Halogenation and anomerization of glycopyranoside by TESH/bromine and BHQ/bromine

Article abstract of DOI:10.1002/jccs.202000150

Treatment of peracetylated glycosides and β-isopropyl glycosides with halogen in the presence of TESH and BHQ has been found to result in the halogenation and the anomerization, respectively. Peracetylatedglycosides treaded with I2/TESH or Br2/TESH leading tothe formation of corresponding glycosyl halides, and b-isopropyl glycosidesreacted with Br2/BHQ resulting in the formation of a-glycosides. The anomerizationof glycosidic bond was considered to be catalyzed by in situ formation of hydrogenbromide from the mixing of Br2/BHQ.

Full text of DOI:10.1002/jccs.202000150

Received: 8 April 2020
Revised: 26 May 2020
Accepted: 26 May 2020
DOI: 10.1002/jccs.202000150
A R T I C L E
Halogenation and anomerization of glycopyranoside by
TESH/bromine and BHQ/bromine
Lai Xu
| Chin-Hung Luo | Chien-Sheng Chen
Department of Chemistry, Fu-Jen
Catholic University, New Taipei City,
24205, Taiwan (ROC)
Abstract
Treatment of peracetylated glycosides and β-isopropyl glycosides with halogen
in the presence of TESH and BHQ has been found to result in the halogenation
and the anomerization, respectively. Peracetylatedglycosides treaded with I2/
TESH or Br2/TESH leading tothe formation of corresponding glycosyl halides,
and b-isopropyl glycosidesreacted with Br2/BHQ resulting in the formation of
a-glycosides. The anomerizationof glycosidic bond was considered to be cata-
lyzed by in situ formation of hydrogenbromide from the mixing of Br2/BHQ.
Correspondence
Chien-Sheng Chen, Department of
Chemistry, Fu-Jen Catholic University,
New Taipei City 24205, Taiwan.
Email: 092847@mail.fju.edu.tw
Funding information
Fu-Jen Catholic University, Taiwan
(ROC); Microlithography Inc.; Ministry of
Science and Technology (MOST)
K E Y W O R D S
anomerization, bromination, halogen, iodination, triethylsilane
1 | INTRODUCTION
be formed with in situ generation of anhydrous HCl. The
synthesis of glycosyl halide has been prepared from per-
The recent discovery on carbohydrate moiety can be
important for the many biological activity and recogni-
tion events of the cellular targets, including cell–cell
adhesion, bacterial attachment, and viral infection.[1–4]
Synthesis of the carbohydrate moiety has been directly
related to the development of new glycosylation methods.
acetylated saccharides with HBr-AcOH,[20] AcBr-AcOH,
Ac2O-HBr-AcOH,[21,22] etc. For environmentally friendly
synthesis, preparation of anhydrous hydrogen halide in
situ can provide a convenient and inexpensive reagent in
the preparation of glycosyl halide. Anhydrous HI can be
generated by mixing solid iodine with triethylsilane[23,24]
or thiolacetic acid[25] and applied in preparation of glyco-
syl halide. In connection with those studies, we attempted
to supplement and intact the production of glycosyl halide
by TESH/halogen and BHQ/Bromine. Meanwhile, dried
hydrogen bromide generated in situ with those conditions
was applied to study the acidic anomerization.
Glycosyl
halide,[5]
glycosyl
imidates,[6]
and
thioglycoside[7,8] have found enormous application in the
synthetic establishment of carbohydrate, especially in the
synthesis of oligosaccharide. Anomeric inversion of gly-
cosidic bond,[9,10] establishing a α-anomer from β-link-
age, provided different assumption. Reported intense
conditions for anomerization using protic[11,12] or Lewis
acid[13–15] limited the glyosidic synthesis for oligosaccha-
ride. Radical hydrogen-atom transfer reactions[16] of gly-
cosyl bond developed to modify cyclodextrin[17] and to
target galactofuranose residue[18] assume the application
possibility about anomerization.
