 3.7 Hz, 1H), 2.64 (ddd, J¼11.6, 4.3, 4.3 Hz, 1H), 2.46
4.1.7. (Z)-
(84.3 mg, 0.262 mmol) in THF (2.4 mL) was added LHMDS (300
1.0 M solution in THF, 0.300 mmol) at 0 ꢀC. After stirring at 0 ꢀC for
b-Alkoxyvinyl (R)-sulfoxide-ester 12. To a solution of 1
mL,

10898
T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
30 min and at room temperature for 30 min, a solution of (R)-2
(207.1 mg, 1.255 mmol) in THF (1.2 mL) was added at ꢁ78 ꢀC. After
stirring at ꢁ20 ꢀC for 2 h, the mixture was quenched with satd
NaHCO3 and extracted with EtOAc. The combined organic layer was
washed with brine, dried over MgSO4, and evaporated in vacuo. The
residue was purified by flash column chromatography (n-hexane/
J¼13.4, 7.9 Hz, 1H), 3.08 (ddd, J¼11.3, 9.2, 4.3 Hz, 1H), 2.88 (dd,
J¼13.4, 4.6 Hz, 1H), 2.42 (s, 3H), 2.26 (ddd, J¼13.7, 4.0, 3.7 Hz, 1H),
2.22 (ddd, J¼11.3, 4.0, 4.0 Hz, 1H), 2.14 (s, 3H), 1.70–1.62 (m, 2H);
13C NMR (75 MHz, CDCl3)
d 170.1, 141.8, 139.6, 137.2, 129.9, 128.3,
126.1, 124.2, 101.8, 76.9, 73.7 (2C), 72.4, 70.2, 69.0, 57.4, 34.5, 33.7,
29.7, 21.5, 21.0; HRMS (EI) calcd for C26H30O7S [M-Hþ] 485.1634,
EtOAc, 1:2) to give vinyl sulfoxide 12 (112.3 mg, 88%) as a white
found 485.1631; Anal. Calcd for C26H29O7S: C, 64.18; H, 6.21. Found
21
20
solid. [
a
]
¼ꢁ155.8 (c 1.18, CHCl3); IR (neat) 2979, 2929, 2874,
C, 63.94; H, 6.20. 15b. [
a
]
¼þ41.5 (c 0.75, CHCl3); IR (KBr) 3037,
D
D
1734, 1624, 1492, 1456, 1395, 1369, 1328, 1306, 1286, 1235, 1201,
2926, 2865, 1739, 1733, 1594, 1495, 1458, 1429, 1395, 1379, 1315,
1286, 1236, 1187, 1159, 1109, 1049, 1034 cmꢁ1 1H NMR (500 MHz,
CDCl3)
7.50 (d, J¼8.2 Hz, 2H), 7.46 (dd, J¼7.9, 2.1 Hz, 2H), 7.38–
1179, 1098, 1030, 1015 cmꢁ1 1H NMR (500 MHz, CDCl3)
;
d
7.50 (d,
;
J¼8.2 Hz, 2H), 7.48–7.46 (m, 2H), 7.40–7.36 (m, 3H), 7.29 (d,
J¼7.9 Hz, 2H), 6.64 (d, J¼5.5 Hz, 1H), 5.52 (s, 1H), 5.47 (d, J¼5.5 Hz,
1H), 4.33 (dd, J¼10.4, 4.9 Hz, 1H), 4.20 (q, J¼7.3 Hz, 2H), 3.99–3.93
(m, 2H), 3.64 (dd, J¼10.4, 10.4 Hz, 1H), 3.56 (ddd, J¼11.6, 8.9, 4.0 Hz,
1H), 3.46 (ddd, J¼9.8, 9.8, 4.9 Hz, 1H), 2.87 (dd, J¼15.6, 3.1 Hz, 1H),
2.58–2.53 (m, 2H), 2.40 (s, 3H), 1.88 (ddd, J¼11.3, 11.3, 11.3 Hz, 1H),
d
7.35 (m, 3H), 7.33 (d, J¼7.9 Hz, 2H), 6.53 (dd, J¼15.3, 5.5 Hz, 1H),
