SmI2-induced cyclization of (E)- and (Z)-β-alkoxyvinyl sulfones with aldehydes

Article abstract of DOI:10.1016/j.tetasy.2010.04.066

SmI₂-induced reaction of (E)- and (Z)-β-alkoxyvinyl sulfones onto an aldehyde function afforded 2,6-syn-2,3-trans- and 2,6-syn-2,3-cis-tetrahydropyran-3-ols, respectively, via stereoselective cyclization. This reaction was applied to the synthesis of 2-methyl- tetrahydropyran, corresponding to the N-ring of gymnocin-A, and 2-exo-methylene-tetrahydropyran, a key intermediate for convergent synthesis of polycyclic ethers based on the Suzuki-Miyaura reaction.

Full text of DOI:10.1016/j.tetasy.2010.04.066

Tetrahedron: Asymmetry 21 (2010) 1389–1395
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
SmI2-induced cyclization of (E)- and (Z)-b-alkoxyvinyl sulfones with aldehydes
*
Tomohiro Kimura, 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:
SmI2-induced reaction of (E)- and (Z)-b-alkoxyvinyl sulfones onto an aldehyde function afforded 2,6-syn-
2,3-trans- and 2,6-syn-2,3-cis-tetrahydropyran-3-ols, respectively, via stereoselective cyclization. This
reaction was applied to the synthesis of 2-methyl-tetrahydropyran, corresponding to the N-ring of gym-
nocin-A, and 2-exo-methylene-tetrahydropyran, a key intermediate for convergent synthesis of polycy-
clic ethers based on the Suzuki–Miyaura reaction.
Received 1 March 2010
Accepted 19 April 2010
Available online 19 June 2010
Dedicated to Professor Henri Kagan on the
occasion of his 80th birthday
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
H
H
H
H
O
O
OH
SmI2
CHO
3
Since the first isolation of brevetoxin-B as a red tide toxin in
1981,1 many marine polycyclic ethers have been isolated, includ-
ing ciguatoxins, gambierol, yessotoxin, gymnocins, and maitotox-
in.2 These natural products exhibit a variety of potent biological
activities such as neurotoxicity, cytotoxicity, and antifungal and
antiviral activities. Their synthetically challenging complex struc-
tures, of which the most characteristic feature is a trans-fused
polycyclic ether ring system, have attracted much interest from
synthetic organic chemists, culminating in total syntheses of many
of these compounds.3 We have already developed an efficient
method for the construction of trans-fused polycyclic ether based
on the SmI2-induced cyclization of b-alkoxyacrylate A1 with a car-
bonyl group, affording 2,6-syn-2,3-trans-tetrahydropyran-3-ol B1
with complete stereoselectivity (Fig. 1).4 This method has been
successfully applied to the synthesis of polycyclic ethers.5,6 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 useful for the synthesis of polycy-
clic ethers. Furthermore, synthetic methods for not only the 2,6-
syn-2,3-trans-tetrahydropyran B, but also the stereoisomers, are
required for the synthesis of several marine polycyclic ethers. In
order to solve this problem, we have recently developed SmI2-in-
duced cyclizations of b-alkoxyvinyl sulfones A27 and b-alkoxyvinyl
6
2
R
R
MeOH
THF
O
O
H
H
A :
A1:
B :
B1:
R = CO2Et
R = SO2Ph
R = S(O)-p-Tol
R = CO2Et
R = SO2Ph
R = S(O)-p-Tol
A2:
B2:
3
3
Figure 1. SmI2-induced reductive cyclizations.
strate 4 was synthesized from the known alcohol 1,5f which was
prepared by SmI2-induced cyclization of b-alkoxyacrylate with an
aldehyde group as the key reaction. Treatment of 1 with LHMDS
and (E)-bis(phenylsulfonyl)-1,2-ethylene 2 at 0 °C to room temper-
ature stereoselectively afforded (E)-b-alkoxyvinyl sulfone 3.9
Reduction of the ester 3 with DIBAH effectively gave aldehyde 4
in 95% yield (two steps). Upon treatment of (E)-4 with 2.5 equiv
10
of SmI2 in the presence of MeOH (2.5 equiv) in THF, reductive
cyclization took place smoothly at 0 °C to give 2,6-syn-2,3-trans-
tetrahydropyran-3-ol 5 in 99% yield as a single product. Acetyla-
tion of 5 with Ac2O in pyridine gave the acetate 6 in 96% yield.
The 2,6-syn-2,3-trans-configuration of 6 was determined by NOE
measurement (Fig. 2) and supported by the coupling constant of
C-3 H; d 3.95 (ddd, J = 9.8, 7.9, 3.4 Hz).
8
sulfoxides A3 onto an aldehyde group. Herein, we describe in de-
Next, SmI2-induced cyclization of (Z)-b-alkoxyvinyl sulfone 9
with an aldehyde group was examined (Scheme 2). The reaction of
1 with LHMDS and (Z)-bis(phenylsulfonyl)-1,2-ethylene 7 afforded
(Z)-b-alkoxyvinyl sulfone 8,9 which was reduced with DIBAH to give
aldehyde 9 in 73% yield (two steps). SmI2-induced cyclization of (Z)-
9 in the presence of MeOH afforded 2,6-syn-2,3-cis-tetrahydropy-
ran-3-ol 10 and 2,6-syn-2,3-trans-isomer 5, which were separated
after acetylation with Ac2O to give the corresponding acetates 11
and 6 in 55% and 11% yields (two steps), respectively. The 2,6-syn-
2,3-cis-configurationof 11was alsoconfirmedby NOE measurement
(Fig. 2) and by the coupling constant of C3-H; d 5.09 (W1/2 = 6.2 Hz).
tail the SmI2-induced cyclization of (E)- and (Z)-b-alkoxyvinyl sulf-
ones A2 with aldehyde and its application to the construction of
key segments for the synthesis of marine polycyclic ethers.
2. Results and discussion
First, we examined the SmI2-induced cyclization of (E)-b-alk-
oxyvinyl sulfone 4 onto an aldehyde group (Scheme 1). The sub-
* Corresponding author.
