Another mode of heterocyclization of an enantiopure C2-symmetric bis-epoxide leading to the symmetric dialkyl sulfide

Article abstract of DOI:10.1016/j.tet.2010.07.064

Reexamination of heterocyclization of an enantiopure C₂- symmetric bis-epoxide (7) with sodium sulfide is described. In addition to the reported processes leading to thiane (4a) and thiepane (6), another mode of cyclization was found to occur t

Full text of DOI:10.1016/j.tet.2010.07.064

Tetrahedron 66 (2010) 7487e7491
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journal homepage: www.elsevier.com/locate/tet
Another mode of heterocyclization of an enantiopure C2-symmetric
bis-epoxide leading to the symmetric dialkyl sulfide
Weijia Xie a, Genzoh Tanabe a, Hiroyuki Morimoto a, Takanori Hatanaka a, Toshie Minematsu a,
,
Xiaoming Wu b, Osamu Muraoka a
*
a School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
b Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2010
Received in revised form 22 July 2010
Accepted 22 July 2010
Available online 30 July 2010
Reexamination of heterocyclization of an enantiopure C2-symmetric bis-epoxide (7) with sodium sulfide
is described. In addition to the reported processes leading to thiane (4a) and thiepane (6), another mode
of cyclization was found to occur to a considerable extent, affording a symmetric dialkyl sulfide (5), and
the structure of the main product reported (4a) has been revised. Conditions for the chemoselective
formation of 6 were established, and effective transformation of 6 into 4 was accomplished by the
modification of the processes.
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Heterocyclization
Bis-epoxide
Thiepane
Thiepine
Sodium sulfide
1. Introduction
their protocol4b,c revealed that structure of the main product
reported (4a) was incorrect, the product being found to be a sym-
Sugars including intracyclic hetero atom possess unique physi-
cochemical properties and exhibit remarkable biological activities.1
For example, these sugar-mimics that inhibit glycosidases or gly-
cotransferases may find therapeutic applications to treat various
diseases as diabetes, cancer, and viral infections.1cee
metrical dimeric isomer, 1,10-thiobis(2,5-anhydro-3,4-di-O-benzyl-
D-glucitol) (5), via another mode of ring opening process. In this
paper is described the rigorous study on this multi-directional re-
action including the structure revision of the main product. Opti-
mization of the reaction conditions to improve the chemoselectivity
A number of synthetic methods utilizing the stereochemistry of
sugars, i.e., transformations starting from appropriate sugars, have
been reported.2 Another prominent approach is the base catalyzed
heterocyclization of enantiomerically pure bis-epoxides.3 Among
them, Le Merrer et al. reported the preparation of enantiomerically
pure sugar-mimics by employing the heterocyclization of C2-sym-
metric bis-epoxides. In the reaction, it is reported that three dif-
ferent evolutions occurred after opening of the first epoxide moiety
at a minor substituted site as illustrated in Scheme 1.4 As a con-
tinuing study on the structureeactivity relationship (SAR) of
leading to 3,4-di-O-benzyl-1,6-dideoxy-1,6-epithio-L-iditol (6), and
modification of the process to convert thiepane (6) into the target
thiane (4b) are also described (Fig. 1).
