Chemo- and regioselective monosulfonylation of nonprotected carbohydrates catalyzed by organotin dichloride under mild conditions

Article abstract of DOI:10.1021/jo301353k

The catalytic regioselective monosulfonylation of nonprotected carbohydrates using organotin dichloride under mild conditions is examined. The carbohydrates were chemo- and regioselectively converted to the corresponding monosulfonates in the presence of

Full text of DOI:10.1021/jo301353k

Article
pubs.acs.org/joc
Chemo- and Regioselective Monosulfonylation of Nonprotected
Carbohydrates Catalyzed by Organotin Dichloride under Mild
Conditions
Wataru Muramatsu*
Graduate School of biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki 852-8521, Japan
S
* Supporting Information
ABSTRACT: The catalytic regioselective monosulfonylation
of nonprotected carbohydrates using organotin dichloride
under mild conditions is examined. The carbohydrates were
chemo- and regioselectively converted to the corresponding
monosulfonates in the presence of monoalcohols using
catalytic dibutyltin dichloride. The regioselectivity of the
sulfonylation is attributed to the intrinsic character of the
carbohydrates derived from the relative stereochemistry between their hydroxy groups.
sulfonylations, poor regioselectivity, use of a stoichiometric
amount of organotin reagents (1−1.5 equiv), and harsh
conditions for the preparation of the stannylene acetal
intermediate. Martinelli reported the catalytic regioselective
monosulfonylation of α-D-Xyl and β-D-Xyl in moderate yield and
selectivity using catalytic Bu2SnO.9c,d Onomura reported
monosulfonylation of partially protected monosaccharides
using catalytic Me2SnCl2.3g However, it is possible that Me2SnCl2
acts not as a controller of regioselectivity but as an activator of the
less hindered hydroxy group in those monosaccharides.10 More
recently, Taylor reported regioselective sulfonylation using
borinic acid catalysis. Unfortunately, the catalysis is not
applicable to carbohydrates with nonprotected primary hydroxy
groups.9e Herein, we report a widely useful regioselective
monosulfonylation of nonprotected carbohydrates catalyzed by
organotin dichloride under mild conditions.
INTRODUCTION
■
The selective functionalization of polyols remains one of the
most fundamental challenges for achieving the efficient access to
building blocks for complex natural products and new drug
development.1 In particular, efficient chemical synthesis of
carbohydrates such as pseudosugars or oligosaccharides is
indispensable to clarify the mechanisms of various biological
phenomena to which carbohydrates are implicated.2 The direct
regioselective functionalization of the secondary hydroxy groups
in carbohydrates in the presence of originally highly reactive
primary hydroxy groups with nonenzymatic catalysts is of long-
standing interest because of the difficulty in functionalizing one
specific hydroxy group among the multiple hydroxy groups
present. Over the last several decades, progress has been made in
the catalytic regioselective acylation,3 alkylation,4 thiocarbony-
lation,5 and glycosylation6 of nonprotected carbohydrates
mediated by organo or organometal catalysts. These catalytic
methods are useful for the protection or functionalization of a
hydroxy group in carbohydrates in a minimum number of steps.
However, some of the catalysts are not applicable to
carbohydrates with nonprotected primary hydroxy groups, and
the resulting monofunctionalized carbohydrates are usually not
the ideal precursors for further functionalization. To resolve such
problems, we began investigating the catalytic regioselective
sulfonylation of nonprotected carbohydrates to afford mono-
sulfonates, which can be used as electrophiles in the synthesis of
biologically interesting pseudosugars and various building blocks
for the development of novel functional materials via
nucleophilic substitution reactions7 or transition metal catalyzed
C−C bond formations.8
RESULTS AND DISCUSSION
■
After a series of optimization studies (Table 1), we found that
selective monosulfonylation at C(2)−OH of methyl α-D-
glucopyranoside proceeded efficiently in the presence of
Bu2SnCl2 (5 mol %), 3,5-difluorobenzenesulfonyl chloride (1.3
equiv), and 1,2,2,6,6-pentamethylpiperidine (PEMP, 2.0 equiv)
in THF at 10 °C (entry 1, 98% yield with no regioisomers). In the
absence of Bu2SnCl2 or PEMP, the desired monosulfonate 1 was
obtained in 0% and <1% yield respectively without any
byproducts (entries 2 and 3). The use of 1 mol % of Bu2SnCl2
gave monosulfonate 1 in 77% yield (entry 4). The addition of a
catalytic amount of nucleophilic catalyst such as N,N-
dimethylaminopyridine (DMAP) or N-methylimidazole
(NMI) with 1 mol % of Bu2SnCl2 produced no significant effect
under the present reaction conditions (entries 5 and 6). An
Ogawa and Tsuda reported selective introduction of p-
toluenesulfonyl group at the C(2)−OH of methyl α-D-
glucopyranoside using (Bu3Sn)2O to give a 53:47 mixture of 2-
and 6-O-monosulfonates in 77% total yield or Bu2SnO to give a
56:44 mixture of 2- and 6-O-monosulfonates in 50% total
yield.9a,b However, both methods suffer from multiple
Received: June 29, 2012
© XXXX American Chemical Society
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Table 1. Regioselective Sulfonylation of Methyl α-D-
Glucopyranoside
Table 2. Scope of the Reaction of α-D-Glucopyranoside with
Sulfonyl Chlorides
entry
variation from the “standard” conditions
yield (%)
entry
R
R′
product
yield (%)
a
1
none
98
0
1
OOc
OPh
OPNP
SEt
3,5-F2−Ph
3,5-F2−Ph
3,5-F2−Ph
3,5-F2−Ph
3,5-F2−Ph
Me
2
80
91
90
95
<1
2
no Bu2SnCl2
2
3
4
5
6
3
a
b
3
no PEMP
<1
77
70
58
4
4
1 mol % of Bu2SnCl2
5
5
1 mol % of Bu2SnCl2, 10 mol % of DMAP
1 mol % of Bu2SnCl2, 10 mol % of NMI
Me2SnCl2, instead of Bu2SnCl2
t-Bu2SnCl2, instead of Bu2SnCl2
Oc2SnCl2, instead of Bu2SnCl2
Ph2SnCl2, instead of Bu2SnCl2
Bu2Sn(OTf)2, instead of Bu2SnCl2
Bu2Sn(OAc)2, instead of Bu2SnCl2
Bu2Sn(OMe)2, instead of Bu2SnCl2
Bu2SnO, instead of Bu2SnCl2
Bu2SnS, instead of Bu2SnCl2
i-Pr2NEt, instead of PEMP
Br
6
c
6
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
7
15 (23)
b
a
7
26
7
Ph
8
20
21
16
90
85
87
80
76
73
40
a
8
<1
88
<1
84
86
91
47
87
70
<1
<1
76
83
98
24
8
a
2-Naphthyl
2-NO2−Ph
3-NO2−Ph
4-NO2−Ph
3-CF3−Ph
3-F−Ph
3-Cl−Ph
3-Br−Ph
3-Me−Ph
4-Me−Ph
3,5-(CF3)2−Ph
3,5-Cl2−Ph
9
9
9
10
11
12
13
14
15
16
17
18
19
20
21
a
10
11
12
13
14
15
16
17
18
19
10
a
11
a
12
a
13
a
14
a
15
a
16
a
c
Pyridine, instead of PEMP
17
26 (34)
2,6-Lutidine, instead of PEMP
DME, instead of THF
18
98
91
d
19
c
c
20
Dioxane, instead of THF
20
Tf
0 (0)
21
22
use of ground α-D-Glc
a
b
c
Reaction was carried out at 20 °C. p-Nitrophenyl. Corresponding
anhydride was used instead of sulfonyl chloride. Sulfonyl chloride
(1.5 equiv) was used.
d
addition of H2O (1.0 equiv)
a
b
1,2,2,6,6-Pentamethylpiperidine. A 49:51 mixture of 2- and 6-O-
sulfonates was observed in 53% total yield. Reaction was carried out
c
at 20 °C.
bromide,12 which is a widely used partner for O- and C-
glycosylation, did not afford the desired product (entry 5).
Further, we examined the scope of this catalytic mono-
sulfonylation with respect to electron-donating and electron-
withdrawing substituents R′ on the electrophile. Using
methanesulfonyl chloride as an electrophile, 2-O-sulfonate 7
was produced in only 15% yield with 46% yield of undesired
disulfonates (entry 6). The use of benzene- and 2-naphthalene-
sulfonyl chloride resulted in poor reactivity at C(2)−OH (entries
7 and 8). In the case of the benzenesulfonyl chloride with
electron-withdrawing groups at the meta and para positions,
sulfonylation proceeded in 73−98% yields without formation of
regioisomers (entries 10−15, 18 and 19). Similarly, use of the
benzenesulfonyl chloride with an electron-donating methyl
group at the meta position afforded the corresponding
monosulfonate 17 in good yield with great regioselectivity
(entry 16). The use of 4-toluenesulfonyl chloride which is a
widely used electrophile gave lower yield (entry 17). On the
other hand, the benzenesulfonyl chloride with an electron-
withdrawing nitro group at the ortho position gave a relatively
poor yield (entry 9). This trend can be attributed to the effect of
steric hindrance at the ortho position. The use of the
corresponding sulfonic anhydride instead of sulfonyl chloride
gave slightly better yield (entries 6 and 17). Using TfCl and Tf2O
as a sulfonyl reagent, insoluble polysaccharides like a rubber was
obtained (entry 20).
attempt to access 1 by treating methyl α-D-glucopyranoside with
Me2SnCl2, used by Onomura,3g instead of Bu2SnCl2 led to the
undesired 6-O-monosulfonate with 1 in 53% total yield (entry 7;
49:51 mixture of 2-O-sulfonate 1 and 6-O-sulfonate). The use of
other alkyl- or aryltin dichlorides instead of Bu2SnCl2 gave only
monosulfonate 1, but in lower yield (entries 8−10), as did the use
of Bu2Sn(OTf)2, Bu2Sn(OAc)2, Bu2Sn(OMe)2, Bu2SnO, or
Bu2SnS (entries 11−15). Nucleophilic bases such as i-Pr2NEt
and pyridine also afforded 1 in lower yield (entries 16 and 17). In
addition, 2,6-lutidine, which is a less nucleophilic base, did not
give any products (entry 18). DME and dioxane could be used in
place of THF as the solvent, at the expense of a slight decrease in
yield (entries 19 and 20; 76 and 83% yield, respectively). Using
ground methyl α-D-glucopyranoside, the catalysis proceeded in
98% yield without formation of regioisomers (entry 21). By
addition of H2O (1.0 equiv) in the reaction, the yield of 1 is
drastically decreased without formation of the regioisomers or
any byproducts (entry 22).