E-mail address: nakata@rs.kagu.tus.ac.jp (T. Nakata).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.04.066

1390
T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
LHMDS, THF
0 °C–rt;
H
H
H
H
H
H
H
H
H
H
H
H
Ph
O
O
Ph
O
OH
CO2Et
Ph
O
O
DIBAH
SO2Ph
CO2Et
SO2Ph
O
O
O
CHO
CH2Cl2, –78 °C
95% (2 steps)
SO2Ph
O
O
O
PhO2S
0 °C – rt
2
1
3
4
H
H
H
H
H
H
H
Ph
O
O
Ph
O
O
Ac2O
SmI2, MeOH
SO2Ph
OAc
SO2Ph
OH
6
2
3
6
2
3
O
O
pyridine, rt
96%
THF, 0 °C
99%
O
O
H
H
H
H
H
6
5
Scheme 1.
H
OAc
SO2Ph
H
3
H
H
SO2Ph
OAc
O
O
3
O
O
H
H
O
O
Ph
O
Ph
O
H
H
6
11
Figure 2. Observed NOEs of 6 and 11.
SO2Ph
SO2Ph
LHMDS, THF
0 °C – rt;
H
H
H
H
H
H
H
H
Ph
O
O
Ph
O
OH
Ph
O
O
O
DIBAH
O
CO2Et
O
CO2Et
H
CHO
CH2Cl2, –78 °C
73% (2 steps)
PhO2S
SO2Ph
O
O
O
H
H
H
7
0 °C – rt
1
8
9
1) SmI2, MeOH
THF, 0 °C
H
H
H
6
H
H
H
H
Ph
O
O
Ph
O
O
SO2Ph
OR
SO2Ph
OR
2
3
6
2
3
+
O
O
2) Ac2O
pyridine, rt
O
O
H
H
H
H
H
10: R = H
11: R = Ac
5: R = H
6: R = Ac
Scheme 2.
Ph
Ph
H
H
O
O
O
O
O
O
H
H
H
H
O
O
O
SmI2
SmI2
4
(E)-
2,6-syn-2,3-trans-5
2,6-syn-2,3-cis-10
Sm
I2
S
S
MeOH
Sm
O
O
O
O
O
I2
i
ii
I2
Sm
I2
Sm
Ph
Ph
H
H
O
O
O
O
O
O
O
S
O
O
H
O
H
S
O
O
O
O
SmI2
SmI2
(Z)-9
MeOH
H
H
iii
iv
Figure 3. Plausible mechanisms for SmI2-induced cyclization of (E)-4 and (Z)-9.
These results can be explained as follows (Fig. 3). In the reaction
of (E)-4, the first single-electron reduction of aldehyde with SmI2
gives a ketyl radical and then C–C bond formation proceeds
through transition state i, involving chelation by Sm(III) and sul-
fone, to give ii. The radical in ii is reduced by a second equiv of
SmI2 to an anion, which is protonated with MeOH to give

T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
1391
2,6-syn-2,3-trans-5. On the other hand, in the reaction of (Z)-9, 2,6-
syn-2,3-cis-10 would be produced as the main product through the
chelated transition states iii and iv, while the minor product 5
would be obtained via a non-chelated intermediate.
segment for convergent synthesis of polycyclic ethers based on
the Suzuki–Miyaura reaction.
4. Experimental
The present reaction was successfully applied to the construc-
tion of key segments for the synthesis of marine polycyclic ethers.
The product 6 corresponds to the MN-ring of gymnocin-A11
(Fig. 4); however, it is necessary to reduce the sulfonyl group, be-
cause the terminal tetrahydropyran N-ring has a C2-methyl group.
Treatment of 6 with Na–Hg afforded the desired 2-methyl-tetrahy-
dropyran ring 12 in 36% yield, but the ring-opened olefin 13 was
obtained in 61% yield (Scheme 3). After several attempts, treat-
ment with Raney Ni was found to give good results (Scheme 4).
Reaction of 6 with Raney Ni in EtOH at 85 °C effected reductive
removal of the sulfone and benzylidene acetal to give diol 14
(74% yield), corresponding to the enantiomer of the MN-ring of
gymnocin-A. After TBS protection of 5, the resulting TBS ether 15
was reduced under the same conditions to give the desired
2-methyl-tetrahydropyran 16 in 84% yield.
4.1. General
Flash column chromatography was performed on Silica Gel 60N
(spherical neutral, 40–100 lm, Kanto Kagaku). Melting points were
measured on a Yanaco MP-S9 and are uncorrected. Optical rota-
tions 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.
4.2. 2-((2R,4aR,6S,7R,8aS)-2-Phenyl-7-((E)-2-(phenylsulfonyl)-
vinyloxy)-hexahydropyrano[3,2-d][1,3]dioxin-6-yl)acetal-
dehyde 4
2-exo-Methylene-tetrahydropyran-3-ol derivatives are key seg-
ments for Sasaki’s convergent synthesis of polycyclic ethers based
on the Suzuki–Miyaura coupling reaction.3k–n We examined the
synthesis of these key intermediates from the present SmI2-in-
duced cyclization product 5 (Scheme 5). Swern oxidation of 5
quantitatively afforded ketone 17. After several attempts, we found
suitable conditions to give 2-exo-methylene-tetrahydropyran-3-ol
derivatives. Treatment of 17 with DBU in MeOH at ꢀ15 to ꢀ5 °C
afforded exo-methylene–ketone, which was immediately treated
To a solution of 1 (49.2 mg, 0.148 mmol) in THF (1.5 mL) was
added LHMDS (240 lL, 1.0 M solution in THF, 0.240 mmol) at
0 °C. After stirring at 0 °C for 30 min and at room temperature for
30 min, (E)-bis(phenylsulfonyl)ethylene 2 (61.1 mg, 0.198 mmol)
was added at 0 °C. After stirring at room temperature for 1 h, the
reaction was quenched with satd NaHCO3 and extracted with
EtOAc. The combined organic layer was washed with brine, dried
over MgSO4, and concentrated in vacuo to give crude vinyl sulfone
12
3. To a solution of 3 in CH2Cl2 (1 mL) was added DIBAH (320 lL,
with NaBH4 and CeCl3 at ꢀ78 to 0 °C to give the desired exo-
0.94 M solution in n-hexane, 0.340 mmol) at ꢀ78 °C. After stirring
at ꢀ78 °C for 1 h, i-PrOH (1 mL) and silica gel were added at room
temperature. The mixture was diluted with EtOAc, stirred for 1 h, fil-
trated through a Celite pad, and concentrated in vacuo. The residue
was purified by flash column chromatography (n-hexane/EtOAc,
methylene alcohol 18 in 78% yield. Acetylation of 18 afforded the
acetate 19 in 81% yield, and treatment of 18 with TBSCl produced
TBS ether 20 in 78% yield.
