Indium(III) triflate: A highly efficient catalyst for reactions of sugars

Article abstract of DOI:10.1080/07328300802458970

Indium(III) trifluoromethanesulfonate has been found to be extremely efficient in catalyzing acyl transfer reactions of various carbohydrates and their derivatives. Selective acetolyses of certain benzyl ethers/isopropylidene acetals of sugars have been possible using In(OTf)3 in Ac2O (neat). Reaction of the per-O-acetate of 2-deoxy-2-phthalimido-D-glucose with benzyl mercaptan in the presence of In(OTf)3 led to the formation of the corresponding thioglycoside in high yield. Facile formation and hydrolysis of the isopropylidene and benzylidene acetals of various carbohydrates have also been achieved very efficiently in the presence of In(OTf)3. The results show great promise for In(OTf)3 in synthetic carbohydrate chemistry.

Full text of DOI:10.1080/07328300802458970

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Indium(III) Triflate: A Highly Efficient
Catalyst for Reactions of Sugars[1]
Santosh Kumar Giri a , Monika Verma a & K. P. Ravindranathan Kartha
a
a Department of Medicinal Chemistry , National Institute of
Pharmaceutical Education and Research , S.A.S. Nagar, Punjab, 160
062, India
Published online: 11 Dec 2008.
To cite this article: Santosh Kumar Giri , Monika Verma & K. P. Ravindranathan Kartha (2008)
Indium(III) Triflate: A Highly Efficient Catalyst for Reactions of Sugars[1] , Journal of Carbohydrate
Chemistry, 27:8-9, 464-478, DOI: 10.1080/07328300802458970
To link to this article: http://dx.doi.org/10.1080/07328300802458970
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Journal of Carbohydrate Chemistry, 27:464–478, 2008
ꢀC
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328300802458970
Indium(III) Triflate: A Highly
Efficient Catalyst for Reactions
of Sugars[1]
Santosh Kumar Giri, Monika Verma,
and K. P. Ravindranathan Kartha
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education
and Research, S.A.S. Nagar, Punjab 160 062, India
Indium(III) trifluoromethanesulfonate has been found to be extremely efficient in cat-
alyzing acyl transfer reactions of various carbohydrates and their derivatives. Selective
acetolyses of certain benzyl ethers/isopropylidene acetals of sugars have been possible
using In(OTf)3 in Ac2O (neat). Reaction of the per-O-acetate of 2-deoxy-2-phthalimido-
D-glucose with benzyl mercaptan in the presence of In(OTf)3 led to the formation of the
corresponding thioglycoside in high yield. Facile formation and hydrolysis of the iso-
propylidene and benzylidene acetals of various carbohydrates have also been achieved
very efficiently in the presence of In(OTf)3. The results show great promise for In(OTf)3
in synthetic carbohydrate chemistry.
Keywords Indium(III) triflate, acyl transfer reactions, acetal formation and hydroly-
sis, thioglycosylation
INTRODUCTION
A wide variety of Lewis acids have been in use for organic syntheses. Most
of the classical reagents of this class, such as AlCl3, BF3/BF3.Et2O, FeCl3,
SnCl4, TiCl4, and ZnCl2, are extremely sensitive to moisture and are dif-
ficult to handle, besides the fact that they are often required in stoichio-
metric quantities for the reaction to be highly effective. Among the more
recently introduced metal-based Lewis acid substances, indium(III) salts have
attracted a great deal of interest, particularly for their good stability in air and
water.[2,3]Among the various In-based reagents, In(III) triflate has emerged
as a useful catalyst in many organic transformations[2–4] including, for
Received May 19, 2008; accepted September 5, 2008.
Address correspondence to K. P. Ravindranathan Kartha, Department of Medici-
nal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S.
Nagar, Punjab 160 062, India. E-mail rkartha@niper.ac.in
464

