Facile preparation of α-glycosyl iodides by in situ generated aluminum iodide: Straightforward synthesis of thio-, seleno-, and o-glycosides from unprotected reducing sugars

Article abstract of DOI:10.1080/07328303.2011.565894

A facile and practical protocol was developed for the synthesis of glycosyl iodides using AlI₃ generated in situ from cheap aluminum metal and molecular iodine. Furthermore, in combination with iodine-catalyzed per-O-acetylation, sequential synthesis of per-acetylated glycosyl iodides, per-acetylated thioglycosides, selenoglycoside, and O-glycosides from unprotected reducing sugars was also achieved with complete diastereocontrol in a one-pot version. Supplemental material is available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328303.2011.565894

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Facile Preparation of α-Glycosyl
Iodides by In Situ Generated Aluminum
Iodide: Straightforward Synthesis of
Thio-, Seleno-, and O-glycosides from
Unprotected Reducing Sugars
Shiue-Shien Weng a , Chia-Ling Li a , Chun-Sheng Liao a , Ting-An
Chen a , Chao-Cheih Huang a & Kuo-Tung Hung a
a Department of Chemistry, ROC Military Academy, Kaohsiung,
Taiwan, ROC
Published online: 08 Apr 2011.
To cite this article: Shiue-Shien Weng , Chia-Ling Li , Chun-Sheng Liao , Ting-An Chen , Chao-
Cheih Huang & Kuo-Tung Hung (2010): Facile Preparation of α-Glycosyl Iodides by In Situ Generated
Aluminum Iodide: Straightforward Synthesis of Thio-, Seleno-, and O-glycosides from Unprotected
Reducing Sugars, Journal of Carbohydrate Chemistry, 29:8-9, 429-440
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Journal of Carbohydrate Chemistry, 29:429–440, 2010
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.565894
Facile Preparation of
α-Glycosyl Iodides by In Situ
Generated Aluminum Iodide:
Straightforward Synthesis of
Thio-, Seleno-, and
O-glycosides from
Unprotected Reducing Sugars
Shiue-Shien Weng, Chia-Ling Li, Chun-Sheng Liao,
Ting-An Chen, Chao-Cheih Huang, and Kuo-Tung Hung
Department of Chemistry, ROC Military Academy, Kaohsiung, Taiwan, ROC
A facile and practical protocol was developed for the synthesis of glycosyl iodides us-
ing AlI3 generated in situ from cheap aluminum metal and molecular iodine. Further-
more, in combination with iodine-catalyzed per-O-acetylation, sequential synthesis of
per-acetylated glycosyl iodides, per-acetylated thioglycosides, selenoglycoside, and O-
glycosides from unprotected reducing sugars was also achieved with complete diastere-
ocontrol in a one-pot version. Supplemental material is available for this article. Go to
the publisher’s online edition of Journal of Carbohydrate Chemistry to view the free
supplemental file.
Keywords Glycosyl iodide; anomeric iodination; aluminum triiodide; thioglycosyla-
tion; thioglycoside
INTRODUCTION
The development of efficient glycosylation methodologies has attracted con-
siderable interest over the past few decades because of the important roles of
oligosaccharides and glycoconjugates in many biological processes and thera-
peutic applications.[1] Of central importance to oligosaccharide synthesis is the
Received November 20, 2010; accepted February 21, 2011.
Address correspondence to Shiue-Shien Weng, Department of Chemistry, ROC Military
Academy, Kaohsiung, Taiwan, ROC. E-mail: Wengss@mail.cma.edu.tw
429

S.-S. Weng et al.