3. Conclusion
2:1) to give aldehyde
¼ ꢀ45:8 (c 1.00, CHCl3); IR (neat) 3068, 3019, 2933, 2875,
1727, 1627, 1609, 1447, 1390, 1371, 1305, 1214, 1185, 1143, 1100,
1006 cmꢀ1 1H NMR (500 MHz, CDCl3) d 9.74 (q, J = 1.2 Hz, 1H),
4 (62.6 mg, 95%) as a colorless oil.
½ ꢁ
a 2D4
In summary, SmI2-induced cyclization of b-alkoxyvinyl sulfone
with aldehyde was developed for the construction of 2,6-syn-2,3-
trans- and 2,6-syn-2,3-cis-tetrahydropyran-3-ol derivatives, which
have a functional one-carbon unit as a C-2 side chain. Furthermore,
the present reaction was applied to the construction of several key
segments for the synthesis of polycyclic ethers. Namely, we
obtained the N-ring, 2-methyl-3-hydroxy-tetrahydropyran, of
gymnocin-A, and also 2-exo-methylene-tetrahydropyran, a key
;
7.87–7.86 (m, 2H), 7.60 (dddd, J = 6.4, 6.4, 1.2, 1.2, 1H), 7.55–7.50
(m, 2H), 7.49 (d, J = 11.9 Hz, 1H), 7.47–7.45 (m, 2H), 7.39–7.35 (m,
3H), 5.87 (d, J = 11.9 Hz, 1H), 5.51 (s, 1H), 4.29 (dd, J = 10.7, 4.9 Hz,
1H), 3.99 (ddd, J = 9.5, 8.5, 3.4 Hz, 1H), 3.91 (ddd, J = 11.0, 9.5,
4.6 Hz, 1H), 3.65 (t, J = 10.1 Hz, 1H), 3.56 (ddd, J = 11.9, 9.2, 4.3 Hz,
1H), 3.45 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H), 2.75 (ddd, J = 16.5, 3.4,
1.2 Hz, 1H), 2.62 (ddd, J = 11.9, 4.3, 4.3 Hz, 1H), 2.58 (ddd, J = 16.5,
8.2, 2.4 Hz, 1H), 1.81 (t, J = 11.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 199.0, 158.4, 141.8, 136.9, 133.0, 129.2, 129.1, 128.3, 126.8,
126.0, 109.4, 101.6, 79.2, 75.4, 74.6, 73.2, 68.7, 45.2 34.6; HRMS
(EI) calcd for C23H24O7S [M]+ 444.1243, found 444.1237.
H
H
H
O
M
OH
Me
H
K
H
J
O
L
N
O
H
O
H
H
H
Me
O
H
H
4.3. Reaction of (E)-4 with SmI2
Figure 4. Partial structure of gymnocin-A.
To a solution of 4 (32.6 mg, 73.3 lmol) and MeOH (8 lL,
0.198 mmol) in THF (0.7 mL) was added SmI2 (1.8 mL, 0.1 M solu-
tion in THF, 0.18 mmol) at 0 °C. After stirring at 0 °C for 15 min, the
reaction 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. The res-
idue was purified by flash column chromatography (n-hexane/
EtOAc, 1:2) to give alcohol 5 (32.5 mg, 99%) as a white solid.
H
H
H
H
O
OH
Me
O
3
2
6
Ph
O
O
H
H
H
H
H
H
Na-Hg
O
OAc
SO2Ph
12 (36%)
Na2HPO4
O
3
2
+
6
MeOH, rt
Ph
O
O
H
H
O
H
H
H
OH
O
6
4.3.1. Benzylidene acetal of (2R,3S,4aR,6R,7R,8aS)-2-(hydroxy-
methyl)-6-(phenylsulfonylmethyl)-octahydropyrano[3,2-b]-
pyran-3,7-diol 5
Ph
O
OH
H
H
13 (61%)
½
a 2D4
ꢁ
¼ ꢀ7:2 (c 1.00, CHCl3); IR (KBr) 3522, 2932, 2868, 1449,
1380, 1364, 1339, 1298, 1237, 1194, 1179, 1148, 1086,
Scheme 3.

1392
T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
H
H
H
H
H
H
H
H
H
O
OAc
SO2Ph
O
M
OAc
Me
Raney Ni
O
O
HO
HO
N
O
2
EtOH, 85 °C
74%
Ph
Ph
O
O
O
O
H
H
H
6
14
H
H
H
H
H
H
H
H
TBSCl
imidazole
O
OH
SO2Ph
O
OTBS
O
SO2Ph
DMF, rt
93%
Ph
O
O
H
H
H
H
5
15
H
H
H
O
OTBS
Me
Raney Ni
HO
HO
M
N
O
2
EtOH, 85 °C
84%
H
H
H
16
Scheme 4.
H
H
H
6
H
H
H
H
(COCl)2, DMSO
CH2Cl2, –78 °C;
DBU, MeOH
–15 ~ –5 °C;
Ph
O
O
Ph
O
O
SO2Ph
OH
SO2Ph
2
3
6
2
3
O
O
Et3N, –78 °C ~ rt
100%
CeCl3·7H2O
NaBH4
–78 °C ~ 0 °C
78%
O
O
O
H
H
H
H
5
17
a) Ac2O
pyridine
rt, 81%
H
H
H
H
H
H
O
Ph
O
O
2
Ph
O
6
6
2
3
3
O
O
b) TBSCl
O
OH
O
OR
imidazole
DMF, rt
78%
H
H
H
H
18
19: R = Ac
20: R = TBS
Scheme 5.
