A 2,4-O-[(Z)-2-butenylene]-bridged glucopyranose: efficient construction of the bicyclic skeleton and its axial-rich twist-boat conformation

Article abstract of DOI:10.1016/j.tet.2009.01.019

Synthesis and conformational analyses of 1-O-acetyl-3,6-di-O-benzyl-2,4-O-[(Z)-2-butenylene]-β-d-glucopyranose are described. The construction of the trioxabicyclo[6.3.1]dodecane skeleton of the compound was initiated from a ring-opened glucose, followed

Full text of DOI:10.1016/j.tet.2009.01.019

Tetrahedron 65 (2009) 2574–2578
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journal homepage: www.elsevier.com/locate/tet
A 2,4-O-[(Z)-2-butenylene]-bridged glucopyranose: efficient construction
of the bicyclic skeleton and its axial-rich twist-boat conformation
*
Yang Cao, Yusuke Kasai, Masafumi Bando, Mayumi Kawagoe, Hidetoshi Yamada
School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 August 2008
Received in revised form 25 December 2008
Accepted 6 January 2009
Available online 14 January 2009
Synthesis and conformational analyses of 1-O-acetyl-3,6-di-O-benzyl-2,4-O-[(Z)-2-butenylene]-b-D-
glucopyranose are described. The construction of the trioxabicyclo[6.3.1]dodecane skeleton of the
compound was initiated from a ring-opened glucose, followed by the successive cyclization of first the
nine-membered ring and then the six-membered ring. The pyranose of the compound was in 3S1, an
axial-rich twist-boat conformation. This result demonstrated an alternative method for the restriction of
the pyranose into the axial-rich twist-boat conformation in contrast to the procedures that use bulky
silyl protecting groups.
Keywords:
Butenylene bridge
Synthetic route
Twist-boat conformation
Axial rich
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Conformation of a pyranose is generally in a chair form that has
more equatorial substituents. Exceptions to this generality have
sporadically occurred during synthetic studies to prove that the
pyranose can stably attain an axial-rich conformer.1 Intentional ring
flips have also been investigated to control diastereoselectivity and
reactivity in glycosidations and carbohydrate-related syntheses.2
Recently, we have demonstrated the significance of twist-boat
forms (e.g., 1, Fig. 1)3 in contrast to the initial concept of axial-rich
conformation assuming the chair form.4 As in 1, steric hindrance
due to bulky trialkylsilyl protecting groups has typically restricted
the pyranose rings in the axial-rich sugars that have been used in
glycosidations. Shoehorning the silyl groups into a tight space in-
troduces these restrictions, and thus, vigorous reaction conditions
are usually required.5 Additionally, owing to the tensioned struc-
ture, a part of the silyl group easily migrates to another hydroxy
group.3b To apply such conformational restriction without these
disadvantages due to the silyl groups, further studies would be
needed to look for alternative method for regulation of a pyranose
OH
PivO
O
HO
OTIPS
O
OH
O
O
SEt
OH
O
O
O
TIPSO
HO
OH
OTIPS
1
2
3
Me
BnO
HO
HO
OH OBn
OH
HO
OH
HO
HO
OH
A
O
O
O
O
O
OH
OH
O
O
O
O
O
6
B
OPMB
OBn
O
3
OH
HO
4
5
OH
BnO
into the axial-rich conformation, hopefully as
structure.
a twist-boat
OBn
BnO
OBn
O
O
OAc
Construction of a bridged structure would be a simple solution
OAc
4
O
2
for the restriction of pyranoses.6 In the common bridged sugars,
O
3
O
S
1,6-anhydro-b-D-glucopyranose (2) and 1,2,4-O-ethylidyne-a-
O
1
OBn
6
* Corresponding author. Tel.: þ81 79 565 8342; fax: þ81 79 565 9077.
E-mail address: hidetosh@kwansei.ac.jp (H. Yamada).
Figure 1.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.019

Y. Cao et al. / Tetrahedron 65 (2009) 2574–2578
2575
D
-glucopyranose (3), the anomeric positions participate as one ends
the ethylthio group was faster, and thereby afforded 9 without
influencing the double bonds. Pyranose 9 was then reduced by
NaBH4 in refluxing ethanol giving the corresponding glucitol in 73%
yield, and subsequent acetylation of the diol provided 7.
