An improved method for the synthesis of protected glycosyl fluorides from thioglycosides using N,N-diethylaminosulfur trifluoride (DAST)

Article abstract of DOI:10.1016/j.carres.2012.07.003

The direct conversion of thioglycosides to glycosyl fluorides frequently used in oligosaccharide synthesis was examined using N,N-diethylaminosulfur trifluoride (DAST). Although the reaction proceeded without N-bromosuccinimide (NBS), in some cases it was found that the electrophilicity of the Vilsmeier-type electrophilic sulfinium cation species was not sufficient for the activation of certain less-reactive thioglycosides. Here, we report the results of fluorination reactions of a series of monosaccharides using DAST in the absence of NBS, and also discuss the acceleration of the reaction in the presence of dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST) resulting in excellent product yields.

Full text of DOI:10.1016/j.carres.2012.07.003

Carbohydrate Research 359 (2012) 81–91
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
An improved method for the synthesis of protected glycosyl fluorides from
thioglycosides using N,N-diethylaminosulfur trifluoride (DAST)
Katsuhiko Suzuki a,b, Yukishige Ito a,b, Osamu Kanie a,b,c,
⇑
a Japan Science and Technology Agency (JST), ERATO, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
b RIKEN Advanced Science Institute (ASI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
c Tokai University, Institute of Glycoscience, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The direct conversion of thioglycosides to glycosyl fluorides frequently used in oligosaccharide synthesis
was examined using N,N-diethylaminosulfur trifluoride (DAST). Although the reaction proceeded without
N-bromosuccinimide (NBS), in some cases it was found that the electrophilicity of the Vilsmeier-type
electrophilic sulfinium cation species was not sufficient for the activation of certain less-reactive thiogly-
cosides. Here, we report the results of fluorination reactions of a series of monosaccharides using DAST in
the absence of NBS, and also discuss the acceleration of the reaction in the presence of dimethyl(methyl-
thio)sulfonium trifluoromethanesulfonate (DMTST) resulting in excellent product yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 19 May 2012
Received in revised form 1 July 2012
Accepted 4 July 2012
Available online 14 July 2012
Keywords:
Phenylthio glycosides
Glycosyl fluorides
DAST
DMTST
1. Introduction
DAST seemed to activate the thioglycoside on its own. However,
the generality of the method remained to be investigated. Here, a
Glycosyl fluoride is one of the most frequently used glycosyl do-
nors in the synthesis of various glycosides.1–3 The considerable
thermal and chemical stabilities of glycosyl fluorides compared to
those of other glycosyl halides facilitate purification prior to the
moisture-sensitive glycosylation reactions.4–6 The activation of
glycosyl fluorides has been achieved under various conditions using
fluorophilic reagents including the effective activator hafnocene
bistrifluoromethanesulfonate [Cp2Hf(OTf)2].7,8 The combined use
of glycosyl fluoride with another important glycosyl donor, thiogly-
coside, known as the orthogonal glycosylation protocol, is a typical
representative method that shows the usefulness of glycosyl fluo-
ride.9–20 On the basis of a series of previous reports utilizing the
orthogonal protocol, we realized the importance of preparing a ser-
ies of monosaccharide units that can be readily used in oligosaccha-
ride synthesis, which may allow for the creation of a large
combinatorial library.21,22 Conversion of thioglycosides to the cor-
responding glycosyl fluorides is commonly achieved by the action
of N,N-diethylaminosulfur trifluoride (DAST) in the presence of
N-bromosuccinimide (NBS).23 However, in this reaction, the accom-
panying formation of by-products is inevitable. To address this
problem, the fluorination reaction using DAST in the absence of
NBS was investigated.20 In this reaction, it was suggested that the
Vilsmeier-type electrophilic sulfinium cation species formed by
series of phenyl thioglycosides of monosaccharides carrying ben-
zyloxy and chloroacetyl groups, or azido functionalities for amino
sugar precursors were used to examine the generality of the meth-
od and to prepare a series of important glycosyl fluorides. In
general, it was shown that the reaction proceeded satisfactorily in
the absence of NBS. However, it was also found that the reactions
of relatively less-reactive substrates resulted in lower yields. In
order to circumvent this problem, the use of dimethyl(methyl-
thio)sulfonium trifluoromethanesulfonate (DMTST)24,25 as an
activator of the thioglycosides was investigated and found to accel-
erate the reactions, resulting in good yields.
2. Results and discussion
2.1. Problems/limitations associated with the method using
DAST–NBS
In order to confirm the problems associated with the use of the
DAST–NBS system23 as a standard method for synthesizing glyco-
syl fluorides, we converted thioglycosides to the corresponding
glycosyl fluorides under the conventional reaction conditions in
the presence of NBS. Under the conditions, two major problems
were found, as follows.
The first issue was the generation of glycosyl bromide as a
by-product. Phenylthio galactosides 1–3 were examined as sub-
strates for the fluorination reaction, which showed formation of
⇑
Corresponding author.
E-mail address: kanie@tokai-u.jp (O. Kanie).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.07.003

82
K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
Table 1
The second problem was the reaction of NBS with olefinic func-
tions, which are often used as protecting groups such as the O-allyl
group. As an example, the reaction of phenylthio 3-O-allyl-manno-
side 10 was examined under the conditions using DAST and NBS. It
was found that the reaction gave a complex diastereomeric mix-
ture according to 1H NMR analysis (Scheme 1). Interestingly, how-
ever, the allyl function was restored upon treatment of the mixture
with tributyltin hydride to give the desired anomeric fluoride (11).
Although we did not elucidate the structures of the products in the
complex mixture obtained after the reaction with DAST and NBS, it
seemed that the anomeric phenylthio group attacked the bromoni-
um ion species generated at O-3.
Reactions of phenylthio glycosides using the DAST–NBS system*
Substrate
Products (ratio**
)
Thioglycoside
R1
R2
a
-Fluoride
b-Fluoride
a-Bromide
126
226
326
Bn
ClAc
Bn
Bn
Bn
ClAc
4
6
8
a27 (0.60)
4b28 (0.38)
6b (0.25)
8b (—)
529 (0.02)
7 (0.22)
9 (0.02)
a
a
(0.52)
(0.98)
*
Reactions were carried out in CH2Cl2 at ꢀ15 °C for 1 h.
The ratios were determined by integration of the 1H NMR signals of H-1.
**
2.2. DAST-promoted fluorination of phenylthio glycosides
The challenges mentioned above prompted us to examine the
generality of a DAST-promoted conversion of phenylthio glyco-
sides to glycosyl fluorides without the use of NBS. It has been re-
ported that the DAST-promoted fluorination of thioglycoside
requires higher reaction temperatures, suggesting that the electro-
philicity of the DAST-derived reactive species is rather low.
Although four galactosyl fluorides were synthesized, thereby
allowing for the creation of a small combinatorial library, the de-
tails of the reaction conditions were not revealed.19,20 In order
for the method to be useful, its generality must be established.
Thus, reaction conditions for the DAST-promoted fluorination to
obtain 6 were first examined using phenylthio glycoside 2, which
carries a chloroacetyl group at O-2, and benzyl groups at O-3, O-
4, and O-6. At room temperature, it was necessary for reactions
to be conducted overnight to achieve complete transformation of
the substrate, even when an excess amount of DAST was used.
Although this reaction was accelerated dramatically at elevated
temperature, an amount of 1.2 M equiv of DAST was not sufficient
for the reaction to reach completion. Finally, it was found that the
reaction went to completion in 3.5 h at 40 °C, resulting in a quasi
Scheme 1. Reaction of O-allyl-protected phenylthio glycoside 10 with DAST and
NBS.
the corresponding galactosyl fluorides 4, 6, and 8, together with the
accompanying bromides 5, 7, and 9, respectively (Table 1). Genera-
tion of the unstable bromides leads to a troublesome purification of
the desired fluorides because the bromides are not converted to
fluorides in situ. These results suggested that NBS was not only the
source of the bromonium ion, but also bromide ion and/or bromine
radical in situ. In fact, glycosyl bromide was immediately generated
in the absence of DAST as well.
Table 2
Conversion of thioglycosides to glycosyl fluorides using DAST and the effect of DMTST on the reaction
Entry
Thioglycoside
DAST (equiv)
DMTST (equiv)
Solvent
Temp (°C)
Time (h)
a
/b*
Product (%)
Recovered SM (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
2 (b)
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
1.5
1.5
1.5
1.5
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
DCM
DCM
DCM
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
40
40
40
40
40
40
40
40
70
40
40
40
70
70
70
60
60
70
70
70
80
80
70
70
70
25
25
25
25
3.5
4.0
2.0
3.0
50
50
15
27
22
38
38
38
22
22
17
44
39
24
18
20
20
20
15
15
15
15
15
15
15
1.00/0.32
1.00/0.10
1.00/0.03
1.00/0.01
1.00/0.93
1.00/0.36
1.00/0.20
1.00/0.59
1.00/0.32
1.00/0.10
1.00/0.29
1.00/0.21
1.00/0.05
1.00/0.05
6 (quant)
14 (93)
15 (89)
8 (95)
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
12 (b)
13 (b)
3 (b)
16 (b)
17 (b)
18 (b)
19 (b)
20 (quant)
21 (95)
22 (94)
23 (97)
28 (91)
29 (92)
30 (76)
31 (98)
35 (96)
36 (94)
37 (89)
41 (97)
42 (94)
43 (60)
48 (97)
49 (99)
50 (95)
50 (3)
24 (
25 (
26 (
27 (
a
a
a
a
)
)
)
)
32 (b)
33 (b)
34 (b)
38 (b)
39 (b)
40 (b)
44 (b)
45 (b)
a
Only
1.00/0.19
1.00/0.08
1.00/0.29
1.00/0.10
1.00/0.06
b Only
—
—
—
—
46 (
47 (b)
10 (
a
)
—
DCE
DCE
DCE
DCE
DCM
DCM
DCM
DCM
a
Only
47 (97)
10 (12)
51 (61)
52 (82)
—
—
—
—
a
)
1.00/0.03
0.35/1.00
b Only
0.11/1.00
b only
11 (73)
53 (38)
54 (11)
53 (quant)
54 (quant)
50 (89)
50 (quant)
51 (b)
52 (b)
51 (b)
52 (b)
46 (
a
)
0.35/1.00
0.83/1.00
47 (b)
*
The ratios were determined by integration of the 1H NMR signals of H-1.

K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
83
quantitative yield when 2.0 equiv of DAST were used (Table 2, en-
try 1). Regioisomers of 2, namely compounds 12, 13, and 3, were
also successfully transformed into the corresponding fluorides
(14, 15, and 8, respectively) using 2 equiv of DAST in CH2Cl2
(DCM) at 40 °C in 2–4 h (entries 2–4). In a similar manner, gluco-
a 2-azido group (32–34 and 38–40) and di-O-acyl derivatives (44–
46) (entries 13–21). Only in the case using compound 47 (the b-
anomer of 46, entry 22) as the substrate was a lower yield ob-
served; this could be due to the generally poor reactivity of the
compound.
(16–19) and manno-type compounds (24–27) were transformed
into the corresponding fluorides (20–23 and 28–31, respectively,
entries 5–12). Since a relatively higher reaction temperature was
required for the reaction, 1,2-dichloroethane (DCE) was examined
as a solvent for the reaction. Indeed, DCE was found to be satisfac-
tory in place of DCM, allowing reactions requiring a higher temper-
ature to be conducted more conveniently (entry 9). In general, a
higher reaction temperature was required for the fluorination reac-
tion in the absence of NBS, but the reaction produced no by-prod-
ucts and the desired fluoride was obtained in almost quantitative
yield. These conditions could also be applied to substrates carrying
In view of the stereochemistry, exclusive formation of the a-
fluorides suggests that the fluoride ion attacked the corresponding
oxocarbenium ion intermediate by the SN1 mechanism. However,
in the case of reactions of 2-azido compounds (34, 46, and 47, en-
tries 15, 21, and 22, respectively), the anomeric configurations of
products 37 and 50 were completely inverted from those of the
corresponding thioglycoside substrates. These results suggest that
these transformations proceeded by the SN2 mechanism. Thus, the
stereochemical outcome of the reaction with DAST seems to de-
pend on the stereo and/or electronic environment of the anomeric
carbon.

84
K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
2.3. DAST-promoted fluorination of an allyl-protected
thioglycoside
(42 mg, 0.236 mmol) at ꢀ15 °C. After being stirred for 30 min, the
mixture was diluted with DCM and washed with saturated NaHCO3.
The organic layer was washed with H2O, dried over Na2SO4 and
concentrated in vacuo. The residue was loaded on silica gel column
chromatography (5:1 n-hexane/EtOAc) to afford products (110 mg)
as a complex mixture. To a toluene (2 mL) solution of this mixture
was added n-Bu3SnH (162 mg, 0.557 mmol) and AIBN (15 mg,
To further demonstrate the usefulness of the current method, the
reaction of a troublesome phenyl thioglycoside (10) carrying an allyl
group, as described above, was re-examined without using NBS. In
this case, successful direct formation of the corresponding 3-O-
allyl-mannosyl fluoride (11) was confirmed (entry 23). The applica-
bility of the present method to substrates carrying alkene moieties is
an obvious advantage over the conventional method using NBS.
93 lmol). After being stirred for 10 min at 100 °C under nitrogen
atmosphere, the reaction mixture was loaded on silica gel column
chromatography (19:1 toluene/EtOAc) to afford compound 11
(77 mg, 85%, a:b = 97:3) as a syrup. a
fluoride; 1H NMR (CDCl3): d
2.4. DMTST-promoted fluorination reactions
7.40–7.19 (m, 15H, aromatic), 5.97–5.89 (m, 1H, OCH2CH@CH2),
5.60 (dd, 1H, J1,2 = 1.8 Hz, J1,F = 50.5 Hz, H-1), 5.33 (br dd, 1H,
J = 1.5 Hz, J = 17.2 Hz, OCH2CH@CH2), 5.20 (br dd, 1H, J = 1.5 Hz,
J = 10.4 Hz, OCH2CH@CH2), 4.87, 4.52 (each d, 2H, J = 10.8 Hz, ben-
zyl), 4.84, 4.73 (each d, 2H, J = 12.4 Hz, benzyl), 4.67, 4.53 (each d,
2H, J = 12.2 Hz, benzyl), 4.13 (br d, 2H, J = 5.4 Hz, OCH2CH@CH2),
4.02 (t, 1H, J3,4 = J4,5 = 9.6 Hz, H-4), 3.91–3.88 (m, 2H, H-2,5), 3.79–
3.75 (m, 2H, H-3,6a), 3.71 (dd, 1H, J5,6b = 1.8 Hz, J6a,6b = 10.9 Hz, H-
6b). 13C NMR (CDCl3): d 138.29, 138.17, 137.91, 134.66, 128.48,
128.39, 128.37, 128.03, 127.90, 127.74, 127.61, 117.08, 106.52 (d,
J1,F = 221.8 Hz, C-1), 78.97 (d, J3,F = 1.3 Hz, C-3), 75.21, 74.19 (d,
J5,F = 1.5 Hz, C-5), 73.97 (C-4), 73.46, 73.33 (J2,F = 33.1 Hz, C-2),
73.27, 71.44, 68.64 (C-6).