1015 cmꢀ1
;
1H NMR (500 MHz, CDCl3) d 7.91 (d, J = 7.1 Hz, 2H),
(m, 2H), 2.46 (ddd, J = 11.6, 4.0, 4.0 Hz, 1H), 2.09 (3H, s), 2.00
(ddd, J = 11.0, 3.4, 3.4 Hz, 1H), 1.51 (q, J = 11.3 Hz, 1H), 1.33 (q,
J = 11.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 169.8, 140.3, 137.0,
133.7, 129.2, 128.8, 128.3, 128.1, 126.1, 101.9, 76.6, 76.4, 75.5,
74.9, 73.5, 68.9, 68.8, 58.0, 34.6, 34.0, 21.0; HRMS (EI) calcd for
7.62 (t, J = 7.3 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.47 (dd, J = 7.9,
2.4 Hz, 2H), 7.39–7.34 (m, 3H), 5.49 (s, 1H), 4.26 (dd, J = 10.4,
4.9 Hz, 1H), 3.75–3.68 (m, 2H), 3.65 (t, J = 10.4 Hz, 1H), 3.50 (ddd,
J = 12.2, 9.2, 4.3 Hz, 1H), 3.41 (m, 1H), 3.33 (dd, J = 14.6, 8.8 Hz,
1H), 3.29 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H), 3.04–2.99 (m, 2H), 2.40–
2.38 (m, 1H), 1.99–1.97 (m, 1H), 1.49 (q, J = 11.3 Hz, 1H), 1.30 (q,
J = 11.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 140.4, 137.5, 134.1,
129.6, 129.3, 128.7, 128.5, 126.5, 102.2, 77.9, 77.8, 77.6, 76.4,
73.8, 69.4, 68.3, 58.7, 38.5, 34.5; HRMS (FAB) calcd for C23H27O7S
[M]+ 447.1477, found 447.1480.
C
25H28O8S [M]+ 488.1505, found 488.1501.
4.5. 2-((2R,4aR,6S,7R,8aS)-2-Phenyl-7-((Z)-2-(phenylsulfonyl)-
vinyloxy)-hexahydropyrano[3,2-d][1,3]dioxin-6-yl)acetalde-
hyde 9
To a solution of 1 (54.0 mg, 0.162 mmol) in THF (1.6 mL) was
4.4. Benzyledene acetal of (2R,3R,4aS,6R,7S,8aR)-7-hydroxy-6-
(hydroxymethyl)-2-(phenylsulfonylmethyl)-octahydropyrano-
[3,2-b]pyran-3-yl acetate 6
added LHMDS (250 lL, 1.0 M solution in THF, 0.250 mmol) at
0 °C. After stirring at 0 °C for 30 min and at room temperature for
30 min, (Z)-bis(phenylsulfonyl)ethylene 7 (66.9 mg, 0.217 mmol)
was added at 0 °C. After stirring at room temperature for 1 h, the
reaction was quenched with satd NaHCO3 and extracted with
EtOAc. The combined organic layer was washed with brine, dried
over MgSO4, and concentrated in vacuo to give crude vinyl sulfone
To a solution of 5 (146.3 mg, 0.328 mmol) in pyridine (2 mL)
was added Ac2O (2 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, 3:2) to give acetate 6 (153.7 mg, 96%). Colorless
8. To a solution of 8 in CH2Cl2 (1.6 mL) was added DIBAH (260 lL,
0.94 M solution in n-hexane, 0.243 mmol) at ꢀ78 °C. After stirring
at ꢀ78 °C for 1 h, i-PrOH (1 mL) and silica gel were added at room
temperature. The mixture was diluted with EtOAc, stirred for 1 h,
filtrated through a Celite pad, and concentrated in vacuo. The res-
idue was purified by flash column chromatography (n-hexane/
EtOAc, 1:1) to give aldehyde 9 (52.6 mg, 73%) as a colorless oil.
needles. Mp 176.5–177.5 °C (EtOAc/n-hexane). ½a D26
¼ ꢀ15:4 (c
ꢁ
1.01, CHCl3); IR (neat) 2939, 2875, 1746, 1457, 1386, 1341, 1297,
1229, 1150, 1085 cmꢀ1 1H NMR (500 MHz, CDCl3) d 7.89 (t,
;
J = 7.3 Hz, 2H), 7.62 (t, J = 7.3 Hz, 1H), 7.52 (t, J = 7.9 Hz, 2H), 7.47
(dd, J = 7.9, 2.4 Hz, 2H), 7.39–7.33 (m, 3H), 5.49 (s, 1H), 4.57
(ddd, J = 10.7, 10.7, 4.6 Hz, 1H), 4.26 (dd, J = 10.7, 4.9 Hz, 1H),
3.95 (ddd, J = 9.8, 7.9, 3.4 Hz, 1H), 3.64 (t, J = 10.4 Hz, 1H), 3.50
(ddd, J = 11.9, 9.2, 4.3 Hz, 1H), 3.33–3.28 (m, 3H), 3.10–3.04
½
a 2D4
ꢁ
¼ ꢀ36:6 (c 1.00, CHCl3); IR (neat) 2915, 2844, 1726, 1618,
1447, 1390, 1304, 1254, 1144, 1083, 1002 cmꢀ1 1H NMR
(500 MHz, CDCl3) d 9.68 (q, J = 0.9 Hz, 1H), 7.94 (dd, J = 6.4,
;

T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
1393
1.2 Hz, 2H), 7.60 (dddd, J = 6.7, 6.7, 1.2, 1.2 Hz, 1H), 7.54–7.51 (m,
2H), 7.46–7.44 (m, 2H), 7.38–7.36 (m, 3H), 6.52 (d, J = 6.4 Hz,
1H), 5.70 (d, J = 6.4 Hz, 1H), 5.48 (s, 1H), 4.28 (dd, J = 10.7, 4.9 Hz,
1H), 3.86 (ddd, J = 9.5, 8.5, 3.4 Hz, 1H), 3.77 (ddd, J = 11.0, 9.5,
4.6 Hz, 1H), 3.61 (t, J = 10.4 Hz, 1H), 3.49 (ddd, J = 11.9, 9.2,
4.3 Hz, 1H), 3.40 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H), 2.60 (ddd, J = 16.5,
3.1, 0.9 Hz, 1H), 2.43 (ddd, J = 10.7, 10.7, 2.7 Hz, 1H), 2.42 (ddd,
J = 16.5, 7.9, 2.4 Hz, 1H), 1.71 (t, J = 11.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 199.2, 153.0, 136.9, 133.2, 129.2, 128.8, 128.3,
127.6, 126.0, 110.3, 101.7, 81.0, 75.5, 74.9, 73.2, 68.8, 44.7, 35.2;
HRMS (EI) calcd for C23H24O7S [M]+ 444.1242, found 444.1239.
9.2, 4.3 Hz, 1H), 3.41 (ddd, J = 10.2, 9.2, 4.9 Hz, 1H), 3.36 (ddd,
J = 10.7, 8.9, 4.3 Hz, 1H), 3.26–3.13 (m, 3H), 2.44 (ddd, J = 11.3,
4.0, 4.0 Hz, 1H), 2.38 (ddd, J = 11.3, 4.3, 4.3 Hz, 1H), 1.69 (t,
J = 11.3 Hz, 1H), 1.48 (t, J = 11.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 137.2, 129.1, 128.3, 126.1, 101.8, 78.4, 77.1, 76.9, 76.4, 73.5, 71.3,
69.2, 38.3, 34.8, 17.8; HRMS (EI) calcd for C17H22O5 [M]+ 306.1466,
found 306.1465.