of the bridge, and thus, they have not been commonly used as
glycosyl donors in glycosidation reactions. Therefore, new designs
are needed for stable axial-rich twist-boat conformers with a re-
movable bridge between discontiguous hydroxy groups at sites
other than the anomeric position. The structure of corilagin (4),7
a natural ellagitannin, is one of the solution to meet the re-
quirements, because its pyranose ring is in a twist-boat or 1C4
conformation.8 Toward synthesis of the 3,6-O-bridged structure,
we know that (1) the direct formation of the bridge involving ring
flip of the pyranose into the contra-thermodynamic conformation
is difficult, and (2) the stepwise construction of the two rings (A
then B) was effective when starting from the acyclic synthetic in-
termediate (5).9 We report herein that this synthetic strategy was
1) NaH, AllylBr
THF, rt
1.5 h, 85%
OBn
1) PhCH(OMe)2
CSA, DMF, 81%
O
SEt
10
2) Et3SiH, BF3·Et2O
0 °C, 2 h, 77%
2) NBS
THF/H2O (2:1)
0 °C, 5 h, 73%
HO
OH
OBn
11
OBn
OBn
O
1)
2)
NaBH4, EtOH
OAc OAc
O
OH
O
reflux, 4 h, 73%
successfully applied to
a
2,4-O-bridged structure, ultimately
Ac2O, pyridine
rt, 4 h, 93%
O
O
affording the derivative of glucose 6, a stable twisted-boat con-
OBn
OBn
9
former (Fig. 1) possessing a removable (Z)-2-butenylene bridge.10
7
Scheme 2. Synthesis of ring-opened precursor 7 for RCM.
2. Results and discussion
The successive intramolecular RCM and reconstruction of the
pyranose ring converted diacetate 7 to 6 (Scheme 3). Thus, treat-
ment of 7 with 20 mol % of Grubbs first generation catalyst in
refluxing dichloromethane prepared the nine-membered ring to
give the desired product 8 in 64% yield as the single Z-geometric
isomer together with 32% of recovered 7. Traces of cross-metathesis
product were detected by ESIMS but were not collected. Techni-
cally, the catalyst was added in four portions during the reaction
time at 12 h intervals to increase the yield. Treatment of 7 with the
Grubbs second generation catalyst produced more cross-metathe-
sis product. No RCM reaction occurred with the corresponding diol,
thus the protection of the hydroxy groups was indispensable.
Methanolysis of the RCM product 8 removed the two acetyl groups
providing diol 12. The regioselective oxidation at the primary al-
cohol of 12 using 2-iodoxybenzoic acid (IBX) reconstructed the
pyranose ring to afford hemiacetal 13 in 62% yield as an inseparable
anomeric mixture. The conformational analysis of the anomeric
mixture 13 was difficult because its 1H NMR was complex. Fortu-
nately, acetylation of 13 provided a single diastereomer 6 in 84%
yield, whose further structural determination was possible in-
cluding its anomeric stereochemistry. The (Z)-2-butenylene bridge
of 6 was smoothly removed according to the Bistri and Sollogoub’s
method10 to give the monocyclic 14.
The following steps achieved the bicyclic structure of 6, that is, (i)
ring opening of the pyranose, (ii) construction of the 2,4-bridge, and
(iii) reconstruction of the pyranose (Scheme 1). The skeleton of 6 is
a
trioxabicyclo[6.3.1]dodecane, and the 2,4-O-(Z)-2-butenylene
bridge secures the pyranose ring in the axial-rich conformation. We
designed an acyclic 7 as the precursor of the stepwise cyclizations
whose allyl groups were first cyclized to prepare the nine-membered
ring providing 8, followed by regioselective oxidation of the
anomeric position to reconstruct the pyranose ring. The key in-
termediate 7 was prepared by the ring opening of the protected
glucose 9, which was easily introduced from the known ethyl-
thioglucoside 10. In this study, we reduced the anomeric aldehyde to
open the pyranose ring because we planned to apply ring closing
metathesis (RCM)11 of two allyl groups in a later step of the synthesis.
Although olefination of the carbonyl group has been the traditional
procedure to open the pyranose ring, we avoided this method due to
potential conflicts with the allyl groups in the RCM step.
OBn
O
OBn
O
O
OAc
O
OAc OAc
(iii)
(ii)
Reconstruction
Construction
of the
O
of the
OBn
OBn
pyranose
2,4-bridge
6
8
OBn
OBn
O
OBn
OH
Grubbs first
OAc OAc
OAc OAc
O
OH
O
O
SEt
OH
(i)
generation catalyst
NaOMe, MeOH
rt, 24 h, 100%
7
CH2Cl2, reflux
48 h, 64%
Ring-opening
of the
O
O
O
O
HO
OBn
OBn
OBn
OBn
OBn
pyranose
8
OH
O
10
9
7
OBn
O
Scheme 1. Retrosynthetic analysis of 6.