Reactions of substrates of considerably low reactivity, however,
resulted in only moderate yields, although the corresponding start-
ing materials were recovered in such cases (entries 24 and 25). Thus,
we searched for a practical additive that can be used in place of NBS.
As a result, it was found that the reaction could be accelerated in the
presence of dimethyl(methylthio)sulfonium trifluoromethanesul-
fonate (DMTST) (entries 26 and 27). Under these conditions, the
stereochemical outcome of the reaction (entries 28 and 29) was
different from that observed in the reactions without DMTST (en-
tries 21 and 22). These results suggest that the oxocarbenium ion
stabilized by a triflate counter ion was the intermediate, which fa-
vors the SN1 mechanism under the given conditions.
b Fluoride; 1H NMR (CDCl3): d 7.44–7.21 (m, 15H, aromatic), 5.91
(m, 1H, OCH2CH@CH2), 5.36 (d, 1H, J1,F = 50.7 Hz, H-1), 5.27 (d, 1H,
J = 17.2 Hz, OCH2CH@CH2), 5.18 (d, 1H, J = 10.4 Hz, OCH2CH@CH2),
4.87, 4.79 (each d, 2H, J = 12.2 Hz, benzyl), 4.77, 4.58 (each d, 2H,
J = 11.0 Hz, benzyl), 4.60, 4.58 (each d, 2H, J = 11.9 Hz, benzyl),
4.04–3.97 (m, 2H, OCH2CH@CH2), 3.95 (br d, 1H, J = 9.5 Hz, H-2),
3.90 (t, 1H, J3,4 = J4,5 = 7.6 Hz, H-4), 3.85 (br d, 1H, J6a,6b = 10.6 Hz,
H-6a), 3.78 (dd, 1H, J5,6b = 5.7 Hz, H-6b), 3.73–3.68 (m, 1H, H-5),
3.55 (br d, 1H, H-3).
3. Conclusions
We successfully demonstrated the direct conversion of thiogly-
cosides to glycosyl fluorides using DAST without NBS. Although the
bromonium cation generated from NBS is generally used to acti-
vate thioglycosides, its use has been problematic, resulting in the
formation of glycosyl bromides. In the absence of NBS, a higher
reaction temperature was required, but the reaction was much
cleaner and the desired fluoride was obtained in almost quantita-
tive yield. In the cases of less reactive thioglycosides, the reaction
could be accelerated in the presence of DMTST. Furthermore, it
was shown that a compound carrying an alkene function was also
an acceptable substrate in the reaction with DAST. We believe that
the method described herein will be generally useful in carbohy-
drate chemistry and the synthesized compounds will find utility
in the combinatorial chemistry of oligosaccharides.
4.3. Synthesis of a series of phenylthioglycosides
Suitably protected thioglycosides (16–19, 24–27, 32–34, and
38–40) were derived from the corresponding alcohols as described
in the literature.31 Typical procedure for the synthesis of O-chloro-
acetylated phenylthioglycoside is described for the preparation of
19. Otherwise physical and chemical data for all compounds were
shown.
4. Experimental
4.3.1. Phenyl 2,3,4-tri-O-benzyl-6-O-chloroacetyl-1-thio-b-D-
glucopyranoside (19)
4.1. General methods
To a solution of phenyl 2,3,4-tri-O-benzyl-1-thio-b-D-glucopy-
ranoside21,31,32 (5.00 g, 9.21 mmol) in DCE (43.6 mL) and pyridine
(2.4 mL) was added ClAcCl (1.11 mL, 13.8 mmol) at 0 °C. The mix-
ture was stirred at room temperature for 2 h and was diluted with
EtOAc. The mixture was washed with 10% aq HCl solution, satu-
rated NaHCO3, and brine. The organic layer was dried over MgSO4
and concentrated in vacuo. The residue was purified on column of
silica gel (6:1 hexane–EtOAc) to give compound 19 (4.76 g, 83%)
Analytical thin layer chromatography (TLC) was performed on
Merck Art. 5715, Kieselgel 60 F254/0.25 mm thickness plates. Visu-
alization was accomplished with UV light and phosphomolybdic
acid and/or sulfuric acid solution followed by heating. Column
chromatography was performed with Merck Art 7734 Silica Gel
60 (70–230 mesh). Optical rotations were measured in a 1.0 dm
tube with a Horiba SEPA-200 polarimeter. Melting points were
measured with Yanaco MP-S3 micro-melting point apparatus. 1H
NMR (500 MHz) spectra were recorded with a AVANCE 500 spec-
trometer (Bruker Biospin Inc.) in deuterated solvents using
(CH3)4Si as the internal standard. 13C NMR chemical shifts were ob-
tained and assigned by HSQC experiments.
as a white solid. Rf 0.18 (6:1 hexane–EtOAc); ½a D26
ꢁ
+17.1 (c 1.05,
CHCl3); mp: 95.5–96.0 °C; 1H NMR (CDCl3): d 7.54–7.24 (m, 20H,
aromatic H), 4.94 (d, 1H, J = 11.0 Hz, benzyl), 4.92 (d, 1H, J =
10.5 Hz, benzyl), 4.87 (d, 1H, J = 10.8 Hz, benzyl), 4.85 (d, 1H,
J = 10.7 Hz, benzyl), 4.74 (d, 1H, J = 10.2 Hz, benzyl), 4.65 (d, 1H,
J1,2 = 9.8 Hz, H-1), 4.60 (d, 1H, J = 11.0 Hz, benzyl), 4.44 (dd, 1H,
4.2. A typical procedure for transformation of thioglycoside into
glycosyl fluoride using DAST and NBS
J5,6 = 1.3 Hz, J6,6 = 12.0 Hz, H-6), 4.27 (dd, 1H, J5,6 = 4.7 Hz, H-60),
4.00 (d, 1H, J = 15.0 Hz, ClCH2CO), 3.96 (d, 1H, J = 14.9 Hz, ClCH2CO),
3.73 (t, 1H, J3,4 = 8.5 Hz, H-3), 3.58–3.51 (m, 2H, H-4,5), and 3.50
(t, 1H, J2,3 = 9.1 Hz, H-2); 13C NMR (CDCl3): d 166.77, 137.96,
137.69, 137.35, 133.14, 132.07, 128.83, 128.46, 128.42, 128.36,
128.10, 128.06, 128.01, 127.87, 127.75, 127.71, 127.65, 87.32 (C-
0
0
4.2.1. 3-O-Allyl-2,4,6-tri-O-benzyl-D-mannopyranosyl fluoride
(11)
To
a
DCM (0.6 mL) solution of compound 1030 (106 mg,
L, 0.728 mmol) and NBS
0.182 mmol) was added DAST (71
l

K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
85
1), 86.56 (C-3), 80.61 (C-2), 76.77 (C-4), 76.39 (C-5), 75.77, 75.39,
74.88, 64.53 (C-6), 40.56. Anal. Calcd for C35H35ClO6S: C, 67.89; H,
5.70. Found: C, 67.79; H, 5.62.
5), 72.20, 72.12 (C-2), 68.60 (C-6), 40.87. Anal. Calcd for
35H35ClN3O6S: C, 67.89; H, 5.70. Found: C, 67.64; H, 5.61.
C
4.3.6. Phenyl 2,4,6-tri-O-benzyl-3-O-chloroacetyl-1-thio-a-D-
mannopyranoside (25)
4.3.2. Phenyl 3,4,6-tri-O-benzyl-2-O-chloroacetyl-1-thio-b-D-
glucopyranoside (16)
½
a 2D8 +49.5 (c 1.07, CHCl3); 1H NMR (CDCl3): d 7.51–7.17 (m, 20H,
ꢁ
½
a 2D8 +19.2 (c 1.01, CHCl3); 1H NMR (CDCl3): d7.52–7.17 (m, 20H,
ꢁ
aromatic), 5.61 (d, 1H, J1,2 = 1.7 Hz, H-1), 5.21 (dd, 1H, J2,3 = 3.3 Hz,
J3,4 = 9.4 Hz, H-3), 4.72–4.68 (m, 2H, benzyl), 4.64, 4.54 (each d, 2H,
J = 11.3 Hz, benzyl), 4.48 (d, 1H, J = 11.9 Hz, benzyl), 4.44 (d, 1H, J =
12.1 Hz, benzyl), 4.34–4.31 (m, 1H, H-5), 4.16 (t, 1H, J4,5 = 9.6 Hz,
aromatic), 5.04–4.79 (m, 1H, H-2), 4.82 (d, 1H, J = 11.6 Hz, benzyl),
4.79 (d, 1H, J = 10.8 Hz, benzyl), 4.64 (d, 1H, J = 11.6 Hz, benzyl),
4.60 (d, 1H, J1,2 = 9.9 Hz, H-1), 4.60 (d, 1H, J = 12.3 Hz, benzyl),
4.59 (d, 1H, J = 10.8 Hz, benzyl), 4.54 (d, 1H, J = 12.0 Hz, benzyl),
3.89 (d, 1H, J = 14.9 Hz, ClCH2CO), 3.79 (dd, 1H, J5,6 = 1.8 Hz,
H-4), 4.13–4.12 (m,1H, H-2), 3.86 (dd, 1H, J5,6a = 4.4 Hz, J6a,6b
=
11.0 Hz, H-6a), 3.78, 3.74 (each d, 2H, J = 14.9 Hz, ClCH2CO), 3.72
(dd, 1H, J5,6b = 1.7 Hz, H-6b). 13C NMR (CDCl3): d 166.48, 138.01,
138.00, 137.36, 133.88, 131.66, 129.03, 128.44, 128.40, 128.30,
128.05, 128.01, 127.90, 127.77, 127.69, 127.60, 127.51, 85.21
(C-1), 76.68 (C-2), 75.66, (C-3), 74.79, 73.42 (C-4), 73.34, 72.48
(C-5), 72.24, 68.63 (C-6), 40.53. Anal. Calcd for C35H35ClN3O6S: C,
67.89; H, 5.70. Found: C, 67.76; H, 5.72.
J6,6 = 11.0 Hz, H-6), 3.74–3.67 (m, 3H, H-3,4,60), 3.72 (d, 1H,
0
ClCH2CO), 3.55–3.52 (m, 1H, H-5). 13C NMR (CDCl3): d 165.89,
138.06, 137.95, 137.67, 132.60, 132.26, 128.86, 128.50, 128.46,
128.35, 128.00, 127.96, 127.87, 127.64, 127.61, 85.54 (C-1), 83.98
(C-3), 79.34 (C-5), 77.83 (C-4), 75.37, 75.14, 73.45, 73.16 (C-2),
68.68 (C-6), 40.66. Anal. Calcd for C35H35ClO6S: C, 67.89; H, 5.70.
Found: C, 67.88; H, 5.69.
4.3.7. Phenyl 2,3,6-tri-O-benzyl-4-O-chloroacetyl-1-thio-a-D-
4.3.3. Phenyl 2,4,6-tri-O-benzyl-3-O-chloroacetyl-1-thio-b-D-
mannopyranoside (26)
glucopyranoside (17)
½
a 2D8 +51.9 (c 0.94, CHCl3); 1H NMR (CDCl3): d7.46–7.22 (m, 20H,
ꢁ
Rf 0.22 (5:1 hexane–EtOAc); ½a D26
ꢀ6.9 (c 1.08, CHCl3); mp: 86.5–
ꢁ
aromatic), 5.57 (d, 1H, J1,2 = 1.4 Hz, H-1), 5.51 (t, 1H,
J3,4 = J4,5 = 9.8 Hz, H-4), 4.70, 4.64 (each d, 2H, J = 12.3 Hz, benzyl),
4.55, 4.42 (each d, 2H, J = 12.2 Hz, benzyl), 4.52, 4.45 (each d, 2H,
J = 11.7 Hz, benzyl), 4.40–4.36 (m, 1H, H-5), 4.00 (m, 1H, H-2),
3.81, 3.78 (each d, 2H, J = 14.7 Hz, ClCH2CO), 3.80–3.70 (m, 1H,
H-3), 3.64 (dd, 1H, J5,6a = 5.6 Hz, J6a,6b = 10.7 Hz, H-6a), 3.59 (dd,
1H, J5,6b = 3.5 Hz, H-6b). 13C NMR (CDCl3): d 166.23, 137.83,
137.66, 137.57, 133.69, 131.65, 129.04, 128.44, 128.35, 128.26,
127.90, 127.85, 127.80, 127.74, 127.62, 127.58, 85.81 (C-1), 76.87
(C-3), 75.54 (C-2), 73.42, 72.19, 71.75, 70.81 (C-4), 70.61 (C-5),
69.50 (C-6), 40.70. Anal. Calcd for C35H35ClN3O6S: C, 67.89; H,
5.70. Found: C, 68.18; H, 5.40.
87.0 °C; 1H NMR (CDCl3): d 7.60–7.15 (m, 20H, aromatic), 5.26
(t, 1H, J3,4 = 9.3 Hz, H-3), 4.86 (d, 1H, J = 11.3 Hz, benzyl), 4.69
(d, 1H, J1,2 = 9.7 Hz, H-1), 4.65 (d, 1H, J = 11.9 Hz, benzyl), 4.56
(d, 1H, J = 11.9 Hz, benzyl), 4.54 (d, 1H, J = 11.4 Hz, benzyl), 4.51
(d, 1H, J = 11.3 Hz, benzyl), 4.47 (d, 1H, J = 11.4 Hz, benzyl), 3.79
0
(dd, 1H, J5,6 = 2.0 Hz, J6,6 = 11.0 Hz, H-6), 3.76 (dd, 1H,
J5,6 = 3.6 Hz, H-60), 3.71 (t, 1H, J4,5 = 9.6 Hz, H-4), 3.52 (ddd, 1H, H-
0
5), 3.48 (t, 1H, J2,3 = 9.4 Hz, H-2), 3.45 (s, 2H, ClCH2CO). 13C NMR
(CDCl3): d 166.22, 137.97, 137.68, 133.28, 132.01, 128.99, 128.46,
128.39, 128.21, 127.99, 127.91, 127.80, 127.71, 87.42 (C-1), 78.83,
78.81 (C-3,5), 78.49 (C-2), 75.65 (C-4), 74.77, 74.40, 73.48, 68.39
(C-6), 40.50. Anal. Calcd for C35H35ClO6S: C, 67.89; H, 5.70. Found:
C, 67.80; H, 5.64.