4.7.2. (2R,4aR,6S,7R,8aS)-6-((R)-2-Hydroxybut-3-enyl)-2-
phenyl-hexahydropyrano[3,2-d][1,3]dioxin-7-ol 13
A
white solid. Mp 101.5–109.5 °C (EtOAc/n-hexane).
¼ ꢀ23:9 (c 0.92, CHCl3); IR (KBr) 3307, 2975, 2927, 2895,
½ ꢁ
a 2D6
4.6. Reaction of (Z)-9 with SmI2 followed by acetylation
2861, 1735, 1498, 1464, 1452, 1432, 1409, 1389, 1367, 1340,
1305, 1287, 1272, 1238, 1221, 1181, 1164, 1120, 1092, 1072,
To a solution of 9 (52.6 mg, 0.118 mmol) and MeOH (12
lL,
1050, 1008 cmꢀ1 1H NMR (500 MHz, CDCl3) d 7.49 (dd, J = 7.9,
;
0.295 mmol) in THF (1.2 mL) was added SmI2 (3.0 mL, 0.1 M solu-
tion in THF , 0.300 mmol) at 0 °C After stirring at 0 °C for 30 min,
the reaction 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 a mixture of alcohols 5 and 10. To a solution of the
mixture in pyridine (1 mL) was added Ac2O (1 mL) at room
temperature. After stirring for 21 h, the mixture was azeotropical-
ly evaporated with benzene in vacuo. The residue was purified by
flash column chromatography (n-hexane/EtOAc, 5:2) to give
1.8 Hz, 2H), 7.39–7.33 (m, 3H), 5.89 (ddd, J = 16.8, 10.4, 5.8 Hz,
1H), 5.52 (s, 1H), 5.29 (d, J = 17.7 Hz, 1H), 5.14 (d, J = 10.7 Hz,
1H), 4.43 (br m, 1H), 4.30 (dd, J = 10.4, 4.9 Hz, 1H), 3.68 (t,
J = 10.4 Hz, 1H), 3.58 (m, 2H), 3.44 (ddd, J = 8.2, 8.2, 3.7 Hz, 1H),
3.39 (ddd, J = 9.8, 9.8, 5.2 Hz, 1H), 2.48 (ddd, J = 11.6, 4.3, 4.3 Hz,
1H), 2.10 (ddd, J = 14.9, 3.7, 3.7 Hz, 1H), 1.77 (ddd, J = 15.9, 7.9,
7,9 Hz, 1H), 1.70 (t, J = 11.6 Hz, 1H) ; 13C NMR (75 MHz, CDCl3) d
140.0, 137.2, 129.1, 128.4, 126.1, 114.9, 101.7, 81.6, 76.4, 73.2,
71.4, 69.5, 69.1, 39.0, 37.8; HRMS (EI) calcd for C17H22O5 [M]+
306.1465, found 306.1461.
syn-cis-acetate 11 (31.7 mg, 55%) and syn-trans-acetate
6
(6.2 mg 11%).
4.8. (2S,3R,4aS,6R,7S,8aR)-7-Hydroxy-6-(hydroxymethyl)-2-
methyl-octahydropyrano[3,2-b]pyran-3-yl acetate 14
4.6.1. Benzylidene acetal of (2R,3S,4aS,6R,7S,8aR)-7-hydroxy-6-
(hydroxymethyl)-2-(phenylsulfonylmethyl)-octahydropyrano-
[3,2-b]pyran-3-yl acetate 11
A solution of Raney Ni in EtOH (2 cm3/4 mL) was added to sul-
fone 6 (40.3 mg, 82.5 lmol) at room temperature. After stirring at
Colorless needles. Mp 204.0–205.0 °C (EtOAc/n-hexane). ½a D24
ꢁ
¼
85 °C for 10.5 h, the reaction mixture was filtrated through a Celite
pad, and evaporated in vacuo. The residue was purified by flash
column chromatography (n-hexane/EtOAc, 1:2) to give diol 14
(15.8 mg, 74%). Colorless crystals. Mp 169.5–170.5 °C (MeOH/
þ0:63 (c 1.01, CHCl3); IR (KBr) 2937, 2877, 1741, 1448, 1371, 1336,
1302, 1232, 1180, 1146, 1082, 1032, 1009 cmꢀ1
;
1H NMR
(500 MHz, CDCl3) d 7.90 (ddd, J = 8.2, 1.8, 1.8 Hz, 2H), 7.64 (dddd,
J = 6.7, 6.7, 1.2, 1.2 Hz, 1H), 7.55–7.52 (m, 2H), 7.48–7.46 (m, 2H),
7.38–7.35 (m, 3H), 5.50 (s, 1H), 5.09 (W1/2 = 6.2 Hz, 1H), 4.25 (dd,
J = 10.4, 4.9 Hz, 1H), 4.16 (ddd, J = 8.8, 2.7, 1.8 Hz, 1H), 3.65 (t,
J = 10.4 Hz, 1H), 3.53 (ddd, J = 11.6, 9.2, 4.3 Hz, 1H), 3.42 (dd,
J = 14.9, 9.2 Hz, 1H), 3.37–3.29 (m, 2H), 3.20 (dd, J = 15.0, 2.8 Hz,
1H), 3.13 (ddd, J = 11.3, 9.2, 4.3 Hz, 1H), 2.26 (ddd, J = 14.0, 3.4,
3.4 Hz, 1H), 2.09 (3H, s), 2.03 (ddd, J = 11.3, 4.0, 4.0 Hz, 1H), 1.71
(ddd, J = 14.0, 11.6, 3.1 Hz, 1H), 1.48 (t, J = 11.6 Hz, 1H) ; 13C NMR
(75 MHz, CDCl3) d 169.2, 139.9, 137.1, 133.8, 129.2, 129.0, 128.4,
128.2, 126.1, 101.8, 76.8, 76.7, 73.9, 73.7, 73.4, 70.3, 69.0, 58.0,
34.2, 33.7, 20.9; HRMS (EI) calcd for C25H28O8S [M]+ 488.1505,
found 488.1496.