2 | RESULTS AND DISCUSSION
2.1 | Bromination and iodination or of
saccharides
Previously, we have reported the anomerization of
.
protected glycoside by using BF3 OEt2/CCl4 under photo-
To standardize the reaction protocol, triethylsilane (1.5
equiv) and bromine (3.0 equiv) were added to a per-O-
acetylated sugar (1.0 equiv) in dichloromethane at 0 oC.
activated radical condition.[19] In case of this anhydrous
condition, the observed and minor glycosyl chloride can
© 2020 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2020;1–7.
http://www.jccs.wiley-vch.de
1

2
XU ET AL.
TABLE 1
Bromination and iodination or of saccharides with Br2/TESH or I2/TESH
Brominationa
Iodinationb
Entry
Saccharide
Product
1Br
Time (hr)
Yield (%)
Product
Time (hr)
Yield (%)
1
2
3
4
5
6
7
8
9
Glucopyranose-(OAc)5 1
Galactopyranose-(OAc)5 2
Mannopyranose-(OAc)5 3
Fucopyranose-(OAc)4 4
N-acetyl glucoamine-(OAc)4 5
Xylospyranose-(OAc)4 6
Cellobiose-(OAc)8 7
2
2
1
2
2
2
2
2
2
93
1I
2I
3I
4I
5I
6I
7I
8I
9I
2
85
2Br
95
2
91
3Br
86
1.5
1.5
2
86
4Br
87
NRc
88
NRc
5Br
d
d
6Br
—
1
—
7Br
85
87
88
2
96
97
92
Maltose-(OAc)8 8
8Br
1.5
2
Lactose-(OAc)8 9
9Br
aWith 1.5 equiv TESH and 3.0 equiv Br2.
bWith 1.5 equiv TESH and 3.0 equiv I2, at 40ꢀC.
cNo reaction.
dHydrolytic by-product was isolated in 62% and 65% yield for bromination and iodination, individually.
An exothermic reaction started immediately, following
bromotriethylsilane and hydrogen bromide were obtained
at room temperature within few minutes. Reducing the
quantity of TESH from 1.5 equiv to 1.0 or 0.5 equiv led a
slower reaction, which was not complete even after 24 hr.
After a series of experiments with monosacchardies and
disacchardies (Table 1), bromination of D-sugar with mix-
ture of triethylsilane and bromine gave complete reaction
within 1–2 hr in good yield, giving only α-D-pyranosyl bro-
mide. The presence of N-acetyl-glucoamine 5 (Table 1,
entry 5) prevented the anomeric bromination, as the HBr
forms an acid/base complex with N-acetyl group such that
the activity of the hydrogen bromide is restricted. With
TESH/Br2 treatment (Table 1, entry 6), the conversion of
xylose 6 into 6Br was observed and examined with proton
NMR experiment. However, the isolation of bromide 6Br
was prevented, and an anomeric hydrolysis was observed
and the product was isolated in 62%.
As shown in Table 1, we applied the same condition to
prepare glucosyl iodide, which proceeded via the treatment
with TESH/I2 (Table 1). In contract to bromination
described above, the iodination of monosaacharides and
disaacharides proceeded at 40ꢀC, and a seated tube or reflux
system as reaction chamber is necessary. A computation for
the titration of TESH with Br2 and I2 in proton NMR spec-
tra presented that the formation of TESBr is faster than
TESI (see the Figure S1 in the Supporting information), in
which TESBr is observed with one equiv Br2, and TESI is
converted fully with two equiv I2. The reactivity of
iodination at the anomeric position with TESH/I2 was
suggested lower than the anomeric bromination with the
TESH/Br2 mixture. Following a standard reaction of glyco-
syl bromination, a series of glycosidic iodide were synthe-
sized in a very similar manner, including the restrictions of
N-acetyl-glucoamine 5 and xylose 6 (Table 1, entry 5–6).
Glycosyl bromides 1-9Br and iodide 1-9I prepared from
commonly available sugars gave acceptable 1H and 13C
NMR spectra that matched data reported in the cited refer-
ences. In most of the cases, a single α-isomer was obtained.