4.3.8. Phenyl 2,3,4-tri-O-benzyl-6-O-chloroacetyl-1-thio-a-D-
4.3.4. Phenyl 2,3,6-tri-O-benzyl-4-O-chloroacetyl-1-thio-b-D-
mannopyranoside (27)
a 2D8 +86.9 (c 1.05, CHCl3); 1H NMR (CDCl3): d7.41–7.24 (m, 20H,
ꢁ
glucopyranoside (18)
½
Rf 0.20 (6:1 hexane–EtOAc); ½a D27
ꢀ24.2 (c 1.02, CHCl3); mp:
ꢁ
aromatic), 5.55 (d, 1H, J1,2 = 1.1 Hz, H-1), 4.96 (d, 1H, J = 10.9 Hz,
benzyl), 4.70 (d, 1H, J = 12.2 Hz, benzyl), 4.65–4.60 (m, 4H, benzyl),
4.43–4.38 (m, 2H, H-6a,6b), 4.31 (dt, 1H, J4,5 = 9.6 Hz, J5,6 = 3.9 Hz,
H-5), 4.00–3.99 (m, 1H, H-2), 3.96, 3.91 (each d, 2H, J = 15.2 Hz,
ClCH2CO), 3.96 (t, 1H, J3,4 = 9.5 Hz, H-4), 3.88 (dd, 1H, J2,3 = 3.0 Hz,
H-3). 13C NMR (CDCl3): d 167.02, 137.89, 137.82, 137.67, 133.80,
131.50, 129.04, 128.45, 128.38, 128.17, 127.89, 127.83, 127.80,
127.57, 85.42 (C-1), 80.10 (C-3), 75.85 (C-2), 75.16, 74.10 (C-4),
72.00, 71.96, 70.59 (C-5), 64.92 (C-6), 40.67. Anal. Calcd for
83.5–84.0 °C; 1H NMR (CDCl3): d 7.58–7.22 (m, 20H, aromatic),
5.07 (m, 1H, J4,5 = 9.5 Hz, H-4), 4.90 (d, 1H, J = 10.2 Hz, benzyl),
4.83 (d, 1H, J = 11.6 Hz, benzyl), 4.73 (d, 1H, J = 10.2 Hz, benzyl),
4.68 (d, 1H, J1,2 = 9.8 Hz, H-1), 4.61 (d, 1H, J = 11.6 Hz, benzyl),
4.49 (d, 1H, J = 11.6 Hz, benzyl), 4.46 (d, 1H, J = 11.6 Hz, benzyl),
3.67 (t, 1H, J3,4 = 9.0 Hz, H-3), 3.61, 3.52 (d, 1H, J = 14.8 Hz,
ClCH2CO), 3.60–3.54 (m, 4H, H-2,5,6,60). 13C NMR (CDCl3): d
166.20, 138.5, 137.68, 133.32, 132.01, 128.99, 128.49, 128.47,
128.36, 128.31, 128.01, 127.94, 127.89, 127.86, 127.75, 127.70,
87.61 (C-1), 83.59 (C-3), 80.73 (C-2), 76.83 (C-5), 75.58, 75.47,
73.63, 72.43 (C-4), 69.60, 40.50. Anal. Calcd for C35H35ClO6S: C,
67.89; H, 5.70. Found: C, 67.82; H, 5.67.
C35H35ClN3O6S: C, 67.89; H, 5.70. Found: C, 67.62; H, 5.88.
4.3.9. Phenyl 2-azido-4,6-di-O-benzyl-3-O-chloroacetyl-2-
deoxy-1-thio-b-D-galactopyranoside (32)
a 2D8
ꢀ3.8 (c 1.07, CHCl3); 1H NMR (CDCl3): d 7.58–7.21 (m, 15H,
4.3.5. Phenyl 3,4,6-tri-O-benzyl-2-O-chloroacetyl-1-thio-a-D-
½ ꢁ
mannopyranoside (24)
aromatic), 4.83 (dd, 1H, J2,3 = 10.3 Hz, J3,4 = 2.8 Hz, H-3), 4.58, 4.54
(each d, 2H, J = 11.6 Hz, benzyl), 4.52 (d, 1H, J = 11.8 Hz, benzyl),
4.49 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.46 (d, 1H, J = 11.8 Hz, benzyl),
4.04 (d, 1H, H-4), 3.96, 3.81 (each d, 2H, J = 14.9 Hz, ClCH2CO),
3.87 (t, 1H, H-2), 3.73 (t, 1H, J5,6 = 7.0 Hz, H-5), 3.67–3.66 (m, 2H,
H-6a,6b). 13C NMR (CDCl3): d 166.44, 137.81, 137.45, 132.89,
131.39, 128.95, 128.46, 128.35, 128.14, 127.92, 127.87, 127.81,
127.78, 86.52 (C-1), 77.17 (C-3), 76.87 (C-5), 74.88, 73.52, 73.07
(C-4), 67.58 (C-6), 59.71 (C-2), 40.38. Anal. Calcd for
½
a 2D8 +83.6 (c 1.02, CHCl3); 1H NMR (CDCl3): d7.49–7.17 (m, 20H,
ꢁ
aromatic), 5.67–5.66 (m, 1H, H-2), 5.54 (d, 1H, J1,2 = 1.3 Hz, H-1),
4.86, 4.50 (each d, 2H, J = 10.7 Hz, benzyl), 4.73, 4.58 (each d, 2H,
J = 11.1 Hz, benzyl), 4.66, 4.46 (each d, 2H, J = 12.0 Hz, benzyl),
4.34–4.31 (m, 1H, H-5), 4.17, 4.13 (each d, 2H, J = 15.3 Hz,
ClCH2CO), 3.97–3.92 (m, 2H, H-3,4), 3.85 (dd, 1H, J5,6a = 4.4 Hz,
J6a,6b = 10.9 Hz, H-6a), 3.71 (dd, 1H, J5,6b = 1.7 Hz, H-6b). 13C NMR
(CDCl3): d 166.77, 138.05, 138.02, 137.29, 133.24, 131.92, 129.10,
128.50, 128.36, 128.29, 128.22, 128.00, 127.90, 127.86, 127.75,
127.73, 127.60, 85.93, 78.33, 75.30, 74.25 (C-4), 73.34, 72.47 (C-
C28H28ClN3O5S: C, 60.70; H, 5.09; N, 7.58. Found: C, 60.63; H,
5.06; N, 7.49.

86
K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
4.3.10. Phenyl 2-azido-3,6-di-O-benzyl-4-O-chloroacetyl-2-
76.54 (C-4), 75.94, 74.95, 64.84 (C-2), 64.13 (C-6), 40.56. Anal.
Calcd for C28H28ClN3O5S: C, 60.70; H, 5.09; N, 7.58. Found: C,
60.85; H, 5.16; N, 7.43.
deoxy-1-thio-b-D-galactopyranoside (33)
½
a 2D8
ꢁ
ꢀ43.1 (c 1.29, CHCl3); 1H NMR (CDCl3): d 7.58–7.27 (m,
15H, aromatic), 4.65 (d, 1H, J3,4 = 1.2 Hz, H-4), 4.70, 4.48 (each d,
2H, J = 10.8 Hz, benzyl), 4.56, 4.45 (each d, 2H, J = 11.7 Hz, benzyl),
4.42–4.38 (m, 1H, H-1), 3.96, 3.86 (each d, 2H, J = 14.9 Hz,
ClCH2CO), 3.75 (t, 1H, H-5), 3.62 (dd, 1H, J5,6a = 5.7 Hz,
J6a,6b = 9.3 Hz, H-6a), 3.52–3.47 (m, 3H, H-2,3,6b). 13C NMR (CDCl3):
d 166.58, 137.24, 136.47, 133.48, 131.01, 128.91, 128.58, 128.51,
128.41, 128.24, 128.16, 128.04, 86.09 (C-1), 79.19 (C-3), 75.48 (C-
5), 73.67, 72.03, 67.27 (C-4 or 6), 67.23 (C-4 or 6), 60.72 (C-2),
40.59. Anal. Calcd for C28H28ClN3O5S: C, 60.70; H, 5.09; N, 7.58.
Found: C, 60.69; H, 5.22; N, 7.39.
4.3.15. Phenyl 2,6-di-O-benzyl-3,4-di-O-chloroacetyl-1-thio-b-D-
galactopyranoside (44)
To a DCM (22 mL) solution of 3,4-diol derivative33 (1.02 g,
2.25 mmol) were added pyridine (2 g) and chloroacetic anhydride
(1.54 g, 8.98 mmol) at 0 °C. After being stirred for 4 h at room tem-
perature, the mixture was diluted with DCM and poured into sat-
urated NaHCO3 followed by DCM extraction. The organic layer
was washed with H2O, dried over Na2SO4 and concentrated in
vacuo. The residue was loaded on silica gel column chromatogra-
phy (3:1 n-hexane/EtOAc) to afford 44 (1.36 g, quant) as a syrup.
4.3.11. Phenyl 2-azido-3,4-di-O-benzyl-6-O-chloroacetyl-2-
½
a 2D9
ꢁ
ꢀ6.2 (c 1.30, CHCl3); 1H NMR (CDCl3): d 7.59–7.55, 7.36–
deoxy-1-thio-b-
D
-galactopyranoside (34)
7.24 (each m, 15H, aromatic), 5.54 (d, 1H, J3,4 = 3.3 Hz, H-4), 5.10
(dd, 1H, J2,3 = 9.6 Hz, H-3), 4.83, 4.57 (each d, 2H, J = 11.0 Hz, ben-
zyl), 4.73 (d, 1H, J1,2 = 9.7 Hz, H-1), 4.55, 4.38 (each d, 2H,
J = 11.9 Hz, benzyl), 3.95, 3.86 (each d, 2H, J = 14.6 Hz, ClCH2CO),
3.89–3.86 (m, 1H, H-5), 3.86, 3.77 (each d, 2H, J = 15.0 Hz,
ClCH2CO), 3.72 (t, 1H, H-2), 3.59 (dd, 1H, J5,6a = 5.8 Hz,
J6a,6b = 9.4 Hz, H-6a), 3.47 (dd, 1H, J5,6b = 7.5 Hz, H-6b). 13C NMR
(CDCl3): d 166.95, 166.30, 137.61, 137.34, 133.01, 132.15, 129.08,
128.53, 128.48, 128.17, 128.16, 128.08, 128.05, 127.95, 87.87
(C-1), 75.79, 75.61, 75.05, 74.89, 73.51, 69.73 (C-4), 66.83 (C-6),
40.52, 40.43. Anal. Calcd for C30H30Cl2O7S: C, 59.51; H, 4.99. Found:
C, 59.55; H, 4.97.
½
a 2D8
ꢁ
ꢀ16.9 (c 1.04, CHCl3); 1H NMR (CDCl3): d 7.58–7.23 (m,
15H, aromatic), 4.92, 4.54 (each d, 2H, J = 11.5 Hz, benzyl), 4.75
(s, 2H, benzyl), 4.39 (d, 1H, J1,2 = 10.1 Hz, H-1), 4.35 (dd, 1H,
J5,6a = 7.0 Hz, J6a,6b = 11.3 Hz, H-6a), 4.14 (dd, 1H, J5,6b = 5.4 Hz, H-
6b), 3.96, 3.92 (each d, 2H, J = 14.9 Hz, ClCH2CO), 3.85 (t, 1H,
J2,3 = 9.9 Hz, H-2), 3.78 (d, 1H, H-4), 3.53 (t, 1H, J = 6.3 Hz, H-5),
3.43 (dd, 1H, J3,4 = 2.6 Hz, H-3). 13C NMR (CDCl3): d 166.84,
137.75, 137.11, 132.96, 131.63, 128.86, 128.61, 128.35, 128.17,
128.06, 128.03, 127.93, 127.83, 86.45 (C-1), 82.43 (C-3), 75.69
(C-5), 74.16, 72.89, 71.54 (C-4), 64.70 (C-6), 61.40 (C-2), 40.56.
Anal. Calcd for C28H28ClN3O5S: C, 60.70; H, 5.09; N, 7.58. Found:
C, 60.78; H, 5.17; N, 7.46.
4.3.16. Phenyl 2,3-di-O-benzyl-4,6-di-O-chloroacetyl-1-thio-b-D-
4.3.12. Phenyl 2-azido-4,6-di-O-benzyl-3-O-chloroacetyl-2-
galactopyranoside (45)
deoxy-1-thio-b-
D
-glucopyranoside (38)
The title compound was synthesized from 4,6-diol derivative34
according to the procedure described for the synthesis of com-
½
a 2D8
ꢁ
ꢀ67.8 (c 1.03, CHCl3); 1H NMR (CDCl3): d 7.62–7.15 (m,
15H, aromatic), 5.11 (t, 1H, J2,3 = J3,4 = 9.6 Hz, H-3), 4.66, 4.57 (each
d, 2H, J = 11.9 Hz, benzyl), 4.57 (d, 1H, J = 11.5 Hz, benzyl), 4.51–
4.46 (m, 2H, H-1, benzyl), 3.86, 3.70 (each d, 2H, J = 14.8 Hz,
ClCH2CO), 3.82–3.77 (m, 2H, H-6a,6b), 3.70 (t, 1H, J4,5 = 9.6 Hz, H-
4), 3.51 (dt, 1H, J5,6 = 2.6 Hz, H-5), 3.33 (t, 1H, J1,2 = 9.9 Hz, H-2).
pound 44. ½a 2D8
ꢁ
+16.2 (c 1.28, CHCl3); 1H NMR (CDCl3): d 7.58–
7.54, 7.40–7.27 (each m, 15H, aromatic), 4.57 (d, 1H, J3,4 = 3.2 Hz,
H-4), 4.77, 4.72 (each d, 2H, J = 10.2 Hz, benzyl), 4.73, 4.52 (each
d, 2H, J = 11.0 Hz, benzyl), 4.66 (d, 1H, J1,2 = 9.5 Hz, H-1), 4.34 (dd,
1H, J5,6a = 7.2 Hz, J6a,6b = 11.4 Hz, H-6a), 4.27 (dd, 1H, J5,6b = 5.9 Hz,
H-6b), 4.17, 4.13 (each d, 2H, J = 15.0 Hz, ClCH2CO), 4.05 (s, 2H,
ClCH2CO), 3.88 (br t, 1H, H-5), 3.69 (dd, 1H, J2,3 = 9.1 Hz, H-3),
3.63 (t, 1H, H-2). 13C NMR (CDCl3): d 166.97, 166.84, 137.83,
136.98, 132.83, 132.43, 128.88, 128.47, 128.36, 128.26, 128.19,
128.05, 127.90, 127.87, 87.64, 80.54, 76.36, 75.82, 73.89, 72.40,
68.61, 63.43, 40.65, 40.51. Anal. Calcd for C30H30Cl2O7S: C, 59.51;
H, 4.99. Found: C, 59.58; H, 4.79.
13C NMR (CDCl3):
d 166.21, 137.89, 137.50, 133.72, 130.75,
129.06, 128.57, 128.51, 128.42, 128.07, 128.02, 127.78, 127.72,
85.97 (C-1), 79.12 (C-5), 77.56 (C-3), 75.02 (C-4), 74.52, 73.49,
68.17 (C-6), 62.97 (C-2), 40.45. Anal. Calcd for C28H28ClN3O5S: C,
60.70; H, 5.09; N, 7.58. Found: C, 60.57; H, 5.06; N, 7.54.