6.38 (dd, J¼15.3, 1.2 Hz, 1H), 5.67 (m, 1H), 5.51 (s, 1H), 4.69 (ddd,
J¼11.0, 9.8, 4.9 Hz, 1H), 4.27 (dd, J¼10.4, 4.9 Hz, 1H), 3.64 (dd,
J¼10.4, 10.4 Hz, 1H), 3.56 (ddd, J¼11.9, 9.2, 4.3 Hz, 1H), 3.44
(ddd, J¼9.8, 9.8, 2.1 Hz, 1H), 3.30 (ddd, J¼9.8, 9.8, 4.5 Hz, 1H), 2.55
(ddd, J¼11.3, 4.6, 4.6 Hz, 1H), 2.41 (s, 3H), 2.10 (s, 3H), 2.08 (s, 3H),
1.96 (ddd, J¼11.9, 9.5, 2.1 Hz, 1H), 1.74–1.68 (m, 2H); 13C NMR
1.29 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 170.2, 150.7, 142.0,
141.0, 137.0, 129.9, 129.2, 128.4, 126.1, 123.8, 115.2, 101.7, 79.7, 76.5,
75.9, 73.2, 69.0, 60.9, 36.7, 35.5, 21.4, 14.2; HRMS (EI) calcd for
C26H30O7S [Mþ] 486.1712, found 486.1716.
(75 MHz, CDCl3)
d 169.84, 169.78, 142.1, 139.9, 137.2, 135.9, 130.2,
129.1, 128.3, 126.1, 125.0, 101.7, 75.9, 75.6, 73.2, 70.2, 69.0, 68.7, 36.3,
34.7, 21.4, 21.1, 21.0; HRMS (EI) calcd for C28H32O8S [Mþ] 528.1818,
found 528.1813.
4.1.8. (Z)-b-Alkoxyvinyl (R)-sulfoxide-aldehyde 13. To a solution of
12 (37.4 mg, 77.3
m
mol) in CH2Cl2 (0.8 mL) was added DIBAH
(b) To a solution of 13 (17.1 mg, 38.6
mmol) and CF3CH2OH
(240
m
L, 0.97 M solution in n-hexane, 0.233 mmol) at ꢁ78 ꢀC. After
(10.4 L, 0.103 mmol) in THF (0.4 mL) was added SmI2 (1.0 mL,
m
stirring at ꢁ78 ꢀC for 1.5 h, i-PrOH (0.5 mL) and water (0.5 mL) were
added at the same temperature and silica gel was added at room
temperature. The mixture was diluted with EtOAc, stirred for 1 h,
filtrated through a Celite pad, and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/EtOAc,
0.1 M solution in THF, 0.100 mmol) at 0 ꢀC. After stirring for 5 min,
the mixture was quenched with satd Na2S2O3 and satd NaHCO3,
and extracted with EtOAc. The combined organic layers were
washed with brine, dried over MgSO4, and evaporated in vacuo. To
a solution of the residue (18.9 mg) in pyridine (1 mL) was added
acetic anhydride (1 mL) at room temperature. After stirring at room
temperature for 68 h, the mixture was azeotropically evaporated
with benzene in vacuo. The residue was purified by flash column
chromatography (n-hexane/EtOAc, 1/1/1/2) to give acetate 14b
(7.7 mg, 45%) and an diacetate 15b (7.9 mg, 27%).
1:2/1:5) to give aldehyde 13 (15.3 mg, 45%) as a white solid.