OH OH
O
IBX, DMSO
rt, 24 h, 60%
Ac2O, pyridine
6
According to the retrosynthetic analysis (Scheme 1), the RCM-
precursor 7 was initiated by treatment of ethylthio 3-O-benzyl-
CH2Cl2, rt, 6 h
86%
O
O
b-D-
OBn
OBn
glucopyranoside (10)12 with benzaldehyde dimethyl acetal and
camphorsulfonic acid (CSA) in DMF, which gave the corresponding
4,6-O-benzylidene compound in 81% yield (Scheme 2). The ben-
zylidene group of this intermediate was then regioselectively
cleaved by triethylsilane and boron trifluoride etherate to give 11 in
77% yield.13 Then, the double allylation of the 2- and 4-hydroxy
groups was undertaken, followed by the hydrolysis of the ethylthio
group to afford 9 in 61% yield (two steps). The hydrolysis was
achieved using NBS as the activator despite the presence of the two
allyl groups that could also react with the reagent. The reaction of
12
13
1)
2)
Pd(PPh3)4
ZnCl2, Bu3SnH
THF, rt, 6 h
OBn
O
OAc
Ac2O, pyridine
rt, 6 h
65% (2 steps)
AcO
OAc
OBn
14
Scheme 3. Synthesis of 6.

2576
Y. Cao et al. / Tetrahedron 65 (2009) 2574–2578
BnO
H
through a cotton pad. The filtrate was evaporated and subjected to
further purification protocols if necessary.
OBn
5
O
The melting points are uncorrected. Specific optical rotations
were determined with a 100 mm cell at 589 nm. The major absor-
bance bands in IR spectra are all reported in wavenumbers (cmꢀ1).
High resolution mass spectra were obtained by electrospray ioni-
zation (ESI) and are reported in units of mass to charge.
1H NMR data are indicated by a chemical shift with the multi-
plicity, the coupling constants, the integration, and the assignment
in parentheses in this order. The multiplicities are abbreviated as s:
singlet, d: doublet, t: triplet, q: quartet, m: multiplet, and br:
broad. 13C NMR data are reported as the chemical shift with the
hydrogen multiplicity obtained from the DEPT spectra in paren-
theses. The multiplicities are abbreviated as s: C, d: CH, t: CH2, and
q: CH3.
1
OAc
H
H
H
O
H
H
O
H
7
10
H
H
6
H
Figure 2. NOE correlations performed for the conformational determination.
Table 1
3JHH between the protons on the pyranose ring of 6 and the calculated dihedral
angles
Position
3JHH (Hz)
Calcd angle (ꢁ)
H-1–H-2
H-2–H-3
H-3–H-4
H-4–H-5
6.2
0.0
3.0
1.3
149
w90
58
4.2. Ethylthio 3,6-di-O-benzyl-b-D-glucopyranoside (11)
w90
A solution of 10 (3.48 g, 11.1 mmol), benzaldehyde dimethyl
acetal (3.04 g, 20.0 mmol), and camphorsulfonic acid (400 mg,
1.69 mmol) in DMF (30 mL) was heated to 100 ꢁC for 1 h. Then the
reaction proceeded under a reduced pressure at w15 mmHg for
additional 2 h to remove methanol. After cooling to room temper-
ature, aqueous NaHCO3 was added to the solution and it was
extracted with CH2Cl2. The combined organic layer was washed
with brine. The concentrated extract was purified by column
chromatography (silica gel 100 g, hexane/ethyl acetate¼8:1 to 3:1)
Complete assignment of the NMR peaks, NOESY experiments,
and analyses of the vicinal proton couplings illustrated the confor-
mation of 6. The assignment of 1H and 13C NMR peaks was per-
formed using H–H COSY, HMQC, and HMBC spectra in benzene-d6.14
The NOESY spectra exhibited diastereotopic assignments of the al-
lylic protons at the 7- and 10-position (Fig. 2). The correlations be-
tween H-1 and H-10
a, between H-3 and H-7b, and between H-4 and
to give ethylthio 3-O-benzyl-4,6-O-benzylidene-b-D-glucopyrano-
H-7 indicated the conformation of the (Z)-2-butenylene moiety.
b
side (3.59 g, 81%) as a white crystal, whose NMR data were identical
to the literature data.13 To a solution of ethylthio 3-O-benzyl-4,6-O-
Additionally, the correlations between H-1 and H-5 revealed that
both of these protons were axiallyoriented, and thus, the C-1–O–C-5
part of the pyranose was not flipped from the thermodynamically
stable form of glucopyranose possessing equatorial acetoxy and
benzyloxymethyl groups on C-1 and C-5, respectively. Analyses of
the coupling constants attributed to the vicinal protons on the py-
ranose rings (3JHH) in the 1H NMR spectra determined the 3S1 con-
formations of the pyranose ring. Table 1 presents the coupling
constants observed in 6 in benzene-d6 as well as the dihedral angles
of the adjacent C–H bonds calculated by the modified Karplus
equation.15 Although the solution of the Karplus equation has two
values for a given coupling constant, the cyclic structure limits the
possible dihedral angles. Therefore, only the most plausible set of
the dihedral angles are listed in the Table. The models prepared
according to these dihedral angles indicated that the pyranose ring
is in a twist-boat conformation (3S1) with three axial (C-2, C-3, and
C-4 positions) and two equatorial substituents (C-1 and C-5 posi-
tions) as in the conformationally represented 6 (Fig. 2).