430
stereoselective construction of glycosidic bonds. Although a number of glyco-
syl donors and activation reagents have been developed for this purpose, the
invention of new methods and reagents for the generation of activated glyco-
syl donors is of continuing interest in this field.[2] Among the activated gly-
cosyl donors developed to date, per-O-acetylated glycosyl iodide is one of the
most valuable and versatile building blocks in the field of carbohydrate chem-
istry due to its extremely high reactivity toward O-, N-, and C-glycosylation,[3]
even under neutral conditions.[4] Methods for the synthesis of these important
compounds include treatment of per-O-acetylated sugars with HI/acetic acid,[5]
BiI3/trialkylsilyl iodide (R3SiI),[6] or expensive and hazardous iodotrimethylsi-
lane (TMS-I).[7] However, due to the high instability of glycosyl iodides, only
a few attempts have successfully generated spectroscopically pure iodoglyco-
sides, thus diminishing their potential utility as glycosyl donors.[8]
Recently, Koreeda and co-workers reported a novel protocol for producing
isolable per-O-acetylated glycosyl iodides that involved the use of in situ gener-
ated HI formed by reacting thioacetic acid (or dithiol) with iodine.[9] Recently,
a more practical one-pot procedure for conversion of glycosyl per-O-acetates
into thioglycosides was described by Field’s group using hexamethyldisilane
[10]
(HMDS)/I2
to generate glycosyl iodides and then subsequent anomeric
substitution of the resulting iodides with thiols. In addition, Iadonisi and
co-workers have reported a straightforward one-pot procedure for the synthe-
sis of thioglycosides via in situ generation of glycosyl iodides with triethylsi-
lane (Et3SiH)/I2 and then subsequent trapping of the unstable iodosugars with
thiourea.[11] Although these procedures are operationally simple and efficient,
chromatographic separation of the disulfide or trialkylsilane-derived byprod-
uct from the mixture and thermally unstable glycosyl iodides still limits the
synthetic utility of such compounds, especially for large-scale preparations.
RESULTS AND DISCUSSION
Inspired by the precedent of reliable methods to create glycosyl iodides by in
situ methods, we expected that in situ generated metal iodides would provide
an alternative method for the production of glycosyl iodides in a more conve-
nient and economical way because metal salts can be easily removed by al-
kali aqueous workup and filtration. We started our studies by assessing the
reactivities of various commercial metal iodides, including MgI2, CaI2, ZnI2,
FeI2, CoI2, BaI2, CeI3, GaI3, InI3, and AlI3, toward the anomeric iodination
of penta-O-acetyl-β-D-glucose 1. We found that only AlI3, InI3, and CeI3 were
able to achieve this iodination reaction stoichiometrically in dichloromethane
at rt with moderate to high yields (Table 1). Among them, AlI3 was found to
catalyze this transformation most efficiently, affording the corresponding α-
glucosyl anomer 1a at a 94% yield (Table1, entry 1) within a short reaction
time, even when a substoichiometric amount of AlI3 was used (40 mol%, 92%

Facile Preparation of α-Glycosyl Iodides
431
Table 1: The anomeric iodination of penta-O-acetyl-α-D-glucose 1 with
commercial or in situ generated metal iodidesa
OAc
O
OAc
X mol% MI3
O
AcO
AcO
AcO
AcO
OAc
CH2Cl2, r.t,
OAc
AcO
1a
I
1
Entry
MI3
mol%
Time
Yield(%)b
1
2
3
4
5
AlI3
100 (40)
100
20 (40) min
24 h
94 (92)
68
InI3
CeI3
Al + I2
100
24 h
21
c
40
100
40 (120) min
24 h
91 (84)
63
d
In + I2
aAll reactions were performed in CH2Cl2 at rt.
bIsolate yield after filtration though a shot pad silica gel and all products were identified by 1
H
and 13C NMR spectroscopy.
c40 mol% Al (powder) and 60 mol% I2 were used (with respect to sugars).
d100 mol% In (powder) and 150 mol% I2 were used (with respect to sugars).
yield; Table 1, entry 1, in parentheses). In contrast, the expensive InI3 and
CeI3 were far less reactive than AlI3, with only 68% and 21% yields obtained,
respectively, even at a prolonged reaction time (Table 1, entries 2 and 3). One
advantage of AlI3-mediated anomeric iodination is that the unstable product,
glucosyl iodide 1a, can be obtained by simple filtration though a short pad of
silica gel after standard workup to remove the insoluble aluminum oxide side-
product. Thus, tedious column chromatographic purification can be avoided.
AlI3 is commercially available and is a strong Lewis acid, and has many
practical applications in iodination chemistry.[12] However, it is highly hy-
groscopic and easily hydrolyzed, which limits its utility due to operational
inconvenience. An alternative method to generate this reagent involves direct
oxidation of elemental aluminum in situ by molecular iodine in aprotic organic
solvents.[13] Inspired by previously reported methods for producing glycosyl
iodides by in situ generation of TMS-I,[10,11] an AlI3 reagent (40 mol% Al pow-
der, 60 mol% molecule iodine in CH2Cl2) generated in situ was further tested
for anomeric iodination of penta-O-acetyl-β-D-glucose 1. As expected, the
desired glucosyl iodide 1a was isolated in a 91% yield after 2 h with complete
α-diastereoselectivity in dichloromethane at rt (Table 1, entry 4). It is notewor-
thy that the same reactivity was observed when anomeric pure penta-O-acetyl-
α-D-glucose was utilized instead of β-anomer, although prolonged reaction
time was required (84%, Table 1, entry 4, in parentheses). In addition, the InI3

S.-S. Weng et al.