Next, we examined the scope of this catalytic regioselective
monosulfonylation under the optimized conditions with respect
to both the anomeric substituent of the α-D-glucopyranoside and
various sulfonyl chlorides as the electrophile (Table 2). When the
R substituents were O-alkyl or O-aryl, monosulfonylation
proceeded in 80−91% yield with no regioisomers (entries 1−
3). Ethyl α-D-thioglucopyranoside,11 a useful glycosyl donor, was
converted to the corresponding monosulfonate 5 in 95% yield
(entry 4). In contrast, the reaction with α-D-glucopyranosyl
Proceeding from these results, this catalytic system was used in
the differentiation of primary or secondary hydroxy groups for a
wide range of monosaccharides (Table 3). Monosulfonylation
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D-mannopyranoside (entries 2 and 3), D-galactopyranoside
(entries 4 and 5), β-D-thiogalactopyranoside (entry 6), L-
fucopyranoside (entries 8 and 9), and α-L-rhamnopyranoside
(entry 10). Unfortunately, sulfonylation of C(2)−OH in β-D-
arabinofuranoside12 with 5 mol % of several organotin catalysts
in THF or acetone was not observed (entry 11). In the case of the
reactions with monosaccharides without cis-1,2-diol moieties, β-
D-glucopyranoside and β-D-xylopyranoside, the less hindered
hydroxy groups in the monosaccharides were selectively
activated by the organotin catalyst and sulfonylated in >99%
yield without formation of the regioisomers or disulfonates
(entries 1 and 7).
Table 3. Regioselective Sulfonylation of Various
Monosaccharides
a
The protocol was applied to the regioselective monosulfony-
lation of a dissacharide with two highly reactive primary hydroxy
groups and five secondary hydroxy groups. Treatment of 4-
methoxyphenyl β-D-lactopyranoside with 3,5-bis-
(trifluoromethyl)benzenesulfonyl chloride (1.5 equiv) and
PEMP (2.0 equiv) in the presence of Bu2SnCl2 (10 mol %) in
THF/DMF (8:1) at 20 °C for 24 h gave 33 in 99% yield with
perfect regioselectivity (Scheme 1).
Scheme 1. Regioselective Sulfonylation of a Disaccharide
In addition, competitive sulfonylation between methyl α-D-
glucopyranoside and monoalcohols in the presence of 5 mol % of
Bu2SnCl2 proceeded to afford 1 in high yields with excellent
chemo- and regioselectivities (Scheme 2).
The regioselectivity of the catalytic monosulfonylation of these
monosaccharides can be explained as follows. Coordination of
the organotin catalyst with the cis-diol moieties in these
monosaccharides is favored after moving freely among diol
Scheme 2. Competitive Sulfonylation between α-D-
Glucopyranoside and Monoalcohols
a
b
For the reaction conditions, see Table 2. R1 = 3,5-difluorobenze-
c
nesulfonyl. R2 = 3,5-bis(trifluoromethyl)benzenesulfonyl. Me2SnCl2
was used instead of Bu2SnCl2. In acetone. Sulfonyl chloride (1.5
equiv) was used. Sulfonyl chloride (1.5 equiv) and PEMP (3.0 equiv)
d
e
f
were used.
was selectively observed only at cis-1,2-diol moieties, with
equatorial−OH groups in derivatives of commercially available
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reaction mixture was quenched with saturated aqueous NH4Cl and
extracted with ethyl acetate. The organic layer was washed with water
and brine, dried over MgSO4, filtrated, and concentrated in vacuo. The
residue was purified by SiO2 column chromatography (hexane/ethyl
acetate = 3/1−0/1) to give methyl 2-O-(3,5-difluorobenzensulfonyl)-α-
D-glucopyranoside 1 (361.4 mg, 98%) as a white solid and disulfonates
(4.4 mg, <1%).
Methyl 2-O-(3,5-Difluorobenzenesulfonyl)-α-D-glucopyranoside
(1). Yield: 361.4 mg, 98%. White solid. Rf = 0.27 (MeOH/CHCl3,
10:90). Mp 38−40 °C. [α]D21 = +94.4 (c 1.13, CH3OH). 1H NMR (400
MHz, (CD3)2CO) δ 7.70−7.60 (m, 2H, 3,5-F-PhH), 7.55−7.45 (m, 1H,
3,5-F-PhH), 4.82 (d, J = 3.7 Hz, 1H, H-1), 4.67 (br s, 1H, OH), 4.48 (br
s, 1H, OH), 4.28 (dd, J = 9.6, 3.7 Hz, 1H, H-2), 3.90−3.60 (m, 4H, H-3,
H-6 and OH), 3.60−3.50 (m, 1H, H-5), 3.39 (t, J = 9.3 Hz, 1H, H-4),
3.34 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J =
252.4 Hz), 163.5 (d, J = 252.4 Hz), 140.8 (t, J = 9.1 Hz), 112.6 (d, J =
19.9 Hz), 112.5 (d, J = 19.9 Hz), 110.2 (t, J = 25.7 Hz), 98.1, 82.2, 73.0,
71.7, 71.6, 62.1, 55.2. 19F NMR (376 MHz, (CD3)2CO) δ −106.4 to
−106.5 (m, 2F). IR (solid) 3377, 2928, 1607, 1443, 1371, 1300, 1179,
962 cm−1. MS m/z (rel intensity) 371 (M + H+, 10), 339 (20), 307 (20),
289 (15), 261 (5), 154 (100), 145 (30), 137 (90). HRMS calcd for
C13H17F2O8S (M + H+): 371.0607, found 371.0629. Anal. calcd for
C13H16F2O8S: C, 42.16; H, 4.35. Found: C, 42.37; H, 4.11.
moieties. As the coordination of metal ions may increase the
acidity of hydroxy groups, even a weak base such as PEMP is
sufficient to induce deprotonation. In addition, as an axial-H
adjacent to the reacting axial−OH group in the cis-1,2-diol
moiety restricts the approach of PEMP (1,3-diaxial interaction),
the most accessible hydroxy group, the equatorial−OH group,
may be attacked by PEMP and hence sulfonylated. Another
possibility is that the deprotection can occur at both equatorial−
OH and axial−OH groups and the sulfonylation proceeded
rapidly at the less hindered equatorial position (Scheme 3).
Scheme 3. Plausible Explanation of the Regioselective
Sulfonylation of Monosaccharides (for example, methyl α-D-
mannopyranoside)
Octyl 2-O-(3,5-Difluorobenzenesulfonyl)-α-D-glucopyranoside (2).
Yield: 373.4 mg, 80%. White solid. Rf = 0.38 (MeOH/CHCl3, 10:90).
Mp 84−85 °C. [α]D20 = +85.4 (c 1.05, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 7.62 (d, J = 4.4 Hz, 2H, 3,5-F-PhH), 7.48 (t, J = 4.4 Hz,
1H, 3,5-F-PhH), 4.92 (d, J = 3.7 Hz, 1H, H-1), 4.67 (br s, 1H, OH), 4.62
(br s, 1H, OH), 4.29 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.84 (t, J = 9.2 Hz,
1H, H-3), 3.80−3.50 (m, 5H, H-4, H-5, H-6 and OH), 3.41 (t, J = 9.5 Hz,
1H, OCH2(CH2)6CH3), 3.32 (dt, J = 9.5, 6.3 Hz, 1H,
OCH2(CH2)6CH3), 1.70−1.50 (m, 2H, OCH2CH2(CH2)5CH3),
1.45−1.10 (m, 10H, OCH2CH2(CH2)5CH3), 0.89 (t, J = 6.7 Hz, 3H,
OCH2(CH2)6CH3). 13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J =
252.4 Hz), 163.4 (d, J = 252.4 Hz), 140.9 (t, J = 9.1 Hz), 112.6 (d, J =
19.9 Hz), 112.5 (d, J = 19.9 Hz), 110.1 (t, J = 25.7 Hz), 97.0, 82.2, 73.1,
71.7, 71.6, 68.5, 62.1, 32.5, 30.0, 29.9, 29.6, 26.8, 23.2, 14.3. 19F NMR
(376 MHz, (CD3)2CO) δ −106.3 to −106.4 (m, 2F). IR (solid) 3289,
2926, 1607, 1443, 1369, 1300, 1180, 1128 cm−1. MS m/z (rel intensity)
469 (M + H+, 20), 339 (25), 321 (30), 261 (45), 177 (35), 145 (100),
127 (95), 85 (35). HRMS calcd for C20H31F2O8S (M + H+): 469.1702,
found 469.1720. Anal. calcd for C20H30F2O8S: C, 51.27; H, 6.45. Found:
C, 51.09; H, 6.64.