benzylidene-b-D-glucopyranoside (1.73 g, 4.30 mmol) and trie-
thylsilane (5.00 g, 43.0 mmol) in dry CH2Cl2 (50 mL), BF3$Et2O
(916 mg, 6.45 mmol) was added at 0 ꢁC. The solution was stirred at
0 ꢁC for 2 h and quenched with aqueous NaHCO3. The aqueous layer
was extracted with CH2Cl2 and the combined organic layer was
washed with brine. The concentrated extract was purified by col-
umn chromatography (silica gel 50 g, hexane/ethyl acetate¼8:1 to
25
4:1) to give 11 (1.33 g, 77%) as a colorless syrup. [
a
]
D
ꢀ52.0 (c 0.92,
CHCl3); IR (thin film) nmax (cmꢀ1): 3445, 3063, 3030, 2870, 1607,
1497, 1454, 1362, 1265, 1209, 1123, 1071, 1028, 739, 698; 1H NMR
(400 MHz, CDCl3)
d
: 7.32–7.18 (m, 10H, Ph), 4.89 (d, J¼11.7 Hz, 1H,
Bn), 4.75 (d, J¼11.7 Hz, 1H, Bn), 4.52 (d, J¼12.1 Hz, 1H, Bn), 4.48 (d,
J¼12.1 Hz, 1H, Bn), 4.26 (d, J¼9.6 Hz, 1H, H-1), 3.68 (dd, J¼10.4,
4.1 Hz,1H, H-6a), 3.65 (dd, J¼10.4, 5.0 Hz,1H, H-6b), 3.56 (dd, J¼9.6,
8.7 Hz, 1H, H-4), 3.46–3.40 (m, 2H, H-2 and H-5), 3.34 (dd, J¼8.7,
8.5 Hz, 1H, H-3), 2.66 (br, 2H, SCH2CH3), 2.40 (br, 2H, OH), 1.23 (t,
J¼7.4 Hz, 3H, SCH2CH3); 13C NMR (100 MHz, CDCl3)
d: 138.5 (s),
137.8 (s), 128.6 (d), 128.4 (d), 128.0 (d), 127.9 (d), 127.7 (d), 127.7 (d),
86.2 (d), 85.1 (d), 78.3 (d), 74.7 (t), 73.6 (t), 72.7 (d), 71.4 (d), 70.4 (t),
24.4 (t), 15.4 (q); ESIHRMS (m/z) [MþNaþ] calcd for C22H28O5S
427.1555, found 427.1551.
3. Conclusion
A 2,4-O-(Z)-2-butenylene bridged glucose derivative 6 was
synthesized via stepwise cyclizations of acyclic 7. This achievement
enhanced the efficacy of the synthetic strategy toward the bridged
bicyclic system restricting the pyranose into an axial-rich confor-
mation. The revealed 3S1 conformation of 6 showed that the 2,4-O-
bridge provides a new method to restrict the conformation of the
pyranose into the twist boat.
4.3. 2,4-Di-O-allyl-3,6-di-O-benzyl-D-glucopyranose (9)
NaH (60% in oil, 0.77 g, 19 mmol) was added to a solution of 11
(1.30 g, 3.22 mmol) in dry THF (30 mL) at room temperature. After
stirring for 30 min, allyl bromide (1.54 g 12.8 mmol) was added.