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
465
example, tetrahydropyranylation of alcohols,[5] Friedel-Crafts acylation of alco-
hols and amines,[6,7] Friedel-Crafts sulfonylation of arenes,[8] and ring opening
of aziridines.[9] However, apart from an observation on the acetylation of an
alditol using Ac2O/In(OTf)[6] in MeCN, to the best of our knowledge no work
3
has been reported in the literature on the use of this reagent in the area of syn-
thetic carbohydrate chemistry. Therefore, an investigation was carried out in
order to explore its possible applications in reactions of sugars and the results
are reported herein.[10]
RESULTS AND DISCUSSION
Per-O-acetylation
Both the ability of the metal center in the In-based reagents to coordinate
with electron-rich centers in organic molecules and the solubility of In(OTf)3
in organic solvents must be of advantage in acyl transfer reactions using Ac2O
as the acyl donor reagent (Fig. 1).
Indeed, when D-galactose (1) was added to a solution of In(OTf)3 in Ac2O,
the sugar went into solution within 10 sec and TLC at this stage revealed the
formation of galactose pentaacetate (2, entry 1, Table 1). The reaction was con-
siderably exothermic and no unreacted galactose or partially acetylated prod-
uct could be detected in the reaction mixture. Aqueous workup yielded a solid
product identical to authentic 2 by TLC and NMR and as observed in the case
of acetylations catalyzed by other Lewis acids,[11,12] the α-anomer was prefer-
entially formed.
Reaction of D-mannose (3) proceeded even faster under these conditions
and the penta-O-acetate 4 (entry 2, Table 1) was obtained in very few seconds.
Acetylation of the monosaccharide 5 and the disaccharides 7, 9, and 11 also
took place in a very short period of time, giving the respective fully acetylated
products in quantitative yields (Table 1, entries 3 and 5–7, respectively).
Peracetylation of the reducing disaccharides containing 1,2-cis- as well as
1,2-trans-configured interglycosidic linkages could thus be carried out with-
out affecting such linkages, unlike in the case of instances under FeCl3[11]
catalysis. Acetylation of D-glucose (5) was then scaled up to 50 g with-
out affecting the yield and portion-wise addition of glucose to the reaction
Figure 1: Proposed In(OTf)3-promoted acetylation of sugers.

S. K. Giri et al.
466
mixture was found necessary to avoid overheating of the reaction mixture (en-
try 4, Table 1). Acetylation of the acetamido derivative 13 was considerably
slower than the parent sugar 5, but the rate of O-acetylation could be increased
by increasing the catalyst concentration (entries 8 and 9, Table 1).
Table 1: Indium(III) triflate-mediated acylation of sugarsa
Sugar (quantity
used)
In(OTf)3
(mg/g sugar)
Reaction
time
Product (yield, %;
anomeric ratio, α:β)
Entry
1
2
1, 1 g
3, 1 g
5
5
∼10 sec
2 (Quant; 9:2)
4 (Quant; 7.7:1)
6 (Quant; 100:7)
6 (Quant; 9:1)
8 (Quant; 9:1)
10 (Quant; 3.7:1)
12 (Quant; 1:1)
14 (Quant; 1:1)
14 (Quant; 1:1)
16 (Quant; —)
18 (90; —)
A few sec
3 min
3
5, 1 g
5
4
50 g
2
30 min
1 min
5
7, 1 g
5
6
9, 1 g
5
A few sec
5 min
7
11, 1 g
13, 1 g
13, 1 g
15, 1 g
17, 0.21 g
19, 0.54 g
21, 0.26 g
23, 0.26 g
5, 1 g
5
8
10
50
3.5
1
2 h
0.5 h
9
10
11
12
13
14
15
A few sec
1 min
1
1 min
20 (93; 5.4:1)
22 (93; —)
1
1 min at –15◦C
1 min at -15 ◦C
2 h
1
24 (92; —)
25 (90; 6:1)
5
aAcetylations were carried out using 5 mL Ac2O/g sugar at rt or as specified; for propionylation
1.05 mol equiv. of propionic anhydride per OH group of the sugar was used at rt.