432
generated in situ from indium metal and molecular iodine[14] was shown to
have equal reactivity as that of commercial reagent (Table 1, compare entries
2 with 5).
We took note of the aforementioned demonstrations of sequential
acetylation-glycosyl iodination-thioglycosylation of unprotected sugars to syn-
thesize thioglycosides in tandem[10,11,15] and turned our attention to one-pot
synthesis of glycosyl iodides from unprotected reducing sugars. The synthetic
sequences started with per-acetylation of unprotected free sugars under Field’s
condition, followed by subsequent anomeric iodination of the corresponding
per-acetylated sugars with in situ generated AlI3 in one pot. Initially, we in-
vestigated the per-acetylation of unprotected saccharide precursors by 1 mol%
of iodine in the presence of stoichiometric amounts of acetic anhydride (1.02
equiv per hydroxyl group) at rt under solventless conditions for the produc-
tion of the corresponding per-acetylated sugars.[10a,16] After completion of the
acetylation reaction (as judged by TLC analysis), without workup, the reaction
mixture was diluted with anhydrous dichloromethane (1 M concentration) and
treated with 40 mol% aluminum and 60 mol% iodine (with respect to reducing
sugars) at ambient temperature to conduct the iodination reaction. After com-
plete consumption of the per-acetylated glycoside, the reaction mixture was
quenched with saturated aqueous NaHCO3 and treated with minimal amounts
of NaHSO3 to remove the acetic acid and excess iodine. To gain insight into
the scope of this reaction, several monosaccharides (1–5), disaccharides (6, 7),
2-deoxyamino sugar 8, and per-O-benzoylated glucoside 9 were subjected to
the sequential one-pot reaction (Table 2). As expected, monosaccharides were
highly tolerant to the steps performed and afforded the corresponding iodosug-
ars (1a–5a) in good to excellent yields, with complete α-selectivity, in a short
period of time (Table 2, entries 1–5).
Due to concerns that the interglycosidic bond would be easily cleaved under
acidic conditions, disaccharides such as maltose and lactose were also exam-
ined under the described reaction conditions. Maltose, with 1ꢁ,2ꢁ-cis geometry
at the interglycosidic bond, remained intact under optimal conditions and af-
forded the desired maltosyl iodide 6a at a 79% yield after two sequential steps
(Table 2, entry 6). These results suggested that the 1ꢁ,2ꢁ-cis geometry of the
glycosidic bond is highly resistant to hydrolysis. In the case of lactose, how-
ever, the reaction was sluggish, and the interglycosidic bond with a 1ꢁ,2ꢁ-trans
geometry was cleaved under the performed condition, as evidenced by TLC
analysis. In fact, TLC analysis showed that a complex mixture was generated
during the reaction and that this mixture was predominantly less polar. Upon
chromatographic purification of the reaction mixture after workup, the less
polar component identified by TLC was isolated at a 53% yield and spectro-
scopically proven to be galactosyl iodide 2a (Table 2, entry 7). Similar results
were found in the anomeric iodination reaction conducted with HI, confirm-
ing the higher susceptibility of the 1ꢁ,2ꢁ-trans geometry of the interglycosidic

Facile Preparation of α-Glycosyl Iodides
433
Table 2: Sequential synthesis of glycopyranosyl iodides from unprotected reducing
sugarsa,b
1. 1 mol% I2,
Stoichiometric
Ac2O
O
O
OH 2. 40 mol% Al
60 mol% I2
1a-9a
HO
AcO
I
Entry
1
Glycoside
Time(h)c
4
Product
Yield,%d
86
D-glucose 1
2
3
D-galactose 2
D-mannose 3
4
3
90
81
4
5
D-arabinose 4
L-fucose 5
3
2
72
92
6e
D-maltose
5
5
79
53
Monohydrate 6
D-lactose 7
7
f
8
6
6
—
—
9g
94
aFirst step (per-acetylation): with 1.02 equiv of Ac2O per hydroxyl group; neat; rt; reaction time:
2 h; ref. 10a.
bSecond step (anomeric iodination): 40 mol% Al (powder) and 60 mol% I2 were used (with
respect to sugars).
cReaction times listed are for the second step.
dIsolate yield after filtration though a shot pad silica gel.
eAn additional 1.02 molar equiv of Ac2O was added in the per-acetylation step in order to
remove hydrate.
fNo desired product was observed.
g1.05 equiv benzoic anhydride in 5 mL CH2Cl2 was used for the first step.