The mixture was stirred for 1.5 h at room temperature and the
reaction was quenched by slow addition of cold methanol. The
solvent and excessive allyl bromide were removed under vacuum,
and then saturated aqueous NH4Cl was added. The mixture was
extracted with ethyl acetate. The combined organic layer was
washed with brine. The concentrated extract was purified by
column chromatography (silica gel 40 g, hexane/ethyl acetate¼
4. Experimental
4.1. General procedure
All moisture and air sensitive reactions were performed under
a positive pressure of nitrogen. Anhydrous MgSO4 was used to dry
organic layers after extraction, and it was removed by filtration
20:1 to 10:1) to give ethylthio 2,4-di-O-allyl-3,6-di-O-benzyl-b-

Y. Cao et al. / Tetrahedron 65 (2009) 2574–2578
2577
D
-glucopyranoside (1.32 g, 85%) as colorless oil. To a solution of
to afford unreacted 7 (79 mg, 32%) and 8 (152 mg, 64%) as a col-
25
ethylthio 2,4-di-O-allyl-3,6-di-O-benzyl- -glucopyranoside (936 mg,
b-D
orless syrup. [
(cmꢀ1): 3025, 2919, 2849, 1740, 1454, 1372, 1235, 1103, 1047, 741,
700; 1H NMR (400 MHz, CDCl3)
7.28–7.19 (m, 10H, Ph),
a
]
ꢀ26.3 (c 0.29, CHCl3); IR (thin film) nmax
D
1.93 mmol) in THF/H2O (2:1, 30 mL) at 0 ꢁC, solid NBS (1.00 g,
5.62 mmol) was added in small portions (ca. 10 mg every 2 min
interval). This procedure took 5 h. Then, solid Na2S2O3 was added
and THF was removed under vacuum. The mixture was extracted
with ethyl acetate and washed with brine. The concentrated
extract was purified by column chromatography (silica gel 30 g,
d:
5.63–5.61 (m, 2H, CH2CH]CHCH2), 5.06 (dt, J¼9.5, 2.8 Hz, 1H,
H-5), 4.96 (dd, J¼13.4, 5.0 Hz, 1H, CHaHCH]CHCH2), 4.72 (dd,
J¼14.8, 3.6 Hz, 1H, CH2CH]CHCHaH), 4.57 (d, J¼11.2 Hz, 1H, Bn),
4.50 (d, J¼11.2 Hz, 1H, Bn), 4.48 (d, J¼12.0 Hz, 1H, Bn), 4.42 (d,
J¼12.0 Hz, 1H, Bn), 4.19 (dd, J¼11.2, 7.7 Hz, 1H, H-1a), 4.04 (dd,
J¼11.2, 5.6 Hz, 1H, H-1b), 4.04–3.95 (m, 2H, CHHbCH]CHCHHb),
3.69 (d, J¼2.8 Hz, 2H, H-6), 3.68 (ddd, J¼7.7, 5.6, 1.2 Hz, 1H, H-2),
3.63 (dd, J¼9.5, 1.2 Hz, 1H, H-4), 3.53 (dd, J¼1.2, 1.2 Hz, 1H, H-3),
hexane/ethyl acetate¼9:1 to 3:1) to give 9 (4:1 anomeric mixture,
24
625 mg, 73%) as white crystals. Mp 89.5–91.0 ꢁC; [
a
]
þ50.6 (c
D
0.47, CHCl3); IR (thin film) nmax (cmꢀ1): 3385, 3029, 2920, 2855,
1725, 1645, 1539, 1454, 1360, 1269, 1090, 916, 745, 698; 13C NMR
(100 MHz, CDCl3)
d: 91.3 (d, C-1 of major isomer), 97.3 (d, C-1 of
1.97 (s, 3H, Ac), 1.94 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3)
d:
minor isomer); ESIHRMS (m/z) [MþNaþ] calcd for C26H34O6
170.7 (s), 169.9 (s), 137.9 (s), 137.8 (s), 131.3 (d), 128.7 (d), 128.4 (d),
128.3 (d), 128.1 (d), 127.8 (d), 127.7 (d), 78.9 (d), 76.7 (d), 75.4 (d),
74.0 (t), 73.3 (t), 72.8 (d), 69.7 (t), 68.1 (t), 66.6 (t), 65.9 (t), 21.1
(q), 20.9 (q); ESIHRMS (m/z) [MþNaþ] calcd for C28H34O8
521.2151, found 521.2129.
463.2097, found 463.2094.