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
467
Thus, while at 0.32 mole% of In(OTf)3 the reaction required 2 h at rt for the
complete conversion of the amino sugar 13 to its peracetate 14, the same trans-
formation was complete in 30 min at 1.6 mole% concentration of the catalyst.
It may be recalled that conversion of 13 to 14 required 2 days for completion
when carried out using I2 at a concentration of 17.7 mole% at rt.[12] Simple
alkyl glycosides such as 15 also could be per-O-acetylated with ease on using
approximately 0.11 mole% of the catalyst in Ac2O at rt (entry 10, Table 1)
without the aglycone group being affected. But with alkyl thioglycosides such
as 17, the amount of In(OTf)3 had to be reduced to approximately one-third for
the desired tetra-O-acetate 18 to be obtained without the loss of the aglycone
moiety (entry 11, Table 1).
Not surprisingly though, it was also observed that further control of the
rate of acylation (as well as avoidance of acetolysis) could be achieved by car-
rying out the reaction at –15◦C instead of rt (see also later). These observations
enabled successful acetylation of partially benzylated sugar derivative 19 (en-
try 12, Table 1) and acetonides 21 and 23 (entries 13 and 14, Table 1) in the cold
by using the triflate reagent in as low a concentration as 0.03 to 0.06 mole%.
The desired monoacetates (20, 22, and 24, respectively) were obtained in ex-
cellent yield in all three instances. The results of the foregoing experiments
clearly show In(OTf)3 to be a lot more of an effective catalyst than Lewis acids
such as FeCl[311] and I[212] reported for this purpose. Possible involvement of
the triflic acid/acetyl triflate that may be formed in situ in the reaction mix-
ture, particularly subsequent to the onset of acetylation in the initial stages
of the reaction, may also account for the enhanced rate of acyl transfer in the
case of In(OTf)3-catalyzed acetylation reactions reported here. Potential of this
reagent for acylation reactions was further evaluated by using neat propionic
anhydride as the acyl donor and 5 as the acyl acceptor (entry 15, Table 1).
Excellent yield of the desired product 25 was obtained with ease.
Acetolysis
The potential of In(OTf)3 for applications in acetolysis reaction was felt
during the acetylation of the thioglycoside 17 as described above. Acetolysis
reactions become of particular interest in synthetic carbohydrate chemistry
when regioselective/chemoselective transformations become possible. With
this in mind, taking compounds 17, 19, 21, 27, 29, and 31 as substrates, the use
of In(OTf)3-Ac2O system was further investigated for its possible applications
in selective/controlled acetolyses (Table 2).
Thus, acetolysis of the methylthio group in thiogalactoside 17 could be
easily carried out by treatment of 17 with the In(OTf)3-Ac2O system un-
der mild conditions to give the pentaacetate 2 in quantitative yield (entry 1,
Table 2). Similarly, treatment of tetra-O-benzyl glucopyranose (19) with the
reagent system led first to the glycosyl acetate 20 and further to the exclusive

S. K. Giri et al.
468
formation of the regioselectively acetolyzed 1,6-di-O-acetate 26 (entry 2,
Table 2) in approximately 5 h. As has been observed in other instances,[12] the
2-O-, 3-O-, and 4-O-benzyl groups remained unaffected. The rate of acetolysis
of the 6-O-benzyl ether could be significantly enhanced by increasing the tri-
flate concentration in the reaction mixture as evident from the formation of the
di-O-acetates 28 and 30 from the corresponding benzyl derivatives 27 and 29
(entries 4 and 5, Table 2). The 2-(trimethylsilyl)ethyl residue in the galactoside
derivative 31, susceptible to acetolysis by BF3 · Et2O[13] (or FeCl3)[14] in Ac2O,
could be successfully transformed into the 3,4-di-O-acetate 32 chemoselec-
tively using In(OTf)3/Ac2O at –15◦C in 75% yield with the remaining product
being the 3,4,6-tri-O-acetate 33. It is interesting to note that acetolysis of the
isopropylidene acetal preceded that of the 6-O-benzyl group in this compound.
Formation and Hydrolysis of Acetals
Acetylation, in particular the preparation of isopropylidene as well as
benzylidene acetals, is an extremely useful reaction in synthetic carbohy-
drate chemistry. In(III) halide-assisted thioacetalation reactions, including
the transthioacetalation of cyclic/acyclic O,O-acetals of many noncarbohydrate
Table 2: Indium(III) triflate-mediated acetolysis of sugar derivativesa
In(OTf)3
(mg sugar)
(mg sugar)
Reaction
time
Product
(yield, %)
Entry
Sugar
α/β
1
17 or 18
19
5
1 min
5 h
2(98)
Neat α -
4:1
2
3
4
5
6
1
5
5
5
1
26 (97)
19
1 min
26 (97)
4:1
27
<1 min
<1 min
30 min at –15◦C
28 (92)
3.5:1
3:1
—
29
30 (92)
31
32 (75) 33 (25)
aAcetolyses were carried out using 1 mL Ac2O/100 mg sugar derivative at rt or as specified.