S.-S. Weng et al.
434
linkage under strong acidic conditions.[9] Although the efficient formation of
glycosyl iodides could be achieved for per-O-acetylated glycosides with AlI3, the
2-deoxyamino sugar, such as N-acetyl glucosamine, did not effect this trans-
formation. This result is probably due to the formation of a bicyclic oxazoline
derivative under strongly acidic conditions (Table 2, entry 8).[17] It is worth
mentioning that 2,3,4,6-tetra-O-benzoylated glucoside was benzoylated with
1.05 equiv benzoic anhydride, catalyzed by 1 mol% I2, and subsequently con-
verted to the corresponding iodide with in situ formed AlI3, indicating that the
benzoate functionality was tolerant of the tandem process (Table 2, entry 9).
With the anomeric iodination protocol in hand, we sought to explore the
thio-, seleno-, and O-glycosylation of the corresponding glycosyl iodides pro-
duced from the aforementioned sequential reactions. Upon complete formation
of the glycosyl iodides, without workup, a solution of 1.5 equiv of nucleophile
(thiol, selenol, or alcohol) in dichloromethane was slowly added at 0◦C, and the
temperature of the reaction mixture was gradually raised to rt over several
hours. This procedure successfully generated the desired thio-, seleno-, and
O-glycosides (Table 3). In general, the thioglycosylation of monosaccharides,
disaccharide, and per-O-benzoylated glucoside with aromatic or aliphatic
thiols or the less nucleophilic thioacetic acid was efficient. The reactions
provided the corresponding thioglycosides 10–15 at high yields with exclusive
β-diastereocontrol afforded by the anchimeric assistance of the acetate at
the C-2 position (Table 3, entries 1–6). Furthermore, it was noteworthy that
N-acetyl glucosamine was converted to the corresponding thioglycoside 16 at
a moderate yield at elevated temperature (40◦C), although we failed to isolate
the per-acetylated iodoglucosamine in the anomeric iodination step (Table 3,
entry 7).
The current protocol was also applicable for the selenoglycosylation of glu-
cosyl iodide with phenyl selenol. As an example, selenoglycoside 17 was ob-
tained at an 81% yield with exclusive β-diastereoselectiviy (Table 3, entry 8).
Despite successful and straightforward synthesis of S- and Se-glycosides in
one-pot reaction, results from more challenging direct O-glycosylation reac-
tions were somewhat unsatisfactory. The sequential addition of primary or
secondary alcohol donors to the in situ generated glucosyl iodide 1a at rt
for 6 h or longer (16 h) afforded the expected adducts 18–21 in moderate
yields primarily with β-selectivity (Table 3, entries 9–13, 23%–57% yields).
In the case of aromatic alcohol such as more nucleophilic 4-methoxyphenol,
the corresponding glycosylation product 22 was isolated in only 23% yield,
despite the fact that complete β-selectivity was obtained (Table 3, entry 13).
In general, the diastereoselectivity increases with the steric bulk of the al-
cohol (hindered 2◦ > 2◦ >1◦), probably due to the steric effect that the
hindered substituent predominately occupied in the less crowded equatorial
position. In addition, the slight decreases in diastereoselectivity in cases of
O-glycosylation might result from the anomerization of the O-glycosidic bond

Facile Preparation of α-Glycosyl Iodides
435
Table 3: Sequential one-pot conversion of unprotected free sugars to thio-,
seleno-, or O-glycosidesa–c
(1) Stoichiometric Ac2O
O
O
1 mol% I2, neat
HO
AcO
(2) 40 mol% Al
OH
XR
60 mol% I2
CH2Cl2
R = alkyl, alkyl, CH3C(O)
X = S, Se, O
(3) R-XH, 0o C to r.t.
Entry
1
Glycoside
Nucleophile Time (h)d
Product
Yield%e
90
D-galactose
PhSH
4
2
3
4
5
D-glucose
D-glucose
D-mannose
D-maltose
c-C6H11SH
CH3C(O)SH
PhSH
4
3
3
2
89
87
84
82
PhSH
monohydrate
6f
4-CH3-PhSH
4-CH3-PhSH
5
5
93
43
7g
8
D-glucose
D-glucose
D-glucose
D-glucose
PhSeH
6
6(16)
16
81
47(52)
57
9
Ph(CH2)2OH
C18H37OH
c-C6H11OH
10
11
16
46
(Continud on next page)

S.-S. Weng et al.