4.3.13. Phenyl 2-azido-3,6-di-O-benzyl-4-O-chloroacetyl-2-
deoxy-1-thio-b-D-glucopyranoside (39)
½
a 2D6
ꢁ
ꢀ56.2 (c 1.33, CHCl3); 1H NMR (CDCl3): d 7.58–7.25 (m,
4.3.17. Synthesis of compounds 46 and 47
15H, aromatic), 5.03–4.98 (m, 1H, H-4), 4.89, 4.61 (each d, 2H,
J = 11.4 Hz, benzyl), 4.50 (d, 1H, J = 11.6 Hz, benzyl), 4.48–4.43
(m, 2H, H-1, benzyl), 3.62, 3.55 (each d, 2H, J = 14.8 Hz, ClCH2CO),
3.59–3.55 (m, 3H, H-5, 6a, 6b), 3.51 (t, 1H, J3,4 = 9.4 Hz, H-3), 3.40
(t, 1H, J1,2 = J2,3 = 9.6 Hz, H-2). 13C NMR (CDCl3): d 166.06, 137.54,
137.34, 133.66, 130.57, 129.08, 128.60, 128.54, 128.38, 128.12,
128.09, 127.87, 127.80, 86.04 (C-1), 82.20 (C-3), 76.88 (C-5),
75.41, 73.60, 72.22 (C-4), 69.35 (C-6), 64.78 (C-2), 40.39.
Compound 46 (a) and 47 (b) were synthesized from the corre-
sponding 3,4-diol derivatives, which were derived from a commer-
cially available 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-D-galactose
as follows.
4.3.17.1. Phenyl 3,4,5-tri-O-acetyl-2-azido-2-deoxy-1-thio-
galactoside. To a mixture of 1,3,4,6-tetra-O-acetyl-2-azido-
2-deoxy- -galactose (1.00 g, 2.68 mmol), thiophenol (354 mg,
D-
D
3.21 mmol), and AW-300 (ca. 4.00 g) in DCE (9.0 mL) was added
methyl trifluoromethanesulfonate (0.48 mL, 2.68 mmol) at 10 °C.
After being stirred for 20 h at room temperature under nitrogen
atmosphere, the mixture was poured into saturated NaHCO3 and
filtered through a Celite pad. The products were extracted with
CHCl3 from the filtrate. The combined organic layer was washed
with H2O, dried over Na2SO4 and concentrated in vacuo. The resi-
due was loaded on silica gel column chromatography (5:1–2:1
4.3.14. Phenyl 2-azido-3,4-di-O-benzyl-6-O-chloroacetyl-2-
deoxy-1-thio-b-D-glucopyranoside (40)
½
a 2D8
ꢁ
ꢀ27.2 (c 1.36, CHCl3); 1H NMR (CDCl3): d 7.57–7.23 (m,
15H, aromatic), 4.90, 4.83 (each d, 2H, J = 10.4 Hz, benzyl), 4.85,
4.57 (each d, 2H, J = 11.1 Hz, benzyl), 4.48 (dd, 1H, J5,6a = 1.6 Hz,
J6a,6b = 11.7 Hz, H-6a), 4.40 (d, 1H, J1,2 = 10.2 Hz, H-1), 4.24 (dd,
1H, J5,6b = 4.7 Hz, H-6b), 3.99, 3.96 (each d, 2H, J = 14.9 Hz,
ClCH2CO), 3.55–3.51 (m, 2H, H-3,5), 3.44 (t, 1H, J3,4 = J4,5 = 9.4 Hz,
H-4), 3.22 (t, 1H, J2,3 = 9.7 Hz, H-2). 13C NMR (CDCl3): d 166.73,
137.21, 137.19, 133.87, 130.51, 128.95, 128.59, 128.55, 128.21,
128.14, 128.12, 128.02, 85.75 (C-1), 85.01 (C-3), 76.67 (C-5),
n-hexane/EtOAc) to afford the phenylthio-glycoside as an
a/b-mix-
ture ( :b = 72:28).
a
a
-Thioglycoside; 1H NMR (CDCl3): d 7.53–7.50,
7.37–7.30 (each m, 5H, aromatic), 5.70 (d, 1H, J1,2 = 5.5 Hz, H-1),
5.49 (d, 1H, J3,4 = 3.3 Hz, H-4), 5.18 (dd, 1H, J2,3 = 11.1 Hz, H-3),

K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
87
4.76 (t, 1H, H-5), 4.32 (dd, 1H, H-2), 4.09 (d, 2H, J5,6 = 6.5 Hz,
H-6), 2.17, 2.07, 1.99 (each s, 9H, OAc), b-thioglycoside; 1H NMR
(CDCl3): d 7.64–7.61, 7.37–7.30 (each m, 5H, aromatic), 5.36
(d, 1H, J3,4 = 3.2 Hz, H-4), 4.86 (dd, 1H, J2,3 = 10.3 Hz, H-3), 4.52
(d, 1H, J1,2 = 10.1 Hz, H-1), 4.18 (dd, 1H, J5,6a = 6.8 Hz,
J6a,6b = 11.3 Hz, H-6a), 4.11 (dd, 1H, J5,6b = 6.3 Hz, H-6b), 3.89 (t,
1H, H-5), 3.66 (t, 1H, H-2), 2.10, 2.05, 2.04 (each s, 9H, OAc).
J = 11.5 Hz, benzyl), 4.38 (t, 1H, H-5), 4.16 (dd, 1H, J2,3 = 9.9 Hz,
H-2), 3.94–3.89 (m, 2H, H-3,4), 3.80 (ddd, 1H, J5,6a = 7.0 Hz,
J6a,6b = 11.3 Hz, J6a,OH = 3.5 Hz, H-6a), 3.65 (ddd, 1H, J5,6b = 5.2 Hz,
J6b,OH = 8.7 Hz, H-6b), 2.33 (d, 1H, J3,OH = 7.5 Hz, OH), 1.57 (dd, 1H,
OH). 13C NMR (CDCl3): d 137.43, 132.92, 132.54, 129.14, 128.76,
128.38, 128.29, 127.89, 87.05, 76.26, 75.43, 71.89, 70.74, 61.88.
4.3.17.4. Phenyl 2-azido-6-O-benzyl-2-deoxy-1-thio-b-
D
-galac-
4.3.17.2. Phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-
galactoside. To a MeOH (25 mL) solution of phenyl 3,4,5-tri-
O-acetyl-2-azido-2-deoxy-1-thio- -galactoside ( :b = 88:12) was
added NaOMe (72 mg, 1.34 mmol). After being stirred for 10 h at
room temperature under nitrogen atmosphere the solution was
neutralized (Dowex 50WX-2) and concentrated in vacuo to obtain
triol derivatives (0.75 g, 94%). To a DCE (44 mL) solution of the triol
D-
topyranoside.
The title compound was synthesized from
phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-b-D-galactopy-
D
a
ranoside (47%) with 3,6-diol derivative (8%) according to the proce-
dure described above. 1H NMR (CDCl3): d 7.61–7.59, 7.38–7.27
(each m, 10H, aromatic), 4.60, 4.57 (each d, 2H, J = 11.8 Hz, benzyl),
4.42 (d, 1H, J1,2 = 9.6 Hz, H-1), 4.03 (br s, 1H, H-4), 3.83 (dd, 1H,
J5,6a = 5.0 Hz, J6a,6b = 10.3 Hz, H-6a), 3.80 (dd, 1H, J5,6b = 4.8 Hz, H-
6b), 3.58 (t, 1H, H-5), 3.53 (t, 1H, J2,3 = 9.4 Hz, H-2), 3.51 (t, 1H,
J3,4 = 3.0 Hz, J3,OH = 7.1 Hz, H-3), 3.13 (d, 1H, J4,OH = 3.0 Hz, OH),
2.86 (d, 1H, OH). 13C NMR (CDCl3): d 137.44, 133.06, 131.76,
129.04, 128.61, 128.26, 128.07, 127.83, 86.61 (C-1), 76.83 (C-5),
74.24 (C-3), 73.86, 69.98 (C-6), 69.03 (C-4), 62.83 (C-2).
(1.3 g, 4.38 mmol, a:b = 88:12) were added benzaldehyde dimeth-
ylacetal (1.3 g, 8.76 mmol) and camphorsulfonic acid (508 mg,
2.19 mmol). After being stirred for 1 h at room temperature, the
mixture was poured into saturated NaHCO3 and the products were
extracted with CHCl3. The combined organic layer was washed with
H2O, dried over Na2SO4 and concentrated in vacuo. The residue was
loaded on silica gel column chromatography (5:1–1:1 n-hexane/
EtOAc) to afford the corresponding 4,6-O-benzylidene derivatives
3,6-Diol derivative; 1H NMR (CDCl3): d 7.60–7.57, 7.41–7.29
(each m, 10H, aromatic), 4.75, 4.72 (each d, 2H, J = 11.7 Hz, benzyl),
4.46 (d, 1H, J1,2 = 9.5 Hz, H-1), 3.94–3.90 (m, 1H, H-6a), 3.82 (br d,
1H, J3,4 = 2.4 Hz, H-4), 3.69–3.64 (m, 1H, H-6b), 3.62 (t, 1H,
J2,3 = 9.6 Hz, H-2), 3.61–3.57 (m, 1H, H-3), 3.55 (dd, 1H, J = 5.7 Hz,
J = 6.7 Hz, H-5), 2.39 (d, 1H, J = 7.2 Hz, OH), 1.83 (d, 1H, J = 5.2 Hz,
OH). 13C NMR (CDCl3): d 137.66, 132.74, 131.77, 129.06, 128.70,
128.24, 128.13, 127.95, 86.52 (C-1), 79.31 (C-5), 75.09, 75.08 (C-
4), 74.62 (C-3), 63.37 (C-2), 62.03 (C-6).
individually (
NMR (CDCl3): d 7.52–7.25 (m, 10H, aromatic), 5.76 (d, 1H, J1,2
5.2 Hz, H-1), 5.61 (s, 1H, benzylidene), 4.34 (d, 1H, J3,4 = 3.7 Hz, H-
4), 4.27–4.26 (br s, 1H, H-5), 4.25 (dd, 1H, J5,6a = 1.4 Hz, J6a,6b
a: 1.36 g, 81%; b: 185 mg, 11%). a
-Derivative; 1H
=
=
12.5 Hz, H-6a), 4.21 (dd, 1H, J2,3 = 10.5 Hz, H-2), 4.13 (dd, 1H,
J5,6b = 1.5 Hz, H-6b), 4.02 (dt, 1H, J3,OH = 10.3 Hz, H-3), 2.58 (d, 1H,
OH). 13C NMR (CDCl3): d 137.10, 133.58, 131.05, 129.44, 129.11,
128.35, 127.40, 126.20, 101.34, 87.21, 75.07, 69.55, 69.17, 63.62,
61.37.
4.3.17.5. Phenyl 2-azido-6-O-benzyl-3,4-di-O -chloroacetyl-2-
deoxy-1-thio-
a-
D
-galactopyranoside (46).
The title com-
b-Derivative; 1H NMR (CDCl3): d 7.75–7.73, 7.43–7.29 (each m,
10H, aromatic), 5.54 (s, 1H, benzylidene), 4.42 (d, 1H, J1,2 = 9.8 Hz,
H-1), 4.40 (dd, 1H, J5,6a = 1.5 Hz, J6a,6b = 12.5 Hz, H-6a), 4.20 (d, 1H,
J3,4 = 3.5 Hz, H-4), 4.04 (dd, 1H, J5,6b = 1.7 Hz, H-6b), 3.65 (dt, 1H,
J2,3 = 9.7 Hz, J3,OH = 9.8 Hz, H-3), 3.54 (t, 1H, H-2), 3.53 (br s, 1H,
H-5), 2.54 (d, 1H, OH).
pound was synthesized from phenyl 2-azido-6-O-benzyl-2-
deoxy-1-thio-a-D-galactopyranoside according to the procedure
described for the synthesis of compound 44. ½a D30
ꢁ
+138.5 (c 1.45,
CHCl3); mp: 74.0–75.0 °C; 1H NMR (CDCl3): d 7.52–7.49, 7.37–
7.23 (each m, 10H, aromatic), 5.68 (d, 1H, J1,2 = 5.5 Hz, H-1), 5.62
(d, 1H, J3,4 = 3.2 Hz, H-4), 5.25 (dd, 1H, J2,3 = 11.1 Hz, H-3), 4.78
(t, 1H, J5,6 = 6.5 Hz, H-5), 4.52, 4.38 (each d, 2H, J = 11.9 Hz, benzyl),
4.32 (dd, 1H, H-2), 4.09, 4.05 (each d, 2H, J = 15.3 Hz, ClCH2CO),
4.01, 3.92 (each d, 2H, J = 14.6 Hz, ClCH2CO), 3.48 (d, 2H, H-6).
4.3.17.3. Phenyl 2-azido-6-O-benzyl-2-deoxy-1-thio-
topyranoside. A mixture of phenyl 2-azido-4,6-O-benzyli-
dene-2-deoxy-1-thio- -galactopyranoside (105 mg, 0.272
a-D-galac-
a-D
13C NMR (CDCl3):
d 166.89, 166.08, 137.22, 132.71, 132.16,
mmol), NaBH3CN (2.2 mL, 1.0 M in THF), and AW-300 (ca
300 mg) was stirred for 1 h at room temperature under nitrogen
atmosphere. To the mixture was added HCl (2.7 mL, 1.0 M in
Et2O) at 0 °C, then stirred for 1 h at room temperature. The mixture
was poured into saturated NaHCO3 and filtered through a Celite
pad. The products were extracted with CHCl3 from the filtrate.
The combined organic layer was washed with H2O, dried over
Na2SO4 and concentrated in vacuo. The residue was loaded on sil-
ica gel column chromatography (4:1–1:1 n-hexane/EtOAc) to
129.19, 128.48, 128.18, 128.03, 127.99, 87.03 (C-1), 73.43, 71.90
(C-3), 69.35 (C-4), 68.01 (C-5), 66.88 (C-6), 58.18 (C-2), 40.41,
40.35. Anal. Calcd for C23H23Cl2N3O6S: C, 51.12; H, 4.29, N; 7.78.
Found: C, 51.22; H, 4.27, N; 7.79.
4.3.17.6. Phenyl 2-azido-6-O-benzyl-3,4-di-O -chloroacetyl-2-
deoxy-1-thio-b-
D-galactopyranoside (47).