Phenyl 2-O-(3,5-Difluorobenzenesulfonyl)-α-D-glucopyranoside
(3). Yield: 391.9 mg, 91%. White solid. Rf = 0.41 (MeOH/CHCl3,
10:90). Mp 145−147 °C. [α]D17 = +127.2 (c 1.10, CH3OH). 1H NMR
(400 MHz, (CD3)2CO) δ 7.63 (d, J = 2.2 Hz, 2H, PhH), 7.50−7.20 (m,
3H, PhH), 7.20−6.95 (m, 3H, PhH), 5.62 (d, J = 3.7 Hz, 1H, H-1), 4.86
(d, J = 4.9 Hz, 1H, OH), 4.61 (d, J = 4.9 Hz, 1H, OH), 4.50 (dd, J = 9.8,
3.7 Hz, 1H, H-2), 4.06 (td, J = 9.3, 4.9 Hz, 1H, H-3), 3.85−3.50 (m, 5H,
H-4, H-5, H-6 and OH). 13C NMR (100 MHz, (CD3)2CO) δ 163.5 (d, J
= 252.4 Hz), 163.4 (d, J = 252.4 Hz), 157.5, 140.5 (t, J = 9.1 Hz), 130.3
(2C), 123.6, 117.8 (2C), 112.6 (d, J = 19.9 Hz), 112.5 (d, J = 19.9 Hz),
110.2 (t, J = 25.7 Hz), 96.5, 81.6, 74.1, 71.7, 71.3, 61.9. 19F NMR (376
MHz, (CD3)2CO) δ −106.1 to −106.2 (m, 2F). IR (solid) 3331, 2938,
1607, 1491, 1443, 1366, 1296, 1175 cm−1. MS m/z (rel intensity) 433
(M + H+, 5), 391 (40), 321 (10), 261 (10), 167 (20), 154 (75), 149
(100), 94 (70). HRMS calcd for C18H19F2O8S (M + H+): 433.0763,
found 433.0744. Anal. calcd for C18H18F2O8S: C, 50.00; H, 4.20. Found:
C, 49.98; H, 4.41.
CONCLUSION
■
A catalytic process for the monosulfonylation of a wide range of
nonprotected monosaccharides and a disaccharide with high
yield and excellent regioselectivity under mild conditions has
been developed. The motif serves as a synthetic handle for the
elaboration of numerous organic functionalities. The regiose-
lectivity of the sulfonylation was found to be intrinsic to the
carbohydrate based on the stereochemical relationship among its
hydroxy groups. In addition, monosaccharides were chemo-
selectively converted to the correspondiong monosulfonates in
the presence of monoalcohols, and the catalyst regioselectively
activated the particular equatrial−OH group in the cis-1,2-diols
of pyranosides. The proposed reaction forms the basis for the
development of a method for the direct functionalization of
nonprotected carbohydrates and also provides new insight into
carbohydrate-metal ion interactions and their activation
processes.
4-Nitrophenyl 2-O-(3,5-Difluorobenzenesulfonyl)-α-D-glucopyra-
noside (4). Yield: 429.0 mg, 90%. White solid. Rf = 0.41 (MeOH/
CHCl3, 10:90). Mp 165−166 °C. [α]D21 = +157.6 (c 1.11, CH3OH). 1H
NMR (400 MHz, (CD3)2CO) δ 8.23 (d, J = 9.0 Hz, 2H, 4-NO2−PhH),
7.70−7.50 (m, 2H, 3,5-F-PhH), 7.50−7.30 (m, 1H, 3,5-F-PhH), 7.32 (d,
J = 9.0 Hz, 2H, 4-NO2−PhH), 5.86 (d, J = 3.7 Hz, 1H, H-1), 4.96 (br s,
1H, OH), 4.69 (br s, 1H, OH), 4.59 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 4.09
(t, J = 8.4 Hz, 1H, H-3), 3.90−3.40 (m, 5H, H-4, H-5, H-6 and OH). 13C
NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J = 252.4 Hz), 163.4 (d, J =
252.4 Hz), 162.0, 143.7, 140.4 (t, J = 9.1 Hz), 126.4 (2C), 117.6 (2C),
EXPERIMENTAL SECTION
■
General Procedure for the Regioselective Monosulfonylation
of Nonprotected Monosaccharides Catalyzed by Organotin
Dichlorides. After stirring a mixture of methyl α-D-glucopyranoside
(194.2 mg, 1.0 mmol) and dibutyltin dichloride (15.2 mg, 0.05 mmol) in
THF (18 mL) in a vial at room temperature for 10 min, 3,5-
difluorobenzenesulfonyl chloride (276.4 mg, 1.3 mmol) and 1,2,2,6,6-
pentamethylpiperidine (0.361 mL, 2.0 mmol) were added to the
suspension at 10 °C. After stirring vigorously for 12 h at 10 °C, the
D
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112.6 (d, J = 19.9 Hz), 112.6 (d, J = 19.9 Hz), 110.3 (t, J = 25.7 Hz), 96.0,
81.2, 74.8, 71.6, 71.0, 61.8. 19F NMR (376 MHz, (CD3)2CO) δ −106.0
to −106.1 (m, 2F). IR (solid) 3368, 2909, 2361, 1591, 1516, 1341, 1234,
1173, 1015 cm−1. MS m/z (rel intensity) 478 (M + H+, 5), 307 (20), 289
(15), 154 (100), 136 (65), 107 (20), 77 (15). HRMS calcd for
C18H18F2NO10S (M + H+): 478.0614, found 478.0609. Anal. calcd for
C18H17F2NO10S: C, 45.29; H, 3.59; N, 2.93. Found: C, 45.02; H, 3.43;
N, 2.88.
(CD3)2CO) δ 8.29 (d, J = 7.8 Hz, 1H, 2-NO2−PhH), 8.10−7.90 (m, 3H,
2-NO2−PhH), 4.82 (d, J = 3.7 Hz, 1H, H-1), 4.65 (d, J = 5.1 Hz, 1H,
OH), 4.56 (d, J = 5.1 Hz, 1H, OH), 4.42 (dd, J = 9.8, 3.7 Hz, 1H, H-2),
3.95−3.85 (m, 1H, H-3), 3.85−3.75 (m, 1H, H-6a), 3.79 (br s, 1H, OH),
3.75−3.60 (m, 1H, H-6b), 3.60−3.50 (m, 1H, H-5), 3.44 (ddd, J = 9.8,
9.0, 4.9, 1H, H-4), 3.29 (s, 3H, OCH3). 13C NMR (100 MHz,
(CD3)2CO) δ 149.1, 136.2, 133.4, 131.9, 130.4, 125.6, 98.0, 82.7, 72.9,
71.8, 71.7, 62.0, 55.2. IR (solid) 3385, 2936, 1541, 1443, 1364, 1184,
1026, 959 cm−1. MS m/z (rel intensity) 380 (M + H+, 5), 348 (10), 307
(20), 289 (15), 186 (10), 154 (100), 149 (45), 137 (55). HRMS calcd
for C13H18NO10S (M + H+): 380.0646, found 380.0667. Anal. calcd for
C13H17NO10S: C, 41.16; H, 4.52; N, 3.69. Found: C, 41.06; H, 4.23; N,
3.59.
Ethyl 2-O-(3,5-Difluorobenzenesulfonyl)-α-D-thioglucopyrano-
side (5). Yield: 381.5 mg, 95%. White solid. Rf = 0.33 (MeOH/
CHCl3, 10:90). Mp 128−129 °C. [α]D23 = +154.7 (c 1.03, CH3OH). 1H
NMR (400 MHz, (CD3)2CO) δ 7.66 (d, J = 4.6 Hz, 2H, 3,5-F-PhH),
7.60−7.40 (m, 1H, 3,5-F-PhH), 5.44 (d, J = 5.6 Hz, 1H, H-1), 4.78 (br s,
1H, OH), 4.54 (br s, 1H, OH), 4.52 (dd, J = 9.8, 5.6 Hz, 1H, H-2), 4.00−
3.88 (m, 1H, H-5), 3.87−3.50 (m, 4H, H-3, H-6 and OH), 3.41 (t, J = 9.3
Hz, 1H, H-4), 2.70−2.45 (m, 2H, SCH2CH3), 1.22 (t, J = 7.3 Hz, 3H,
SCH2CH3). 13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J = 252.4
Hz), 163.4 (d, J = 252.4 Hz), 140.7 (t, J = 9.1 Hz), 112.8 (d, J = 19.9 Hz),
112.7 (d, J = 19.9 Hz), 110.3 (t, J = 25.7 Hz), 83.0, 81.4, 73.9, 72.5, 71.6,
62.1, 24.5, 14.9. 19F NMR (376 MHz, (CD3)2CO) δ −106.2 to −106.4
(m, 2F). IR (solid) 3308, 2910, 1609, 1443, 1300, 1179, 1128, 988 cm−1.
MS m/z (rel intensity) 401 (M + H+, 15), 339 (45), 321 (40), 261 (30),
177 (35), 145 (100), 127 (75). HRMS calcd for C14H19F2O7S2 (M +
H+): 401.0535, found 401.0568. Anal. calcd for C14H18F2O7S2: C, 41.99;
H, 4.53. Found: C, 42.15; H, 4.24.
Methyl 2-O-(3-Nitrobenzenesulfonyl)-α-D-glucopyranoside (11).
Yield: 341.9 mg, 90%. White solid. Rf = 0.33 (MeOH/CHCl3, 10:90).
Mp 55−57 °C. [α]D21 = +34.4 (c 1.04, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 8.72 (t, J = 2.2 Hz, 1H, 3-NO2−PhH), 8.61 (ddd, J = 8.3,
2.2, 1.0 Hz, 1H, 3-NO2−PhH), 8.39 (ddd, J = 7.8, 2.2, 1.0 Hz, 1H, 3-
NO2−PhH), 8.10−7.95 (m, 1H, 3-NO2−PhH), 4.83 (d, J = 3.7 Hz, 1H,
H-1), 4.61 (d, J = 5.1 Hz, 1H, OH), 4.45 (d, J = 4.9 Hz, 1H, OH), 4.30
(dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.85−3.73 (m, 2H, H-3 and H-6a), 3.73−
3.60 (m, 2H, H-6b and OH), 3.60−3.47 (m, 1H, H-5), 3.44−3.30 (m,
1H, H-4), 3.32 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ
149.1, 139.4, 134.6, 131.9, 129.1, 123.9, 98.1, 82.2, 73.0, 71.8, 71.6, 62.1,
55.2. IR (solid) 3383, 2936, 1609, 1533, 1350, 1186, 1026, 962 cm−1. MS
m/z (rel intensity) 380 (M + H+, 5), 348 (10), 307 (15), 289 (20), 167
(20), 154 (100), 145 (80), 137 (75). HRMS calcd for C13H18NO10S (M
+ H+): 380.0646, found 380.0657. Anal. calcd for C13H17NO10S: C,
41.16; H, 4.52; N, 3.69. Found: C, 41.39; H, 4.18; N, 3.64.