2. Results and discussion
Thus, according to the procedure reported,4b,c bis-epoxide,
1,2:5,6-dianhydro-3,4-bis-O-benzyl-
-iditol4d (7) was treated with
L
sodium sulfide. Work-up and purification of the products afforded
two major compounds in a ratio of ca. 2:1 (Table 1, run 1). 1H and
13C NMR spectroscopic properties of the major product were con-
sistent with those of the compound assigned as 4a by Le Merrer et
al.4c The Birch reduction of the product gave the corresponding
debenzylated product, the NMR spectroscopic properties of which
were also in accord with those of the compound assigned as 4b.4c
An alternative synthesis of thiosugar (4b) had already been
reported by Yuasa et al.7a and its 13C NMR data were listed in Table
2. Szczepina et al. reported the synthesis of 4b, providing with 1H
NMR data assigned also in Table 2.7b With respect to these 1H and
salacinol,5,6 a potent
a-glucosidase inhibitor bearing the thiosugar
moiety, the authors could have synthesized deoxynojirimycin (2)
efficiently by employing this method, and led 2 to a salacinol aza-
analog (3).6g However, attempts to synthesize the corresponding
thio-analog 1,5-dideoxy-1,5-epithio- -glucitol (4b), according to
D
* Corresponding author. E-mail address: muraoka@phar.kindai.ac.jp (O. Muraoka).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.064

7488
W. Xie et al. / Tetrahedron 66 (2010) 7487e7491
OP OH
bis-opening
NuH
O
*
*
HNu
O
NuH 2nd eq of NuH
*
OH OP
O
O
O-cyclization
HO
NuH
OH
NuH
OP
*
*
O
*
PO
O
OP
*
+
A
HO
PO
H
H
OP
NuH
1 eq
H
PO
OP
H
PO
OP
or
OP
Nu
Nu
O
O
Nu
O
Nu-cyclization
HO
HO
*
*
OH
+
*
*
*
NuH = nucleophile
HO
OP
P = H or protecting group
PO
OP
OP
PO
OP
B
Scheme 1.
OH
OH
H
S
S
OH
N
O
O
HO
RO
OH
HO
H
S
OH
HO
-
N+ OSO3
-
S+ OSO3
HO
HO
HO
BnO
OH
OBn
OH
HO
HO
OH
OBn
BnO
OBn
BnO
OR
4
OH
OH
OH
OH
HO
6
5
1
a : R = Bn
b : R = H
2
3
Figure 1.
Table 1
experiments indicated the presence of a carbon chain comprised of
six carbons. On the basis of intensive two-dimensional NMR
spectroscopic studies, structure of the product was elucidated to be
5 as shown in Scheme 2.
The relative stereo-structure was clarified by ROESY experi-
ments, in which NOE correlations were observed between the
proton pairs as shown in Scheme 2. On the basis of above evidences,
the absolute stereo-structure of the product was elucidated to be 5.
Thus, signals at dC 84.7 and dC 81.6 were reasonably assigned as
Thiocyclization of epoxide 7 with Na2S
Run
Solvent
Concentration
of 7 (mM)
Time
(h)
Product
distribution 5/6
5: 43,a 6: 24a
ca. 1/12b
Trace/1b
6: 94a
1
2
3
4
EtOH
EtOH
MeCN
MeCNeH2O
223
25
25
<0.5
0.5
5
22
0.5
a
Isolated yield (%).
b
Product distributions were determined on the basis of 1H NMR spectrum.
a-carbons to the oxygen in the tetrahydrofuran ring. Small coupling
Table 2
1H and 13C NMR data for compound 4b (
d in ppm and J in Hz)
Le Merrer’s data4c
Szczepina’s data7b
Le Merrer’s data4c
Yuasa’s data 7a
a
b
a
b
dH
dH
dC
dC
H-1ax
H-1eq
H-2
H-3
H-4
H-5
H-6a
H-6b
2.86 (dd, J¼15.4, 7.2)
3.00 (dd, J¼15.4, 6.8)
4.12 (ddd, J¼7.2, 6.8, 3.2)
3.88e3.96 (m)
2.62 (dd, J¼13.3, 11.0)
2.71 (dd, J¼13.3, 4.6)
3.64 (m)
C-1
31.6
32.4
C-2
C-3
C-4
C-5
C-6
80.2
87.8
82.9
78.4
63.6
74.2c
79.7c
74.7c
49.4
3.19 (t, J¼9.1)
3.88e3.96 (m)
3.48 (dd, J¼10.2, 9.1)
2.88 (m)
3.97 (ddd, J¼5.2, 4.1, 2.8)
3.62e3.68 (dd, J¼11.6, 5.2)
3.62e3.682 (dd, J¼11.6, 4.1)
3.75 (dd, J¼11.9, 6.4)
61.8
3.90 (dd, J¼11.9, 3.2)
a
In CD3OD.