With anhydrous halogenation of saccharide in hand,
we turned our attention to realize the reactive formation of
HBr, which proceeded via the bromination of sugar formed
in situ with di-t-butyl-1,4-benzohydroquinone (BHQ)/Br2
mixture (Table 2). In contract to pyranosyl bromination in
Table 1, the anomeric bromination with BHQ/Br2 was
monitored by TLC, and the reaction mixture was accom-
plished with longer reaction time in good to moderate
yield. Anhydrous hydrogen bromide was generated mildly
in site by the reaction of liquid bromine and BHQ. How-
ever, the presence of BHQ/Br2 mixture prevented the
anomeric iodination of sugar, as HI forms more slowly
such that the activity of hydrogen iodide is restricted.
2.2 | Anomerization of saccharides
After the successful outcome of the anomeric halogena-
tion of sugar, the application of the TESH/X2 system for

XU ET AL.
3
TABLE 2
Bromination of
saccharides with Br2/BHQa
Entry
Saccharide
Product
1Br
Time (hr)
Yield (%)
1
2
3
4
5
6
7
Glucopyranose-(OAc)5 1
Galactopyranose-(OAc)5 2
Mannopyranose-(OAc)5 3
Fucopyranose-(OAc)4 4
Cellobiose-(OAc)8 7
Maltose-(OAc)8 8
4
4
4
4
8
8
8
87
75
89
92
68
70
75
2Br
3Br
4Br
7Br
8Br
Lactose-(OAc)8 9
9Br
aWith 1.5 equiv BHQ and 3.0 equiv Br2.
TABLE 3
Anomerization of saccharides with Br2/TESH or I2/TESH
Entry
Hexose
10β
10β
10β
10β
10β
10β
10β
10β
10β
11β
11β
11β
11β
11β
11β
TESH (equiv)
Br2 (equiv)
I2 (equiv)
Time (hr)
Yield (%)
α/βa
4.4/1
4.6/1
4.4/1
3.4/1
5.4/1
5.2/1
4.1/1
5.5/1
5.5/1
3.4/1
3.7/1
4.0/1
4.0/1
4.0/1
4.2/1
1
1.2
1.2
1.2
0.6
0.6
0.6
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
0.6
0.6
0.6
—
—
—
—
—
—
—
1
94
97
66
100
74
80
85
88
74
89
84
66
88
83
63
2
3
3
24
3
4
5
6
6
24
3
7
1.2
8
—
1.2
1.2
6
9
—
24
2
10
11
12
13
14
15
1.2
1.2
1.2
—
—
—
—
6
24
2
1.2
—
1.2
1.2
6
—
24
aNMR result, see Supporting Information Figure S2.
the anomerization of monosaccharide and disaccharide
was also examined. Thus β-O-isopropyl monosaccharides
10–11β and disaccharides 12–14β were prepared in single
isomer, and the 1,2-trans-glycoside were obtained, which
is due to the neighboring group participation of the acetyl
group at C-2, followed by the attack of isopropanol. To
optimize the anomerization condition, TESH (1.2 equiv)
and Br2 (1.2 equiv) were added to a solution of
saccharides 10–14β. The results are presented in Table 3.
As shown in entries 1–3, β-glucose 10β provides the
corresponding α/β anomers in the same ratio of 4.4/1 in
1 hr and 24 hr with 94% and 66% yields, respectively. The
isolated yield was lower after longer reaction, during
which O-isopyopyl pyranose underwent anomeric hydro-
lysis. Decreasing the quantity of TESH and Br2 from 1.2
to 0.6 equiv led to an α/β ratio of 3.4/1 after 3 hr, while

4
XU ET AL.