20
[
a]
¼ꢁ145.2 (c 0.91, CHCl3); IR (neat) 3015, 2977, 2932, 2873,
D
2733, 1732, 1621, 1493, 1456, 1392, 1372, 1339, 1314, 1303, 1287,
1267, 1235, 1185, 1152, 1100, 1031 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
9.81 (br d, J¼1.8 Hz, 1H), 7.51–7.47 (m, 4H), 7.38–7.36 (m, 3H), 7.30
(d, J¼7.9 Hz, 1H), 6.62 (d, J¼5.5 Hz, 1H), 5.52 (s, 1H), 5.50 (d,
J¼5.5 Hz, 1H), 4.32 (dd, J¼10.4, 4.9 Hz, 1H), 4.06 (ddd, J¼8.5, 8.5,
3.1 Hz, 1H), 3.85 (ddd, J¼11.0, 9.8, 4.9 Hz, 1H), 3.66 (dd, J¼10.4,
10.4 Hz,1H), 3.57 (ddd, J¼11.9, 9.2, .4.3 Hz,1H), 3.48 (ddd, J¼9.8, 9.8,
4.9 Hz, 1H), 2.99 (dd, J¼16.5, 3.1 Hz, 1H), 2.64 (ddd, J¼16.5, 8.4,
2.7 Hz,1H), 2.59 (ddd, J¼11.6, 4.6, 4.6 Hz,1H), 2.40 (s, 3H),1.90 (ddd,
4.1.10. (Z)-
b
-Alkoxyvinyl (S)-sulfoxide-ester 16. To a solution of 1
L,
(51.2 mg, 0.159 mmol) in THF (1.6 mL) was added LHMDS (190
m
1.0 M solution in THF, 0.190 mmol) at 0 ꢀC. After stirring at 0 ꢀC for
30 min and at room temperature for 30 min, a solution of (S)-3
(140.3 mg, 0.855 mmol) in THF (1.6 mL) was added at ꢁ78 ꢀC. After
stirring at ꢁ20 ꢀC for 2 h, the mixture was quenched with satd
NaHCO3 and extracted with EtOAc. The combined organic layer was
washed with brine, dried over MgSO4, and evaporated in vacuo. The
residue was purified by flash column chromatography (n-hexane/
J¼11.3, 11.3, 11.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 199.2, 150.6,
141.8, 141.1, 136.9, 129.9, 129.3, 128.4, 126.1, 123.8, 115.6, 101.8, 80.0,
75.7, 75.1, 73.3, 68.9, 45.1, 35.4, 21.4; HRMS (EI) calcd for C24H26O6S
[Mþ] 442.1450, found 442.1450.
EtOAc, 1:1) to give vinyl sulfoxide 16 (70.6 mg, 91%) as a white solid.
20
4.1.9. Reaction of (Z)-(R)-13 with SmI2 followed by acetylation. (a)
[a
]
¼þ178.5 (c 1.51, CHCl3); IR (neat) 2980, 2927, 2875, 1737,
D
To a solution of 13 (25.8 mg, 0.058 mmol) and MeOH (7.9
mL,
1626, 1493, 1456, 1390, 1369, 1351, 1328, 1306, 1286, 1236, 1200,
0.390 mmol) in THF (0.5 mL) was added SmI2 (1.5 mL, 0.1 M solu-
tion in THF, 0.150 mmol) at 0 ꢀC. After stirring for 10 min, the
mixture was quenched with satd Na2S2O3 and satd NaHCO3 and
extracted with EtOAc. The combined organic layer was washed
with brine, dried over MgSO4, and concentrated in vacuo. To a so-
lution of the residue (27.6 mg) in pyridine (1 mL) was added acetic
anhydride (1 mL) at room temperature. After stirring at room
temperature for 24 h, the mixture was azeotropically evaporated
with benzene in vacuo. The residue was purified by flash column
chromatography (n-hexane/EtOAc, 1:1/1:2) to give an acetate 14b
1180, 1098, 1031, 1015 cmꢁ1 1H NMR (500 MHz, CDCl3)
;
d
7.53 (d,
J¼8.2 Hz, 2H), 7.48 (dd, J¼7.6, 2.1 Hz, 2H), 7.40–7.32 (m, 3H), 7.29 (d,
J¼8.2 Hz, 2H), 6.62 (d, J¼5.5 Hz, 1H), 5.51 (s, 1H), 5.47 (d, J¼5.5 Hz,
1H), 4.31 (dd, J¼10.4, 4.9 Hz, 1H), 4.21–4.15 (m, 2H), 3.96–3.89 (m,
2H), 3.66 (dd, J¼10.4,10.4 Hz,1H), 3.55 (ddd, J¼11.6, 8.9, 4.0 Hz,1H),
3.46 (ddd, J¼9.8, 9.8, 4.9 Hz, 1H), 2.67 (dd, J¼15.3, 3.1, 1H), 2.60
(ddd, J¼11.9, 4.1, 4.1 Hz, 1H), 2.46 (dd, J¼15.6, 7.3 Hz, 1H), 2.40 (s,
3H), 1.95 (ddd, J¼11.3, 11.3, 11.3 Hz, 1H), 1.28 (t, J¼7.0 Hz, 3H); 13C
NMR (75 MHz, CDCl3) d 170.1, 150.7, 142.0, 141.0, 137.0, 129.8, 128.3,
126.1, 124.0, 115.1, 101.7, 80.0, 76.3, 75.8, 73.1, 68.9, 60.8, 36.9, 35.4,
21.3, 14.1; HRMS (EI) calcd for C26H30O7S [Mþ] 486.1712, found
486.1700.