In D2O.
Assigned in the present study.
b
c
13C NMR spectroscopic data, there appeared apparent discrepancies
between Le Merrer’s results4c and those by the other two groups. Le
Merrer et al. reported that the molecular formula of the cyclization
product was C20H24O4S on the basis of both the CIMS measurement
and the elemental analysis. However, in our careful reexamination
of FABMS measurements, the compound showed peaks at m/z 685
and 687 corresponding to [MꢀH]ꢀ and [MþH]þ ions, run in nega-
tive- and positive-ion modes, respectively. By the HR-FABMS
analysis, its molecular formula was elucidated to be C40H46O8S.
Almost doubled molecular formula and far less 13C NMR signals
compared to the number of carbons involved in the molecule
suggested that the major product was symmetric. 1He1H COSY
constants between H-2 and H-3 in the 1H NMR spectrum were also
well interpreted.
The formation of 5 would be ascribed to predominant attack of
an initially formed sulfide ion (intermediate A) to the reactant (7)
(route c), followed by another mode of cyclization via the in-
termediate B as shown in Scheme 2.
Next, reaction conditions of this multi-mode reaction were
examined to increase the chemoselectivity. Firstly, in order to
reduce the attack of the intermediate A to bis-epoxide (7), the
reaction was carried out under diluted conditions (25 mM, Table 1,
run 2), where predominant 7-endo-tet S-cyclization (route a)
occurred, giving 6 as the major product (5/6¼ca. 1/12). When

W. Xie et al. / Tetrahedron 66 (2010) 7487e7491
7489
a
The yield of transformation of thiepane (6) into the target
thiane (4b) was improved up to 71% by modification of the
processes.
-
S
S
O
O
O
OH
OBn
b
HO
BnO
Na2S
a
OH
c
OBn
BnO
OBn
BnO
A
6
4. Experimental
4.1. General
b
7
O
O
S
c
HO
BnO
OBn
BnO
-
Mps were determined on a Yanagimoto MP-3S micromelting
point apparatus, and mps and bps are uncorrected. IR spectra were
measured on either a Shimadzu IR-435 grating spectrophotometer
or a Shimadzu FTIR-8600PC spectrophotometer. NMR spectra were
recorded on a JEOL JNM-GSX 270 (270 MHz 1H, 67.5 MHz 13C), a JEOL
AL 400 (400 MHz 1H, 100 MHz 13C), a JEOL JNM-ECA 500 (500 MHz
1H, 125 MHz 13C), a JEOL JNM-ECA 600 (600 MHz 1H, 150 MHz 13C)
or a JEOL JNM-ECA 700 (700 MHz 1H, 175 MHz 13C) spectrometer.
OH
7
OBn
4a
-
O
O
O
O
c
c
S
BnO
OBn
OBn
BnO
B
c
δC 81.6
δC 84.7
O
O
S
OH
HO
Chemical shifts (d) and coupling constants (J) are given in parts per
H2
H3
H5
million and hertz, respectively. Low-resolution and high-resolution
mass spectra were recorded on a JEOL JMS-HX 100 spectrometer.
Optical rotations were determined with a JASCODIP-370 digital
polarimeter. Column chromatography was effected over Fuji Silysia
Chemical silica gel BW-200. All the organic extracts were dried over
anhydrous sodium sulfate prior to evaporation.
BnO
OBn
BnO
BnO
NOE
5
Scheme 2.
acetonitrile was used as the solvent, 6 was obtained as almost the
sole product, although longer reaction time (5 h) was required
owning probably to the less solubility of sodium sulfide in ace-
tonitrile (run 3). Aqueous acetonitrile was found to be more ef-
fective, thiepane (6) being obtained in 94% yield in a shorter
reaction time (run 4).