TABLE 4
Anomerization of saccharides with TESH/Br2 and BHQ/Br2
a
b
TESH/Br2
BHQ/Br2
Entry
Saccharide
10β
Time (hr)
Yield (%)
α/βc
8.6/1
9.5/1
9.2/1
6.0/1
5.2/1
5.6/1
3.1/1
7.2/1
3.2/1
4.9/1
4.3/1
4.0/1
Time (hr)
Yield (%)
α/βc
7.6/1
8.5/1
8.2/1
6.8/1
7.3/1
7.1/1
7.5/1
7.4/1
4.6/1
4.5/1
5.3/1
5.1/1
1
0.5
1
93
91
92
94
96
93
97
98
99
98
98
97
0.5
1
95
97
93
97
96
91
95
94
99
98
99
97
2
10β
3
10β
6
6
4
11β
0.5
1
0.5
1
5
11β
6
11β
6
6
7
12β
2
2
8
12β
4
4
9
13β
2
2
10
11
12
13β
4
4
14β
2
2
14β
4
4
aWith 1.2 equiv TESH and 1.2 equiv Br2.
bWith 1.2 equiv BHQ and 1.2 equiv Br2.
cNMR result, see Supporting Information Figure S3 and S4.
SCHEME 1 Postulated acidic TESH/Br2 or BHQ/Br2 mediated anomerization of isopropyl glycosides

XU ET AL.
5
following a longer reaction time of 6 and 24 hr, the α/β
ratios were 4.7/1 and 5.2/1, respectively (entries 4–6).
With I2 (Table 3, entry 7–9) treatment, the anomerization
of β-anomer 10β into ratios of 4.1/1 and 5.5/1 after 3 and
24 hr, respectively. The same conditions were applied to
galactosyl derivative 11β (entries 10–15). The resulting
α/β ratios were 4.0 for TESH/Br2 and 4.2 for TESH/I2
treatment in 24 hr, and the acidic inversion of reactant in
acetonitrile 11β showed lower yield (~65%).
glycoside as well as anomeric bromination with BHQ/
Br2. Furthermore, those activated conditions were also
examined with anomerization of 1-isopropyl monosac-
charides and disaccharide and interpreted mechanisti-
cally. Further investigation on this will include
subjecting the above conditions with photo-activated
anomerization for the internal glycosidic bond of
oligosaccharide.
To further reduce the involuted hydrolytic by-prod-
uct, dried CH2Cl2 was selected as solvent to replace
CH3CN. The results are presented in Table 4. Results in
the formation of the corresponding anomers were iso-
lated in good to excellent isolated yields. As shown in
entries 1–6 of the table with TESH/Br2, β-glucoside 10β
and β-galactoside 11β provided the corresponding α/β
anomers in ratios of 9.5/1 and 5.2/1 in 1 hr and within
isolated yields 92% and 96% in 6 hr (entry 3 and 6). The
hydrolytic reaction is restricted in dried dichloromethane.
For the disaccharide 12β, 13β, and 14β (entries 9–14), the
α/β ratios of obtained with anomerization were 7.2/1,
4.5/1, and 4.0/1 in 4 hr, respectively. Significant α/β
anomerization for the internal glycosidic bond of the avail-
able disaccharides was not observed. We applied the
BHQ/Br2 condition to pyranosyl saccharides 10β–14β. The
presented results are similar to that treated with acidic
TESH/Br2. This result indicated that hydrogen bromide
generated from BHQ/Br2 catalyzed the anomerization in a
similar reaction pathway as HBr from TESH/Br2.
4 | EXPERIMENTAL
General experiment: Acetonitrile and dichloromethane
were dried and distilled from CaH2. Flash column chroma-
tography was carried out with silica gel 60 (230–400 mesh,
E. Merck). TLC was performed on precoated glass plates of
silica gel 60 F254 (0.25 mm, E. Merck); detection was exe-
cuted by spraying with cerium ammonium sulfate and sub-
sequent heating on a hot plate. TESH, BHQ, glucose penta-
acetylated 1, and glactose penta-acetylate 2 were purchased
from Sigma-Aldrich. Acetylatedoligosaccharide 3–9 were
prepared from relative saccharide by per-O-acetylation with
Ac2O/pyridine.[25] 1H and 13C NMR spectra were recorded
with 300 MHz instruments. Proton chemical shifts are in
ppm from CHCl3 lock signal at 7.26 ppm, and carbon
chemical shifts are in ppm from CHCl3 lock signal at
77 ppm. Mass spectra were obtained in the EI or
FAB mode.
A postulated mechanism is illustrated in Scheme 1.