(7.7 mg, 27%) as colorless crystals and a diacetate 15b (7.9 mg, 26%)
21
as a white solid. 14b: Mp 241.0–242.0 ꢀC (EtOAc); [
a]
¼þ22.3 (c
D
0.75, CHCl3); IR (KBr) 3042, 2977, 2952, 2925, 2883, 1734, 1598,
1494, 1460, 1447, 1414, 1397, 1373, 1239, 1185, 1147, 1110, 1086, 1052,
4.1.11. (Z)-b-Alkoxyvinyl (S)-sulfoxide-aldehyde 17. To a solution of
16 (180.9 mg, 0.372 mmol) in CH2Cl2 (3.8 mL) was added DIBAH
1043, 1026 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
7.51 (d, J¼8.2 Hz,
2H), 7.50–7.47 (m, 2H), 7.39–7.35 (m, 3H), 7.33 (d, J¼7.9 Hz, 2H),
5.52 (s, 1H), 5.11 (br s, W1/2¼5.6 Hz, 1H), 4.27 (dd, J¼10.7, 4.9 Hz,
1H), 3.81 (ddd, J¼5.9, 4.6, 1.2 Hz, 1H), 3.66 (dd, J¼10.4, 10.4 Hz, 1H),
3.56 (ddd, J¼11.6, 8.9, 4.0 Hz, 1H), 3.44–3.37 (m, 2H), 3.14 (dd,
(760
m
L, 0.97 M solution in n-hexane, 0.737 mmol) at ꢁ78 ꢀC. After
stirring at ꢁ78 ꢀC for 20 min, i-PrOH (1.0 mL) and water (1.0 mL)
were added at the same temperature and silica gel was added at
room temperature. The mixture was diluted with EtOAc, stirred for

T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
10899
1 h, filtrated through a Celite pad, and evaporated in vacuo. The
residue was purified by flash column chromatography (n-hexane/
2H), 7.40–7.32 (m, 3H), 7.31 (d, J¼8.2 Hz, 2H), 5.55 (s, 1H), 4.31 (dd,
J¼10.4, 4.6 Hz, 1H), 3.77 (ddd, J¼10.7, 8.9, 1.8 Hz, 1H), 3.71
(dd, J¼10.4, 10.4 Hz, 1H), 3.61 (ddd J¼11.6, 8.9, 4.0 Hz, 1H), 3.48
(ddd, J¼10.7, 8.9, 1.8 Hz, 1H), 3.41 (ddd, J¼9.8, 9.8, 4.9 Hz, 1H), 3.30
(ddd, J¼11.3, 9.3, 4.9 Hz, 1H), 3.23 (dd, J¼13.4, 2.1 Hz, 1H), 3.19 (ddd,
J¼11.9, 9.2, 4.0 Hz, 1H), 2.60 (dd, J¼13.1, 11.0 Hz, 1H), 2.51 (ddd,
J¼11.3, 4.3, .4.3 Hz, 1H), 2.41 (3H, s), 2.35 (ddd, J¼11.6, 4.3, 4.3 Hz,
1H), 1.70 (ddd, J¼11.6, 11.6, 11.6 Hz, 1H), 1.60 (ddd, J¼11.6, 11.6,
11.6 Hz, 1H), 0.85 (s, 9H), 0.05 (s, 3H), ꢁ0.03 (s, 3H); 13C NMR
EtOAc, 1:1/1:3) to give aldehyde 17 (120.9 mg, 73%) as colorless
21
crystals. Mp 135.0–136.0 ꢀC (EtOAc); [
a
]
¼þ162.7 (c 1.69, CHCl3);
D
IR (KBr) 3034, 2920, 2879, 1722, 1635, 1457, 1387, 1342, 1288, 1269,
1241, 1187, 1101, 1076, 1028, 1002 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