The title com-
pound was synthesized from phenyl 2-azido-6-O-benzyl-2-
deoxy-1-thio-b-D-galactopyranoside according to the procedure
afford phenyl 2-azido-6-O-benzyl-2-deoxy-1-thio-a-D-galactopy-
described for the synthesis of compound 44. ½a D25
ꢀ49.4 (c 0.99,
ꢁ
ranoside (85 mg, 81%) and 3,6-diol derivative (10 mg, 9%), respec-
CHCl3); 1H NMR (CDCl3): d 7.61–7.59, 7.38–7.26 (each m, 10H, aro-
matic), 5.52 (d, 1H, J3,4 = 2.9 Hz, H-4), 4.96 (dd, 1H, J2,3 = 10.3 Hz, H-
3), 4.57, 4.40 (each d, 2H, J = 11.9 Hz, benzyl), 5.54 (d, 1H,
J1,2 = 7.7 Hz, H-1), 4.06, 4.02 (each d, 2H, J = 15.3 Hz, ClCH2CO),
3.92, 3.84 (each d, 2H, J = 14.7 Hz, ClCH2CO), 3.91–3.87 (m, 1H,
tively. ½a 3D0
ꢁ
+215.7 (c 1.29, CHCl3); 1H NMR (CDCl3): d 7.51–7.48
(each m, 10H, aromatic), 5.66 (d, 1H, J1,2 = 5.5 Hz, H-1), 4.60, 4.52
(each d, 2H, J = 11.8 Hz, benzyl), 4.48 (t, 1H, H-5), 4.18 (dd, 1H,
J2,3 = 10.4 Hz, H-2), 4.15 (br s, 1H, H-4), 3.83 (ddd, 1H, J3,4
3.3 Hz, J3,OH = 8.1 Hz, H-3), 3.80 (dd, 1H, J5,6a = 4.6 Hz, J6a,6b
=
=
0
H-5), 3.64 (t, 1H, H-2), 3.61 (dd, 1H, J5,6 = 5.7 Hz, J6,6 = 9.3 Hz, H-
10.5 Hz, H-6a), 3.77 (dd, 1H, J5,6b = 4.5 Hz, H-6b), 3.47 (d, 1H,
J4,OH = 1.9 Hz, OH), 2.78 (d, 1H, OH). 13C NMR (CDCl3): d 137.17,
133.30, 132.12, 129.05, 128.55, 128.03, 127.76, 127.67, 87.41,
73.82, 70.45, 70.36, 70.02, 69.29, 61.16.
6), 3.48 (dd, 1H, J5,6 = 7.7 Hz, H-60). 13C NMR (CDCl3): d 166.74,
0
166.16, 137.19, 133.46, 130.72, 129.09, 128.67, 128.52, 128.13,
128.06, 86.53 (C-1), 75.14 (C-5), 74.50 (C-3), 73.45, 68.40 (C-4),
66.54 (C-6), 59.25 (C-2), 40.39, 40.34. Anal. Calcd for
3,6-Diol derivative; ½a D30
ꢁ
+202.6 (c 1.05, CHCl3); mp: 135.0–
136.0 °C; 1H NMR (CDCl3): d 7.51–7.48, 7.41–7.27 (each m, 10H,
aromatic), 5.66 (d, 1H, J1,2 = 5.4 Hz, H-1), 4.77, 4.74 (each d, 2H,
C23H23Cl2N3O6S: C, 51.12; H, 4.29, N; 7.78. Found: C, 51.22; H,
4.27, N; 7.79.

88
K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
4.4. Synthesis of a series of glycosyl fluorides using DAST
4.4.3. 2,4,6-Tri-O-benzyl-3-O-chloroacetyl-D-glucopyranosyl
fluoride (21)
Typical procedure for the transformation of thioglycoside into
glycosyl fluoride using DAST in the absence of NBS is as follows.
a
Fluoride; ½a 2D8
ꢁ
+28.2 (c 1.03, CHCl3); 1H NMR (CDCl3): d 7.37–
7.13 (m, 15H, aromatic), 5.58 (dd, 1H, J1,2 = 2.6 Hz, J1,F = 52.6 Hz,
H-1), 5.49 (dd, 1H, J2,3 = J3,4 = 9.7 Hz, H-3), 4.64, 4.57 (each d, 2H,
J = 12.3 Hz, benzyl), 4.64, 4.50 (each d, 2H, J = 11.9 Hz, benzyl),
4.49, 4.46 (each d, 2H, J = 11.4 Hz, benzyl), 3.99–3.96 (m, 1H, H-5),
3.80 (t, 1H, J4,5 = 9.8 Hz, H-4), 3.78 (dd, 1H, J5,6a = 2.8 Hz,
J6a,6b = 11.2 Hz, H-6a), 3.70–3.78 (m, 2H, H-6b, ClCH2CO), 3.64 (d,
1H, J = 14.6 Hz, ClCH2CO), 3.52 (ddd, 1H, J2,3 = 9.9 Hz, J2,F = 24.7 Hz,
H-2). 13C NMR (CDCl3): d 166.13, 137.57, 137.34, 137.20, 128.58,
128.48, 128.46, 128.19, 128.13, 127.99, 127.92, 127.90, 104.75 (d,
J1,F = 229.5 Hz, C-1), 76.63 (d, J2,F = 27.7 Hz, C-2), 74.74 (C-4),
74.64 (C-3), 74.52, 73.63, 73.05, 72.31 (d, J5,F = 3.9 Hz, C-5), 67.30
(C-6), 40.53.
4.4.1. 2-Azido-4,6-di-O-benzyl-3-O-chloroacetyl-2-deoxy-D-
glucopyranosyl fluoride (41)
To a DCE (10 mL) solution of 3-O-chloroacetyl derivative 38
(1.08 g, 1.99 mmol) was added DAST (0.49 mL, 3.96 mmol) at
0 °C, and the mixture was stirred for 44 h at 60 °C under nitrogen
atmosphere. The reaction mixture was diluted with EtOAc, and
washed with saturated NaHCO3 and brine. The combined organic
layer was dried over Na2SO4 and concentrated in vacuo. The resi-
due was loaded on silica gel column chromatography (6:1 n-hex-
ane/EtOAc) to afford the corresponding fluoride (0.90 g, 97%,
a:b = 84:16) as a pale brown syrup.
a
Fluoride; 1H NMR (CDCl3):
b Fluoride; 1H NMR (CDCl3): d 7.36–7.12 (m, 15H, aromatic), 5.30
d
7.38–7.15 (m, 10H, aromatic), 5.73 (dd, 1H, J1,2 = 2.6 Hz,
(dd, 1H, J1,2 = 6.6 Hz, J1,F = 52.8 Hz, H-1), 5.19 (t, 1H, J2,3 =
J1,F = 52.4 Hz, H-1), 5.51 (dd, 1H, J2,3 = 10.4 Hz, J3,4 = 9.5 Hz, H-3),
4.65 (d, 1H, J = 12.0 Hz, benzyl), 4.57–4.52 (m, 2H, benzyl), 4.52
(d, 1H, J = 11.4 Hz, benzyl), 4.04–4.01 (m, 1H, H-5), 3.90, 3.75 (each
d, 2H, J = 14.9 Hz, ClCH2CO), 3.90 (t, 1H, J4,5 = 9.7 Hz, H-4), 3.82 (dd,
1H, J5,6a = 2.7 Hz, J6a,6b = 11.7 Hz, H-6a), 3.72 (dd, 1H, J5,6b = 2.0 Hz,
H-6b), 3.30 (ddd, 1H, J2,F = 25.7 Hz, H-2). 13C NMR (CDCl3): d
166.23, 137.38, 137.30, 128.53, 128.51, 128.08, 128.07, 128.03,
127.92, 106.27 (d, J1,F = 228.0 Hz, C-1), 74.75, 74.56 (C-4), 73.65,
73.30 (C-3), 72.85 (d, J5,F = 3.6 Hz, C-5), 67.15 (C-6), 61.27 (d,
J2,F = 24.7 Hz, C-2), 40.37.
J3,4 = 8.9 Hz, H-3), 4.80, 4.67, 4.56, 4.54 (each d, 4H, J = 12.0 Hz, ben-
zyl), 4.51, 4.45 (each d, 2H, J = 11.4 Hz, benzyl), 3.82 (t, 1H,
J4,5 = 9.4 Hz, H-4), 3.77–3.76 (m, 2H, H-6), 3.66–3.62 (m, 1H, H-5),
3.61, 3.55 (each d, 2H, J = 14.8 Hz, ClCH2CO), 3.48 (ddd, 1H,
J2,3 = 8.6 Hz, J2,F = 11.1 Hz, H-2). 13C NMR (CDCl3):
d 166.26,
137.55, 137.51, 137.29, 128.47, 128.45, 128.14, 128.03, 128.12,
127.99, 127.91, 127.89, 109.39 (d, J1,F = 216.1, C-1), 78.14 (d,
J2,F = 24.0, C-2), 76.29 (d, J3,F = 12.0 Hz, C-3), 74.86 (C-4), 74.41,
74.40 (d, J5,F = 2.3 Hz, C-5), 73.67, 73.63 (d, J = 1.8 Hz), 67.66 (C-6),
40.50.
b Fluoride; 1H NMR (CDCl3): d 7.38–7.14 (m, 10H, aromatic),
5.14 (dd, 1H, J1,2 = 7.2 Hz, J1,F = 52.0 Hz, H-1), 5.06 (t, 1H,
J2,3 = J3,4 = 9.6 Hz, H-3), 4.68, 4.55 (each d, 2H, J = 11.9 Hz, benzyl),
4.54, 4.47 (each d, 2H, J = 11.4 Hz, benzyl), 3.89, 3.73 (each d, 2H,
J = 14.9 Hz, ClCH2CO), 3.85 (t, 1H, J4,5 = 9.6 Hz, H-4), 3.81–3.77 (m,
2H, H-6a,6b), 3.59–3.53 (m, 2H, H-2,5). 13C NMR (CDCl3): d
166.13, 137.38, 137.24, 128.54, 128.48, 128.42, 128.39, 128.13,
128.10, 128.08, 128.06, 128.04, 127.97, 127.93, 127.71, 107.81 (d,
J1,F = 215.5 Hz, C-1), 74.94, 74.89, 74.85, 74.58, 73.71, 67.38 (C-6),
63.94 (d, J2,F = 23.2 Hz, C-2), 40.36.
4.4.4. 2,3,6-Tri-O-benzyl-4-O-chloroacetyl-D-glucopyranosyl
fluoride (22)
a
Fluoride; 1H NMR (CDCl3): d 7.37–7.22 (m, 15H, aromatic),
5.52 (dd, 1H, J1,2 = 2.5 Hz, J1,F = 52.8 Hz, H-1), 5.20 (t, 1H,
J3,4 = 9.9 Hz, H-4), 4.89, 4.81, 4.70, 4.64 (each d, 4H, J = 11.8 Hz,
benzyl), 4.51, 4.42 (each d, 2H, J = 11.9 Hz, benzyl), 4.00 (dt, 1H,
J4,5 = 10.3 Hz, J5,6a = J5,6b = 3.6 Hz, H-5), 3.91 (t, 1H, J2,3 = 9.5 Hz, H-
3), 3.66–3.58 (m, 1H, H-2), 3.59, 3.53 (each d, 1H, J = 14.7 Hz,
ClCH2CO), 3.52 (dd, 1H, J6a,6b = 10.8 Hz, H-6a), 3.44 (dd, 1H, H-
6b). 13C NMR (CDCl3): d 165.88, 138.10, 137.30, 137.21, 128.61,
128.47, 128.45, 128.40, 128.38, 128.21, 128.08, 128.06, 128.00,
127.88, 127.85, 105.22 (d, J1,F = 227.3 Hz, C-1), 79.03 (d,
J2,F = 24.3 Hz, C-2), 78.19 (C-3), 75.33, 73.67, 73.60, 70.71 (C-4),
70.58 (d, J5,F = 3.7 Hz, C-5), 67.75 (C-6), 40.44.
4.4.2. 3,4,6-Tri-O-benzyl-2-O-chloroacetyl-D-glucopyranosyl
fluoride (20)
a
Fluoride; ½a 2D6
ꢁ
+61.7 (c 1.45, CHCl3); 1H NMR (CDCl3): d 7.36–
7.15 (m, 15H, aromatic), 5.73 (dd, 1H, J1,2 = 2.7 Hz, J1,F = 53.8 Hz, H-
1), 4.94 (ddd, 1H, J2,3 = 9.9 Hz, J2,F = 24.4 Hz, H-2), 4.86, 4.72 (each
d, 2H, J = 11.5 Hz, benzyl), 4.83, 4.55 (each d, 2H, J = 10.8 Hz, ben-
zyl), 4.62, 4.51 (each d, 2H, J = 12.1 Hz, benzyl), 4.01 (t, 1H,
J3,4 = 9.7 Hz, H-3), 3.96, 3.80 (each d, 2H, J = 15.2 Hz, ClCH2CO),
3.97–3.96 (m, 1H, H-5), 3.84 (t, 1H, J4,5 = 9.6 Hz, H-4), 3.78 (dd,
1H, J5,6a = 3.3 Hz, J6a,6b = 11.0 Hz, H-6a), 3.69 (dd, 1H, J5,6b = 1.8 Hz,
b Fluoride; 1H NMR (CDCl3): d 5.27 (dd, 1H, J1,2 = 6.3 Hz,
J1,F = 52.4 Hz, H-1), 5.13 (t, 1H, J3,4 = J4,5 = 9.3 Hz, H-4), 4.85–4.81
(m, 2H, benzyl), 4.58, 4.47 (each d, 2H, J = 11.8 Hz, benzyl). 13C
NMR (CDCl3):
d 109.46 (d, J1,F = 217.4 Hz, C-1), 81.12 (d,
J2,F = 22.2 Hz, C-2), 72.70 (d, J5,F = 5.4 Hz, C-5), 71.50 (C-4), 68.84
(C-6).
H-6b). 13C NMR (CDCl3):
d 166.67, 138.07, 137.62, 137.54,
128.49, 128.45, 127.92, 127.87, 127.85, 127.73, 104.1 (d,
J1,F = 226.5 Hz, C-1), 79.24 (C-3), 76.67 (C-4), 75.61, 75.29, 74.20
(d, J2,F = 25.5 Hz, C-2), 73.52, 72.90 (d, J5,F = 4.0 Hz, C-5), 67.48 (C-
6), 40.39.