Hydrogen bromide initially generated from mixture of Br2
with TESH or BHQ reacts with pyranosyl oxygen and exo-
cyclic oxygen to yield the possible oxonium cation I and
II, respectively. Owing to neighboring group participation
of 2-O-acetoxyl group and the formation of transition
structure III, such that it can accept an O-isopropyl group
from the Si-face to predominately produce β-anomer. In
contract, glycoside 10β reacts with HBr to give the proton-
ated intermediate I. Unlike in the case of oxonium cation
II where the protonated derivative is derived front the
reaction at exocyclic oxygen, the protonation at the
pyranosyl O-5 to give the reactive intermediate I. Upon a
subsequent endocyclic ring-opening generates IV in the
open-chain form. Due to thermodynamic anomeric effect,
the ring closure takes place in favor of the more stable
axial orientation of the α-anomer moiety.
4.1 | 1-Bromo-tetra-O-acetate-α-D-
monosaccharides (1Br–4Br) and 1-Bromo-
hepta-O-acetate-α-D-disaccharides
(7Br–9Br)
To a solid of per-OAc saccharide (0.26 mmol) in dichloro-
methane (1 ml), the mixture was added bromine (40 μl,
0.78 mmol) and triethylsilane (63 μl, 0.39 mmol) at 0ꢀC
for the reaction time listed in Table 1. The reaction pro-
gress was monitored with TLC (EA/Hex = 1/2) until the
per-OAc saccharide disappeared. The reaction was
diluted with ethyl acetate (60 ml), and extracted with
water, 10% Na2S2O3, 10% NaHCO3, and brine. The
organic layer was dried over MgSO4, concentrated under
reducing pressure, and dried in vaco. The crude mixture
was purified by flash column chromatography (EA/
Hex = 1/2) to afford the product.
To a solid of per-OAc saccharide (0.26 mmol) in
dichloro-methane (1 ml), the mixture was added bromine
(40 μl, 0.78 mmol) and di-tert-butylhydroquinone (87 mg,
0.39 mmol) at 0ꢀC for the reaction time listed in Table 2.
The reaction progress was monitored with TLC (EA/
Hex = 1/2) until the per-OAc saccharide disappeared.
3 | CONCLUSIONS
In summary, triehtylsilane/bromine and triehtylsilane/
iodine systems have been demonstrated to be highly
effective for preparation of bromo- and iodo-linked

6
XU ET AL.
The reaction was diluted with ethyl acetate (60 ml), and
extracted with water, 10% Na2S2O3, 10% NaHCO3, and
brine. The organic layer was dried over MgSO4, concen-
trated under reducing pressure, and dried in vaco. The
crude mixture was purified by flash column chromatog-
raphy (EA/Hex = 1/2) to afford the product.
time listed in Table 1. The reaction progress was moni-
tored with TLC (EA/Hex = 1/2) until the per-OAc sac-
charide disappeared. The reaction was diluted with ethyl
acetate (60 ml), and extracted with water, 10% Na2S2O3,
10% NaHCO3, and brine. The organic layer was dried
over MgSO4, concentrated under reducing pressure, and
dried in vaco. The crude mixture was purified by flash
column chromatography (EA/Hex = 1/2) to afford the
product.
7Br21: 1H NMR (300 MHz, CDCl3) δ 6.520 (d,
J = 3.9 Hz, 1H), 5.549 (t, J = 9.66, 1H), 5.172 (t, J = 9.27,
1H), 5.093 (t, J = 9.44, 1H), 4.954 (t, J = 8.50, 1H), 4.775
(dd, J = 9.96, 4.05, 1H), 4.547–4.499 (m, 2H), 4.385 (dd,
J = 12.48, 4.44, 1H), 4.212–4.132 (m, 2H), 4.064 (dd,
J = 12.45, 2.19, 1H), 3.859 (t, J = 9.72, 1H), 3.690 (ddd,
J = 9.63, 4.38, 2.25, 1H), 2.125 (s, 3H), 2.078 (s, 3H), 2.032
(s, 3H), 1.998 (s, 3H), 1.974 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 170.64 (C), 170.41 (C), 170.26 (C), 170.13 (C),
169.45 (C), 169.13 (C), 100.71 (CH), 86.57 (CH), 77.62
(CH), 77.19 (CH), 76.77 (CH), 75.37 (CH), 73.16 (CH),
73.09 (CH), 72.20 (CH), 71.75 (CH), 70.92 (CH), 69.58
(CH), 67.92 (CH), 61.76 (CH2), 61.09 (CH2), 20.96 (CH3),
20.83 (CH3), 20.73 (CH3), 20.69 (CH3).