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
469
substances as well as In(III) triflate-mediated conversion of aromatic/aliphatic
carbonyl compounds to oxathiolanes by reaction with 2-mercaptoethanol, have
been reported. In view of these facts, and in light of a recent report on the ap-
plication of V(OTf)3 in the preparation of sugar acetals, the reaction of acetone
with simple aldoses in the presence of In(OTf)3 was investigated (Table 3).
Typically, pentoses such as arabinose (34) and xylose (36) yielded their
respective known di-O-isopropylidene derivatives 35 and 37, respectively, in
about 10 min at reflux temperature in the presence of 3.2 mole% of the catalyst
Table 3: Indium(III) triflate-mediated acetylation/transacetylation of sugars/their
derivatives
Entry
Sugar (wt)
Reaction time
Product
Yield, %
1a
34 (1 g)
36 (1 g)
1 (1 g)
3 (1 g)
5 (1 g)
5 (10 g)
39 (1 g)
15 (1 g)
42 (1 g)
3 (1 g)
15
10 min
10 min
6 h
35
Quant.
Quant.
82
2a
37
3a
23
4a
10 min
8 h
38
Quant.
90
5a
21
6b
12 h
21
91
Quant.
93
7a
10 min
2 h
40
8c
41
9c
4 h
43
95
93
83
97
73
10c
11d
12d
13e
30 min
2 min
2 min
2 min
44
41
43 (see entry 9)
45
42
42
a0.032 mol equiv of In(OTf)3 in 50 mL of acetone (HPLC grade) at reflux temperature was
used.
b6.4 × 10–3 mol equiv of In(OTf)3 in 200 mL of acetone (HPLC grade) at reflux temperature
was used.
c0.25 mol equiv of In(OTf)3 in PhCHO (neat, 5 mol equiv) at rt was used.
d15 mol equiv of PhCH(OMe)2 (neat) and In(OTf)3 (4 mg/100 mg sugar) were used at rt.
e15 mol equiv of Me2C(OMe)2 (neat) and In(OTf)3 (4 mg/100 mg) were used at rt.

S. K. Giri et al.
470
in acetone (entries 1 and 2, Table 3). In the case of hexoses, while D-galactose
(1) and D-glucose (5) required 6 and 8 h, respectively, for the reaction (entries
3 and 5, Table 3), it was complete in 10 min in the case of D-mannose (3, entry
4, Table 3). D-Mannitol (39) also likewise gave the known tri-O-acetal 40 in
10 min at reflux temperature (entry 7, Table 3). Arabinose, xylose, mannose,
and mannitol yielded the respective isopropylidene derivatives in quantitative
yield, but the diacetonides of galactose and glucose were obtained in 82% and
90% yield, respectively (Table 3). The crude products obtained in all cases were
pure enough for subsequent transformations.
Reaction of neat benzaldehyde with hexosides for the preparation of the
respective 4,6-O-benzylidene acetals was subsequently investigated. Thus, the
glucoside 15 and the galactoside 42 underwent facile acetylation reaction giv-
ing the respective 4,6-O-benzylidene acetals 41 and 43, respectively, the iso-
lated yields in both cases being more than 90% (entries 8 and 9, Table 3).
Although the benzylidene acetals were indeed also obtained in the presence of
solvents such as MeCN and DMF, it was noted that neat PhCHO best suited
the purpose, as was revealed from the poorer yields (40%–60% only, results
not shown) of these products obtained in the former. In neat reaction with Ph-
CHO, D-mannose likewise gave the expected di-O-benzylidene acetal 44, also
in excellent yield (entry 10, Table 3). Transacetylations using the respective
dimethylacetal derivatives of acetone/benzaldehyde as the carbonyl equiva-
lents could also be carried out successfully (entries 11 and 12, Table 3) in the
presence of In(OTf)3.
Encouraged by the successful preparation of the acetals, the applicability
of In(III) triflate in their hydrolysis was studied and the results are summa-
rized in Table 4. The hydrolytic cleavage of acetals took place in a very facile
manner when carried out at 50◦C or 70◦C in aq dioxane in the presence 10%
(w/w) of the metal triflate.
The diacetonide 21 underwent selective cleavage of the exocyclic acetal as
expected giving the monoisopropylidene derivative 46 in good isolated yield.
As to be expected, the reactions proceeded at a significantly faster rate at