EtOAc/n-hexane). ½a D23
ꢁ
¼ ꢀ37:8 (c 0.95, CHCl3); IR (KBr) 3295,
2942, 2845, 1735, 1468, 1377, 1254, 1138, 1112, 1065 cmꢀ1
;
1H
NMR (500 MHz, CDCl3) d 4.53 (ddd, J = 11.3, 9.8, 4.9 Hz, 1H), 3.85
(dd, J = 11.9, 4.0 Hz, 1H), 3.79 (dd, J = 11.6, 4.6 Hz, 1H), 3.70 (ddd,
J = 11.3, 9.5, 4.9 Hz, 1H), 3.42 (m, 1H), 3.24 (ddd, J = 8.8, 4.3,
4.3 Hz, 1H), 3.14 (ddd, J = 11.6, 9.2, 4.3 Hz, 1H), 3.06 (ddd,
J = 11.3, 9.2, 4.0 Hz, 1H), 2.43 (ddd, J = 11.6, 4.6, 4.6 Hz, 1H), 2.40
(ddd, J = 10.7, 3.7, 3.7 Hz, 1H), 2.07 (3H, s), 1.52 (t, J = 11.3 Hz,
1H), 1.45 (t, J = 11.3 Hz, 1H), 1.19 (d, J = 6.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 170.0, 81.2, 76.0, 75.7, 75.6, 72.2, 66.6, 62.9,
38.1, 34.9, 21.1, 17.7; HRMS (EI) calcd for
260.1259, found 260.1263.
C
12H20O6 [M]+
4.7. Reaction of 6 with Na–Hg
4.9. Benzylidene acetal of (2R,3S,4aR,6R,7R,8aS)-7-(tert-butyl-
dimethylsilyloxy)-2-(hydroxymethyl)-6-(phenylsulfonylmeth-
yl)-octahydropyrano[3,2-b]pyran-3-ol 15
To a solution of 6 (33.1 mg, 61.4 lmol) and Na2HPO4 (ca. 1.2 g)
in MeOH (30 mL) was added Na–Hg (ca. 1.3 g) at room tempera-
ture. After stirring at room temperature for 10.5 h, the mixture
was filtrated through Hyflo-Super-Cel, and concentrated in vacuo.
The residue was purified by flash column chromatography (n-hex-
ane/EtOAc, 5:2–2:1) to give alcohol 12 (6.8 mg, 36%) and olefin 13
(11.4 mg, 61%).
To a solution of 5 (45.3 mg, 0.101 mmol) and imidazole (94.0 mg,
1.381 mmol) in DMF (0.2 mL) was added TBSCl (98.2 mg,
0.639 mmol) at room temperature. After stirring for 43.5 h, the reac-
tion was quenched with MeOH and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/EtOAc,
2:1) to give silyl ether 15 (52.7 mg, 93%). Colorless needles. Mp
4.7.1. Benzylidene acetal of (2R,3S,4aR,6S,7R,8aS)-2-(hydroxy-
methyl)-6-methyl-octahydropyrano[3,2-b]pyran-3,7-diol 12
211.0–212.0 °C (EtOAc/n-hexane). ½a D21
¼ ꢀ21:4 (c 1.00, CHCl3); IR
ꢁ
(KBr) 2932, 2880, 2849, 1479, 1455, 1394, 1362, 1339, 1315, 1294,
A white solid. Mp 225.0–226.0 °C (EtOAc/n-hexane). ½a D26
ꢁ
¼
1251, 1198, 1147, 1094, 1012 cmꢀ1 1H NMR (500 MHz, CDCl3) d
;
ꢀ15:0 (c 1.00, CHCl3); IR (KBr) 3581, 2974, 2962, 2930, 2873,
7.90 (d, J = 7.6 Hz, 2H), 7.60 (t, J = 7.0 Hz, 1H), 7.50 (t, J = 7.9 Hz,
2H), 7.48–7.46 (m, 2H), 7.39–7.35 (m, 3H), 5.50 (s, 1H), 4.26 (dd,
J = 10.4, 4.9 Hz, 1H), 3.70 (t, J = 9.2 Hz, 1H), 3.65 (t, J = 10.4 Hz, 1H),
3.57 (d, J = 14.0 Hz, 1H), 3.50 (ddd, J = 11.6, 9.2, 4.0 Hz, 1H), 3.41
(ddd, J = 10.7, 10.7, 4.6 Hz, 1H), 3.29 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H),
1453, 1392, 1377, 1334, 1321, 1291, 1235, 1179, 1154, 1111,
1074, 1039, 1009 cmꢀ1 1H NMR (500 MHz, CDCl3) d 7.49 (dd,
;
J = 7.9, 2.1 Hz, 2H), 7.38–7.34 (m, 3H), 5.53 (s, 1H), 4.32 (dd,
J = 10.7, 4.9 Hz, 1H), 3.70 (t, J = 10.4 Hz, 1H), 3.60 (ddd, J = 11.6,

1394
T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
3.24 (dd, J = 14.6, 9.8 Hz, 1H), 3.02–3.00 (m, 2H), 2.31 (ddd, J = 11.9,
4.0, 4.0 Hz, 1H), 1.97 (ddd, J = 11.3, 3.7, 3.7 Hz, 1H), 1.51 (q,
J = 11.0 Hz, 1H), 1.29 (q, J = 11.3 Hz, 1H), 0.88 (s, 9H), 0.07 (6H, s);
13C NMR (75 MHz, CDCl3) d 140.6, 137.1, 133.4, 129.2, 128.7, 128.4,
128.1 126.1, 101.8, 77.9, 76.8, 76.2, 76.0, 73.5, 69.0, 68.9, 58.1,
38.7, 34.1, 25.6, 17.8, ꢀ4.0, ꢀ4.8; HRMS (FAB) calcd for C29H41O7SSi
[M]+ 561.2342, found 561.2339.
stirring at ꢀ78 °C for 30 min, the mixture was warmed up to
0 °C. After stirring for 30 min, the reaction was quenched with
H2O and satd NaHCO3, and extracted with EtOAc. The combined or-
ganic layer was washed with brine, dried over MgSO4, filtrated
through a Celite pad, and concentrated in vacuo. The residue was
purified by flash column chromatography (n-hexane/EtOAc, 2:1)
to give exo-methylene 18 (30.4 mg, 78%) as
¼ þ9:6 (c 0.77, CHCl3); IR (KBr) 3505, 2925, 2863, 1732,
1657, 1469, 1456, 1416, 1389, 1388, 1368, 1298, 1227, 1179,
1116, 1075, 1031 cmꢀ1 1H NMR (300 MHz, CDCl3) d 7.50 (d,
a yellow oil.