To
a
solid of isopropyl-tetra-OAc-β-saccharide
(0.26 mmol) in Pyrex tube, the mixture was added dic-
hloromethane (1 ml) and bromine (15 μl, 0.31 mmol) and
di-tert-butylhydroquinone (69 mg, 0.31 mmol) at 0ꢀC for
the reaction time listed in Table 4. The reaction progress
was monitored with TLC (EA/Hex = 1/2). The reaction
was diluted with ethyl acetate (60 ml), and extracted with
water, 10% Na2S2O3, 10% NaHCO3, and brine. The
organic layer was dried over MgSO4, concentrated under
reducing pressure, and dried in vaco. The crude mixture
was checked and examined with NMR and purified by
flash column chromatography (EA/Hex = 1/2) to afford
the product.
8Br21: 1H NMR (300 MHz, CDCl3) 6.508 (d,
J = 3.9 Hz, 1H), 5.644 (t, J = 9.45 Hz, 1H), 5.428 (d,
J = 3.9 Hz, 1H), 5.377 (d, J = 10.5 Hz, 1H), 5.111 (t,
J = 9.9 Hz, 1H), 4.891 (dd, J = 10.5, 3.9 Hz, 1H), 4.734
(dd, J = 9.9, 3.9 Hz, 1H), 4.540–4.506 (m, 1H), 4.283–
4.220 (m, 3H), 4.129–4.036 (m, 2H), 3.970–3.917 (m, 2H),
2.149 (s, 3H), 2.101 (s, 3H), 2.081 (s, 3H), 2.070 (s, 3H),
2.040 (s, 3H), 2.031 (s, 3H), 2.010 (s, 3H); 13C NMR
(75 MHz, CDCl3) 170.85 (C), 170.68 (C), 170.46 (C),
170.03 (C), 169.69 (C), 169.61 (C), 95.93 (CH), 86.20 (CH),
72.69 (CH), 72.49 (CH), 71.72 (CH), 71.17 (CH), 70.17
(CH), 69.40 (CH), 68.79 (CH), 68.06 (CH), 62.00 (CH2),
61.49 (CH2), 21.02 (CH3), 20.93 (CH3), 20.83 (CH3), 20.79
(CH3), 20.75 (CH3).
10α: 1H NMR (300 MHz, CDCl3)
δ 5.472 (t,
J = 9.8 Hz,1H), 5.181 (d, J = 3.8 Hz, 1H), 5.037 (t,
J = 9.8 Hz, 1H), 4.797 (dd, J = 10.3, 3.8 Hz, 1H), 4.251
(dd, J = 11.9, 4.4 Hz, 1H), 4.127–4.050 (m, 2H), 3.895–
3.813 (m, 1H), 2.085 (s, 3H), 2.054 (s, 3H), 2.029 (s, 3H),
2.012 (s, 3H), 1.235 (d, J = 6.1 Hz, 3H), 1.116 (d,
J = 6.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.69 (C),
170.21 (C), 170.16 (C), 169.66 (C), 94.13 (CH), 71.39
(CH),70.94 (CH), 70.14 (CH), 68.65 (CH), 67.06 (CH),
61.94 (CH2), 23.06 (CH3), 21.54 (CH3), 20.70 (CH3), 20.64
(CH3). HRMS (ESI, M + Na+) calcd for C17H26O10Na:
413.1424, found 413.1426.