Methyl 2-O-Methanesulfonyl-α-D-glucopyranoside (7).9b,13 Yield:
40.2 mg, 15%. White solid. Rf = 0.19 (MeOH/CHCl3, 10:90). Mp 105−
106 °C (lit.9b 120−121 °C). [α]D = +99.4 (c 0.50, CH3OH) {lit.13
26
[a]DRT = +106.4 (c 1.00, CH3OH)}. 1H NMR (400 MHz, (CD3OD) δ
4.90 (d, J = 3.7 Hz, 1H, H-1), 4.28 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.82
(dd, J = 12.0, 2.3 Hz, 1H, H-6a), 3.79 (t, J = 9.3 Hz, 1H, H-3), 3.68 (dd, J
= 12.0, 5.6 Hz, 1H, H-6b), 3.60−3.50 (m, 1H, H-5), 3.45−3.35 (m, 1H,
H-4), 3.42 (s, 3H, OCH3), 3.14 (s, 3H, CH3). 13C NMR (100 MHz,
(CD3OD) δ 99.3, 81.5, 73.5, 72.3, 71.9, 62.3, 55.7, 38.3. IR (solid) 3368,
1470, 1381, 1175, 1119, 1028, 953, 887 cm−1. MS m/z (rel intensity)
295 (M + Na+, 5), 194 (20), 154 (100), 137 (70), 107 (25), 88 (20), 77
(20). HRMS calcd for C8H16O8S (M + Na+): 295.0464, found 295.0463.
Methyl 2-O-Benzenesulfonyl-α-D-glucopyranoside (8).9b Yield:
66.8 mg, 20%. White solid. Rf = 0.19 (MeOH/CHCl3, 10:90). Mp
180−182 °C (lit.9b 201−203 °C). [α]D19 = +97.6 (c 0.53, CH3OH). 1H
NMR (400 MHz, (CD3)2CO) δ 7.97 (d, J = 8.1 Hz, 2H, PhH), 7.77 (t, J
= 7.3 Hz, 1H, PhH), 7.67 (t, J = 7.3 Hz, 2H, PhH), 4.65 (d, J = 3.7 Hz,
1H, H-1), 4.56 (br s, 1H, OH), 4.40 (br s, 1H, OH), 4.19 (dd, J = 9.5, 3.7
Hz, 1H, H-2), 3.85−3.70 (m, 2H, H-3 and H-6a), 3.70−3.55 (m, 2H, H-
6b and OH), 3.55−3.50 (m, 1H, H-5), 3.38 (t, J = 9.8 Hz, 1H, H-4), 3.23
(s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 138.0, 134.7, 130.1
(2C), 128.7 (2C), 98.1, 81.3, 73.0, 71.8, 71.7, 62.2, 55.2. IR (solid) 3383,
2934, 1449, 1358, 1186, 1175, 1024, 966 cm−1. MS m/z (rel intensity)
335 (M + H+, 5), 319 (5), 307 (30), 289 (20), 154 (100), 137 (50), 107
(25), 77 (25). HRMS calcd for C13H19O8S (M + H+): 335.0795, found
335.0829.
Methyl 2-O-(4-Nitrobenzenesulfonyl)-α-D-glucopyranoside (12).14
Yield: 322.0 mg, 85%. White solid. Rf = 0.33 (MeOH/CHCl3, 10:90).
Mp 151−153 °C (lit.14 148 °C). [α]D20 = +98.0 (c 1.15, CH3OH) {lit.14
23
[a]D = +107.0 (c 1.58, (CH3)2CO)}. 1H NMR (400 MHz,
(CD3)2CO) δ 8.49 (d, J = 9.2 Hz, 2H, 4-NO2−PhH), 8.26 (d, J = 9.2
Hz, 2H, 4-NO2−PhH), 4.79 (d, J = 3.7 Hz, 1H, H-1), 4.57 (d, J = 5.1 Hz,
1H, OH), 4.43 (d, J = 4.9 Hz, 1H, OH), 4.29 (dd, J = 9.8, 3.7 Hz, 1H, H-
2), 3.85−3.70 (m, 2H, H-3 and H-6a), 3.70−3.60 (m, 2H, H-6b and
OH), 3.55−3.45 (m, 1H, H-5), 3.41−3.34 (m, 1H, H-4), 3.30 (s, 3H,
OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 143.2, 130.4 (2C), 125.2
(3C), 98.1, 82.3, 73.1, 71.8, 71.7, 62.1, 55.2. IR (solid) 3343, 2905, 1533,
1352, 1320, 1186, 1015, 988 cm−1. MS m/z (rel intensity) 380 (M + H+,
5), 348 (5), 307 (20), 289 (15), 154 (100), 137 (70), 107 (20), 77 (15).
HRMS calcd for C13H18NO10S (M + H+): 380.0646, found 380.0646.
Anal. calcd for C13H17NO10S: C, 41.16; H, 4.52; N, 3.69. Found: C,
41.09; H, 4.41; N, 3.61.
Methyl 2-O-(3-Trifluoromethylbenzenesulfonyl)-α-D-glucopyra-
noside (13). Yield: 351.0 mg, 87%. White solid. Rf = 0.36 (MeOH/
21
1
CHCl3, 10:90). Mp 36−38 °C. [α]D = +82.6 (c 1.06, CH3OH). H
NMR (400 MHz, (CD3)2CO) δ 8.35−8.20 (m, 2H, 3-CF3−PhH), 8.12
(d, J = 7.8 Hz, 1H, 3-CF3−PhH), 7.95 (t, J = 7.8 Hz, 1H, 3-CF3−PhH),
4.80 (d, J = 3.7 Hz, 1H, H-1), 4.68 (d, J = 5.1 Hz, 1H, OH), 4.51 (d, J =
4.9 Hz, 1H, OH), 4.29 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.90−4.60 (m, 4H,
H-3, H-6 and OH), 3.60−3.50 (m, 1H, H-5), 3.45−3.35 (m, 1H, H-4),
3.29 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 139.0, 132.6,
131.7 (q, J = 33.1 Hz), 131.5, 131.3 (q, J = 4.1 Hz), 125.5 (q, J = 4.1 Hz),
124.3 (q, J = 272.3 Hz), 98.1, 81.9, 72.9, 71.7, 71.5, 62.1, 55.2. 19F NMR
(376 MHz, (CD3)2CO) δ −62.3 (s, 3F). IR (solid) 3356, 2938, 1435,
1368, 1325, 1179, 1128, 1026 cm−1. MS m/z (rel intensity) 403 (M +
H+, 5), 391 (60), 371 (40), 353 (40), 293 (40), 209 (75), 149 (100), 145
(85). HRMS calcd for C14H18F3O8S (M + H+): 403.0669, found
403.0679. Anal. calcd for C14H17F3O8S: C, 41.79; H, 4.26. Found: C,
41.51; H, 4.33.
Methyl 2-O-(2-Naphthalene)sulfonyl-α-D-glucopyranoside (9).
Yield: 81.4 mg, 21%. White solid. Rf = 0.29 (MeOH/CHCl3, 10:90).
Mp 39−40 °C. [α]D18 = +78.0 (c 1.05, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 8.62 (s, 1H, NaphH), 8.19 (d, J = 8.0 Hz, 1H, NaphH),
8.16 (d, J = 8.8 Hz, 1H, NaphH), 8.08 (d, J = 8.0 Hz, 1H, NaphH), 7.94
(dd, J = 8.8, 2.0 Hz, 1H, NaphH), 7.80−7.68 (m, 2H, NaphH), 4.70 (d, J
= 3.4 Hz, 1H, H-1), 4.56 (br d, J = 4.9 Hz, 1H, OH), 4.41 (br d, J = 4.6
Hz, 1H, OH), 4.25 (dd, J = 9.8, 3.4 Hz, 1H, H-2), 3.82 (ddd, J = 9.8, 8.8,
5.1 Hz, 1H, H-3), 3.77−3.70 (m, 1H, H-6a), 3.70−3.58 (m, 2H, H-6b
and OH), 3.55−3.45 (m, 1H, H-5), 3.36 (ddd, J = 9.8, 8.8, 4.9 Hz, 1H,
H-4), 3.21 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 136.2,
135.0, 132.9, 130.4, 130.3, 130.3, 130.3, 128.9, 128.7, 123.8, 98.2, 81.4,
73.0, 71.8, 71.7, 62.2, 55.2. IR (solid) 3372, 2932, 1456, 1352, 1175,
1028, 966, 864 cm−1. MS m/z (rel intensity) 385 (M+H+, 5), 353 (5),
279 (10), 191 (20), 167 (20), 149 (100), 127 (30), 115 (10). HRMS
calcd for C17H21O8S (M + H+): 385.0952, found 385.0964.
Methyl 2-O-(3-Fluorobenzenesulfonyl)-α-D-glucopyranoside (14).
Yield: 280.1 mg, 80%. White solid. Rf = 0.32 (MeOH/CHCl3, 10:90).
Mp 36−39 °C. [α]D19 = +93.2 (c 1.07, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 7.84 (dd, J = 1.7, 1.0 Hz, 1H, 3-F-PhH), 7.80−7.70 (m,
2H, 3-F-PhH), 7.65−7.50 (m, 1H, 3-F-PhH), 4.75 (d, J = 3.7 Hz, 1H, H-
1), 4.66 (d, J = 5.1 Hz, 1H, OH), 4.49 (d, J = 4.9 Hz, 1H, OH), 4.24 (dd, J
= 9.8, 3.7 Hz, 1H, H-2), 3.90−3.60 (m, 4H, H-3, H-6 and OH), 3.52
(ddd, J = 9.8, 4.9, 2.4 Hz, 1H, H-5), 3.40 (ddd, J = 9.8, 4.9, 1.0 Hz, 1H, H-
Methyl 2-O-(2-Nitrobenzenesulfonyl)-α-D-glucopyranoside (10).