4.2. Thiocyclization of bis-epoxide (7)
4.2.1. Method A (in EtOH, concentration of 7: 223 mM). According to
the literature,4c a mixture of bis-epoxide (7, 290 mg, 0.89 mmol),
Na2S$9H2O (427 mg, 1.8 mmol), and EtOH (4 ml) was heated under
reflux for 30 min. The mixture was poured into ice-water (25 ml)
and extracted with Et2O. The extract was washed with brine and
evaporated to give a pale brown oil (291 mg), which on column
chromatography (n-hexaneeacetone, 25:1) gave 1,10-thiobis(2,5-
The thiepane (6) thus obtained was subjected to the ring con-
traction reaction by treatment with a mixture of Ph3P and CBr4 to
give 3,4-di-O-benzyl-6-bromo-1,5,6-trideoxy-1,5-epithio-D-gluci-
tol4c (4c) as the main product. However, 4c was found to be labile
and decomposed while purification through column chromatog-
raphy, the yield being limited to around up to 30%.4c Therefore, the
crude bromide (4c) was converted to the corresponding formate,
anhydro-3,4-di-O-benzyl-
D-glucitol) (5, 131 mg, 43%) and 3,4-di-O-
benzyl-1,6-dideoxy-1,6-epithio-
L-iditol (6, 77 mg, 24%).
26
4.2.1.1. Compound 5. Colorless oil. [
a
]
þ75.6 (c 0.68, CH2Cl2),
D
3,4-di-O-benzyl-1,5-dideoxy-1,5-epithio- -glucitol 6-formate (4d)
D
lit.4c þ76 (c 0.585, CH2Cl2). IR (neat): 3423, 1497, 1454, 1396, 1353,
1207, 1100, 1053 cmꢀ1 1H NMR (600 MHz, DMSO-d6)
. d: 2.76 (2H,
by treatment with sodium formate, and by the subsequent hydro-
lysis of 4d, the desired thiane (4a) was obtained in 78% overall yield
from 6. Finally, the Birch reduction of 4a gave the desired 4b in 91%
yield. Thus the overall yield of this sequence via four steps from 6
was improved up to 71%, an efficient and practical alternative route
to 4b being developed (Scheme 3).
dd, J¼13.4, 6.7, H-1a), 2.81 (2H, dd, J¼13.4, 7.2, H-1b), 3.38 (2H, ddd,
J¼11.0, 6.7, 5.7, H-6a), 3.44 (2H, ddd, J¼11.0, 5.7, 5.7, H-6b), 3.79 (2H,
ddd, J¼6.7, 5.7, 2.6, H-5), 3.94 (2H, d, J¼3.6, H-3), 3.96 (2H, d, J¼2.6,
H-4), 4.02 (2H, ddd, J¼7.2, 6.7, 3.6, H-2), 4.42/4.57 (each 2H, d,
J¼12.0, PhCH2), 4.54 (4H, s-like, PhCH2), 4.82 (2H, t, J¼5.7, OH),
4.25e7.37 (20H. m, arom.). 13C NMR (150 MHz, DMSO-d6)
d: 30.8
(C-1), 62.2 (C-6), 70.76/70.84 (PhCH2), 81.1 (C-2), 82.3 (C-3), 83.2 (C-
4), 85.0 (C-5), 127.6/127.7/128.4 (d, arom), 138.2/138.37 (s, arom.).
FABMS m/z: 687 [MþH]þ (Pos.), 685 [MꢀH]ꢀ (Neg.). FABHRMS m/z:
687.3001 (C40H47O8S requires 687.2992). The 1H and 13C NMR
spectral data in CDCl3 were in good accordance with those reported
by Le Merrer4c as were summarized in Table 3 and 4, respectively.