9.76 (t, J¼2.1 Hz, 1H), 7.52 (d, J¼7.9 Hz, 2H), 7.49 (dd, J¼7.9,
2.1 Hz, 2H), 7.40–7.36 (m, 3H), 7.30 (d, J¼7.9 Hz, 1H), 6.57 (d,
J¼5.5 Hz, 1H), 5.52 (s, 1H), 5.50 (d, J¼5.5 Hz, 1H), 4.31 (dd, J¼10.7,
4.9 Hz, 1H), 4.04 (ddd, J¼9.5, 7.9, 4.5 Hz, 1H), 3.79 (ddd, J¼11.3, 9.5,
4.9 Hz, 1H), 3.66 (dd, J¼10.4, 10.4 Hz, 1H), 3.56 (ddd, J¼11.9, 9.2,
4.3 Hz, 1H), 3.50 (ddd, J¼9.8, 9.8, 4.6 Hz, 1H), 2.68 (ddd, J¼16.2, 4.3,
2.1 Hz, 1H), 2.62 (ddd, J¼11.6, 4.3, 4.3 Hz, 1H), 2.58 (ddd, J¼15.9,
7.6, 2.4 Hz, 1H), 2.40 (s, 3H), 1.96 (ddd, J¼11.6, 11.6, 11.6 Hz, 1H); 13C
(75 MHz, CDCl3) d 141.7, 141.5, 137.2, 129.9, 129.1, 128.3, 126.1, 124.1,
101.7, 76.6, 76.52, 76.45, 76.38, 73.6, 69.9, 69.1, 61.1, 38.9, 34.6, 25.6,
21.4, 17.8, ꢁ4.1, ꢁ4.8; HRMS (FAB) calcd for C30H43O6SSi [MþHþ]
559.2549, found 559.2546; Anal. Calcd for C30H42O6SSi: C, 64.48; H,
7.58; S, 5.74. Found C, 64.62; H, 7.54; S, 6.09.
NMR (75 MHz, CDCl3)
d 199.1, 150.2, 141.9, 141.2, 136.9, 130.0, 126.1,
124.0, 115.6, 101.7, 80.3, 75.7, 75.0, 73.2, 68.8, 45.6, 35.4, 21.3;
HRMS (EI) calcd for C24H26O6S [Mþ] 442.1450, found 442.1448;
Anal. Calcd for C24H26O6S: C, 65.14; H, 5.92. Found C, 65.27; H,
6.00.
4.1.14. Aldehyde 22. To a solution of 21 (44.1 mg, 78.9 mmol) in
MeCN (0.8 mL) were added pyridine (63.6 mg, 0.789 mmol) and
trifluoroacetic anhydride (84.2 mg, 0.395 mmol) at 0 ꢀC. After stir-
ring for 20 min, K2CO3 (63.2 mg, 0.455 mmol) and H2O (0.2 mL)
were added at 0 ꢀC. After stirring at 0 ꢀC for 2.5 h, the mixture was
diluted with EtOAc. The combined organic layer was washed with
brine, dried over MgSO4, and evaporated in vacuo. The residue was
4.1.12. Reaction of (Z)-(S)-aldehyde 17 with SmI2 followed by acety-
lation. To a solution of 17 (24.4 mg, 0.055 mmol) and MeOH
(6.7 mL, 0.17 mmol) in THF (0.6 mL) was added SmI2 (1.4 mL, 0.1 M
solution in THF, 0.14 mmol) at 0 ꢀC. After stirring at 0 ꢀC for 10 min,
the mixture was quenched with satd Na2S2O3 and satd NaHCO3 and
extracted with EtOAc. The combined organic layer was washed
with brine, dried over MgSO4, and evaporated in vacuo. To a solu-