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
471
Table 4: Indium(III) triflate-mediated hydrolysis of acetal derivatives of sugarsa
Entry
Starting sugar
Temp (◦C)
Time (h)
Product (yield, %)
1
2
3
4
5
6
7
8
21
21
21
47
47
48
50
52
50
70
70
50
70
70
70
70
2
1
46 (71)
46 (75)
5 (85)
15 (98)
15 (98)
49 (99)
51 (90)
53 (99)
10
1.5
0.5
0.5
3.5
1.5
aReactions were carried out in aqueous dioxane [10%, (v/v) 1 mL/100 mg sugar] con-
taining In(OTf)3 [10% (w/w) sugar].
the higher temperature employed (Table 4). It may be emphasized that un-
like in the case of the use of methanolic iodine,[15] for this category of re-
actions the present method is devoid of any risk of formation of methyl
glycosides as by-products. Also, other acid-sensitive groups such as the 2-
(trimethylsilyl)ethyl group (entry 6, Table 4) were stable and no loss of acetates
or acetyl migrations were observed (see entries 6 and 7, Table 4). Stabil-
ity of the glycosidic thiomethyl group as well as the phthalimido function-
ality under these hydrolytic conditions is evident from the high yield of the
diol 53 obtained in the hydrolysis of the benzylidene derivative 52 (entry 8,
Table 4). Compound 53 was further characterized as its corresponding acetate
derivative, methyl 4,6-di-O-acetyl-3-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-
D-glucopyranoside (54).
Thioglycosylation
Potential for further use of this metal triflate was indicated when 1,3,4,6-
tetra-O-acetyl-2-deoxy-2-phthalimido-α-D-glucopyranose (55)[16] was treated
with benzyl mercaptan (this particular thiol was chosen on account of
its relatively high boiling point; it also facilitates the reaction monitor-
ing by TLC using UV detection) in the presence of In(OTf)3 at 40◦C
to 50◦C whereby benzyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D-
glucopyranoside (56)[17] was obtained in 96% isolated yield. The reaction could
be facilitated successfully in the presence of one-fourth mol equiv of the triflate
reagent (as compared to the glycosyl acetate substrate 55 used) in refluxing
CH2Cl2 or in DCE at 50◦C, and as to be expected the product was exclusively
of 1,2-trans-cofiguration. Further work required in the optimization of the re-
action conditions and to explore the applicability of the method in preparing
various other thioglycosides are currently under way in our laboratory.
CONCLUSION
The use of indium(III) trifluoromethanesulfonate in various reactions (such
as acetylation and acetolysis, formation and hydrolysis of cyclic O-acetals,