S
S
d
R
a
4b
HO
BnO
OH
OBn
OH
BnO
OBn
4
6
c : R = Br
d : R = OCOH
a : R = OH
b
c
Table 3
1H NMR data of 5 in CDCl3
Scheme 3. Reagents and conditions: (a) Ph3P, CBr4, MeCN, 60 ꢁC; (b) 4.5% aq HCO2Na,
60 ꢁC; (c) 20% aq NaOH, MeOH, rt; (d) Na, liq. NH3, ꢀ60 ꢁC.
d
Observed (600 MHz)
d
Lit.4c (250 MHz)
H-1a
H-1b
H-2
H-3
H-4
2.82 (dd, J¼13.7, 6.2)
2.8 (dd, J¼13.5, 6.3)
3.00 (dd, J¼13.5, 7)
4.19 (ddd, J¼7, 6.3, 3.7)
3.94 (d, J¼3.7)
4.02 (m)
3.02 (dd, J¼13.7, 7.0)
4.22 (ddd, J¼7.0, 6.3, 3.7)
3.96 (dd, J¼3.7, 0.8)
3. Conclusion
4.02 (m)
As the result, the third mode of cyclization leading to the
symmetrical dialkyl sulfide (5) was found to occur in the thio-
cyclization of bis-epoxide (7) by sodium sulfide, and the struc-
ture of the main product was revised. The reaction proceeded in
a highly chemoselctive manner under diluted conditions to af-
ford the 7-endo-tet S-cyclization product (6) in excellent yield.
H-5
4.03 (m)
4.02 (m)
3.6 (m)
3.73 (m)
d
H-6a
H-6b
OH
PhCH2
arom.
3.61 (br ddd-like, J¼11.6, 6.0, 3.2)
3.75 (br ddd-like, J¼11.6, 3.2, 3.2)
2.51 (br, dd-like, J¼6.0, 3.2)
4.43/4.58 (d, J¼11.5), 4.50/4.54 (d, J¼12.0)
7.28e7.38 (m)
4.59e4.89 (J¼11.7)
7.29 (m)

7490
W. Xie et al. / Tetrahedron 66 (2010) 7487e7491
Table 4
(C-6), 71.7 (C-2), 74.9/75.4 (PhCH2), 79.8 (C-4), 85.7 (C-3), 127.6/
13C NMR data of 5 in CDCl3
127.9/128.1/128.1/128.6/128.8 (d, arom.), 137.3/137.9 (s, arom.),
160.5 (OCHO). MS m/z (%): 388 (Mþ, 0.11), 191 (21.9), 91 (100).
HRMS m/z: 388.1358 (C21H24O5S requires 388.1344).
d
Observed (150 MHz)
d
lit.4c (63 MHz)
C-1
30.8
30.8
C-2
81.7
81.6
C-3
C-4
82.5
82.6
82.5
82.5
4.3.2. 3,4-Di-O-benzyl-1,5-dideoxy-1,5-epithio- -glucitol (4a). To a
D
solution of crude formate 4d (12.8 g) in MeOH (160 ml) was added
dropwise 20% aqueous solution of sodium hydroxide (15 ml) at
0 ꢁC. After being stirred at room temperature for 1 h, the reaction
mixture was concentrated in vacuo. The residue was diluted with
AcOEt (300 ml), and the resulting mixture was washed with brine.
The washings were re-extracted with AcOEt, and the combined
extracts were evaporated to give a pale brown oil (11.8 g), which on
column chromatography (n-hexaneeAcOEt, 5:1) gave the title
C-5
C-6
PhCH2
arom.