Yield: 61.6 mg, 16%. White solid. Rf = 0.20 (MeOH/CHCl3, 10:90). Mp
21
1
44−46 °C. [α]D = +34.4 (c 1.04, CH3OH). H NMR (400 MHz,
E
dx.doi.org/10.1021/jo301353k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
17
4), 3.45 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 163.0 (d, J
= 249.1 Hz), 139.7 (d, J = 7.4 Hz), 132.3 (d, J = 8.3 Hz), 124.9 (d, J = 3.3
Hz), 121.8 (d, J = 21.5 Hz), 115.9 (d, J = 25.7 Hz), 98.1, 81.7, 73.0, 71.7,
71.6, 62.1, 55.2. 19F NMR (376 MHz, (CD3)2CO) δ −110.4 to −110.6
(m, 1F). IR (solid) 3385, 2934, 1439, 1364, 1229, 1177, 1024, 964 cm−1.
MS m/z (rel intensity) 353 (M + H+, 10), 321 (40), 303 (15), 243 (20),
149 (100), 145 (90), 137 (65), 127 (75). HRMS calcd for C13H18FO8S
(M + H+): 353.0701, found 353.0704. Anal. calcd for C13H17FO8S: C,
44.32; H, 4.86. Found: C, 44.55; H, 5.11.
Methyl 2-O-(3-Chlorobenzenesulfonyl)-α-D-glucopyranoside (15).
Yield: 281.4 mg, 76%. White solid. Rf = 0.30 (MeOH/CHCl3, 10:90).
Mp 38−39 °C. [α]D23 = +88.8 (c 1.05, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 8.05−7.90 (m, 2H, 3-Cl-PhH), 7.80 (ddd, J = 8.1, 2.0, 1.0
Hz, 1H, 3-Cl-PhH), 7.70 (t, J = 8.1 Hz, 1H, 3-Cl-PhH), 4.77 (d, J = 3.7
Hz, 1H, H-1), 4.72 (br s, 1H, OH), 4.55 (br s, 1H, OH), 4.27 (dd, J = 9.8,
3.7 Hz, 1H, H-2), 3.82 (t, J = 9.3 Hz, 1H, H-3), 3.80 (br s, 1H, OH), 3.79
(dd, J = 11.8, 2.2 Hz, H-6a), 3.68 (dd, J = 11.8, 4.9 Hz, 1H, H-6b), 3.54
(ddd, J = 9.8, 4.9, 2.2 Hz, 1H, H-5), 3.42 (t, J = 9.8 Hz, 1H, H-4), 3.29 (s,
3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 139.4, 135.3, 134.6,
131.8, 128.4, 127.2, 98.0, 81.6, 72.8, 71.6, 71.4, 62.0, 55.2. IR (solid)
3372, 2934, 1462, 1362, 1180, 1026, 964, 851 cm−1. MS m/z (rel
intensity) 369 (M + H+, 10), 337 (40), 319 (15), 259 (15), 175 (40),
145 (100), 137 (80), 127 (85). HRMS calcd for C13H18ClO8S (M +
H+): 369.0405, found 369.0425. Anal. calcd for C13H17ClO8S: C, 42.34;
H, 4.65. Found: C, 42.05; H, 4.55.
(MeOH/CHCl3, 10:90). Mp 108−109 °C. [α]D = +79.5 (c 1.29,
1
CH3OH). H NMR (400 MHz, (CD3)2CO) δ 8.55 (s, 2H, 3,5-CF3−
PhH), 8.47 (s, 1H, 3,5-CF3−PhH), 4.88 (d, J = 3.7 Hz, 1H, H-1), 4.66
(br s, 1H, OH), 4.45 (br s, 1H, OH), 4.37 (dd, J = 9.8, 3.7 Hz, 1H, H-2),
3.79 (t, J = 9.3 Hz, 1H, H-3), 3.85−3.72 (m, 2H, H-6a and OH), 3.65
(dd, J = 11.7, 5.1 Hz, 1H, H-6b), 3.54−3.50 (m, 1H, H-5), 3.36 (t, J = 9.3
Hz, 1H, H-4), 3.36 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ
140.4, 133.0 (q, J = 34.8 Hz, 2C), 129.7 (q, J = 3.3 Hz, 2C), 128.4 (sept, J
= 3.3 Hz), 123.6 (q, J = 272.3 Hz, 2C), 98.2, 82.5, 73.1, 71.8, 71.6, 62.1,
55.2. 19F NMR (376 MHz, (CD3)2CO) δ −62.4 (s, 6F). IR (solid) 3377,
2932, 1381, 1362, 1279, 1179, 1134, 974 cm−1. MS m/z (rel intensity)
471 (M + H+, 10), 421 (35), 361 (30), 277 (30), 213 (35), 154 (25), 145
(100), 127 (70). HRMS calcd for C15H17F6O8S (M + H+): 471.0543,
found 471.0559. Anal. calcd for C15H16F6O8S: C, 38.30; H, 3.43. Found:
C, 38.29; H, 3.14.
Methyl 2-O-(3,5-Dichloro)benzenesulfonyl-α-D-glucopyranoside
(20). Yield: 336.8 mg, 91%. White solid. Rf = 0.35 (MeOH/CHCl3,
10:90). Mp 51−53 °C. [α]D22 = +86.6 (c 1.05, CH3OH). 1H NMR (400
MHz, (CD3)2CO) δ 8.00−7.80 (m, 3H, 3,5-Cl-PhH), 4.84 (d, J = 3.7
Hz, 1H, H-1), 4.76 (br s, 1H, OH), 4.55 (br s, 1H, OH), 4.31 (dd, J = 9.8,
3.7 Hz, 1H, H-2), 3.90−3.75 (m, 3H, H-3, H-6a and OH), 3.75−3.60
(m, 1H, H-6b), 3.60−3.50 (m, 1H, H-5), 3.42 (t, J = 8.9 Hz, 1H, H-4),
3.34 (s, 3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 140.6, 136.4
(2C), 134.3, 127.3 (2C), 98.1, 82.2, 72.9, 71.7, 71.5, 62.1, 55.2. IR
(solid) 3354, 2934, 1570, 1369, 1184, 1144, 1026, 962 cm−1. MS m/z
(rel intensity) 403 (M + H+, 5), 391 (10), 371 (10), 307 (10), 289 (10),
154 (100), 145 (35), 137 (90). HRMS calcd for C13H17Cl2O8S (M +
H+): 403.0016, found 403.0026. Anal. calcd for C13H16O8S: C, 38.72; H,
4.00. Found: C, 38.44; H, 3.79.
Methyl 6-O-(3,5-Difluorobenzenesulfonyl)-β-D-glucopyranoside
(22). Yield: 368.5 mg, >99%. White solid. Rf = 0.21 (MeOH/CHCl3,
10:90). Mp 63−64 °C. [α]D19 = −16.3 (c 1.00, CH3OH). 1H NMR (400
MHz, (CD3)2CO) δ 7.70−7.40 (m, 3H, 3,5-F-PhH), 4.51 (dd, J = 12.7,
2.0 Hz, 1H, H-6a), 4.50 (br s, 1H, OH), 4.45−4.25 (m, 3H, H-6b and
OH), 4.16 (d, J = 7.8 Hz, 1H, H-1), 3.45−3.55 (m, 1H, H-5), 3.45−3.25
(m, 2H, H-3 and H-5), 3.39 (s, 3H, OCH3), 3.15−3.00 (m, 1H, H-2).
13C NMR (100 MHz, (CD3)2CO) δ 163.8 (d, J = 252.4 Hz), 163.6 (d, J
Methyl 2-O-(3-Bromobenzenesulfonyl)-α-D-glucopyranoside (16).
Yield: 300.0 mg, 73%. White solid. Rf = 0.31 (MeOH/CHCl3, 10:90).
Mp 37−39 °C. [α]D23 = +78.1 (c 1.18, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 8.11 (s, 1H, 3-Br-PhH), 7.96 (dd, J = 15.1, 8.1, 2H, 3-Br-
PhH), 7.64 (t, J = 8.1 Hz, 1H, 3-Br-PhH), 4.75 (d, J = 3.7 Hz, 1H, H-1),
4.70 (d, J = 5.1 Hz, 1H, OH), 4.51 (d, J = 4.9 Hz, 1H, OH), 4.25 (dd, J =
9.8, 3.7 Hz, 1H, H-2), 3.90−3.60 (m, 4H, H-3, H-6 and OH), 3.60−3.50
(m, 1H, H-5), 3.48−3.35 (m, 1H, H-4), 3.29 (s, 3H, OCH3). 13C NMR
(100 MHz, (CD3)2CO) δ 139.7, 137.6, 132.0, 131.2, 127.6, 123.1, 98.0,
81.7, 72.9, 71.7, 71.5, 62.1, 55.2. IR (solid) 3366, 2932, 1460, 1362, 1180,
1024, 964, 849 cm−1. MS m/z (rel intensity) 413 (M + H+, 5), 383 (15),
381 (15), 307 (15), 154 (100), 145 (35), 137 (75), 127 (25). HRMS
calcd for C13H18BrO8S (M + H+): 412.9900, found 412.9914. Anal.
calcd for C13H17BrO8S: C, 37.78; H, 4.15. Found: C, 37.68; H, 3.86.
Methyl 2-O-(3-Toluenesulfonyl)-α-D-glucopyranoside (17). Yield:
138.8 mg, 40%. White solid. Rf = 0.35 (MeOH/CHCl3, 10:90). Mp 33−
= 252.4 Hz), 140.2 (t, J = 9.1 Hz), 112.5 (d, J = 19.9 Hz), 112.4 (d, J =
19.9 Hz), 110.3 (t, J = 25.7 Hz), 104.8, 77.5, 74.5, 74.2, 71.8, 70.4, 56.7.
19F NMR (376 MHz, (CD3)2CO) δ −105.9 to −106.1 (m, 2F). IR
(solid) 3347, 2922, 1607, 1443, 1364, 1300, 1180, 988 cm−1. MS m/z
(rel intensity) 371 (M + H+, 15), 339 (35), 321 (30), 289 (10), 154
(100), 136 (85), 107 (30), 77 (30). HRMS calcd for C13H17F2O8S (M +
H+): 371.0607, found 371.0619. Anal. calcd for C13H16F2O8S: C, 42.16;
H, 4.35. Found: C, 42.37; H, 4.06.