tion of the residue in pyridine (1 mL) was added acetic anhydride
(1 mL) at room temperature. After stirring at room temperature for
21 h, the mixture was azeotropically evaporated with benzene in
vacuo. The residue was purified by flash column chromatography
(n-hexane/EtOAc, 1:1) to give (E)-diacetate 19b (2.0 mg, 7%) and
a mixture of syn-trans-9b, syn-cis-18b, and others (16.7 mg). 1H
NMR sample of 18b was obtained by further flash column chro-
purified by flash column chromatography (n-hexane/EtOAc, 3:1) to
22
give aldehyde 22 (24.6 mg, 72%) as a white solid. [
a
]
¼ꢁ26.0 (c
D
1.00, acetone); IR (KBr) 2952, 2930, 2879, 1741, 1469, 1454, 1391,
1361, 1339, 1314, 1287, 1251, 1212, 1177, 1162, 1102, 1021, cmꢁ1 1H
NMR (500 MHz, benzene-d)
9.51 (d, J¼2.1 Hz, 1H), 7.69–7.66 (m,
;
d
2H), 7.21 (t, J¼7.0 Hz, 2H), 7.15–7.12 (m, 1H), 5.36 (s, 1H), 4.26 (dd,
J¼10.4, 4.9 Hz, 1H), 3.60 (ddd, J¼10.7, 9.5, 4.6 Hz, 1H), 3.49 (dd,
J¼10.0, 10.0 Hz, 1H), 3.39 (dd, J¼9.2, 2.1 Hz, 1H), 3.28 (ddd, J¼9.2,
9.2, 4.6 Hz,1H), 3.18 (ddd, J¼11.0, 9.5, 4.0 Hz,1H), 2.79–2.70 (m, 2H),
2.37 (ddd, J¼11.0, 3.7, 3.7 Hz, 1H), 2.24 (ddd, J¼11.0, 4.3, 4.3 Hz, 1H),
1.72 (ddd, J¼11.0, 11.0, 11.0 Hz, 1H), 1.48 (ddd, J¼11.0, 11.0, 11.0 Hz,
1H), 0.91 (s, 9H), 0.01 (s, 3H), ꢁ0.04 (s, 3H); 13C NMR (75 MHz,
matography. 18b (600 MHz, CDCl3):
d
7.54 (d, J¼7.8 Hz, 2H), 7.51
benzene-d) d 196.8, 138.3, 129.1, 128.5, 126.7, 101.9, 85.1, 77.2, 76.3,
(dd, J¼7.8, 1.2 Hz, 2H), 7.40–7.36 (m, 3H), 7.33 (d, J¼7.8 Hz, 2H), 5.56
(s, 1H), 5.05 (br s, W1/2¼7.0 Hz, 1H), 4.30 (dd, J¼10.2, 4.8 Hz, 1H),
4.21 (br d, J¼10.2 Hz, 1H), 3.71 (dd, J¼10.1, 10.2 Hz, 1H), 3.52–3.41
(m, 3H), 2.82 (dd, J¼13.2, 10.2 Hz, 1H), 2.73 (dd, J¼13.2, 1.8 Hz, 1H),
2.55 (ddd, J¼11.4, 4.2, 4.2 Hz, 1H), 2.41 (s, 3H), 2.06 (s, 3H), 1.84
(ddd, J¼11.4, 11.4, 11.4 Hz, 1H), 1.78 (ddd, J¼13.8, 12.0, 3.0 Hz, 1H).
75.8, 73.9, 69.3, 66.4, 39.4, 35.0, 25.8, 18.0, ꢁ4.3, ꢁ4.8; HRMS (FAB)
calcd for C23H35O6Si [MþHþ] 435.2202, found 435.2202.
Acknowledgements
This work was financially supported by the Uehara Memorial
Foundation and by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science and Technology,
Japan.