84.7
62.8
84.7
62.8
71.7/71.9
127.6/127.9/127.98/128.00/
128.50/128.54 (d) 137.3/137.5(s)
71.6/71.8
127.5/127.8/128.4(d) 137.3/
137.5 (s)
4.2.1.2. Compound
6. Colorless
needles
(from
þ123.6 (c 0.84,
n-hex-
aneeAcOEt). Mp 100e101.5, lit.4c 98 ꢁC. [
a
]
25
D
compound 4a as a colorless solid (3.8 g, 78% from 6). Mp
CH2Cl2), lit.4c þ124 (c 0.91, CH2Cl2). 1H and 13C NMR spectral
26
123.5e125 ꢁC. [
a
]
þ56.3 (c 1.09, CHCl3). IR (KBr): 3356, 1107,
D
properties of 6 were in accordance with those reported.4c
1054, 1045 cmꢀ1. 1H NMR (500 MHz, CDCl3)
d
: 1.90 (1H, dd, J¼6.6,
5.6, OH), 2.57 (1H, dd, J¼13.5, 9.7, H-1ax), 2.82 (1H, d, J¼4.0, OH),
2.85 (1H, dd, J¼13.5, 4.0, H-1eq), 2.93 (1H, ddd, J¼8.9, 5.5, 4.3, H-5),
3.32 (1H, dd, J¼8.0, 8.0, H-3), 3.74 (1H, dd, J¼8.9, 8.0, H-4), 3.81
(1H, ddd-like, J¼9.7, 8.0, 4.0, H-2), 3.81 (1H, ddd-like, J¼12.0, 5.6,
4.3, H-6a), 3.90 (1H, ddd, J¼12.0, 6.6, 5.5, H-6b), 4.68/4.93 (each
1H, d, J¼11.5, PhCH2), 4.72/4.86 (each 1H, d, J¼11.2, PhCH2),
4.2.2. Method B (in EtOH, concentration of 7: 25 mM). Following the
method A, a mixture of 7 (100 mg, 0.31 mmol), Na2S$9H2O (144 mg,
0.6 mmol), and EtOH (12 ml) was heated under reflux for 30 min.
Work-up gave a mixture of 5 and 6 as a pale yellow solid (95.4 mg,
5/6¼ca. 1/12).
7.29e7.39 (10H, m, arom.). 13C NMR (125 MHz, CDCl3)
d: 30.8 (C-1),
4.2.3. Method C (in MeCN, concentration of 7: 25 mM). Following
the method B, a mixture of 7 (100 mg, 0.31 mmol), Na2S$9H2O
(144 mg, 0.6 mmol), and MeCN (12 ml) was heated under reflux for
5 h. Work-up gave a mixture of 5 and 6 as a pale yellow solid
(103 mg), 1H NMR spectrum of the crude mixture showed the for-
mation of trace amount of 5.
48.0 (C-5), 61.9 (C-6), 71.8 (C-2), 74.8/75.4 (PhCH2), 80.7 (C-4), 85.8
(C-3), 127.8/128.0/128.1/128.6/128.7 (d, arom.), 137.6/138.0 (s,
arom.). MS m/z (%): 360 (Mþ, 0.06), 269 (7), 163 (20), 91 (100).
HRMS m/z: 360.1389 (C20H24O4S requires 360.1395).
4.3.3. 1,5-Dideoxy-1,5-epithio- -glucitol (4b). To a mixture of 4a
D
(2.4 g, 6.7 mmol), THF (50 ml), and liquid ammonia (ca. 100 ml) was
added sodium (790 mg, 34.3 mg-atom) in small portions at ꢀ70 ꢁC,
and the mixture was stirred at ꢀ60 ꢁC for 3 h. After addition of
MeOH (30 ml) to the mixture, ammonia was gradually removed by
increasing the temperature of the mixture, and the resulting mix-
ture was neutralized with concd hydrochloric acid. The resulting
precipitates were filtered and washed with MeOH. The combined
filtrate and washings were evaporated in vacuo. The residue
(2.93 g) was purified on column chromatography (CHCl3eMeOH,
10:1) to give the title compound 4b (1.09 g, 91%) as a colorless solid.
4.2.4. Method D (in aq MeCN, concentration of 7: 22 mM). Follow-
ing the method B, a mixture of 7 (100 mg, 0.31 mmol), Na2S$9H2O
(144 mg, 0.6 mmol), MeCN (12 ml), and water (2 ml) was heated
under reflux for 30 min. Work-up gave a pale yellow solid (115 mg),
which on column chromatography (benzeneeacetone, 10:1) gave 6
(103 mg, 94%) as a colorless solid.