S. K. Giri et al.
472
and thioglycosylation) of carbohydrates has been demonstrated in the present
work.
ACKNOWLEDGMENTS
We would like to thank the Department of Science & Technology, New Delhi,
India, for financial support.
EXPERIMENTAL
All reagents (Aldrich) were used as purchased without further purification.
Reactions were monitored by TLC, which was performed with 0.2-mm Merck
precoated silica gel 60 F254 aluminum sheets. Compounds were detected un-
der UV light and by dipping the TLC plates in an ethanolic solution of sul-
phuric acid (4% v/v) followed by heating. Silica gel 60–120 mesh (Spectrochem
Pvt. Ltd., India)/silica gel 200–400 mesh (SD Fine-Chem. Pvt. Ltd., India) was
used for column chromatography. Hexane refers to a mixture of isomeric hex-
anes. Melting points (uncorrected) were determined on a Digital Melting Point
Apparatus (Perfit, India). Optical rotations were recorded on a Rudolph AU-
TOPOL IV Polarimeter at approximately 24◦C. 1H NMR spectra were recorded
at 300 MHz on a Bruker DPX300 spectrometer in deuteriochloroform. Chemi-
cal shifts are expressed relative to that of the residual proton in the deuterated
solvents (δ 7.25). 13C NMR spectra were recorded at 75.47 MHz. Assignments
of resonances are based on published data. The anomeric ratios of products
reported in the tables were determined from their NMR spectra. All the com-
pounds, except 32, reported here have been reported previously; many are com-
mercially available and therefore analytical data for compound 32 only have
been listed here. The physical constants obtained for the known compounds
agreed with the literature data and their spectral data were in agreement with
the values expected for their respective structures. Room temperature refers
to approximately 30◦C.
General Procedure for Acetylation/Acetolysis
The sugar (or its derivative) was suspended (or dissolved as the case is)
in acetic anhydride (5 mL/g of sugar for acetylation and 10 mL/g of sugar for
acetolysis, see Tables 1 and 2) and stirred. In(OTf)3 (5 to 50 mg/g sugar or its
derivative, see Tables 1 and 2) was added and stirring was continued until TLC
showed the reaction to be complete. In small-scale reactions the reaction mix-
ture was diluted with CH2Cl2 and was washed successively with aq Na2CO3
and water. The organic layer was then dried (Na2SO4) and concentrated to
give the product. In large-scale acetylations the reaction mixture was poured
into ice-cold dilute sodium carbonate solution with stirring. The products were
allowed to crystallize in the refrigerator and were separated by filtration.

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
473
The products thus obtained were pure enough in most cases for use else-
where directly or else were purified by column chromatography.
The following compounds were prepared:
Compounds 2, 4, 6, 8, 10, 12, 14,[18,19] 16,[20] 18, 27, 29,[21] 20[23] (from
19[22]), 22, 24,[26] 25,[27,28] 26,[29] 28, 30,[12] 32,[32] and 33[33](from 31[30,31]).
Typical Procedure for the Acetylation of D-Glucose
D-Glucose (5, 1g, 5.55 mmol) was taken in acetic anhydride (5 mL) and
stirred at rt (32◦C) after the addition of In(OTf)3 (5 mg, 0.009 mmol). The im-
mediate warming of the reaction mixture indicated the onset of acetylation
and was soon led to the dissolution of the sugar indicating completion of the
reaction, which was confirmed by TLC (EtOAc:n-Hex, 1:1, v/v) on comparison
with authentic α-D-glucose penta-O-acetate. A colorless homogeneous reaction
mixture was obtained within a few minutes. The reaction mixture was diluted
with CH2Cl2 (20 mL) and was poured into a beaker containing crushed ice fol-
lowed by neutralization with aqueous Na2CO3. The product was extracted with
CH2Cl2 (20 mL × 2), and the combined organic extracts were washed succes-
sively with aq Na2CO3 as well as brine, dried (Na2SO4), and concentrated un-
der reduced pressure followed by crystallization (diethylether and petroleum
ether, bp. 60–80◦C). The product was obtained (2.1 g) as a colorless crystalline
solid in quantitative yield.
In large-scale preparations (5–50 g or more), the sugar was added to the
acid anhydride in portions and upon completion of the reaction, the mixture
was directly poured into a beaker containing crushed ice, neutralized with
aqueous Na2CO3, and left for a few hours in a fridge for crystallization. The
resulting solids were filtered, washed with ice-cold water, and dried under
reduced pressure. The product was obtained as white powder in quantitative
yield.
Preparation of 28
In(OTf)3 (5 mg, 0.009 mmol) was added to a stirred solution of 2,3,4,6-
tetra-O-benzyl-1-thio-β-D-glucopyranoside (27, 100 mg, 0.55mmol) in acetic
anhydride (1.5 mL) at rt (32◦C), and the stirring was continued until the
reaction was complete by TLC (EtOAc:n−Hex, 1:2, v/v). Aqueous workup as
discussed above yielded the desired product, 1,6-di-O-acetyl-2,3,4-tri-O-benzyl
D-glucopyranoside (28, α:β, 3.5:1),[12] as a colorless crystalline solid (yield, 86
mg, 92%).
General Procedure for Acetylation/Transacetylation
To a mixture of the sugar/sugar derivative in acetone (HPLC grade) or neat
PhCHO/PhCH(OMe)2/Me2C(OMe)2, depending upon the reaction, In(OTf)3