19b: 1H NMR (400 MHz, CDCl3)
d 7.49–7.44 (m, 4H), 7.38–7.31 (m,
5H), 6.50 (dd, J¼15.2, 5.8 Hz, 1H), 6.41 (d, J¼15.2 Hz, 1H), 5.65 (ddd,
J¼9.4, 5.6, 3.8 Hz, 1H), 5.50 (s, 1H), 4.66 (ddd, J¼10.9, 10.9, 4.8 Hz,
1H), 4.27 (dd, J¼10.6, 4.8 Hz, 1H), 3.62 (dd, J¼10.4, 10.4 Hz, 1H), 3.55
(ddd, J¼12.1, 9.1, 4.3 Hz, 1H), 3.44 (ddd, J¼9.6, 9.6, 2.0 Hz, 1H), 3.30
(ddd, J¼9.9, 9.9, 4.8 Hz, 1H), 2.54 (ddd, J¼11.4, 4.3, 4.3 Hz, 1H), 2.41
(s, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 1.97 (ddd, J¼11.9, 9.6, 2.0 Hz, 1H),
1.72–1.03 (m, 2H).
References and notes
1. For reviews on polycyclic ethers, see: (a) Yasumoto, T.; Murata, M. Chem. Rev.
1993, 93, 1897; (b) Shimizu, Y. Chem. Rev. 1993, 93, 1685; (c) Murata, M.;
Yasumoto, T. Nat. Prod. Rep. 2000, 17, 293; (d) Yasumoto, T. Chem. Rec. 2001, 1,
228; (e) Deranas, A. H.; Norte, M.; Ferna´ndez, J. J. Toxicon 2001, 39, 1101.
2. For reviews on synthetic methods and total syntheses, see: (a) Alvarez, E.;
4.1.13. TBS–ether 21. To a solution of 7 (86.8 mg, 0.196 mmol) and
MeOH (15.8 mL, 0.490 mmol) in THF (1.9 mL) was added SmI2
´
´
Candenas, M.-L.; Perez, R.; Ravelo, J.; Martın, J. D. Chem. Rev. 1995, 95, 1953; (b)
Fujiwara, K.; Hayashi, N.; Tokiwano, T.; Murai, A. Heterocycles 1999, 50, 561; (c)
Mori, Y. Chem. Eur. J. 1997, 3, 849; (d) Marmsa¨ter, F. P.; West, F. G. Chem. Eur. J.
2002, 8, 4347; (e) Inoue, M. Org. Biomol. Chem. 2004, 2, 1811; (f) Fujiwara, K.;
Murai, A. Bull. Chem. Soc. Jpn. 2004, 77, 2129; (g) Sasaki, M.; Fuwa, H. Synlett
2004, 1811; (h) Kadota, I.; Yamamoto, Y. Acc. Chem. Res. 2005, 38, 423; (i) Inoue,
M. Chem. Rev. 2005, 105, 4379; (j) Nakata, T. Chem. Rev. 2005, 105, 4314; (k)
Clark, J. S. Chem. Commun. 2006, 3571; (l) Nicolaou, K. C.; Frederick, M. O.;
Aversa, R. J. Angew. Chem., Int. Ed. 2008, 47, 7182.
(5.0 mL, 0.1 M solution in THF, 0.500 mmol) at 0 ꢀC. After stirring at
0 ꢀC for 15 min, the mixture was quenched with satd Na2S2O3 and
satd NaHCO3 and extracted with EtOAc. The combined organic layer
was washed with brine, dried over MgSO4, and concentrated in
vacuo to give crude alcohol 9a (79.0 mg). To a solution of 9a in DMF
(0.4 mL) were added imidazole (170.0 mg, 2.50 mmol) and TBSCl
(192.7 mg, 1.25 mmol) at room temperature. After stirring for 48 h,
the mixture was quenched with MeOH, and concentrated in vacuo.
The residue was purified by flash column chromatography (n-
3. (a) Hori, N.; Matsukura, H.; Matsuo, G.; Nakata, T. Tetrahedron Lett. 1999, 40,
2811; (b) Hori, N.; Matsukura, H.; Nakata, T. Org. Lett. 1999, 1, 1099; (c) Matsuo,
G.; Hori, N.; Nakata, T. Tetrahedron Lett. 1999, 40, 8859; (d) Suzuki, K.; Matsu-
kura, H.; Matsuo, G.; Koshino, H.; Nakata, T. Tetrahedron Lett. 2002, 43, 8653; (e)
Matsuo, G.; Kadohama, H.; Nakata, T. Chem. Lett. 2002, 148; (f) Hori, N.; Matsuo,
G.; Matsukura, H.; Nakata, T. Tetrahedron 2002, 58, 1853.