4.4.5. 2,3,4-Tri-O-benzyl-6-O-chloroacetyl-D-glucopyranosyl
fluoride (23)
a
Fluoride; 1H NMR (CDCl3): d 7.37–7.25 (m, 15H, aromatic),
5.50 (dd, 1H, J1,2 = 2.5 Hz, J1,F = 52.8 Hz, H-1), 4.99 (d, 1H,
J = 10.8 Hz, benzyl), 4.90 (d, 1H, J = 11.0 Hz, benzyl), 4.87–4.77
(m, 2H, benzyl), 4.71 (d, 1H, J = 11.8 Hz, benzyl), 4.61 (d, 1H,
J = 11.0 Hz, benzyl), 4.38 (dd, 1H, J5,6a = 2.0 Hz, J6a,6b = 12.1 Hz, H-
6a), 4.30 (dd, 1H, J5,6b = 4.0 Hz, H-6b), 4.03–3.95 (m, 2H, H-3,5),
3.99, 3.95 (each d, 2H, J = 14.9 Hz, ClCH2CO), 3.57–3.50 (m, 1H,
H-2), 3.55 (t, 1H, J3,4 = J4,5 = 9.4 Hz, H-4). 13C NMR (CDCl3): d
166.83, 138.09–127.86, 105.05 (d, J1,F = 227.97 Hz, C-1), 81.31 (C-
3), 79.27 (d, J2,F = 24.64 Hz, C-2), 75.89, 75.61 (C-4), 75.03, 73.54,
70.82 (d, J5,F = 4.3 Hz, C-5), 63.80 (C-6), 40.58.
b Fluoride; ½a 2D7
ꢁ
+22.4 (c 2.19, CHCl3); 1H NMR (CDCl3): d 7.36–
7.16 (m, 15H, aromatic), 5.24 (dd, 1H, J1,2 = 6.5 Hz, J1,F = 52.6 Hz,
H-1), 5.12 (ddd, 1H, J2,3 = 8.4 Hz, J2,F = 10.9 Hz, H-2), 4.80, 4.67 (each
d, 2H, J = 11.7 Hz, benzyl), 4.78, 4.56 (each d, 2H, J = 10.8 Hz, ben-
zyl), 4.62, 4.55 (each d, 2H, J = 12.1 Hz, benzyl), 3.92, 3.78 (each d,
2H, J = 15.0 Hz, ClCH2CO), 3.85 (t, 1H, J3,4 = 9.2 Hz, H-4), 3.74–3.73
(m, 2H, H-6), 3.69 (t, 1H, H-3), 3.65 (dt, 1H, J4,5 = 9.7 Hz,
J5,6 = 3.5 Hz, H-5). 13C NMR (CDCl3): d 165.88, 137.67, 137.63,
137.43, 128.51, 128.46, 128.41, 127.98, 127.96, 127.93, 127.85,
127.77, 106.43 (d, J1,F = 217.4, C-1), 81.28 (d, J3,F = 8.3 Hz, C-3),
76.80 (C-4), 75.01 (d, J5,F = 2.5 Hz, C-5), 75.0, 74.81, 74.13 (d,
J2,F = 26.2 Hz, C-2), 73.56, 68.10 (C-6), 40.41.
b Fluoride; 1H NMR (CDCl3): d 7.37–7.25 (m, 15H, aromatic),
5.28 (dd, 1H, J1,2 = 6.4 Hz, J1,F = 52.7 Hz, H-1), 4.91 (d, 1H, J =
11.0 Hz, benzyl), 4.87–4.77 (m, 3H, benzyl), 4.69 (d, 1H, J =

K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
89
11.1 Hz, benzyl), 4.60 (d, 1H, J = 11.0 Hz, benzyl), 4.45 (dd, 1H,
J5,6a = 1.8 Hz, J6a,6b = 11.9 Hz, H-6a), 4.28 (dd, 1H, J5,6b = 4.4 Hz, H-
6b), 4.03, 3.97 (each d, 2H, J = 15.1 Hz, ClCH2CO), 3.71 (t, 1H,
J2,3 = J3,4 = 8.3 Hz, H-3), 3.70–3.67 (m, 1H, H-5), 3.65 (t, 1H,
J4,5 = 9.4 Hz, H-4), 3.62–3.58 (m, 1H, H-2). 13C NMR (CDCl3): d
166.91, 137.86, 127.86, 109.34 (d, J1,F = 217.37, C-1), 83.33 (d,
J3,F = 10.23, C-3), 81.04 (d, J2,F = 22.4 Hz, C-2), 75.61 (C-4), 75.27,
74.82, 74.27 (d, J = 1.7 Hz), 72.59 (d, J5,F = 4.9 Hz, C-5), 64.04 (C-
6), 40.62.
1), 5.54 (t, 1H, J3,4 = J4,5 = 9.9 Hz, H-4), 4.80, 4.66 (each d, 2H,
J = 12.2 Hz, benzyl), 4.59, 4.47 (each d, 2H, J = 12.1 Hz, benzyl),
4.54, 4.48 (each d, 2H, J = 11.8 Hz, benzyl), 4.01–3.97 (m, 1H, H-
5), 3.88–3.87 (m, 1H, H-2), 3.82 (dt, 1H, J2,3 = J2,F = 2.6 Hz, H-3),
3.76, 3.73 (each d, 2H, J = 14.8 Hz, ClCH2CO), 3.59 (dd, 1H,
J5,6a = 4.9 Hz, J6a,6b = 10.7 Hz, H-6a), 3.56 (dd, 1H, J5,6b = 4.1 Hz, H-
6b). 13C NMR (CDCl3): d 166.12, 137.61, 137.53, 137.43, 128.47,
128.45, 128.34, 127.97, 127.91, 127.74, 127.63, 106.24 (d,
J1,F = 223.6 Hz, C-1), 76.14 (C-3), 73.54, 73.46, 72.58 (d,
J2,F = 34.2 Hz, C-2), 72.24, 71.90 (d, J5,F = 1.4 Hz, C-5), 69.85 (C-4),
68.98 (C-6), 40.60.
4.4.6. 3,4,6-Tri-O-benzyl-2-O-chloroacetyl-D-mannopyranosyl
fluoride (28)
b Fluoride; 1H NMR (CDCl3): d 7.33–7.25 (m, 15H, aromatic), 5.41
(br d, 1H, J1,F = 51.9 Hz, H-1), 5.43–5.40 (m, 1H, H-4), 4.71, 4.67
(each d, 2H, J = 12.2 Hz, benzyl), 4.58, 4.47 (each d, 2H, J = 12.3 Hz,
benzyl), 4.51, 4.48 (each d, 2H, J = 11.9 Hz, benzyl), 3.88–3.71
(m, 6H, H-2,5,6a,6b, ClCH2CO), 3.64 (dd, 1H, J2,3 = 3.2 Hz,
J3,4 = 7.1 Hz, H-3). 13C NMR (CDCl3): d 166.14, 137.64, 137.34,
137.31, 128.43, 128.38, 128.11, 127.93, 127.81, 127.76, 106.11
(d, J1,F = 224.2 Hz, C-1), 74.51 (d, J3,F = 5.1 Hz, C-3), 73.53, 72.81,
71.96, 71.76 (d, J2,F = 19.4 Hz, C-2), 69.99 (C-4), 69.75 (C-6), 40.59.
a
Fluoride; ½a 2D8
ꢁ
+14.9 (c 1.01, CHCl3); 1H NMR (CDCl3): d 7.35–
7.14 (m, 15H, aromatic), 5.64 (dd, 1H, J1,2 = 1.5 Hz, J1,F = 48.9 Hz,
H-1), 5.53–5.52 (m, 1H, H-2), 4.83, 4.49 (each d, 2H, J = 10.7 Hz,
benzyl), 4.71, 4.56 (each d, 2H, J = 11.1 Hz, benzyl), 4.66, 4.50 (each
d, 2H, J = 12.1 Hz, benzyl), 4.17, 4.14 (each d, 2H, J = 15.3 Hz,
ClCH2CO), 4.00–3.92 (m, 3H, H-3,4,5), 3.80 (dd, 1H, J5,6a = 2.6 Hz,
J6a,6b = 10.9 Hz, H-6a), 3.70 (br d, 1H, H-6b). 13C NMR (CDCl3): d
166.63, 137.86, 137.79, 137.24, 128.48, 128.35, 128.13, 128.00,
127.87, 127.82, 127.78, 127.73, 105.01 (d, J1,F = 220.36 Hz, C-1),
75.30, 73.71 (d, J5,F = 2.2 Hz, C-5), 73.44, 73.02 (C-4), 72.27, 68.71
(d, J2,F = 41.4 Hz, C-2), 67.93 (C-6), 40.68.
4.4.9. 2,3,4-Tri-O-benzyl-6-O-chloroacetyl-D-mannopyranosyl
fluoride (31)
b Fluoride; ½a 2D8
ꢁ
ꢀ1.9 (c 1.22, CHCl3); 1H NMR (CDCl3): d 7.34–
a
Fluoride; ½a 2D9
ꢁ
+38.7 (c 1.05, CHCl3); 1H NMR (CDCl3): d 7.37–
7.16 (m, 15H, aromatic), 5.65–5.64 (m, 1H, H-2), 5.39 (br d, 1H,
J1,F = 49.2 Hz, H-1), 4.78, 4.51 (each d, 2H, J = 10.9 Hz, benzyl),
4.70 (d, 1H, J = 11.4 Hz, benzyl), 4.63 (d, 1H, J = 12.1 Hz, benzyl),
4.55–4.51 (m, 2H, benzyl), 4.22, 4.18 (each d, 2H, J = 15.4 Hz,
ClCH2CO), 3.84 (t, 1H, J3,4 = J4,5 = 8.5 Hz, H-4), 3.82–3.76 (m, 2H,
H-6a,6b), 3.73 (dd, 1H, J2,3 = 3.1 Hz, H-3), 3.66–3.63 (m, 1H, H-5).
7.29 (m, 15H, aromatic), 5.52 (dd, 1H, J1,2 = 1.6 Hz, J1,F = 50.3 Hz,
H-1), 4.94, 4.62 (each d, 2H, J = 11.0 Hz, benzyl), 4.80 (d, 1H,
J = 12.1 Hz, benzyl), 4.69 (d, 1H, J = 11.7 Hz, benzyl), 4.67–4.64
(m, 2H, benzyl), 4.46 (dd, 1H, J5,6a = 2.0 Hz, J6a,6b = 12.0 Hz, H-6a),
4.35 (dd, 1H, J5,6b = 4.4 Hz, H-6b), 4.02, 3.98 (each d, 2H,
J = 15.0 Hz, ClCH2CO), 4.00–3.87 (m, 4H, H-2,3,4,5). 13C NMR
(CDCl3): d 167.05, 137.80, 137.68, 137.59, 128.50, 128.48, 128.46,
128.21, 127.97, 127.88, 127.79, 127.71, 106.09 (d, J1,F = 223.2 Hz,
C-1), 79.15 (C-3), 75.14, 73.29, 73.14 (d, J2,F = 36.8 Hz, C-2), 72.96
(C-4), 72.46, 72.11 (d, J5,F = 1.6 Hz, C-5), 64.29 (C-6), 40.69.
13C NMR (CDCl3):
d 166.87, 137.86, 137.63, 136.94, 128.52,
128.41, 128.36, 128.16, 128.09, 127.95, 127.90, 127.82, 127.70,
104.39 (d, J1,F = 218.1 Hz, C-1), 77.90 (d, J3,F = 6.1 Hz, C-3), 75.08
(d, J5,F = 4.3 Hz, C-5), 74.74, 73.49, 73.13 (C-4), 72.03, 68.79 (d,
J2,F = 18,1 Hz, C-2), 68.53 (C-6), 40.75.
b Fluoride; 1H NMR (CDCl3): d 7.41–7.24 (m, 15H, aromatic), 5.34
(br d, 1H, J1,F = 50.9 Hz, H-1), 4.83, 4.72 (each d, 2H, J = 12.1 Hz, ben-
zyl), 4.80 (d, 1H, J = 11.3 Hz, benzyl), 4.62 (d, 1H, J = 11.9 Hz, ben-
zyl), 4.57 (d, 1H, J = 12.1 Hz, benzyl), 4.52 (d, 1H, J = 11.8 Hz,
benzyl), 4.51 (dd, 1H, J5,6a = 3.3 Hz, J6a,6b = 11.8 Hz, H-6a), 4.42
(dd, 1H, J5,6b = 5.9 Hz, H-6b), 4.03, 3.99 (each d, 2H, J = 15.0 Hz,
ClCH2CO), 3.97–3.95 (m, 1H, H-2), 3.85 (t, 1H, J3,4 = J4,5 = 7.5 Hz,
H-4), 3.72 (ddd, 1H, H-5), 3.64 (dd, 1H, J2,3 = 3.0 Hz, H-3). 13C
NMR (CDCl3): d 167.02, 137.73, 137.54, 137.43, 128.49, 128.46,
128.32, 128.09, 128.02, 127.87, 127.82, 127.71, 106.88 (d,
J1,F = 220.20 Hz, C-1), 78.48 (d, J3,F = 7.0 Hz, C-3), 74.22, 73.39,
73.11 (C-4), 73.07 (d, J5,F = 4.5 Hz, C-5), 72.55 (d, J2,F = 18.0 Hz,
C-2), 72.11, 64.93 (C-6), 40.71.
4.4.7. 2,4,6-Tri-O-benzyl-3-O-chloroacetyl-D-mannopyranosyl
fluoride (29)
a
Fluoride; ½a 2D8
ꢁ
ꢀ7.4 (c 1.02, CHCl3); 1H NMR (CDCl3): d 7.37–
7.15 (m, 15H, aromatic), 5.62 (dd, 1H, J1,2 = 1.9 Hz, J1,F = 50.4 Hz,
H-1), 5.23–5.20 (m, 1H, H-3), 4.71–4.66 (m, 2H, benzyl), 4.62,
4.53 (each d, 2H, J = 11.3 Hz, benzyl), 4.57 (d, 1H, J = 12.2 Hz, ben-
zyl), 4.52 (d, 1H, J = 12.1 Hz, benzyl), 4.16 (t, 1H, J3,4 = J4,5 = 9.7 Hz,
H-4), 4.03–4.01 (m, 1H, H-2), 3.97–3.94 (m, 1H, H-5), 3.80 (dd,
1H, J5,6a = 3.8 Hz, J6a,6b = 11.2 Hz, H-6a), 3.77, 3.73 (each d, 2H,
J = 14.9 Hz, ClCH2CO), 3.71 (dd, 1H, J5,6b = 1.8 Hz, H-6b). 13C NMR
(CDCl3): d 166.45, 137.79, 137.13, 128.52, 128.40, 128.36, 128.17,
128.04, 127.95, 127.82, 127.74, 127.71, 105.84 (d, J1,F = 224.1 Hz,
C-1), 74.71, 74.53 (C-3), 73.99 (d, J2,F = 34.9 Hz, C-2), 73.73 (d,
J3,F = 1.3 Hz, C-3), 73.54, 73.49, 72.28 (C-4), 67.96 (C-6), 40.45.
b Fluoride; 1H NMR (CDCl3): d 7.38–7.17 (m, 15H, aromatic),
5.43 (dd, 1H, J1,2 = 0.9 Hz, J1,F = 51.1 Hz, H-1), 5.06 (dd, 1H,
J2,3 = 3.5 Hz, J3,4 = 7.8 Hz, H-3), 4.78 (d, 1H, J = 12.2 Hz, benzyl),
4.63, 4.56 (each d, 2H, J = 12.0 Hz, benzyl), 4.60–4.56 (m, 2H, ben-
zyl), 4.55 (d, 1H, J = 11.4 Hz, benzyl), 4.04–4.00 (m, 2H, H-2,4),
3.82–3.73 (m, 3H, H-5,6a,6b), 3.75, 3.67 (each d, 2H, J = 15.1 Hz,
ClCH2CO). 13C NMR (CDCl3): d 166.56, 137.82, 137.48, 137.38,
128.45, 128.40, 128.37, 128.26, 128.07, 127.95, 127.81, 127.74,
106.22 (d, J1,F = 220.2 Hz, C-1), 74.72 (d, J5,F = 2.6 Hz, C-5), 74.03,
73.64, 73.51, 73.32 (d, J3,F = 7.2 Hz, C-3), 72.49 (C-4), 72.46 (d,
J2,F = 19.7 Hz, C-2), 68.69 (C-6), 40.39.