4.3. Modification of reaction conditions to convert thiepane
(6) into thiane (4b)
Mp 131.5e132.5 ꢁC, lit.7a 132e134 ꢁC, lit.7b 110e115 ꢁC. [
a
]
D
24 þ25.9
4.3.1. 3,4-Di-O-benzyl-1,5-dideoxy-1,5-epithio-D-glucitol 6-O-Formate
(c 1.25, CH3OH), lit.7b þ27.4, (c 1.2, CH3OH). 1H NMR (500 MHz, D2O)
(4d). To a solution of CBr4 (9.02 g, 27.2 mmol) in MeCN (180 ml)
were added successively triphenylphosphine (7.13 g, 27.1 mmol)
and 6 (4.9 g, ca. 13.7 mmol), and the reaction mixture was heated at
60 ꢁC for 9 h. Deposited solids were filtered and washed with
MeCN. To a mixture of the filtrate and washings containing the
corresponding bromide, 3,4-di-O-benzyl-6-bromo-1,5,6-trideoxy-
d
: 2.63 (1H, dd, J¼13.2, 11.2, H-1ax), 2.72 (1H, dd, J¼13.2, 4.6, H-
1eq), 2.90 (1H, ddd, J¼10.6, 6.6, 3.2, H-5), 3.20 (1H, dd, J¼9.2, 9.2,
H-3), 3.49 (1H, dd, J¼10.4, 9.2, H-4), 3.65 (1H, ddd, J¼11.2, 9.2, 4.6,
H-2), 3.76 (1H, dd, J¼11.8, 6.6, H-6a), 3.91 (1H, dd, J¼11.8, 3.2, H-6b).
13C NMR (125 MHz, D2O)
d: 33.8 (C-1), 50.8 (C-5), 63.2 (C-6), 75.6
(C-2), 76.1 (C-4), 81.1 (C-3).
1,5-epithio- -glucitol (4c), was added aqueous solution (100 ml) of
D
sodium formate (4.63 g, 68 mmol). After being heated at 80 ꢁC for
1 h, the reaction mixture was concentrated in vacuo, and the resi-
due was dissolved in Et2O (300 ml) and washed with brine. The
organic phase was evaporated to give the title formate (4d) as a pale
brown oil (12.8 g), which was used in the next step without puri-
fication. Analytical sample of 4d was obtained by means of PTLC (n-
hexaneeAcOEt¼1:1).
Acknowledgements
This work was supported by ‘High-Tech Research Center’ Project
for Private Universities: matching fund subsidy from MEXT (Min-
istry of Education, Culture, Sports. Science and Technology),
2007e2011.
Supplementary data
24
4.3.1.1. Compound 4d. Colorless oil. [
a]
þ72.1 (c 1.35, CHCl3).
D
IR (neat): 3339, 1719, 1306, 1168, 1093, 1076, 1024 cmꢀ1
.
1H NMR
: 2.56 (1H, dd, J¼13.5, 9.7, H-1ax), 2.78 (br s, OH),
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.07.064.
(500 MHz, CDCl3)
d
2.84 (1H, dd, J¼13.5, 3.8, H-1eq), 3.06 (1H, ddd, J¼8.8, 5.9, 3.9, H-5),
3.33 (1H, t, J¼8.1, H-3), 3.70 (1H, dd, J¼8.8, 8.1, H-4), 3.83 (1H, ddd,
J¼9.7, 8.1, 3.8, H-2), 4.43 (1H, dd, J¼11.5, 5.9, H-6a), 4.5 (1H, dd,
J¼11.5, 3.9, H-6b), 4,62/4,85 (each 1H, d, J¼11.2, PhCH2), 4,67/4,93
(each 1H, d, J¼11.5, PhCH2), 7.28e7.40 (10H, m, arom.), 8.02 (1H, s,
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