436
Table 3: Sequential one-pot conversion of unprotected free sugars to thio-,
seleno-, or O-glycosidesa–c (Continued)
Entry
12
Glycoside
D-glucose
Nucleophile
l-(-)-menthol
Time (h)d
18
Product
Yield%e
42
13
D-galactose
4-CH3O-C6H5OH
24
23
aFirst step (per-acetylation): 1.02 equiv of Ac2O per hydroxyl group; neat; rt; reaction time: 2 h;
ref. 10a.
bSecond step (anomeric iodination): 40 mol% of Al and 60 of mol% I2 were used (with respect
to sugars).
cThird step (glycosylation): 1.5 equiv protic nucleophile was used.
dReaction times listed refer to the third step.
eOverall yields of two steps after chromatographic purification.
f1.05 equiv benzoic anhydride in 5 mL CH2Cl2 was used for first step.
gReaction temperature: 40◦C.
during the course of reaction. This anomerization phenomenon frequently oc-
curred in the O-glycosylation reaction if the reaction was performed in the
presence of Lewis acids or Brønsted acids.[18] Transesterification of the acetate
of the per-acetylated sugar, anomeric deacetylation, and partial deacetylation
of the 2-O-acetyl group were found to be the main side reactions of the de-
scribed O-glycosylation reaction. We assumed that the remaining AlI3 and a
small amount of HI in the reaction mixture were responsible for the observed
transesterification.[14,18–20]
CONCLUSION
In conclusion, we have demonstrated the anomeric iodination of per-acetylated
glycosides by employing in situ generated AlI3 from cheap aluminum metal
and elemental iodine to afford unstable but synthetically useful glycosyl io-
dides. Taking advantage of iodine-catalyzed per-acetylation technology, glyco-
syl iodides could be produced in excellent yields within short reaction times
after simple filtration by sequential per-acetylation of unprotected reducing
sugars and iodination of the anomeric acetate in one pot. Without workup,
the subsequent addition of thiols or selenol to the reaction mixture generated
the corresponding thioglycosides and selenoglycoside in good yields with ex-
clusive β-selectivity. The current tandem procedure was not well adapted for
O-glycosylation due to the undesired side reactions caused by excess AlI3 or

Facile Preparation of α-Glycosyl Iodides
437
HI. Efforts are currently under way in our laboratory to optimize these O-
glycosylation procedures to boost yields.
EXPERIMENTAL
1H NMR and 13C NMR spectra were recorded on Jeol JVM-EX400 (400 MHz,
1H; 100 MHz, 13C) or Varian UNITY INOVA-500 (500 MHz, 1H; 125 MHz, 13C)
spectrometers in deuterochloroform with chloroform as an internal reference
unless otherwise stated. Chemical shifts are reported in ppm (δ). Coupling con-
stants, J, are reported in Hz. Elemental analyses were obtained on a Heraeus
CHN-OS Rapid analyzer or by the Northern Instrument Center of Taiwan.
Electrospray (ESI) mass spectra were reported with data in the form m/e (in-
tensity relative to base peak). Optical rotations were recorded on a JASCO
DIP-1000 digital polarimeter and are reported as follows: [α]T (c = g/100 mL,
solvent). Analytical TLC was visualized with UV light or with phosphomolyb-
dic acid (PMA) and KMnO4 staining agents. Column (flash) chromatography
was performed using 32–63 m silica gel. All reactions were run under nitrogen
or argon atmosphere and the end products were isolated as spectroscopically
pure materials.
General Procedure for Synthesis of Glycosyl Iodide
from Unprotected Reducing Sugars
To a solution of unprotected reducing sugars (1.0 mmol) in acetic anhy-
dride (1.02 equiv per hydroxyl group) was added I2 (2.5 mg, 0.01 mmol) at rt
under nitrogen atmosphere. The reaction was stirred at ambient temperature
for 2 h and monitored by TLC. After completion of the acetylation reaction, the
reaction was diluted with 10 mL CH2Cl2 and aluminum powder (11 mg, 0.4
mmol) and molecular iodine (152 mg, 0.6 mmol) were subsequently added. The
reaction mixture was allowed to stir at ambient temperature for an indicated
period of time (Table 2). After completion of the anomeric iodination, the re-
action was quenched with 10 mL saturated aqueous NaHCO3 and minimum
amount of saturated aqueous NaHSO3. The organic layer was extracted with
30 mL CH2Cl2, dried over MgSO4, and filtered. The crude product was filtrated
though a short pad of silica gel with ether as eluent or purified by flash column
chromatography and afforded the authentic glycosyl iodides.