4.4.10. 2-Azido-4,6-di-O-benzyl-3-O-chloroacetyl-2-deoxy-D-
galactopyranosyl fluoride (35)
a
Fluoride; ½a 2D8
ꢁ
+100.0 (c 0.99, CHCl3); 1H NMR (CDCl3): d 7.37–
7.25 (m, 10H, aromatic), 5.71 (dd, 1H, J1,2 = 2.6 Hz, J1,F = 52.8 Hz, H-
1), 5.30 (dd, 1H, J3,4 = 2.9 Hz, H-3), 4.62, 4.57 (each d, 2H, J = 11.4 Hz,
benzyl), 4.54, 4.47 (each d, 2H, J = 11.8 Hz, benzyl), 4.25 (t, 1H,
J5,6 = 6.8 Hz, H-5), 4.18 (br d, 1H, H-4), 3.99, 3.84 (each d, 2H,
J = 15.0 Hz, ClCH2CO), 3.94 (ddd, 1H, J2,3 = 11.0 Hz, J2,F = 25.2 Hz,
H-2), 3.64–3.58 (m, 2H, H-6a,6b). 13C NMR (CDCl3): d 166.45,
137.40, 137.28, 128.50, 128.34, 128.27, 128.16, 127.98, 127.88,
106.23 (d, J1,F = 191.8 Hz, C-1), 75.29, 73.52, 72.49 (C-3), 71.33 (d,
J5,F = 2.7 Hz, C-5), 67.12 (C-6), 57.91 (d, J2,F = 23.7 Hz, C-2), 40.29.
b Fluoride; 1H NMR (CDCl3): d 7.37–7.25 (m, 10H, aromatic), 5.06
(dd, 1H, J1,2 = 7.4 Hz, J1,F = 52.3 Hz, H-1), 4.75 (dd, 1H, J2,3 = 10.9 Hz,
J3,F = 2.9 Hz, H-3), 4.59 (s, 2H, benzyl), 4.53, 4.47 (each d, 2H,
J = 11.7 Hz, benzyl), 4.04–4.02 (m, 1H, H-4), 3.98 (ddd, 1H,
J2,F = 12.5 Hz, H-2), 3.96, 3.79 (each d, 2H, J = 15.1 Hz, ClCH2CO),
3.77 (t, 1H, J5,6 = 6.7 Hz, H-5), 3.70–3.65 (m, 2H, H-6a,6b). 13C
4.4.8. 2,3,6-Tri-O-benzyl-4-O-chloroacetyl-D-mannopyranosyl
fluoride (30)
a
Fluoride; ½a 2D8
ꢁ
+15.1 (c 1.62, CHCl3); 1H NMR (CDCl3): d 7.37–
7.25 (m, 15H, aromatic), 5.57 (dd, 1H, J1,2 = 1.7 Hz, J1,F = 50.2 Hz, H-

90
K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
NMR (CDCl3): d 166.44, 137.40, 137.18, 128.72, 128.51, 128.50,
128.35, 128.28, 128.13, 128.09, 128.04, 127.97, 127.95, 127.88,
108.08 (d, J1,F = 214.9 Hz, C-1), 75.16, 74.55 (d, J3,F = 10.8 Hz, C-3),
73.61, 73.32 (d, J5,F = 4.6 Hz, C-5), 72.43 (C-4), 67.09 (C-6), 61.18
(d, J2,F = 22.5 Hz, C-2), 40.24.
4.4.14. 2-Azido-3,4-di-O-benzyl-6-O-chloroacetyl-2-deoxy-D-
glucopyranosyl fluoride (43)
a
Fluoride; 1H NMR (CDCl3): d 7.40–7.24 (m, 10H, aromatic), 5.63
(dd, 1H, J1,2 = 2.4 Hz, J1,F = 52.5 Hz, H-1), 4.93 (d, 1H, J = 10.5 Hz,
benzyl), 4.91–4.88 (m, 2H, benzyl), 4.63 (d, 1H, J = 11.1 Hz, benzyl),
4.43 (dd, 1H, J5,6a = 1.9 Hz, J6a,6b = 12.2 Hz, H-6a), 4.28 (dd, 1H,
J5,6b = 3.9 Hz, H-6b), 4.04 (ddd, 1H, J4,5 = 10.2 Hz, H-5), 4.00, 3.96
(each d, 2H, J = 14.9 Hz, ClCH2CO), 3.98 (t, 1H, J3,4 = 9.6 Hz, H-3),
3.64 (t, 1H, H-4), 3.47 (ddd, 1H, J2,3 = 10.2 Hz, J2,F = 25.8 Hz, H-2).
4.4.11. 2-Azido-3,6-di-O-benzyl-4-O-chloroacetyl-2-deoxy-D-
galactopyranosyl fluoride (36)
a
Fluoride; ½a 2D6
ꢁ
+52.7 (c 1.08, CHCl3); 1H NMR (CDCl3): d 7.38–
13C NMR (CDCl3):
d 166.71, 137.12, 137.03, 128.58, 128.55,
7.23 (m, 10H, aromatic), 5.78 (dd, 1H, J3,4 = 2.4 Hz, H-4), 5.63 (dd,
1H, J1,2 = 2.5 Hz, J1,F = 52.6 Hz, H-1), 4.79, 4.50 (each d, 2H,
J = 10.6 Hz, benzyl), 4.56, 4.43 (each d, 2H, J = 11.8 Hz, benzyl),
4.27 (t, 1H, J5,6 = 6.4 Hz, H-5), 4.02, 3.94 (each d, 2H, J = 15.0 Hz,
ClCH2CO), 3.96 (dd, 1H, J2,3 = 10.5 Hz, H-3), 3.69 (ddd, 1H,
J2,F = 25.8 Hz, H-2), 3.55 (dd, 1H, J5,6a = 5.7 Hz, J6a,6b = 9.3 Hz, H-
6a), 3.49–3.45 (m, 1H, H-6b). 13C NMR (CDCl3): d 166.42, 137.02,
136.30, 128.54, 128.51, 128.48, 128.22, 128.12, 128.03, 105.88 (d,
J1,F = 228.0 Hz, C-1), 73.78 (C-3), 73.62, 71.84, 69.80 (d,
J5,F = 3.2 Hz, C-5), 67.57 (C-4), 66.82 (C-6), 58.91 (d, J2,F = 24.2 Hz,
C-2), 40.51.
128.22, 128.15, 128.07, 105.67 (d, J1,F = 227.7 Hz, C-1), 79.91
(C-3), 76.19 (C-4), 75.76, 75.08, 71.30 (d, J5,F = 4.1 Hz, C-5), 63.40
(C-6), 63.30 (d, J2,F = 24.6 Hz, C-2), 40.51.
b Fluoride; 1H NMR (CDCl3): d 7.38–7.26 (m, 10H, aromatic),
5.12–5.00 (m, 1H, H-1), 4.92, 4.84 (each d, 2H, J = 10.6 Hz, benzyl),
4.87, 4.61 (each d, 2H, J = 11.0 Hz, benzyl), 4.45 (d, 1H,
J6a,6b = 12.0 Hz, H-6a), 4.26 (dd, 1H, J5,6b = 2.6 Hz, H-6b), 4.03, 3.98
(each d, 2H, J = 15.0 Hz, ClCH2CO), 3.64–3.51 (m, 4H, H-2,3,4,5).
13C NMR (CDCl3):
d 166.83, 137.15, 136.97, 128.64, 128.60,
128.31, 128.27, 128.21, 128.18, 128.16, 128.11, 107.73 (d,
J1,F = 216.4 Hz, C-1), 82.19 (d, J3,F = 9.3 Hz, C-3), 75.85 (C-4), 75.72,
75.00, 72.83 (d, J5,F = 6.0 Hz, C-5), 65.91 (d, J2,F = 21.2 Hz, C-2),
63.68 (C-6), 40.56.
b Fluoride; 1H NMR (CDCl3): d 7.39–7.29 (m, 10H, aromatic),
5.64–5.63 (m, 1H, H-4), 5.02 (dd, 1H, J1,2 = 7.6 Hz, J1,F = 52.0 Hz,
H-1), 4.77, 4.50 (each d, 2H, J = 11.0 Hz, benzyl), 4.58, 4.44 (each
d, 2H, J = 11.7 Hz, benzyl), 4.07, 3.98 (each d, 2H, J = 15.0 Hz,
ClCH2CO), 3.80 (t, 1H, H-5), 3.66 (ddd, 1H, J2,3 = 10.3 Hz,
J2,F = 13.2 Hz, H-2), 3.61 (d, 1H, J5,6a = 5.4 Hz, J6a,6b = 9.3 Hz, H-6a),
3.52 (d, 1H, J5,6b = 7.6 Hz, H-6b), 3.47 (d, 1H, J3,4 = 3.0 Hz, H-3).
4.4.15. 2,6-Di-O-benzyl-3,4-di-O-chloroacetyl-D-
galactopyranosyl fluoride (48)
a
Fluoride; 1H NMR (CDCl3): d 7.38–7.23 (m, 10H, aromatic),
13C NMR (CDCl3):
d 166.59, 136.94, 136.30, 128.56, 128.51,
5.62 (d, 1H, J3,4 = 3.2 Hz, H-4), 5.61 (dd, 1H, J1,2 = 2.6 Hz,
J1,F = 52.4 Hz, H-1), 5.39 (dd, 1H, J2,3 = 10.4 Hz, H-3), 4.71, 4.67
(each d, 2H, J = 12.2 Hz, benzyl), 4.55, 4.37 (each d, 2H,
J = 12.1 Hz, benzyl), 4.40–4.35 (m, 1H, H-5), 3.97, 3.94 (each d,
2H, J = 15.1 Hz, ClCH2CO), 3.91, 3.84 (each d, 2H, J = 14.5 Hz,
ClCH2CO), 3.88–3.80 (m, 1H, H-2), 3.52 (dd, 1H, J5,6a = 5.7 Hz,
J6a,6b = 9.4 Hz, H-6a), 3.42 (dd, 1H, 5,6b = 7.6 Hz, H-6b). 13C NMR
(CDCl3): d 166.70, 166.18, 137.14, 137.07, 128.57, 128.51, 128.48,
128.42, 128.22, 128.16, 128.08, 128.04, 128.00, 127.89, 105.38 (d,
J1,F = 230.1 Hz, C-1), 73.57, 73.44, 72.45 (d, J2,F = 23.9 Hz, C-2),
71.05, 69.58, 69.01 (d, J5,F = 3.8 Hz, C-5), 66.42, 40.40, 40.33.
b Fluoride; 1H NMR (CDCl3): d 5.50 (br s, 1H, H-4), 5.27 (dd, 1H,
J1,2 = 7.1 Hz, J1,F = 52.0 Hz, H-1), 5.06 (dd, 1H, J2,3 = 10.1 Hz,
J3,4 = 3.0 Hz, H-3), 3.73 (ddd, 1H, J2,F = 12.9 Hz, H-2), 3.60 (dd, 1H,
J = 5.8 Hz, J = 9.3 Hz).
128.32, 128.27, 128.16, 107.75 (d, J1,F = 216.0 Hz, C-1), 76.97 (d,
J3,F = 9.3 Hz, C-3), 73.76, 72.22, 71.97 (d, J5,F = 5.0 Hz, C-5), 66.64
(C-6), 66.62 (C-4), 62.40 (d, J2,F = 21.0 Hz, C-2), 40.58.
4.4.12. 2-Azido-3,4-di-O-benzyl-6-O-chloroacetyl-2-deoxy-a-D-
galactopyranosyl fluoride (37)
½
a 2D8 +36.7 (c 1.07, CHCl3); 1H NMR (CDCl3): d7.45–7.27 (m, 10H,
ꢁ
aromatic), 5.66 (dd, 1H, J1,2 = 2.4 Hz, J1,F = 53.2 Hz, H-1), 4.94, 4.57
(each d, 2H, J = 11.4 Hz, benzyl), 4.80 (s, 2H, benzyl), 4.28 (dd,
1H, J5,6a = 6.9 Hz, J6a,6b = 11.2 Hz, H-6a), 4.16 (dd, 1H, J5,6b = 5.5 Hz,
H-6b), 4.09 (t, 1H, J = 6.2 Hz, H-5), 4.01 (ddd, 1H, J2,3 = 10.3 Hz,
J2,F = 25.2 Hz, H-2), 4.00, 3.95 (each d, 2H, J = 15.0 Hz, ClCH2CO),
3.98–3.93 (m, 2H, H-3,4). 13C NMR (CDCl3): d 166.80, 137.33,
136.88, 128.70, 128.53, 128.37, 128.29, 128.17, 127.98, 106.23
(d, J1,F = 227.1 Hz, C-1), 74.61, 72.75, 72.02 (C-4), 70.93 (d, J5,F
2.8 Hz, C-5), 64.27 (C-6), 59.47 (d, J2,F = 23.3 Hz, C-2), 40.53.
=
4.4.16. 2,3-Di-O-benzyl-4,6-di-O-chloroacetyl-D-
4.4.13. 2-Azido-3,6-di-O-benzyl-4-O-chloroacetyl-2-deoxy-D-
galactcopyranosyl fluoride (49)
glucopyranosyl fluoride (42)
a
Fluoride; 1H NMR (CDCl3): d 7.37–7.28 (m, 10H, aromatic), 5.63
a
Fluoride; ½a 2D7
ꢁ
+28.5 (c 1.33, CHCl3); 1H NMR (CDCl3): d 7.38–
(br s, 1H, H-4), 5.58 (dd, 1H, J1,2 = 2.6 Hz, J1,F = 51.2 Hz, H-1), 4.85,
4.68 (each d, 2H, J = 11.8 Hz, benzyl), 4.76, 4.59 (each d, 2H,
J = 11.1 Hz, benzyl), 4.35 (t, 1H, J = 6.6 Hz, H-5), 4.25 (d, 2H,
J = 6.5 Hz, H-6), 4.12 (q, 2H, J = 2.4 Hz, ClCH2CO), 4.08 (s, 2H,
ClCH2CO), 4.01 (dd, 1H, J2,3 = 10.0 Hz, J3,4 = 3.2 Hz, H-3), 3.76 (ddd,
1H, J2,F = 25.3 Hz, H-2). 13C NMR (CDCl3): d 166.88, 166.79, 137.64,
137.22, 128.53, 128.51, 128.11, 128.08, 128.03, 127.98, 105.87
(d, J1,F = 228.6 Hz, C-1), 75.01 (C-3), 74.39 (d, J2,F = 23.6 Hz, C-2),
74.04, 72.53, 69.02 (C-4), 68.52 (d, J5,F = 3.8 Hz, C-5), 63.02 (C-6),
40.59, 40.53.