9Br21: 1H NMR (300 MHz, CDCl3) 6.532 (d,
J = 3.9 Hz, 1H), 5.588 (t, J = 9.6 Hz, 1H), 5.365 (dd,
J = 3.3, 0.9 Hz, 1H), 5.160 (dd, J = 10.5, 7.95 Hz, 1H),
4.982 (dd, J = 10.5, 3.6 Hz, 1H), 4.784 (dd, J = 9.9, 4.2 Hz,
1H), 4.521–4.486 (m, 2H), 4.215–4.047 (m, 4H), 3.909–
3.828 (m, 2H), 2.164 (s, 3H), 2.136 (s, 3H), 2.095 (s, 3H),
2.070 (s, 3H), 2.064 (s, 3H), 2.057 (s, 3H), 1.969 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 170.52(C), 170.35 (C),
170.32 (C), 170.25 (C), 170.15 (C), 169.41 (C), 169.14 (C),
100.96 (CH), 86.55 (CH), 75.12 (CH), 73.14 (CH), 71.16
(CH), 71.01 (CH), 70.95 (CH), 69.76 (CH), 69.19 (CH),
66.77 (CH), 61.21 (CH2), 61.04 (CH2), 20.96 (CH3), 20.82
(CH3), 20.66 (CH3).
1-Iodo-tetra-O-acetate-α-D-monosaccharides (1I–4I)
and 1-Iodo-hepta-O-acetate-α-D-disaccharides (7I–9I): To
a solid of per-OAc saccharide (0.26 mmol), iodine
(198 mg, 0.78 mmol) in seat tubein, the mixture was
added dichloromethane (1 ml) and triethylsilane (63 μl,
0.39 mmol) at 0ꢀC and stirred at 60ꢀC for the reaction
11α: H NMR (300 MHz, CDCl3) δ 5.443 (dd, J = 3.4,
1
1.0 Hz, 1H), 5.334 (dd, J = 10.9, 3.4 Hz, 1H), 5.213 (d,
J = 3.8 Hz, 1H), 5.054 (dd, J = 10.9, 3.8 Hz, 1H), 4.304 (t,
J = 6.6 Hz, 1H), 4.092–4.068 (m, 2H), 3.915–3.791 (m,
1H), 2.136 (s, 3H), 2.065 (s, 3H), 2.036 (s, 3H), 1.983 (s,
3H), 1.229 (d, J = 6.2 Hz, 3H), 1.113 (d, J = 6.2 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 170.38 (C), 170.22 (C),
170.00 (C), 94.67 (CH), 71.24 (CH), 68.25 (CH), 68.12
(CH), 67.59 (CH), 66.05 (CH), 61.79 (CH2), 23.00 (CH3),
21.59 (CH3), 20.69 (CH3), 20.60 (CH3). HRMS (ESI, M
+ Na+) calcd for C17H26O10Na: 413.1424, found 413.1428.
12α: 1H NMR (300 MHz, CDCl3) δ 5.513 (dd,
J = 10.1, 8.9 Hz, 1H), 5.415–5.351 (m, 2H), 5.100–5.034
(m, 1H), 4.870 (dd, J = 10.6, 3.9 Hz, 1H), 4.672 (dd,
J = 10.1, 3.9 Hz, 1H), 4.433 (dd, J = 12.1, 2.6 Hz, 1H),
4.241–4.203 (set, 1H), 4.122–4.023 (m, 2H), 3.993–3.913
(m, 2H), 3.859 (set, J = 6.2 Hz, 1H), 2.136 (s, 3H), 2.101
(s, 3H), 2.074 (s, 3H), 2.025 (s, 3H), 2.020 (s, 3H), 2.004 (s,
6H), 1.278 (d, J = 6.2 Hz, 3H), 1.130 (d, J = 6.2 Hz, 3H);

XU ET AL.
7
13C NMR (75 MHz, CDCl3) δ 170.69 (C), 170.55 (C),
170.35 (C), 169.96 (C), 169.84 (C), 169.46 (C), 95.58 (CH),
94.06 (CH), 72.95 (CH), 72.69 (CH), 71.58 (CH), 69.98
(CH), 69.40(CH), 68.43 (CH), 68.01 (CH), 67.45 (CH),
62.87 (CH2), 61.44 (CH2), 23.12 (CH3), 21.62 (CH3), 20.98
(CH3), 20.81 (CH3), 20.67 (CH3), 20.60 (CH3). HRMS
(ESI, M + Na+) calcd for C29H42O18Na: 701.2269, found
701.2270.