4.4. 1,5-Di-O-acetyl-2,4-di-O-allyl-3,6-di-O-benzyl-
D
-glucitol (7)
NaBH4 (300 mg, 7.89 mmol) was added to a solution of 9
4.6. 3,6-Di-O-benzyl-2,4-O-(Z-2-buten-1,4-yl)-D-glucitol (12)
(869 mg, 1.98 mmol) in ethanol (100 mL), and the mixture was
heated to reflux for 4 h. After cooling, ethanol was removed under
vacuum. Water was then added to the residue and the mixture was
extracted with ethyl acetate. The combined organic layer was
washed with brine. The concentrated extract was purified by col-
umn chromatography (silica gel 15 g, hexane/ethyl acetate¼2:1) to
Sodium methoxide (8.0 mg, 0.15 mmol) was added to the solu-
tion of 8 (152 mg, 0.305 mmol) in MeOH (10 mL), and the solution
was stirred for 24 h at ambient temperature. The mixture was
neutralized with Amberlite IR-120 (Hþ), filtered through a cotton
pad, and concentrated to give 12 as a colorless syrup (126 mg,
24
give 2,4-di-O-allyl-3,6-di-O-benzyl-
D
-glucitol (639 mg, 73%) as
-glu-
100%). [
a
]
ꢀ16.6 (c 0.96, CHCl3); IR (thin film) nmax (cmꢀ1): 3445,
D
colorless syrup. A mixture of 2,4-di-O-allyl-3,6-di-O-benzyl-
D
3029, 2920, 1651, 1454, 1356, 1101, 739, 698; 1H NMR (400 MHz,
citol (148 mg, 0.335 mmol), acetic anhydride (1 mL), and pyridine
(2 mL) was stirred for 4 h at room temperature. Then methanol
(2 mL) was added and the solution was stirred for additional
20 min. The excessive reagents were removed under vacuum. Then
1 M HCl was added and the solution was extracted with ethyl ac-
etate. The combined organic layer was successively washed with
H2O and brine. The concentrated extract was purified by column
CDCl3) d: 7.31–7.18 (m, 10H, Ph), 5.64–5.59 (m, 2H, CH2CH]CHCH2),
5.00 (dd, J¼13.6, 5.6 Hz, 1H, CHaHCH]CHCH2), 4.72 (dd, J¼16.0,
2.8 Hz, 1H, CH2CH]CHCHaH), 4.65 (d, J¼11.6 Hz, 1H, Bn), 4.59 (d,
J¼11.6 Hz, 1H, Bn), 4.50 (d, J¼11.6 Hz, 1H, Bn), 4.46 (d, J¼11.6 Hz, 1H,
Bn), 3.99 (dd, J¼13.6, 4.4 Hz, 1H, CHHbCH]CHCH2), 3.89 (dd,
J¼16.0, 2.4 Hz, 1H, CH2CH]CHCHHb), 3.85 (br s, 1H, H-2), 3.83
(ddd, J¼8.8, 4.6, 2.8 Hz, 1H, H-5), 3.73 (dd, J¼11.0, 8.8 Hz, 1H, H-6a),
3.64 (dd, J¼9.6, 2.8 Hz, 1H, H-4), 3.56–3.53 (m, 2H, H-1), 3.44 (dd,
J¼11.0, 4.6 Hz, 1H, H-6b), 3.24 (dd, J¼9.4, 1.0 Hz, 1H, H-3); 13C NMR
chromatography (silica gel 5 g, hexane/ethyl acetate¼3:1) to give 7
25
(164 mg, 93%) as a colorless syrup. [
a
]
D
þ4.0 (c 1.11, CHCl3); IR (thin
film) nmax (cmꢀ1): 3030, 2917, 2868, 1740, 1647, 1496, 1454, 1372,
(100 MHz, CDCl3) d: 138.5 (s), 137.7 (s), 131.6 (d), 128.5 (d), 128.5 (d),
1238, 1098, 739, 700; 1H NMR (400 MHz, CDCl3)
d
: 7.33–7.26 (m,
128.3 (d), 128.0 (d), 127.9 (d), 127.9 (d), 127.6 (d), 82.4 (d), 79.4 (d),
75.6 (d), 74.1 (t), 73.4 (t), 71.1 (t), 70.3 (d), 69.6 (t), 66.5 (t), 65.0 (t);
ESIHRMS (m/z) [MþNaþ] calcd for C24H30O6 437.1940, found
437.1938.
10H, Ph), 5.89 (dddd, J¼17.2, 6.0, 6.0, 2.8 Hz, 1H, OCH2CH]CH2),
5.87 (dddd, J¼17.2, 5.6, 5.6, 2.0 Hz, 1H, OCH2CH]CH2), 5.27–5.19
(m, 3H, OCH2CH]CH2 and H-5), 5.17–5.11 (m, 2H, OCH2CH]CH2),
4.65 (s, 2H, Bn), 4.52 (d, J¼12.0 Hz, 1H, Bn), 4.47 (d, J¼12.0 Hz, 1H,
Bn), 4.30 (dd, J¼12.0, 4.0 Hz, 1H, H-1a), 4.19 (dd, J¼12.0, 6.4 Hz,
1H, H-1b), 4.16–4.05 (m, 4H, OCH2CH]CH2), 3.85 (dd, J¼5.2, 4.8 Hz,
1H, H3), 3.83 (dd, J¼11.0, 3.6 Hz, 1H, H6a), 3.78 (ddd, J¼6.4, 5.2,
4.0 Hz, 1H, H2), 3.69 (dd, J¼11.0, 6.0 Hz, 1H, H6b), 3.68 (dd, J¼4.8,
4.8 Hz, 1H, H4), 2.04 (s, 3H, Ac), 2.00 (s, 3H, Ac); 13C NMR (100 MHz,
4.7. 3,6-Di-O-benzyl-2,4-O-(Z-2-buten-1,4-yl)-D-
glucopyranse (13)
A
solution of 12 (26 mg, 0.063 mmol) and IBX (52 mg,
CDCl3)
d
: 170.7 (s), 170.1 (s),138.0 (s), 137.9 (s), 134.7 (d), 128.4 (d),
0.19 mmol) in DMSO (2 mL) was stirred at ambient temperature for
24 h. After the addition of water, the mixture was filtered through
a cotton–Celite pad and the residue was washed with ethyl acetate.