General Procedure for Synthesis of Thio-, Seleno-,
and O-Glycosides from Unprotected Reducing Sugars
Glycosyl iodides were prepared from unprotected reducing sugars as men-
tioned above. After complete formation of the glycosyl iodide (monitored by

S.-S. Weng et al.
438
TLC), the reaction mixture was cooled to 0◦C. A solution of 1.5 equiv protic nu-
cleophile (thiol, thioacetic acid, phenyl selenol, or alcohol) in 5 mL CH2Cl2 was
added to the above solution via cannula. The temperature of the reaction mix-
ture was gradually raised to rt over several hours. After complete consumption
of the glycosyl iodide, the reaction mixture was quenched with 10 mL satu-
rated aqueous NaHCO3 and 5 mL saturated aqueous NaHSO3. The organic
layer was separated, extracted with 30 mL CH2Cl2, and washed successively
with 10 mL saturated aqueous NaHCO3, NaHSO3, and brine. The crude prod-
uct was loaded directly on top of an eluent-filled silica gel column and purified
by flash column chromatography, to afford the corresponding thio-, seleno-, or
O-glycosides. The anomeric ratios of glycosides 10–22 were estimated from the
relative intensity of signals corresponding to anomeric carbon atoms in 13C
1
spectra or H NMR. Pure anomeric O-glycosides 18–21 can be obtained via
preparative TLC.
SUPPLEMENTARY MATERIAL AVAILABLE
1H and 13C NMR spectra of glycosyl iodides 1a–6a and 9a, thioglycosides
10–16, selenoglycoside 17, and glycosides 18–22 are matched with the data
1
reported in the literature. Full characterization data and copies of H and 13
C
NMR spectra of all products are presented in the SUPPLEMENTARY MATE-
RIAL file, available online, for the sake of simplicity of the printed page.
ACKNOWLEDGMENTS
We acknowledge the National Science Council of the Republic of China for fi-
nancially supporting this research (98-2119-M-145-001-MY2). We thank the
Mass laboratory of National Taiwan Normal University and the NMR labora-
tory of National Sun Yat-sen University for NMR spectra measurements.
REFERENCES
1. (a) Dwek, R.A. Glycobiology: toward understanding the function of sugars. Chem.
Rev. 1996, 96, 683–720. (b) Bertozzi, C.R.; Kiessling, L.L. Chemical glycobiology. Sci-
ence 2001, 291, 2357–2364. (c) Helenius, A.; Aebi, M. Intracellular functions of N-
linked glycans. Science 2001, 291, 2364–2369.
2. (a) Toshima, K.; Tatsuta, K. Recent progress in O-glycosylation methods and
its application to natural products synthesis. Chem. Rev. 1993, 93, 1503–1531.
(b) Schmidt, R.R.; Kinzy, W. Anomeric oxygen activation for glycoside synthesis. Adv.
Carbohydr. Chem. Biochem. 1994, 50, 121–123. (c) Zhu, X.; Schmidt, R.R. New princi-
ples of glycoside bond formation. Angew. Chem. Int. Ed. 2009, 48, 1900–1935. (d) Davis,
B.G. Recent developments in glycoconjugates. J. Chem. Soc. Perkin Trans. 1, 2000, 2137.
(e) Marzabadi, C.H.; Franck, R.W. The synthesis of 2-deoxyglycosides: 1988–1999.
Tetrahedron 2000, 45, 8385. (f) Bashkin, J.K., Ed. Frontiers in carbohydrate research.
Chem. Rev. 2000, 100, 4265–4711. (g) Boons, G.-J. Carbohydrate Chemistry; Thomson

Facile Preparation of α-Glycosyl Iodides
439
Science: London, 1998. (h) Danishefsky, S.J.; Bilodeau, M.T. Glycals in organic syn-
thesis: the evolution of comprehensive strategies for the assembly of oligosaccharides
and glycoconjugates of biological consequence. Angew. Chem. Int. Ed. Engl. 1996, 35,
1380.