23
35 °C. [α]D = +68.0 (c 1.07, CH3OH). 1H NMR (400 MHz,
(CD3)2CO) δ 7.85−7.70 (m, 2H, 3-Me-PhH), 7.65−7.50 (m, 2H, 3-
Me-PhH), 4.63 (d, 3.7 Hz, 1H, H-1), 4.63 (br s, 1H, OH), 4.49 (br s, 1H,
OH), 4.18 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.90−3.60 (m, 4H, H-3, H-6
and OH), 3.58−3.45 (m, 1H, H-5), 3.39 (t, J = 8.4 Hz, 1H, H-4), 3.22 (s,
3H, OCH3), 2.46 (s, 3H, 3-CH3-Ph). 13C NMR (100 MHz, (CD3)2CO)
δ 140.3, 137.8, 135.3, 129.9, 128.9, 125.8, 98.0, 81.1, 72.9, 71.7, 71.5,
62.1, 55.2, 21.1. IR (solid) 3368, 2930, 1435, 1358, 1172, 1026, 968, 873
cm−1. MS m/z (rel intensity) 349 (M + H+, 10), 317 (65), 299 (20), 281
(10), 239 (15), 155 (85), 127 (100), 91 (100). HRMS calcd for
C14H21O8S (M + H+): 349.0952, found 349.0937. Anal. calcd for
C14H20O8S·0.5 H2O: C, 47.05; H, 5.92. Found: C, 47.16; H, 6.24.
Methyl 2-O-(4-Toluenesulfonyl)-α-D-glucopyranoside (18).9b
Yield: 90.6 mg, 26%. White solid. Rf = 0.23 (MeOH/CHCl3, 10:90).
Mp 135−137 °C (lit.9b 140−142 °C). [α]D27 = +79.0 (c 0.60, CH3OH).
1H NMR (400 MHz, (CD3)2CO) δ 7.84 (d, J = 8.2 Hz, 2H, 4-Me-PhH),
7.47 (d, J = 8.2 Hz, 2H, 4-Me-PhH), 4.64 (d, 3.7 Hz, 1H, H-1), 4.57 (br s,
1H, OH), 4.47 (br s, 1H, OH), 4.15 (dd, J = 9.8, 3.7 Hz, 1H, H-2), 3.83−
3.70 (m, 1H, H-6a), 3.79 (t, J = 9.2 Hz, 1H, H-3), 3.65 (br s, 1H, OH),
3.65 (dd, J = 11.5, 5.1 Hz, 1H, H-6b), 3.51 (dd, J = 10.1, 5.1 Hz, 1H, H-
5), 3.38 (t, J = 9.3 Hz, 1H, H-4), 3.24 (s, 3H, OCH3), 2.46 (s, 3H, 4-CH3-
Ph). 13C NMR (100 MHz, (CD3)2CO) δ 145.7, 135.1, 130.6 (2C),
128.8 (2C), 98.1, 81.0, 73.0, 71.8, 71.7, 62.2, 55.2, 21.5. IR (solid) 3383,
2928, 1687, 1358, 1175, 1032, 970, 849 cm−1. MS m/z (rel intensity)
349 (M + H+, 15), 317 (100), 299 (25), 281 (10), 239 (15), 155 (90),
145 (95), 127 (90). HRMS calcd for C14H21O8S (M + H+): 349.0952,
found 349.0942.
Methyl 3-O-(3,5-Difluorobenzenesulfonyl)-α-D-mannopyranoside
(23). Yield: 352.3 mg, 95%. White solid. Rf = 0.32 (MeOH/CHCl3,
10:90). Mp 29−32 °C. [α]D26 = +24.1 (c 1.05, CH3OH). 1H NMR (400
MHz, (CD3)2CO) δ 7.70−7.55 (m, 2H, 3,5-F-PhH), 7.46 (tt, J = 9.0, 2.4
Hz, 1H, 3,5-F-PhH), 4.79 (br s, 1H, OH), 4.67 (d, J = 1.7 Hz, 1H, H-1),
4.64 (dd, J = 9.8, 3.3 Hz, 1H, H-3), 4.53 (br d, J = 5.4 Hz, 1H, OH),
4.10−4.06 (m, 1H, H-2), 3.98 (td, J = 9.8, 6.1 Hz, 1H, H-4), 3.78 (dd, J =
11.5, 2.3 Hz, 1H, H-6a), 3.69 (dd, J = 11.5, 4.9 Hz, 1H, H-6b), 3.55−3.45
(m, 1H, H-5), 3.34 (s, 3H, OCH3), 3,14 (br s, 1H, OH). 13C NMR (100
MHz, (CD3)2CO) δ 163.5 (d, J = 252.4 Hz), 163.4 (d, J = 252.4 Hz),
141.2 (t, J = 9.1 Hz), 112.5 (d, J = 19.9 Hz), 112.4 (d, J = 19.9 Hz), 110.0
(t, J = 25.7 Hz), 102.0, 85.6, 74.2, 70.2, 65.2, 62.2, 54.9. 19F NMR (376
MHz, (CD3)2CO) δ −106.4 to −106.6 (m, 2F). IR (solid) 3406, 2938,
1368, 1300, 1179, 1128, 1055, 961 cm−1. MS m/z (rel intensity) 371 (M
+ H+, 20), 339 (35), 307 (15), 289 (15), 249 (15), 154 (100), 149 (30),
137 (90). HRMS calcd for C13H17F2O8S (M + H+): 371.0607, found
371.0614. Anal. calcd for C13H16F2O8S: C, 42.16; H, 4.35. Found: C,
42.44; H, 4.07.
Methyl 3-O-[3,5-Bis(trifluoromethyl)benzenesulfonyl]-β-D-man-
nopyranoside (24). Yield: 459.9 mg, 98%. White solid. Rf = 0.30
20
(MeOH/CHCl3, 10:90). Mp 47−50 °C. [α]D = −52.0 (c 1.01,
1
CH3OH). H NMR (400 MHz, (CD3)2CO) δ 8.54 (s, 2H, 3,5-CF3−
PhH), 8.45 (s, 1H, 3,5-CF3−PhH), 4.67 (dd, J = 8.5, 3.2 Hz, 1H, H-3),
4.61 (br d, J = 5.6 Hz, 1H, OH), 4.55 (s, 1H, H-1), 4.20−4.00 (m, 1H,
OH), 4.13 (d, J = 3.2 Hz, 1H, H-2), 3.93 (td, J = 9.5, 5.1 Hz, 1H, H-4),
Methyl 2-O-[3,5-Bis(trifluoromethyl)benzenesulfonyl]-α-D-gluco-
pyranoside (19). Yield: 460.2 mg, 98%. White solid. Rf = 0.31
F
dx.doi.org/10.1021/jo301353k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
3.78 (dd, J = 11.7, 2.4 Hz, 1H, H-6a), 3.66 (dd, J = 11.7, 5.0 Hz, 1H, H-
6b), 3.45 (s, 3H, OCH3), 3.30−3.20 (m, 1H, H-5). 13C NMR (100
MHz, (CD3)2CO) δ 140.8, 133.0 (q, J = 34.8 Hz, 2C), 129.6 (q, J = 4.1
Hz, 2C), 128.3 (sept, J = 3.3 Hz), 123.6 (q, J = 273.1 Hz, 2C), 101.3,
87.0, 77.1, 70.8, 65.4, 62.3, 56.8. 19F NMR (376 MHz, (CD3)2CO) δ
−62.3 (s, 6F). IR (solid) 3435, 2940, 1360, 1277, 1175, 1134, 1072, 943
cm−1. MS m/z (rel intensity) 471 (M + H+, 30), 439 (100), 421 (15),
349 (20), 277 (40), 213 (50), 145 (65), 137 (50). HRMS calcd for
C15H17F6O8S (M + H+): 471.0543, found 471.0550. Anal. calcd for
C15H16F6O8S: C, 38.30; H, 3.43. Found: C, 38.01; H, 3.15.
Methyl 3-O-(3,5-Difluorobenzenesulfonyl)-α-D-galactopyrano-
side (25). Yield: 364.2 mg, 98%. White solid. Rf = 0.32 (MeOH/
CHCl3, 10:90). Mp 132−133 °C. [α]D18 = +152.6 (c 1.02, CH3OH). 1H
NMR (400 MHz, (CD3)2CO) δ 7.70−7.50 (m, 2H, 3,5-F-PhH), 7.50−
7.35 (m, 1H, 3,5-F-PhH), 4.75−4.60 (m, 1H, H-3), 4.71 (d, J = 3.9 Hz,
1H, H-1), 4.59 (d, J = 5.1 Hz, 1H, OH), 4.22 (t, J = 3.9 Hz, 1H, H-4),
4.10−3.97 (m, 1H, H-2), 3.90−3.65 (m, 5H, H-5, H-6 and OH), 3.33 (s,
3H, OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J = 252.4
Hz), 163.4 (d, J = 252.4 Hz), 141.5 (t, J = 9.1 Hz), 112.5 (d, J = 19.9 Hz),
112.4 (d, J = 19.9 Hz), 110.0 (t, J = 25.7 Hz), 101.0, 84.7, 71.4, 69.2, 67.2,
61.9, 55.3. 19F NMR (376 MHz, (CD3)2CO) δ −106.5 to −106.6 (m,
2F). IR (solid) 3283, 2940, 1609, 1449, 1352, 1306, 1173, 1132 cm−1.
MS m/z (rel intensity) 371 (M + H+, 15), 339 (20), 307 (20), 289 (15),
249 (5), 154 (100), 145 (15), 137 (90). HRMS Calcd for C13H17F2O8S
(M + H+): 371.0607, found 371.0648. Anal. calcd for C13H16F2O8S: C,
42.16; H, 4.35. Found: C, 42.34; H, 4.07.