S. K. Giri et al.
474
was added at the desired temperature and was stirred until TLC showed com-
plete conversion. Aqueous workup yielded the products.
The following compounds were prepared:
Compounds 21,[24,25] 23,[24] 35,[34] 37,[35] 38,[25] 40,[36] 41,[37] 43,[38] 44,[39]
and 45.[40]
Preparation of 21
In(OTf)3 (100 mg, 0.18 mmol) was added to a suspension of D-Glucose
(1.0 g, 5.55 mmol) in acetone (50 mL) at reflux temperature and stirring was
continued until TLC (EtOAc:n-Hex, 1:1, v/v) showed complete conversion. No
undissolved sugar was visible at this stage. Aqueous workup yielded crys-
talline 1,2;5,6-di-O-isopropylidene-α-D-glucofuranose (21, 1.30 g, 90%).
In large-scale preparations most of the acetone used for the reaction could
be recovered by distillation of the reaction mixture under reduced pressure and
was suitable for recycling.
Preparation of 41
PhCH(OMe)2 (2.25 mL, 15 mol equiv) was added to methyl α-D-glucoside
(15, 194 mg, 1 mmol) followed by the addition of In(OTf)3 (4 mg/100 mg
sugar derivative) and the reaction mixture was stirred until dissolution of the
sugar derivative occurred (cf. 2 min). TLC (EtOAc:n-Hex, 2:1, v/v) at this stage
showed completion of the reaction. Aqueous workup followed by column chro-
matography (eluent, EtOAc:n-Hex, 1:4 followed by 1:1, v/v) yielded crystalline
41 (235 mg, 83%).
General Procedure for the Hydrolysis of Acetals
To the respective sugar derivative dissolved in aq dioxane (10%, v/v) was
added In(OTf)3, and the solution was stirred at 50◦C to 70◦C until TLC showed
complete conversion. The reaction mixture was then concentrated under re-
duced pressure and either directly passed through a column of silica gel for
purification (eluent, 25% MeOH in CH2Cl2) or subjected to acetylation as de-
scribed above to yield the corresponding acetylated sugar derivative.
The following compounds were prepared:
Compounds 46,[41] 15 (from 47[42]), 49[44] (from 48[44]), 51[46](from50[45]),
and 53[17] (from 52[43]).
Preparation of 46/5
To a solution of diacetone glucose (21, 100 mg) in aq dioxane (1 mL, 10%,
v/v) was added In(OTf)3 (10 mg) and it was stirred at 50◦C for 2 h when TLC
(EtOAc) showed completion of the reaction. It was then concentrated to a small

Indium(III) Triflate-Catalyzed Carbohydrate Reactions
475
volume and the product was isolated by passing through a short column of sil-
ica gel (eluent, EtOAc:n-Hex, 2:1) to yield the desired mono-O-acetone glucose
46 as white solid (60 mg, 71%). Similar reaction carried out at 70◦C for 1 h
yielded 46 in an isolated yield of 75% (64 mg) and at 50◦C for 10 h yielded
D-glucose (5, 59 mg) in 85% isolated yield.
General Procedure for Thioglycosylation
To a solution of the respective per-O-acetylated sugar derivative in CH2Cl2
(or DCE) was added benzyl mercaptan (3 mol equiv) followed by In(OTf)3
(0.25 mol equiv), and the solution was stirred at 40◦C (50◦C could be used if
DCE is employed as solvent, which was found to result in faster reactions)
until TLC showed complete consumption of the starting material. Aqueous
workup followed by purification by crystallization (Et2O-n-Hex) yielded the de-
sired thioglycoside.
Compound prepared in this manner: 56[17] from 55.[16]
Preparation of 56
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-phthalimido-α-D-glucopyranose (55, 238
mg, 0.5 mmol) was taken up in CH2Cl2 (2 mL) and to this was added benzyl
mercaptan (85 µL, 0.55 mmol) followed by In(OTf)3 (140 mg, 0.25 mmol). It was
then stirred for 2 h at 40◦C when TLC (EtOAc:n-Hex, 1:4) showed completion
of the reaction. The mixture was then diluted with CH2Cl2 and was subjected
to aq workup following which the product (56) was obtained as crystalline solid
(260 mg, 96%).
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