3. (a) Toshima, K. Glycosyl halides: In Glycoscience; Fraser-Reid, B.; Tatsuta, K.;
Thiem, J., Eds.; Springer: Berlin, Heidelberg, 2008; pp 429–449. (b) Hadd, M.J.; Gervay,
J. Glycosyl iodides are highly efficient donors under neutral conditions. Carbohydr. Res.
1999, 320, 61. (c) Bhat, A.S.; Gervay-Hague, J. Efficient syntheses of α-cyanosugars
using glycosyl iodides derived from per-O-silylated mono- and disaccharides. Org. Lett.
2001, 3, 2081. (d) Lam, S.N.; Gervay-Hague, J. Solution- and solid-phase oligosaccha-
ride synthesis using glucosyl iodides: a comparative study. Carbohydr. Res. 2002, 337,
1953. (e) Lam, S.N.; Gervay-Hague, J. Solution-phase hexasaccharide synthesis using
glucosyl iodides. Org. Lett. 2002, 4, 2039. (f) Dabideen, D.R.; Gervay-Hague, J. Unique
reactions of glycosyl iodides with oxa- and thiocycloalkane acceptors. Org. Lett. 2004, 6,
973. (g) Miquel, N.; Vignando, S.; Russo, G.; Lay, L. Efficient synthesis of O-, S-, N- and
C-glycosides of 2-amino-2-deoxy-D-glucopyranose from glycosyl iodides. Synlett 2004,
2, 341.
4. (a) Gervay, J.; Hadd, M.J. Anionic additions to glycosyl iodides: highly stereoselec-
tive syntheses of β C-, N-, and O-glycosides. J. Org. Chem. 1997, 62, 6961. (b) Ying,
L.; Gervay-Hague, J. General methods for the synthesis of glycopyranosyluronic acid
azides. Carbohydr. Res. 2003, 338, 835.
5. Ness, R.K.; Fletcher, H.G. Jr.; Hudson, C.S. The reaction of 2,3,4,6-tetrabenzoyl-
α-D-glucopyranosyl bromide and tetrabenzoyl-α-D-mannopyraosyl bromide with
methanol. Certain benzoylated 2,3,4,6-D-derivatives of D-glucose and D-mannose.
J. Am. Chem. Soc. 1950, 72, 2200.
6. Montero, J.-L.; Winum, J.-Y.; Leydet, A.; Kamal, M.; Pavia, A. A.; Roque, J.-P. A
convenient synthesis of peracetylated glycosyl halides using bismuth(III) halides as
catalysts. Carbohydr. Res. 1997, 297, 175.
7. (a) Kartha, K.P.R.; Field, R.A. Iodine and its interhalogen compounds: versatile
reagents in carbohydrate chemistry VIII. A simple, practical method for the preparation
of glycosyl iodides from per-O-acetyl or other derivatives of carbohydrates. Carbohydr.
Lett. 1998, 3, 179. (b) Gervay, J.; Nguyen, T.N.; Hadd, M.J. Mechanistic studies on
the stereoselective formation of glycosyl iodides: first characterization of β-D-glycosyl
iodides. Carbohydr. Res. 1997, 300, 119.
8. Kronzer, F.J.; Schuerch, C. The use of 2,3,4,6-tetra-O-benzyl-α-D-glycopyranosyl
iodides in α-glycoside synthesis. Carbohydr. Res. 1974, 34, 71.
9. (a) Chervin, S.M.; Abada, P.; Koreeda, M. Convenient, in situ generation of
anhydrous hydrogen iodide for the preparation of α-glycosyl iodides and vicinal
iodohydrins and for the catalysis of ferrier glycosylation. Org. Lett. 2000, 2, 369.
(b) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Iodine/triethylsilane as a
convenient promoter system for the activation of disarmed glycosyl trichloro- and N-
(Phenyl)trifluoroacetimidates. Synlett 2002, 269. (c) Adinolfi, M.; Iadonisi, A.; Ravida`,
A.; Schiattarella, M. Efficient and direct synthesis of saccharidic 1,2-ethylidenes, or-
thoesters, and glycals from peracetylated sugars via the in situ generation of glycosyl
iodides with I2/Et3SiH. Tetrahedron Lett. 2003, 44, 7863. (d) Pastore, A.; Adinolfi, M.;
Iadonisi, A. BiBr3-promoted activation of peracetylated glycosyl iodides: straightfor-
ward access to synthetically useful 2-O-deprotected allyl glycosides. Eur. J. Org. Chem.
2008, 6206.