7.25 (m, 10H, aromatic), 5.67 (dd, 1H, J1,2 = 2.5 Hz, J1,F = 52.4 Hz,
H-1), 5.28 (t, 1H, J4,5 = 9.8 Hz, H-4), 4.87, 4.62 (each d, 2H,
J = 11.4 Hz, benzyl), 4.52, 4.44 (each d, 2H, J = 11.8 Hz, benzyl),
4.04 (t, 1H, J5,6b = 3.7 Hz, H-5), 3.94 (t, 1H, J3,4 = 9.8 Hz, H-3), 3.61,
3.55 (each d, 2H, J = 14.7 Hz, ClCH2CO), 3.60–3.52 (m, 2H, H-
2,6a), 3.49 (dd, 1H, J6a,6b = 10.8 Hz, H-6b). 13C NMR (CDCl3): d
165.82, 137.17, 137.11, 128.59, 128.41, 128.16, 128.09, 127.93,
105.63 (d, J1,F = 228.2 Hz, C-1), 77.34 (C-3), 75.18, 73.64, 71.20
(C-4), 70.97 (d, J5,F = 3.6 Hz, C-5), 67.82 (C-6), 63.15 (d, J2,F
=
24.0 Hz, C-2), 40.31.
b Fluoride; 1H NMR (CDCl3): d 5.21 (dd, 1H, J1,2 = 6.5 Hz,
J1,F = 51.9 Hz, H-1).
b Fluoride; 1H NMR (CDCl3): d 7.38–7.25 (m, 10H, aromatic),
5.15 (t, 1H, J4,5 = 9.4 Hz, H-4), 5.08 (dd, 1H, J1,2 = 7.4 Hz,
J1,F = 51.9 Hz, H-1), 4.85, 4.61 (each d, 2H, J = 11.6 Hz, benzyl),
4.51, 4.46 (each d, 2H, J = 11.8 Hz, benzyl), 3.65–3.53 (m, 6H,
H-2,5,6a,6b, ClCH2CO), 3.49 (t, 1H, J2,3 = J3,4 = 9.4 Hz, H-3). 13C
NMR (CDCl3): d 165.92, 137.20, 137.13, 128.56, 128.43, 128.16,
128.13, 128.09, 128.06, 127.95, 107.72 (d, J1,F = 217.4 Hz, C-1),
79.22 (d, J3,F = 9.7 Hz, C-3), 75.14, 73.72, 72.85 (d, J5,F = 5.4 Hz,
C-5), 71.58 (C-4), 68.59 (C-6), 65.74 (d, J2,F = 21.5 Hz, C-2), 40.31.
4.4.17. 2-Azido-6-O-benzyl-3,4-di-O-chloroacetyl-2-deoxy-D-
galactopyranosyl fluoride (50)
a
Fluoride; ½a 2D5
ꢁ
+70.3 (c 0.85, CHCl3); 1H NMR (CDCl3): d 7.38–
7.25 (each m, 5H, aromatic), 5.75 (dd, 1H, J1,2 = 2.6 Hz,
J1,F = 52.1 Hz, H-1), 5.66 (d, 1H, J3,4 = 3.1 Hz, H-4), 5.41 (dd, 1H,
J2,3 = 11.0 Hz, H-3), 4.57, 4.40 (each d, 2H, J = 12.0 Hz, benzyl),

K. Suzuki et al. / Carbohydrate Research 359 (2012) 81–91
91
4.40–4.38 (m, 1H, H-5), 4.08, 4.06 (each d, 2H, J = 15.4 Hz, ClCH2CO),
3.97, 3.89 (each d, 2H, J = 14.6 Hz, ClCH2CO), 3.79 (ddd, 1H,
134.12, 131.49, 129.20, 128.38, 128.15, 128.14, 127.59, 126.07,
123.56, 105.07 (d, J1,F = 216.0 Hz, C-1), 101.50, 82.38 (C-4), 74.19,
73.74 (d, J3,F = 9.0 Hz, C-3), 68.39 (C-6), 65.76 (d, J5,F = 5.4 Hz, C-5),
55.76 (d, J2,F = 21.3 Hz, C-2).
0
J2,F = 24.8 Hz, H-2), 3.56 (dd, 1H, J5,6 = 5.7 Hz, J6,6 = 9.3 Hz, H-6),
3.46 (dd, 1H, J5,6 = 8.0 Hz, H-60). 13C NMR (CDCl3): d 166.66,
0
166.14, 137.03, 136.62, 133.63, 131.41, 129.45, 128.81, 128.58,
128.15, 127.87, 127.59, 105.84 (J1,F = 229.6 Hz, C-1), 73.57, 69.99
(C-3), 69.52 (J5,F = 3.2 Hz, C-5), 68.68 (C-4), 66.25 (C-6), 57.52
(J2,F = 23.8 Hz, C-2), 40.30.
Acknowledgments
The research leading to these results were carried out by Ms.
Rumiko Kato, Mitsubishi Kagaku Institute of Life Sciences, and
was supported by New Energy and Industrial Technology Develop-
ment Organization.
b Fluoride; ½a 2D5
ꢁ
ꢀ38.1 (c 0.60, CHCl3); 1H NMR (CDCl3): d 7.38–
7.24 (m, 5H, aromatic), 5.50 (br s, 1H, H-4), 5.13 (dd, 1H,
J1,2 = 7.5 Hz, J1,F = 51.6 Hz, H-1), 4.92 (dd, 1H, J2,3 = 10.8 Hz,
J3,4 = 3.2 Hz, H-3), 4.58, 4.39 (each d, 2H, J = 12.0 Hz, benzyl), 4.09,
4.05 (each d, 2H, J = 15.3 Hz, ClCH2CO), 4.01, 3.89 (each d, 2H,
J = 14.7 Hz, ClCH2CO), 3.94 (br t, 1H, H-5), 3.81 (ddd, 1H,
J2,F = 12.6 Hz, H-2), 3.61 (dd, 1H, J5,6a = 5.7 Hz, J6a,6b = 9.3 Hz, H-
6a), 3.51 (dd, 1H, J5,6b = 7.7 Hz, H-6b). 13C NMR (CDCl3): d 166.75,
166.10, 136.87, 128.56, 128.21, 128.17, 128.12, 107.88 (C-1,
J1,F = 216.4 Hz), 73.56, 72.13 (C-3, J3,F = 10.9 Hz), 71.68 (C-5,
J5,F = 5.2 Hz), 67.61, 65.96, 60.81 (C-2, J2,F = 22.9 Hz), 40.27, 40.24.
References
1. Shimizu, M.; Togo, H.; Yokoyama, M. Synthesis 1998, 799–822.
2. Toshima, K. Carbohydr. Res. 2000, 327, 15–26.
3. Shoda, S.-I. Glycoside Synthesis from Anomeric Halides: Glycosyl Fluorides. In
Handbook of Chemical Glycosylation: Advance in Stereoselectivity and Therapeutic
Relevance; Demchenko, A. V., Ed.; Wiley-VCH, 2008; pp 29–58.
4. Micheel, F.; Klemer, A. Adv. Carbohydr. Chem. 1961, 16, 85–103.
5. Penglis, A. A. E. Adv. Carbohydr. Chem. Biochem. 1981, 38, 195–285.
6. Tsuchiya, T. Adv. Carbohydr. Chem. Biochem. 1990, 48, 91–277.
7. Matsumoto, T.; Katsuki, M.; Suzuki, K. Tetrahedron Lett. 1988, 29, 6935–6938.
8. Matsumoto, T.; Katsuki, M.; Jona, H.; Suzuki, K. J. Am. Chem. Soc. 1991, 113,
6982–6992.
4.5. Synthesis of glycosyl fluoride using DAST and DMTST
Typical procedure for the transformation of thioglycoside into
glycosyl fluoride using DAST and DMTST is as follows.
9. Nicolaou, K. C.; Randall, J. L.; Furst, G. T. J. Am. Chem. Soc. 1985, 107, 5556–5558.
10. Nicolaou, K. C.; Chucholowski, A.; Dolle, R. E.; Randall, J. L. J. Chem. Soc., Chem.
Commun. 1984, 1155–1156.
11. Nicolaou, K. C.; Dolle, E. E.; Papahatjis, D. P.; Randall, J. L. J. Am. Chem. Soc. 1984,
106, 4189–4192.
12. Nicolaou, K. C.; Caulfield, T. J.; Kataoka, H.; Stylianides, N. A. J. Am. Chem. Soc.
1990, 112, 3693–3695.
13. Johnson, J. N.; Paquette, L. A. Tetrahedron Lett. 1995, 36, 4341–4344.
14. Nicolaou, K.; Bockvich, N. J.; Carcanague, D. R. J. Am. Chem. Soc. 1993, 115,
8843–8844.
15. Mukaiyama, T.; Ikegai, K.; Jona, H.; Hashihayata, T.; Takeuchi, K. Chem. Lett.
2001, 30, 840–841.
16. Hashihayata, T.; Ikegai, K.; Takeuchi, K.; Jona, H.; Mukaiyama, T. Bull. Chem. Soc.
Jpn. 2003, 76, 1826–1848.
17. Kanie, O.; Ito, Y.; Ogawa, T. J. Am. Chem. Soc. 1994, 116, 12073–12074.
18. Ito, Y.; Kanie, O.; Ogawa, T. Angew. Chem., Int. Ed. 1996, 35, 2510–2512.
19. Kanie, O.; Ohtsuka, I.; Ako, T.; Daikoku, S.; Kanie, Y.; Kato, R. Angew. Chem., Int.
Ed. 2006, 45, 3851–3854.
20. Ohtsuka, I.; Ako, T.; Kato, R.; Daikoku, S.; Koroghi, S.; Kanemitsu, T.; Kanie, O.
Carbohydr. Res. 2006, 341, 1476–1487.
21. Ako, T.; Daikoku, S.; Ohtsuka, I.; Kato, R.; Kanie, O. Chem. Asian J. 2006, 1, 798–
813.
4.5.1. 2,3,4,6-Tetra-O-acetyl-
To a DCM (0.25 mL) solution of 51 (44 mg, 0.10 mmol) was
added DAST (39.0 L) and DMTST solution [prepared from MeSSMe
(13.5 L, 0.15 mmol) and MeOTf (17.0 L, 0.15 mmol) at room tem-
perature in DCM (0.25 mL) prior to the reaction] at ꢀ15 °C under
nitrogen atmosphere. After being stirred 16 h at room temperature,
the mixture was poured into saturated NaHCO3 and the products
were extracted with CHCl3. The organic layer was washed (H2O),
dried (Na2SO4) and concentrated in vacuo. The residue was loaded
on silica gel column chromatography (3:1–1:1 n-hexane/EtOAc) to
D-galactopyranosyl fluoride (53)
l
l
l
afford the corresponding fluorides 52 (35 mg, quant, a:b = 10:90). a
Fluoride; 1H NMR (CDCl3): d 5.81 (dd, 1H, J1,2 = 2.7 Hz, J1,F = 53.3 Hz,
H-1), 5.53 (dd, 1H, J3,4 = 3.2 Hz, J4,5 = 1.1 Hz, H-4), 5.37 (dd, 1H,
J2,3 = 10.9 Hz, H-3), 5.23–5.15 (m, 1H, H-2), 4.41 (br t, 1H,
J5,6a = J5,6b = 7.0 Hz, H-5), 4.17 (dd, 1H, J6a,6b = 11.4 Hz, H-6a), 4.12
(dd, 1H, H-6b).
22. Boons, G. J. Strategies and Tactics in Oligosaccharide Synthesis. In Carbohydrate
Chemistry; Boons, G. J., Ed.; Blackie Academic & Professional: London, 1998; pp
175–222.
23. Nicolaou, K. C.; Dolle, R. E.; Papahatjis, D. P.; Randall, J. L. J. Am. Chem. Soc. 1984,
106, 4189–4192.
b Fluoride; 1H NMR (CDCl3): d 5.42 (br s, 1H, H-4), 5.32 (dd, 1H,
J1,2 = 7.1 Hz, J2,3 = 10.1 Hz, J2,F, 15.0 Hz, H-2), 5.26 (dd, 1H, J1,F
51.1 Hz, H-1), 5.05 (dd, 1H, J3,4 = 3.4 Hz, H-3), 4.23 (dd, 1H, J5,6a
=
=
24. Ravenscroft, M.; Roberts, R. M. G.; Tillett, J. G. J. Chem. Soc., Perkin Trans. 2 1982,
1569–1572.
6.6 Hz, J6a,6b = 11.5 Hz, H-6a), 4.20 (dd, 1H, J5,6b = 6.6 Hz, H-6b),
4.06 (t, 1H, H-5), 2.18, 2.11, 2.07, 2.01 (each s, 12H, OAc). These
spectral data were in agreement with literature data.35,36
25. Fügedi, P.; Garegg, P. J. Carbohydr. Res. 1986, 149, C9–C12.
26. Garegg, P. J.; Henrichso, C.; Norberg, T. Carbohydr. Res. 1983, 116, 162–165.
27. Nicolaou, K. C.; Caulfield, T. J.; Katoaka, H. Carbohydr. Res. 1990, 202, 177–191.
28. Graziani, A.; Passacantilli, P.; Piancatelli, G.; Tani, S. Tetrahedron: Asymmetry
2000, 11, 3921–3937.
4.5.2. 3-O-Benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimide-b-
29. Dasgpta, F.; Garegg, P. G. Acta Chem. Scand. 1989, 43, 471–475.
30. Matsuo, I.; Wada, M.; Manabe, S.; Yamaguchi, Y.; Otake, K.; Kato, K.; Ito, Y. J.
Am. Chem. Soc. 2003, 125, 3402–3403.
31. Suzuki, K.; Ohtsuka, I.; Kanemitu, T.; Ako, T.; Kanie, O. J. Carbohydr. Chem. 2005,
24, 219–236.
32. Pfaeffli, P. J.; Hixon, S. H.; Anderson, L. Carbohydr. Res. 1972, 31, 195–206.
33. Janczuk, A. J.; Zang, W.; Andreana, P. R.; Warrick, P. G.; Wang, P. G. Carbohydr.
Res. 2002, 337, 1247–1259.
34. Compani-Batissou, M.; Mesrari, L.; Anker, D.; Doutheau, A. Carbohydr. Res.
1999, 316, 201–205.
D
-glucopyranosyl fluoride (54)
Compound 54 was obtained by the reaction of thioglycoside
5237 as a substrate. ½a 2D5
ꢁ
+67.9 (c 1.00, CHCl3); mp: 175.0–
176.0 °C; 1H NMR (CDCl3): d 7.77–7.71, 7.54–7.51, 7.43–7.38,
7.00–6.86 (each m, 14H, aromatic), 5.90 (dd, 1H, J1,2 = 7.9 Hz,
J1,F = 53.4 Hz, H-1), 5.65 (s, 1H, benzylidene), 4.80, 4.51 (each d,
2H, J = 12.4 Hz, benzyl), 4.48–4.44 (m, 2H, H-3,6a), 4.32 (ddd, 1H,
J2,3 = 10.4 Hz, J2,F = 14.2 Hz, H-2), 3.91 (t, 1H, J5,6b = J6a,6b = 10.2 Hz,
H-6b), 3.88 (t, 1H, J3,4 = J4,5 = 9.1 Hz, H-4), 3.73 (ddd, 1H,
J5,6a = 5.1 Hz, H-5). 13C NMR (CDCl3): d 167.58, 137.59, 137.02,
35. Thiem, J.; Deger, H. M.; Fritsche-Lang, W.; Kreuzer, M. US Patent, No. 4751291,
1988.
36. Chambers, R. D.; Sandfield, G. US Patent, No. 5789580, 1998.
37. Ciara, J. L.; García, Á.; Cristóbal-Lumbroso, G. J. Org. Chem. 2005, 70, 4142–4151.