The filtrate was extracted with ethyl acetate and the combined
organic layer was washed with brine. The concentrated extract was
purified by column chromatography (silica gel 6 g, hexane/ethyl
acetate¼5:1 to 2:1) to afford 13 (15.6 mg, 60%) as a colorless syrup,
together with recovered 12 (7 mg, 27%). IR (thin film) nmax (cmꢀ1):
3447, 3029, 2920, 2861, 1732, 1454, 1096, 739, 698; 1H NMR
128.3 (d), 128.3 (d), 127.7 (d), 127.6 (d), 117.4 (t), 116.9 (t), 78.2 (d),
78.2 (d), 76.7 (d), 74.6 (t), 73.4 (t), 73.2 (d), 73.1 (t), 72.2 (t), 68.2 (t),
64.1 (t), 21.1 (q), 20.9 (q); ESIHRMS (m/z) [MþNaþ] calcd for
C30H38O8 549.2464, found 549.2448.
4.5. 1,5-Di-O-acetyl-3,6-di-O-benzyl-2,4-O-(Z-2-buten-1,4-yl)-
D
-glucitol (8)
(400 MHz, CDCl3) d: 7.29–7.17 (m, 10H, Ph), 5.78–5.46 (m, 2H),
To a solution of 7 (250 mg, 0.475 mmol) in dried dichloro-
5.27–5.05 (m, 1H), 4.87–4.71 (m, 1H), 4.60–4.32 (m, 6H), 4.26–4.11
methane (400 mL) was added Grubbs first generation catalyst
(20 mg, 0.024 mmol), and then the solution was heated to reflux
for 12 h. Then the catalyst was further added (60 mg, 0.072 mmol)
in three portions every 12 h. The total reaction time was 48 h. The
solution was concentrated to 10 mL and subjected to column
chromatography (silica gel 25 g, hexane/ethyl acetate¼5:1 to 2:1)
(m, 1H), 3.81–3.56 (m, 5H), 3.47–3.44 (m, 1H), 2.91 (s, 1H, OH); 13C
NMR (100 MHz, CDCl3) d: 138.3 (s), 137.6 (s), 131.8 (d), 131.6 (d),
128.9 (d), 128.4 (d), 128.3 (d), 127.9 (d), 127.7 (d), 127.5 (d), 88.7 (d),
78.1 (d), 75.5 (d), 74.6 (d), 73.5 (t), 73.4 (t), 72.2 (t), 71.6 (t), 70.7 (d),
70.2 (t); ESIHRMS (m/z) [MþNaþ] calcd for C24H28O6 435.1784,
found 435.1782.

2578
Y. Cao et al. / Tetrahedron 65 (2009) 2574–2578
4.8. 1-O-Acetyl-3,6-di-O-benzyl-2,4-O-(Z-2-buten-1,4-yl)-
glucopyranose (6)
b-
D-
(q); ESIHRMS (m/z) [MþNaþ] calcd for C26H30O9 509.1788, found
509.1778.
A mixture of 13 (14 mg, 0.034 mmol), acetic anhydride (0.1 mL),
and pyridine (0.2 mL) in CH2Cl2 (2 mL) was stirred for 6 h at room
temperature. Then the solvent and excessive reagents were re-
moved under vacuum, and the resulting residue was purified by
Acknowledgements
This work was partly supported by KAKENHI (17035086).
column chromatography (silica gel 6 g, hexane/ethyl acetate¼6:1 to
Supplementary data
24
3:1) to afford 6 (13.2 mg, 86%) as a colorless syrup. [
a]
ꢀ16.2
D
(c 0.27, CHCl3); IR (thin film) nmax (cmꢀ1): 3029, 2920, 2853, 1753,
Detailed General procedure and Table for full assignment of 1H
and 13C NMR of 6. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/j.tet.2009.01.019.