10. (a) Mukhopadhyay, B.; Kartha, K.P.R.; Russell, D.A.; Field, R.A. Streamlined syn-
thesis of per-O-acetylated sugars, glycosyl iodides, or thioglycosides from unprotected
reducing sugars. J. Org. Chem. 2004, 69, 7758. (b) Kartha, K.P.R.; Field, R.A. Iodine

S.-S. Weng et al.
440
and its interhalogen compounds: versatile reagents in carbohydrate chemistry V. Syn-
thesis of 1,2-trans-linked 1-thioglycosides from the per-O-acetylated glycoses. J. Carbo-
hydr. Chem. 1998, 17, 693. (c) Lin, C.-C.; Huang, L.-C.; Liang, P.-H.; Liu, C.-Y.; Lin, C.-C.
Large scale synthesis of per-O-acetylated saccharides and their sequential transforma-
tion to glycosyl bromides and thioglycosides. J. Carbohydr. Chem. 2006, 25, 303–313.
11. (a) Valerio, S.; Iadonisi, A.; Adinolfi, M.; Ravida`, A. Novel approaches for the syn-
thesis and activation of thio- and selenoglycoside donors. J. Org. Chem. 2007, 72, 6097.
(b) Adinolfi, M.; Iadonisi, A.; Pezzella, A.; Ravida`, A. Regioselective phenol or carbinol
glycosidation of 17β-estradiol and derivatives thereof. Synlett 2005, 1848.
12. (a) Eisch, J.J.; Liu, Z.R.; Ma, X.; Zheng, G.-X. High regioselectivity in the alter-
native, halogenative cleavages of terminal epoxides with Lewis acid metal halides. J.
Org. Chem. 1992, 57, 5140. (b) Po¨schl, U.; Hassler, K. Synthesis and spectroscopy of
halogenated cyclopentasilane. Organometallics 1996, 15, 3238.
13. (a) Martin Gil, F.J.; Salgado, M.A.; Martin Gil, J. On the synthesis of triiodides of
aluminium, gallium and indium. Synth. React. Inorg. Met.-Org. Chem. 1986, 16, 663.
(b) Xue, B.; Fu, Z.; Li, H.; Liu, X.; Cheng, S.; Yao, J.; Li, D.; Chen, L.; Meng, Q. Cheap and
environmentally benign electrochemical energy storage and conversion devices based
on AlI3 electrolytes. J. Am. Chem. Soc. 2006, 128, 8720.
14. Ranu, B.C.; Dutta, P.; Sarkar, A. A simple and efficient procedure for transesteri-
fication catalyzed by indium triiodide. J. Org. Chem. 1998, 63, 6027.
15. Tai, C.-A.; Kulkarni, S.S.; Hung, S.-C. Facile Cu(OTf)2-catalyzed preparation of
per-O-acetylated hexopyranoses with stoichiometric acetic anhydride and sequential
one-pot anomeric substitution to thioglycosides under solvent-free conditions. J. Org.
Chem. 2003, 68, 8719.
16. Kartha, K.P.R.; Field, R.A. Iodine: a versatile reagent in carbohydrate chemistry
IV. Per-O-acetylation, regioselective acylation and acetolysis. Tetrahedron 1997, 53,
11753.
17. Wei, G.; Lv, X.; Du, Y. FeCl3-catalyzed α-glycosidation of glycosamine pentaac-
etates. Carbohydr. Res. 2008, 343, 3096.
18. Chatterjee, S.K.; Nuhn, P. Stereoselective α-glycosidation using FeCl3 as a Lewis
acid catalyst. Chem. Commun. 1998, 1730.
19. Wei, G.; Zhang, L.; Cai, C.; Cheng, S.; Du, Y. Selective cleavage of sugar anomeric
O-acyl groups using FeCl3·6H2O. Tetrahedron Lett. 2008, 49, 5488.
20. (a) Limousin, C.; Cleophax, J.; Petit, A.; Loupy, A.; Lukacs, G.J. Solvent-free syn-
thesis of decyl D-glycopyranosides under focused microwave irradiation. Carbohydr.
Chem. 1997, 16, 327. (b) Aich, U.; Loganathan, D. Zeolite-catalyzed Helferich-type
glycosylation of long-chain alcohols. Synthesis of acetylated alkyl 1,2-trans glycopy-
ranosides and alkyl 1,2-cis C2-hydroxy-glycopyranosides. Carbohydr. Res. 2007, 342,
704. (c) Ferlin, N.; Duchet, L.; Kovensky, J.; Grand, E. Microwave-assisted synthesis of
long-chain alkyl glucopyranosides. Carbohydr. Res. 2008, 343, 2819.