½ ꢁ
a 2D2
4.10. (2R,3S,4aR,6S,7R,8aS)-7-(tert-Butyldimethylsilyloxy)-2-
(hydroxymethyl)-6-methyl-octahydropyrano[3,2-b]pyran-3-ol 16
;
J = 7.6 Hz, 2H), 7.38 (d, J = 7.0 Hz, 3H), 5.53 (s, 1H), 4.69 (s, 1H),
4.66 (s, 1H), 4.32 (dd, J = 10.7, 4.9 Hz, 1H), 4.23 (ddd, J = 10.7,
10.7, 4.3 Hz, 1H), 3.70 (t, J = 10.4 Hz, 1H), 3.60 (ddd, J = 11.9, 9.2,
4.3 Hz, 1H), 3.44 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H), 3.41–3.36 (m, 2H),
2.53 (ddd, J = 11.0, 3.4, 3.4 Hz, 1H), 2.48 (ddd, J = 10.7, 4.0, 4.0 Hz,
1H), 1.80 (q, J = 11.3 Hz, 1H), 1.55 (q, J = 11.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 161.2, 137.1, 129.2, 128.4, 126.1, 101.9, 92.7,
77.5, 76.8, 76.0, 73.6, 69.1, 66.3, 38.3, 34.8; HRMS (EI) calcd for
A solution of Raney Ni in EtOH (0.6 cm3/1 mL) was added to sul-
fone 15 (19.4 mg, 34.6 lmol) at room temperature. After stirring at
85 °C for 10.5 h, the mixture was filtrated through a Celite pad and
the filtrate was evaporated in vacuo. The residue was purified by
flash column chromatography (n-hexane/EtOAc, 2:1) to give diol
16 (9.6 mg, 83%). Colorless needles. Mp 128.0–129.0 °C. (EtOAc/n-
hexane). ½a 2D1
ꢁ
¼ ꢀ24:2 (c 1.00, CHCl3); IR (KBr) 3409, 2928, 2858,
1463, 1362, 1323, 1287, 1258, 1104, 1030, 1008 cmꢀ1
;
1H NMR
C
17H20O5 [M]+ 304.1309, found 304.1312.
(500 MHz, CDCl3) d 3.87 (dd, J = 11.6, 4.0 Hz, 1H), 3.79 (dd,
J = 11.3, 4.9 Hz, 1H), 3.70 (ddd, J = 11.0, 9.2, 4.6 Hz), 3.32 (ddd,
J = 10.7, 8.9, 4.6 Hz, 1H), 3.25–3.20 (m, 2H), 3.09–3.00 (m, 2H),
2.40 (ddd, J = 11.6, 4.6, 4.6 Hz, 1H), 2.27 (ddd, J = 11.6, 4.3, 4.3 Hz,
1H), 1.48 (q, J = 11.3, 1H), 1.46 (q, J = 11.3 Hz, 1H), 1.23 (d,
J = 6.1 Hz, 3H), 0.88 (s, 9H), 0.07 (d, J = 2.4 Hz, 6H) ; 13C NMR
(75 MHz, CDCl3) d 81.1, 78.6, 76.2, 75.7, 72.0, 66.8, 63.0, 39.0,
38.3, 25.7, 18.1, 17.9, ꢀ4.2, ꢀ4.8; HRMS (FAB) calcd for C16H33O5Si
[M]+ 333.2097, found 333.2100.
4.13. Benzylidene acetal of (3R,4aS,6R,7S,8aR)-7-hydroxy-6-
(hydroxymethyl)-2-methylene-octahydropyrano[3,2-b]pyran-
3-yl acetate 19
To a solution of 18 (7.7 mg, 25.3 lmol) in pyridine (0.5 mL) was
added Ac2O (0.5 mL) at room temperature. After stirring for 21.5 h,
the mixture was azeotropically evaporated with benzene in vacuo.
The residue was purified by flash column chromatography (n-hex-
ane/EtOAc, 2:1) to give acetate 19 (7.1 mg, 81%). Colorless needles.
4.11. Benzylidene acetal of (2R,4aS,6R,7S,8aR)-7-hydroxy-6-
(hydroxymethyl)-2-(phenylsulfonylmethyl)-hexahydropyrano-
[3,2-b]pyran-3(2H)-one 17
Mp 158.5–159.5 °C (EtOAc/n-hexane). ½a D22
¼ þ4:5 (c 0.66, CHCl3);
ꢁ
IR (KBr) 2925, 2889, 2863, 1750, 1658, 1457, 1373, 1340, 1298,
1289, 1243, 1228, 1181, 1113, 1074, 1022, 1005 cmꢀ1 1H NMR
;
(500 MHz, CDCl3) d 7.49 (dd, J = 8.2, 2.1 Hz, 2H), 7.40–7.35 (m,
3H), 5.53 (s, 1H), 5.35 (dddd, J = 10.4, 5.8, 1.5, 1.5 Hz, 1H), 4.67 (s,
1H), 4.46 (s, 1H), 4.32 (dd, J = 10.7, 4.9 Hz, 1H), 3.70 (t,
J = 10.4 Hz, 1H), 3.61 (ddd, J = 11.6, 8.9, 4.0 Hz, 1H), 3.48–3.42 (m,
3H), 2.54 (ddd, J = 11.6, 3.7, 3.7 Hz, 1H), 2.50 (ddd, J = 11.3, 11.3,
4.3 Hz, 1H), 2.14 (s, 3H), 1.82 (q, J = 11.3 Hz, 1H), 1.62 (q,
J = 10.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 169.5, 156.1, 137.1,
129.2, 128.4, 126.1, 101.9, 93.3, 77.2, 76.7, 75.5, 73.6, 69.0, 66.9,
34.9, 34.8, 21.1; HRMS (EI) calcd for C19H22O6 [M]+ 346.1417, found
346.1417.
A solution of oxalyl chloride (1.00 g, 7.77 mmol) in CH2Cl2
(19 mL) was added DMSO (1.32 g, 16.39 mmol) at ꢀ78 °C. After
stirring at the same temperature for 30 min, a solution of 5
(840.8 mg, 1.88 mmol) in CH2Cl2 (10 mL) was added. After stirring
at ꢀ78 °C for 1 h, the reaction was quenched with Et3N at ꢀ78 °C.