= 252.4 Hz), 140.6 (t, J = 9.1 Hz), 112.7 (d, J = 19.9 Hz), 112.6 (d, J =
19.9 Hz), 110.3 (t, J = 25.7 Hz), 105.3, 80.9, 74.6, 74.2, 63.5, 56.8. 19
F
NMR (376 MHz, (CD3)2CO) δ −106.3 to −106.4 (m, 2F). IR (solid)
3491, 3098, 1607, 1439, 1371, 1299, 1186, 962 cm−1. MS m/z (rel
intensity) 341 (M + H+, 10), 307 (20), 289 (15), 154 (100), 136 (85),
115 (25), 107 (25), 77 (20). HRMS calcd for C12H15F2O7S (M + H+):
341.0501, found 341.0529. Anal. calcd for C12H14F2O7S: C, 42.35; H,
4.15. Found: C, 42.41; H, 4.11.
Methyl 3-O-(3,5-Difluorobenzenesulfonyl)-α-L-fucopyranoside
(29). Yield: 352.5 mg, >99%. White solid. Rf = 0.46 (MeOH/CHCl3,
10:90). Mp 122−123 °C. [α]D22 = −165.1 (c 1.02, CH3OH). 1H NMR
(400 MHz, (CD3)2CO) δ 7.70−55 (m, 2H, 3,5-F-PhH), 7.53−7.40 (m,
1H, 3,5-F-PhH), 4.72 (dd, J = 10.0, 2.9 Hz, 1H, H-3), 4.65 (d, J = 3.7 Hz,
1H, H-1), 4.50 (d, J = 5.6 Hz, 1H, OH), 4.05−3.85 (m, 3H, H-2, H-4 and
H-5), 3.74 (d, J = 9.0 Hz, 1H, OH), 3.32 (s, 3H, OCH3), 1.20 (d, J = 6.6
Hz, 3H, H-6). 13C NMR (100 MHz, (CD3)2CO) δ 163.5 (d, J = 252.4
Hz), 163.4 (d, J = 252.4 Hz), 141.5 (t, J = 9.1 Hz), 112.4 (d, J = 19.9 Hz),
112.3 (d, J = 19.9 Hz), 109.9 (t, J = 25.7 Hz), 101.0, 84.8, 71.6, 66.8, 66.6,
55.4, 16.4. 19F NMR (376 MHz, (CD3)2CO) δ −106.5 to −106.6 (m,
2F). IR (solid) 3422, 2941, 1607, 1445, 1350, 1304, 1132, 953 cm−1. MS
m/z (rel intensity) 355 (M + H+, 15), 323 (90), 305 (20), 249 (65), 154
(100), 136 (80), 107 (30), 77 (25). HRMS calcd for C13H17F2O7S (M +
H+): 355.0658, found 355.0689. Anal. calcd for C13H16F2O7S: C, 44.07;
H, 4.55. Found: C, 44.22; H, 4.21.
Methyl 3-O-(3,5-Difluorobenzenesulfonyl)-β-L-fucopyranoside
(30). Yield: 353.8 mg, >99%. White solid. Rf = 0.46 (MeOH/CHCl3,
10:90). Mp 32−35 °C. [α]D19 = −39.9 (c 1.10, CH3OH). 1H NMR (400
MHz, (CD3)2CO) δ 7.70−7.55 (m, 2H, 3,5-F-PhH), 7.50−7.40 (m, 1H,
3,5-F-PhH), 4.55 (dd, J = 9.8, 3.4 Hz, 1H, H-3), 4.18 (br s, 2H, OH),
4.17 (d, J = 7.6 Hz, 1H, H-1), 3.91 (d, 1H, H-2.7 Hz, 1H, H-4), 3.74 (q, J
= 6.3 Hz, 1H, H-5), 3.69 (dd, J = 9.8, 7.6 Hz, 1H, H-2), 3.41 (s, 3H,
OCH3), 1.25 (d, J = 6.3 Hz, 3H, H-6). 13C NMR (100 MHz,
(CD3)2CO) δ 163.3 (d, J = 251.6 Hz), 163.3 (d, J = 251.6 Hz), 141.2 (t, J
= 9.1 Hz), 112.5 (d, J = 19.9 Hz), 112.4 (d, J = 19.9 Hz), 109.8 (t, J = 25.7
Hz), 104.8, 86.4, 71.1, 70.4, 68.9, 56.6, 16.5. 19F NMR (376 MHz,
(CD3)2CO) δ −106.7 to −106.9 (m, 2F). IR (solid) 3462, 2940, 1609,
1443, 1368, 1300, 1169, 988 cm−1. MS m/z (rel intensity) 355 (M + H+,
10), 323 (95), 305 (30), 249 (100), 187 (75), 154 (55), 129 (80), 101
(60). HRMS calcd for C13H17F2O7S (M + H+): 355.0658, found
355.0648. Anal. calcd for C13H16F2O7S: C, 44.07; H, 4.55. Found: C,
44.23; H, 4.83.
Methyl 3-O-[3,5-Bis(trifluoromethyl)benzenesulfonyl]-β-D-galac-
topyranoside (26). Yield: 471.0 mg, >99%. White solid. Rf = 0.34
21
(MeOH/CHCl3, 10:90). Mp 144−146 °C. [α]D = +37.4 (c 1.10,
1
CH3OH). H NMR (400 MHz, (CD3)2CO) δ 8.53 (s, 2H, 3,5-CF3−
PhH), 8.45 (s, 1H, 3,5-CF3−PhH), 4.64 (dd, J = 9.9 Hz, 1H, H-3), 4.58
(s, 1H, OH), 4.57 (s, 1H, OH), 4.30−4.20 (m, 1H, H-4), 4.14 (d, J = 7.6
Hz, 1H, H-1), 4.00−3.90 (m, 1H, H-5), 3.85−3.65 (m, 3H, H-2, H-6a
and OH), 3.61 (dd, J = 11.7, 5.9 Hz, 1H, H-6b), 3.39 (s, 3H, OCH3). 13
C
NMR (100 MHz, (CD3)2CO) δ 140.8, 132.8 (q, J = 34.8 Hz, 2C), 129.6
(q, J = 3.9 Hz, 2C), 128.2 (sept, J = 3.9 Hz), 123.6 (q, J = 272.2 Hz, 2C),
105.0, 86.7, 75.1, 69.4, 68.7, 61.7, 56.8. 19F NMR (376 MHz,
(CD3)2CO) δ −62.4 (s, 6F). IR (solid) 3445, 2922, 1358, 1277, 1198,
1134, 1074, 961 cm−1. MS m/z (rel intensity) 471 (M + H+, 15), 439
(35), 349 (20), 277 (15), 213 (15), 154 (100), 136 (85), 77 (35).
HRMS calcd for C15H17F6O8S (M + H+): 471.0556, found 471.0562.
Anal. calcd for C15H16F6O8S: C, 38.30; H, 3.43. Found: C, 38.57; H,
3.03.
Methyl 3-O-(3,5-Difluorobenzenesulfonyl)-α-L-rhamnopyrano-
side (31). Yield: 351.8 mg, >99%. White solid. Rf = 0.48 (MeOH/
23
1
CHCl3, 10:90). Mp 34−35 °C. [α]D = −16.1 (c 0.64, CH3OH). H
NMR (400 MHz, (CD3)2CO) δ 7.68−7.55 (m, 2H, 3,5-F-PhH), 7.55−
7.40 (m, 1H, 3,5-F-PhH), 4.60 (d, J = 1.2 Hz, 1H, H-1), 4.59 (dd, J = 9.0,
3.2 Hz, 1H, H-3), 4.23 (br s, 2H, OH), 4.04 (dd, J = 3.2, 1.2 Hz, 1H, H-
2), 3.65 (t, J = 9.5 Hz, 1H, H-4), 3.60−3.50 (m, 1H, H-5), 3.32 (s, 3H,
OCH3), 1.22 (d, J = 6.1 Hz, 3H, H-6). 13C NMR (100 MHz,
(CD3)2CO) δ 163.6 (d, J = 252.4 Hz), 163.5 (d, J = 252.4 Hz), 141.4 (t, J
= 9.1 Hz), 112.5 (d, J = 19.9 Hz), 112.5 (d, J = 19.9 Hz), 110.0 (t, J = 25.7
Hz), 102.0, 85.4, 70.4, 70.4, 69.5, 54.9, 18.0. 19F NMR (376 MHz,
(CD3)2CO) δ −106.5 to −106.6 (m, 2F). IR (solid) 3449, 2936, 1609,
1443, 1364, 1300, 1179, 1049 cm−1. MS m/z (rel intensity) 355 (M +
H+, 5), 323 (85), 305 (10), 247 (95), 187 (30), 154 (80), 137 (100), 129
(90). HRMS calcd for C13H17F2O7S (M + H+): 355.0658, found
355.0683. Anal. calcd for C13H16F2O7S: C, 44.07; H, 4.55. Found: C,
44.31; H, 4.42.