1454, 1370, 1219, 1105, 739, 698; 1H NMR (400 MHz, C6D6)
d:
7.23–7.04 (m, 10H), 6.82 (d, J¼6.2 Hz, 1H), 5.49–5.43 (m, 1H), 5.14
(dd, J¼13.5, 9.4 Hz, 1H), 5.08 (ddd, J¼11.7, 4.1, 3.2 Hz, 1H), 4.68 (d,
J¼3.0 Hz, 1H), 4.57 (br dd, J¼8.2, 6.0 Hz, 1H), 4.40 (br d, J¼6.2 Hz,
1H), 4.40–4.33 (m, 1H), 4.38 (d, J¼11.9 Hz, 1H), 4.35 (d, J¼11.9 Hz,
1H), 4.26 (d, J¼11.9 Hz, 1H), 4.23 (d, J¼11.9 Hz, 1H), 3.86 (dd, J¼9.6,
8.2 Hz, 1H), 3.80 (ddd, J¼3.0, 1.3, 1.3 Hz, 1H), 3.75 (dd, J¼9.6, 6.0 Hz,
1H), 3.64 (dd, J¼13.5, 6.6 Hz, 1H), 3.31 (ddd, J¼18.1, 4.1, 1.2 Hz, 1H),
References and notes
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1.65 (s, 3H); 13C NMR (100 MHz, C6D6)
d: 169.3 (s), 138.9 (s), 138.4
(s), 133.3 (d), 128.6 (d), 128.5 (d), 128.5 (d), 127.9 (d), 127.8 (d), 127.8
(d), 127.6 (d), 90.9 (d), 79.6 (d), 78.8 (d), 78.5 (d), 75.5 (d), 73.3 (t),
71.6 (t), 71.2 (t), 70.2 (t), 61.6 (t), 20.6 (q); ESIHRMS (m/z) [MþNaþ]
calcd for C26H30O7 477.1889, found 477.1884.
4.9. 1,2,4-Tri-O-acetyl-3,6-di-O-benzyl-b-D-glucopyranose (14)
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To a stirred mixture of 6 (2.6 mg, 5.7
mmol), and ZnCl2 (11.7 mg, 86 m
m
mol), Pd(PPh3)4 (3.3 mg,
mol) in THF (0.2 mL) was added
mol). The mixture was stirred for 6 h at rt. THF
2.9
Bu3SnH (25 mg, 86
m
was evaporated from the mixture, and the resulting residue was
purified by column chromatography (silica gel 1 g, hexane/ethyl
acetate¼8:1 to 2:1) to afford 1-O-acetyl-3,6-di-O-benzyl-
D-gluco-
pyranose, which molecular weight was confirmed by ESILRMS (m/
z) [MþNaþ] calcd for C22H26O7 425.2, found 425.2. The compound
was then diluted with pyridine (0.1 mL) and Ac2O (0.1 mL) was
added to the mixture. It was stirred for 6 h at rt and then evapo-
rated. The resulting residue was purified by column chromatogra-
phy (silica gel 1 g, hexane/AcOEt¼5:1 to 4:1) to afford 14 (1.8 mg,
65%). IR (thin film) nmax (cmꢀ1): 3090, 3063, 3033, 2919, 2874, 1755,
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1367, 1221, 1063, 1035, 909, 741, 700; 1H NMR (400 MHz, CDCl3)
d:
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7.35–7.22 (m, 10H), 5.65 (d, J¼8.0 Hz, 1H, H-1), 5.17 (dd, J¼9.6,
9.4 Hz, 1H, H-4), 5.16 (dd, J¼9.4, 8.0 Hz, 1H, H-2), 4.60 (s, 2H, Bn),
4.51 (d, J¼11.9 Hz, 1H, Bn), 4.48 (d, J¼11.9 Hz, 1H, Bn), 3.74 (dd,
J¼9.4, 9.4 Hz, 1H, H-3), 3.70 (ddd, J¼9.6, 5.0, 3.4 Hz, 1H, H-5), 3.57
(dd, J¼10.8, 3.4 Hz, 1H, H-6), 3.52 (dd, J¼10.8, 5.0 Hz, 1H, H-6), 2.09
ˇ
ꢀ
ˇ
´
12. Vesely´, J.; Rohlenova´, A.; Dzoganova´, M.; Trnka, T.; Tislerova, I.; Saman, D.
Synthesis 2006, 699–705.
(s, 3H), 1.97 (s, 3H), 1.87 (s, 3H); 13C NMR (100 MHz, C6D6)
d: 169.6
13. Debenham, S. D.; Toone, E. J. Tetrahedron: Asymmetry 2000, 11, 385–387.
14. Table for the full assignment of 1H and 13C NMR signals of 6 in C6D6 is in
Supplementary data.
15. Haasnoot, C. A. G.; de Leeuw, F. A. A. M.; Altona, C. Tetrahedron 1980, 36,
2783–2792.
(s), 169.5 (s), 169.3 (s), 137.9 (s), 137.8 (s), 128.6 (d, 2C), 128.5 (d, 2C),
128.2 (d, 2C),128.0 (d),128.0 (d, 2C),127.9 (d), 92.3 (d), 80.2 (d), 74.4
(d), 74.1 (t), 73.8 (t), 71.8 (d), 70.3 (d), 70.0 (t), 20.1 (q), 20.9 (q), 20.9