After stirring at the same temperature for 20 min, the mixture was
diluted with EtOAc, warmed up to room temperature. The organic
layer was washed with brine, dried over MgSO4, and concentrated
in vacuo. The residue was purified by flash column chromatogra-
phy (n-hexane/EtOAc, 1:1) to give ketone 17 (842.7 mg, 100%). Col-
orless crystals. Mp 194.0–196.0 °C (EtOAc). ½a D20
ꢁ
¼ þ5:5 (c 1.00,
4.14. Benzylidene acetal of (2R,3S,4aR,7R,8aS)-7-(tert-butyldi-
methylsilyloxy)-2-(hydroxymethyl)-6-methylene-octahydro-
pyrano[3,2-b]pyran-3-ol 20
CHCl3); IR (KBr) 2965, 2886, 1735, 1587, 1457, 1450, 1400, 1388,
1368, 1310, 1245, 1231, 1143, 1102, 1081, 1024, 1012 cmꢀ1 1H
;
NMR (500 MHz, CDCl3) d 7.91 (dd, J = 8.2, 1.2 Hz, 2H), 7.64 (dddd,
J = 6.7, 6.7, 1.2, 1.2 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.48 (dd,
J = 7.3, 3.4 Hz, 2H), 7.40–7.36 (m, 3H), 5.53 (s, 1H), 4.42 (dd,
J = 8.2, 2.4 Hz, 1H), 4.30 (dd, J = 10.7, 4.9 Hz, 1H), 3.86 (dd,
J = 15.3, 2.4 Hz, 1H), 3.69 (t, J = 10.4 Hz, 1H), 3.61 (ddd, J = 11.6,
9.2, 4.3 Hz, 1H), 3.49–3.46 (m, 2H), 3.43–3.37 (m, 2H), 3.01 (dd,
J = 15.9, 4.6 Hz, 1H), 2.50 (dd, J = 15.9, 11.3 Hz, 1H), 2.27 (ddd,
J = 11.6, 4.0, 4.0 Hz, 1H), 1.54 (q, J = 11.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 201.1, 140.1, 137.0, 133.8, 129.2, 129.0, 128.3,
128.0, 126.1, 101.8, 78.4, 76.4, 76.1, 75.6, 73.1, 68.8, 56.0, 44.3,
To a solution of 18 (22.1 mg, 72.6 lmol) and imidazole (30.3 mg,
0.445 mmol) in DMF (0.3 mL) was added TBSCl (35.5 mg,
0.231 mmol) at room temperature. After stirring for 17.5 h, the reac-
tion was quenched with MeOH and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/EtOAc,
5:1) to give silyl ether 20 (23.7 mg, 78%). Colorless crystals. Mp
148.0–149.0 °C (n-hexane). ½a D22
¼ ꢀ4:1 (c 1.04, CHCl3); IR (KBr)
ꢁ
2954, 2931, 2878, 2858, 1656, 1471, 1451, 1408, 1373, 1319, 1299,
1250, 1230, 1180, 1148, 1109, 1075, 1006 cmꢀ1
;
1H NMR
34.1; HRMS (EI) calcd for
444.1254.
C
23H24O7S [M]+ 444.1243, found
(500 MHz, CDCl3) d 7.49 (d, J = 7.0 Hz, 2H), 7.39–7.34 (m, 3H), 5.53
(s, 1H), 4.68 (s, 1H), 4.66 (s, 1H), 4.31 (dd, J = 10.4, 4.9 Hz, 1H), 4.18
(dd, J = 11.0, 5.5 Hz, 1H), 3.70 (t, J = 10.4 Hz, 1H), 3.60 (ddd, J = 11.6,
9.2, 4.3 Hz, 1H), 3.44 (ddd, J = 9.8, 9.8, 4.9 Hz, 1H), 3.39–3.31 (m,
2H), 2.53 (ddd, J = 11.6, 4.0, 4.0 Hz, 1H), 2.34 (ddd, J = 11.0, 4.0,
4.0 Hz, 1H), 1.78 (q, J = 11.0 Hz, 1H), 1.62 (q, J = 11.0 Hz, 1H), 0.93
(s, 9H), 0.11 (d, J = 2.4 Hz, 6H); 13C NMR (75 MHz, CDCl3) d 161.4,
137.2, 129.1, 128.3, 126.1, 101.8, 93.4, 77.8, 76.8, 76.1, 73.5, 69.1,
66.8, 39.1, 34.9, 25.7, 18.1, ꢀ5.0, ꢀ5.1; HRMS (EI) calcd for
4.12. Benzylidene acetal of (2R,3S,4aR,7R,8aS)-2-(hydroxyme-
thyl)-6-methylene-octahydropyrano[3,2-b]pyran-3,7-diol 18
To a solution of 17 (56.8 mg, 0.128 mmol) in MeOH (0.6 mL)
was added DBU (102.0 mg, 0.657 mmol) at ꢀ15 °C. After stirring
at ꢀ15 to ꢀ5 °C for 30 min, CeCl3ꢂ7H2O (157.6 mg, 0.423 mmol)
and NaBH4 (12.0 mg, 0.317 mmol) were added at ꢀ78 °C. After
C
23H35O5Si [M]+ 419.2253, found 419.2250.

T. Kimura, T. Nakata / Tetrahedron: Asymmetry 21 (2010) 1389–1395
1395
G.; Hori, N.; Nakata, T. Tetrahedron Lett. 1999, 40, 8859; (d) Suzuki, K.;
Matsukura, 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.
5. Selected papers: (a) Sato, K.; Sasaki, M. Angew. Chem., Int. Ed. 2007, 46, 2518; (b)
Fuwa, H.; Ebine, M.; Bourdelais, A. J.; Baden, D. G.; Sasaki, M. J. Am. Chem. Soc.
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Matsuda, K.; Satake, M.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 11893; (e)
Nagumo, Y.; Oguri, H.; Shindo, Y.; Sasaki, S.; Oishi, T.; Hirama, M.; Tomioka, Y.;
Mizugaki, M.; Tsumuraya, T. Bioorg. Med. Chem. Lett. 2001, 11, 2037; (f) Matsuo,
G.; Kawamura, K.; Hori, N.; Matsukura, H.; Nakata, T. J. Am. Chem. Soc. 2004,
126, 14374; (g) Takahashi, S.; Kubota, A.; Nakata, T. Angew. Chem., Int. Ed. 2002,
41, 4751.
Acknowledgements
This work was financially supported by the Uehara Memorial
Foundation and a Grant-in-Aid for Scientific Research from the Min-
istry of Education, Culture, Sports, Science, and Technology, Japan.
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