Isopropyl 3-O-(3,5-Difluorobenzenesulfonyl)-β-D-thiogalactopyr-
anoside (27). Yield: 390.5 mg, 94%. White solid. Rf = 0.39 (MeOH/
CHCl3, 10:90). Mp 123−125 °C. [α]D26 = +16.6 (c 1.04, CH3OH). 1H
NMR (400 MHz, (CD3)2CO) δ 7.70−7.55 (m, 2H, 3,5-F-PhH), 7.45
(tt, J = 9.0, 2.2 Hz, 1H, 3,5-F-PhH), 4.62 (dd, J = 9.3, 3.2 Hz, 1H, H-3),
4.58 (d, J = 5.6 Hz, 1H, OH), 4.49 (d, J = 9.5 Hz, 1H, H-1), 4.44 (d, J =
5.6 Hz, 1H, OH), 4.30−4.20 (m, 1H, H-4), 3.93 (br s, 1H, OH), 3.85−
3.60 (m, 4H, H-2, H-5, H-6), 3.18 (sept, J = 6.8 Hz, 1H, SCH(CH3)2),
1.25 (d, J = 6.8 Hz, 3H, SCH(CH3)2), 1.23 (d, J = 6.8 Hz, 3H,
SCH(CH3)2). 13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J = 252.4
Hz), 163.3 (d, J = 252.4 Hz), 141.4 (t, J = 9.1 Hz), 112.7 (d, J = 19.9 Hz),
112.6 (d, J = 19.9 Hz), 110.0 (t, J = 25.7 Hz), 87.6, 86.4, 79.2, 69.0, 68.5,
61.9, 35.1, 24.3, 24.3. 19F NMR (376 MHz, (CD3)2CO) δ −106.7 to
−106.8 (m, 2F). IR (solid) 3397, 2965, 1607, 1447, 1364, 1298, 1177,
1074 cm−1. MS m/z (rel intensity) 415 (M + H+, 20), 397 (20), 339
(40), 307 (10), 289 (10), 249 (25), 154 (100), 136 (75). HRMS calcd
for C15H21F2O7S2 (M + H+): 415.0691, found 415.0720. Anal. calcd for
C15H20F2O7S2: C, 43.47; H, 4.86. Found: C, 43.78; H, 4.87.
Methyl 4-O-(3,5-Difluorobenzenesulfonyl)-β-D-xylopyranoside
(28). Yield: 340.0 mg, >99%. White solid. Rf = 0.48 (MeOH/CHCl3,
10:90). Mp 133−135 °C. [α]D21 = −63.1 (c 1.04, CH3OH). 1H NMR
(400 MHz, (CD3)2CO) δ 7.70−7.60 (m, 2H, 3,5-F-PhH), 7.55−7.45
(m, 1H, 3,5-F-PhH), 4.60 (br s, 1H, OH), 4.54 (br s, 1H, OH), 4.38 (td,
J = 9.3, 5.4 Hz, 1H, H-4), 4.18 (d, J = 7.3 Hz, 1H, H-1), 4.05 (dd, J = 11.7,
5.4 Hz, 1H, H-5a), 3.59 (td, J = 9.3, 4.2 Hz, 1H, H-3), 3.50 (dd, J = 11.7,
10.0 Hz, 1H, H-5b), 3.42 (s, 3H, OCH3), 3.19 (t, J = 8.1 Hz, 1H, H-2).
13C NMR (100 MHz, (CD3)2CO) δ 163.6 (d, J = 252.4 Hz), 163.5 (d, J
Methyl 5-O-[3,5-bis(trifluoromethyl)benzenesulfonyl]-β-D-arabi-
nofuranoside (32). Yield: 312.7 mg, 71%. White solid. Rf = 0.50
25
(MeOH/CHCl3, 10:90). Mp 65−67 °C. [α]D = +56.2 (c 1.28,
1
CH3OH). H NMR (400 MHz, (CD3)2CO) δ 8.53 (s, 2H, 3,5-CF3−
PhH), 8.49 (s, 1H, 3,5-CF3−PhH), 4.70−4.10 (m, 1H, OH), 4.54 (d, J =
1.5 Hz, 1H, H-1), 4.54 (dd, J = 11.4, 2.9 Hz, 1H, H-5a), 4.41 (dd, J =
11.4, 6.2 Hz, 1H, H-5b), 4.04 (td, J = 6.3, 2.9 Hz, 1H, H-4), 3.95 (dd, J =
3.4, 1.5 Hz, 1H, H-2), 3.84 (dd, J = 6.3, 3.4 Hz, 1H, H-3), 3.20 (s, 3H,
OCH3). 13C NMR (100 MHz, (CD3)2CO) δ 140.0, 133.3 (q, J = 34.8
Hz, 2C), 129.5 (q, J = 4.1 Hz, 2C), 128.6 (sept, J = 3.3 Hz), 123.6 (q, J =
273.1 Hz, 2C), 110.4, 82.7, 81.9, 78.3, 72.5, 54.9. 19F NMR (376 MHz,
(CD3)2CO) δ −62.3 (s, 6F). IR (solid) 3414, 2936, 1360, 1279, 1177,
G
dx.doi.org/10.1021/jo301353k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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1136, 1109, 951 cm−1. MS m/z (rel intensity) 441 (M + H+, 5), 439
(10), 409 (55), 391 (25), 361 (30), 277 (40), 213 (60), 115 (100).
HRMS Calcd for C14H15F6O7S (M + H+): 441.0437, found 441.0409.
Regioselective Sulfonylation of Disaccharide Catalyzed by
Organtin Dichloride. After stirring the mixture of 4-methoxyphenyl β-
D-lactopyranoside (224.2 mg, 0.50 mmol) and dibutyltin dichloride
(15.2 mg, 0.05 mmol) in THF/DMF (18 mL, 8: 1) in vial at room
temperature for 10 min, 3,5-bis(trifluoromethyl)benzenesulfonyl
chloride (234.5 mg, 0.75 mmol) and 1,2,2,6,6-pentamethylpiperidine
(0.181 mL, 1.0 mmol) were added to the suspension at 20 °C. After
stirring vigorously for 24 h at 20 °C, the reaction mixture was quenched
with saturated aqueous NH4Cl and extracted with ethyl acetate. The
organic layer was washed with water and brine, dried over MgSO4,
filtrated, and concentrated in vacuo. The residue was purified by SiO2
column chromatography (hexane/ethyl acetate = 3/1−0/1) to give 4-
methoxyphenyl 3′-O-[3,5-bis(trifluoromethyl)benzenesulfonyl]-β-D-
lactopyranoside 33 (357.9 mg, 99%) as a white solid and disulfonates
(4.3 mg, <1%).
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4-Methoxyphenyl 3′-O-[3,5-Bis(trifluoromethyl)benzenesulfonyl]-
β-D-lactopyranoside (33). Yield: 357.9 mg, 99%. White solid. Rf = 0.50
24
(MeOH/CHCl3, 20:80). Mp 142−145 °C. [α]D = −4.8 (c 0.52,
1
CH3OH). H NMR (400 MHz, (CD3)2CO) δ 8.55 (s, 2H, 3,5-CF3−
PhH), 8.46 (s, 1H, 3,5-F-PhH), 7.00 (dd, J = 6.8, 2.2 Hz, 2H, CH3O-
PhH), 6.83 (dd, J = 6.8, 2.2 Hz, 2H, CH3O-PhH), 5.05 (br s, 1H, OH),
4.84 (br s, 1H, OH), 4.84 (d, J = 7.6 Hz, 1H, H-1), 4.77 (dd, J = 9.8, 3.2
Hz, 1H, H-3′), 4.50 (d, J = 7.8 Hz, 1H, H-1′), 4.27 (d, J = 3.2 Hz, 1H, H-
4′), 3.90 (t, J = 8.8 Hz, 1H, H-2′), 3.87−3.40 (m, 11H, H-2, H-3, H-4, H-
5, H-6, H-5′, H-6′ and OH), 3.74 (s, 3H, OCH3). 13C NMR (100 MHz,
(CD3)2CO) δ 155.9, 152.6, 140.7, 132.9 (q, J = 34.8 Hz, 2C), 129.6 (q, J
= 4.1 Hz, 2C), 128.3 (sept, J = 4.1 Hz), 123.6 (q, J = 272.2 Hz, 2C), 118.8
(2C), 115.1 (2C), 104.1, 102.6, 86.1, 80.3, 76.0, 75.9, 75.5, 74.3, 69.2,
68.9, 61.9 (2C), 55.7. 19F NMR (376 MHz, (CD3)2CO) δ −62.3 (s, 6F).
IR (solid) 3383, 2920, 1508, 1360, 1279, 1229, 1180, 1134, 1030 cm−1.
MS m/z (rel intensity) 747 (M + Na+, 15), 725 (M + H+, 5), 601 (5),
349 (10), 277 (15), 202 (55), 124 (100). HRMS calcd for C27H31F6O14S
(M + H+): 725.1333, found 725.1323. Anal. calcd for C27H30F6O14S: C,
44.76; H, 4.17. Found: C, 44.59; H, 4.33.
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2011, 133, 13926−13929.
Competitive Sulfonylation between Methyl α-D-Glucopyranoside
and Monoalcohols. 3,5-Difluorobenzenesulfonyl chloride (276.4 mg,
1.3 mmol) and 1,2,2,6,6-pentamethylpiperidine (0.361 mL, 2.0 mmol)
were added to the suspension of the mixture of methyl α-D-
glucopyranoside (194.2 mg, 1.0 mmol), cyclohexanemethanol (0.122
mL, 1.0 mmol) and dibutyltin dichloride (15.2 mg, 0.05 mmol) in THF
(18 mL) at 10 °C in vial. After stirring vigorously for 12 h at 10 °C, the
reaction mixture was quenched with saturated aqueous NH4Cl and
extracted with ethyl acetate. The organic layer was washed with water
and brine, dried over MgSO4, filtrated, and concentrated in vacuo. The
residue was purified by SiO2 column chromatography (hexane/ethyl
acetate = 3/1−0/1) to give methyl 2-O-(3,5-difluorobenzenesulfonyl)-
α-D-glucopyranoside 1 (355.9 mg, 96%) as a white solid and disulfonates
(14.2 mg, 3%).
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ASSOCIATED CONTENT
* Supporting Information
Copies of spectra for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
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(10) Generally, a reaction using organotin catalyst regioselectively
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his report, however, the sulfonylation of methyl 3-O-benzoyl-α-D-
galactopyranoside with Me2SnCl2 gave a 6-O-monosulfonate selectively
without formation of 2-O-monosulfonate. See ref 3g.
AUTHOR INFORMATION
Corresponding Author
*muramatu@nagasaki-u.ac.jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the Sasakawa Scientific Research
Grant form Japan Science Society and Special Coordination
Funds for Promoting Science and Technology from the Ministry
of Education, Culture, Sports, Science and Technology, Japan.
H
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Article
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I
dx.doi.org/10.1021/jo301353k | J. Org. Chem. XXXX, XXX, XXX−XXX