4. Selected papers: (a) Clark, J. S.; Hayes, S. T.; Blake, A. J.; Gobbi, L. Tetrahedron
Lett. 2007, 48, 2501; (b) Sato, K.; Sasaki, M. Angew. Chem., Int. Ed. 2007, 46, 2518;
(c) Fuwa, H.; Ebine, M.; Bourdelais, A. J.; Baden, D. G.; Sasaki, M. J. Am. Chem.
Soc. 2006, 128, 16989; (d) Fuwa, H.; Kakinuma, N.; Tachibana, K.; Sasaki, M.
hexane/EtOAc, 3:1) to give TBS–ether 21 (98.6 mg, 90%, two steps)
23
as colorless crystals. Mp 155.5–156.5 ꢀC (EtOAc); [
a]
¼ꢁ113.9 (c
D
1.06, CHCl3); IR (KBr) 2954, 2929, 2876, 2856, 1472, 1456, 1401,
1368, 1336, 1315, 1287, 1249, 1196, 1087, 1016 cmꢁ1 1H NMR
(500 MHz, CDCl3)
7.56 (d, J¼7.9 Hz, 2H), 7.50 (dd, J¼7.9, 1.8 Hz,
;
d

10900
T. Kimura et al. / Tetrahedron 65 (2009) 10893–10900
J. Am. Chem. Soc. 2002, 124, 14983; (e) Kadota, I.; Takamura, H.; Sato, K.;
10. (a) Namy, J. L.; Girard, P.; Kagan, H. B. Nouv. J. Chim. 1977, 1, 5; (b) Girard, P.;
Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693; (c) Kagan, H. B. New J.
Chem. 1990, 14, 453.
11. Edmons, D. J.; Muir, K. W.; Procter, D. J. J. Org. Chem. 2003, 68, 3190.
12. Treatment of 15b with K2CO3 in THF/MeOH effected methanolysis of the
diacetate and intramolecular cyclization, and subsequent acetylation gave
Ohno, A.; Matsuda, K.; Satake, M.; Yamamoto, Y. J. Am. Chem. Soc. 2003,
125, 11893; (f) Nagumo, Y.; Oguri, H.; Shindo, Y.; Sasaki, S.; Oishi, T.; Hir-
ama, M.; Tomioka, Y.; Mizugaki, M.; Tsumuraya, T. Bioorg. Med. Chem. Lett.
2001, 11, 2037; (g) Matsuo, G.; Kawamura, K.; Hori, N.; Matsukura, H.;
Nakata, T. J. Am. Chem. Soc. 2004, 126, 14374; (h) Takahashi, S.; Kubota, A.;
Nakata, T. Angew. Chem., Int. Ed. 2002, 41, 4751.
a
2:3 mixture of 2,6-syn-2,3-cis-tetrahydropyran 14b and 2,6-anti-2,3-
5. Kimura, T.; Nakata, T. Tetrahedron Lett. 2007, 48, 43.
trans-isomer. The result confirmed the
group in 15b.
b-configuration of the 3-acetoxy
6. Kimura, T.; Hagiwara, M.; Nakata, T. Tetrahedron Lett. 2007, 48, 9171.
7. Lee et al. reported the same type of reaction using acyclic compounds Jung, J.
H.; Kim, Y. W.; Kim, M. A.; Choi, S. Y.; Chung, Y. K.; Kim, T.-R.; Shin, S.; Lee, E. Org.
Lett. 2007, 9, 3225.
13. The products were difficult to isolate. Thus, yields of the products were cal-
culated based on 1H NMR analysis of the mixture. Other products might con-
tain 2,6-anti-2,3-cis-11b and (Z)-
g-acetoxyvinyl sulfoxide isomer.
8. (a) Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J. Org. Chem. 1987,
52, 1078; (b) Solladie, G.; Hutt, J.; Girardin, A. Synthesis 1987, 173.
9. Keum, G.; Kang, S. B.; Kim, Y.; Lee, E. Org. Lett. 2004, 6, 1895.
14. Alkaline methanolysis of 19b followed by acetylation mainly afforded 2,6-anti-
2,3-trans-tetrahydropyran. The result confirmed the
acetoxy group in 19b.
b-configuration of the 3-