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13α: 1H NMR (300 MHz, CDCl3)
δ 5.420 (t,
[8] C. C. Wang, S. S. Kulkarni, J. C. Lee, S. Y. Luo, S. C. Hung,
Nature Protocols 2008, 3, 97.
J = 9.8 Hz, 1H), 5.155–5.023 (m, 3H), 4.910 (t, J = 8.2 Hz,
1H), 4.699 (dd, J = 10.2, 3.9 Hz, 1H), 4.489 (d, J = 8.2 Hz,
1H), 4.439 (dd, J = 12.0, 1.9 Hz, 1H), 4.358 (dd, J = 12.5,
4.6 Hz, 1H), 4.100 (dd, J = 12.0, 4.6 Hz, 1H), 4.045–3.961
(m, 2H), 3.841–3.738 (m, 1H), 3.699–3.614 (m, 2H), 2.100
(s, 3H), 2.068 (s, 3H), 2.021 (s, 6H), 2.001 (s, 3H), 1.988 (s,
3H), 1.963 (s, 3H), 1.203 (d, J = 6.2 Hz, 3H), 1.087 (d,
J = 6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.48 (C),
170.40 (C), 170.31 (C), 170.23 (C), 169.56 (C), 169.25 (C),
169.07 (C), 100.79 (CH), 94.15 (CH), 73.03 (CH), 71.86
(CH), 71.66 (CH), 71.50 (CH), 71.17 (CH), 69.63 (CH),
68.06 (CH), 67.73 (CH), 61.91 (CH2), 61.52 (CH2), 23.07
(CH3), 21.58 (CH3), 20.79 (CH3), 20.62 (CH3), 20.54
(CH3), 20.49 (CH3). HRMS (ESI, M + Na+) calcd for
C29H42O18Na: 701.2269, found 701.2267.
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297, 175.
14α: 1H NMR (300 MHz, CDCl3)
δ 5.462 (t,
J = 9.7 Hz, 1H), 5.345 (dd, J = 3.4, 0.8 Hz, 1H), 5.148–
5.081 (m, 2H), 4.951 (dd, J = 10.3, 3.4 Hz, 1H), 4.716 (dd,
J = 10.3, 3.8 Hz, 1H), 4.479 (d, J = 7.4 Hz, 1H), 4.431 (dd,
J = 11.9, 1.9 Hz, 1H), 4.159–4.045 (m, 3H), 4.025–3.985
(m, 1H), 3.888–3.678 (m, 3H), 2.156 (s, 3H), 2.114 (s, 3H),
2.058 (s, 3H), 2.054 (s, 3H), 2.046 (s, 6H), 1.963 (s, 3H),
1.224 (d, J = 6.2 Hz, 3H), 1.109 (d, J = 6.2 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 170.47 (C), 170.42 (C), 170.35
(C), 170.19 (C), 170.11 (C), 169.53 (C), 169.12 (C), 101.15
(CH), 94.21 (CH), 71.54 (CH), 71.32 (CH), 71.13 (CH),
70.62 (CH), 69.99 (CH), 69.19 (CH), 68.06 (CH), 66.62
(CH), 62.07 (CH2), 60.79 (CH2), 23.11 (CH3), 21.63 (CH3),
20.93 (CH3), 20.83 (CH3), 20.65 (CH3), 20.50 (CH3).
HRMS (ESI, M + Na+) calcd for C29H42O18Na: 701.2269,
found 701.2267.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
ACKNOWLEDGMENTS
This work was supported by Microlithography Inc., Min-
istry of Science and Technology (MOST), and Fu-Jen
Catholic University, Taiwan (ROC).
How to cite this article: Xu L, Luo C-H,
Chen C-S. Halogenation and anomerization of
glycopyranoside by TESH/bromine and BHQ/
bromine. J Chin Chem Soc. 2020;1–7. https://doi.
org/10.1002/jccs.202000150
ORCID
Lai Xu https://orcid.org/0000-0003-1776-3269
REFERENCES
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