Solvent-free mechanochemical glycosylation in ball mill

Article abstract of DOI:10.1016/j.carres.2013.06.018

Starting from acetobromosugars and an alcohol (alkyl/substituted alkyl/akenyl/alkynyl/glyceryl/cyclohexyl/steryl) various O-glycosides have been prepared mechanochemically under solvent-free conditions employing a planetary ball mill in the presence of metal carbonates (environmentally benign or otherwise) as promoters. The method was proven to be mild and efficient and applicable on preparative scale for the synthesis of various mono- and disaccharide glycosides. 4-Pentenyl glycoside so produced could, in four successive reactions in the same pot, be converted in high isolated yields into triazole-substituted pentyl glycoside that can find application in the area of medicinal chemistry.

Full text of DOI:10.1016/j.carres.2013.06.018

Carbohydrate Research 379 (2013) 55–59
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Solvent-free mechanochemical glycosylation in ball mill
⇑
Mohit Tyagi, Darpan Khurana, K. P. Ravindranathan Kartha
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Punjab, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 April 2013
Received in revised form 19 June 2013
Accepted 20 June 2013
Available online 29 June 2013
Starting from acetobromosugars and an alcohol (alkyl/substituted alkyl/akenyl/alkynyl/glyceryl/cyclo-
hexyl/steryl) various O-glycosides have been prepared mechanochemically under solvent-free conditions
employing a planetary ball mill in the presence of metal carbonates (environmentally benign or other-
wise) as promoters. The method was proven to be mild and efficient and applicable on preparative scale
for the synthesis of various mono- and disaccharide glycosides. 4-Pentenyl glycoside so produced could,
in four successive reactions in the same pot, be converted in high isolated yields into triazole-substituted
pentyl glycoside that can find application in the area of medicinal chemistry.
Keywords:
Mechanochemical glycosylation
Metal carbonate-mediated glycosylation
Solvent-free glycosylation
Ó 2013 Elsevier Ltd. All rights reserved.
Multi-step mechanochemical reactions
1. Introduction
such that attempts to react acetylated glycosyl bromides with
the alcohol in the presence of potassium carbonate led to the for-
Carbohydrates play a manifold role in many of life’s important
biological processes and have hence been of considerable interest
to both chemists and biologists.1–7 Compounds ranging from sim-
ple glycosides to complex glycoconjugates have indeed been of
great interest and of ever-growing demand. For chemists, besides
many other important specific reasons, simple glycosides serve
as building blocks for complex synthetic operations and are there-
fore most often required in multi-gram quantities. Preparation and
use of these compounds in synthetic operations very often involve
toxic and hazardous solvents and reagents. In addressing environ-
mental concerns, thus, chemists have continued efforts towards
applying environmentally benign chemical substances in the syn-
thetic operations involved. Eliminating the use of solvents in
chemical reactions and doing them ‘neat’ can go a long way to-
wards achieving the goals of green chemistry.2 Mechanochemical
reactions carried out under solvent-free conditions with the help
of a ball mill have therefore become of increasing significance.8–10
We had recently reported on a highly efficient solvent-free
mechanochemical method for the synthesis of alkyl- and aryl thio-
glycosides, one of the most important classes of sugar derivatives
applied as starting materials in oligosaccharide synthesis, as well
as O-aryl glycosides.11 The method has now been extended to cov-
er the preparation of various other glycosides, such as pentenyl,
propargyl, allyl, (2-trimethylsilyl)ethyl, etc. glycosides, that are
also applied in synthetic carbohydrate chemistry very widely.12–
15 In the synthesis of the latter class of compounds the main stum-
bling block was the low nucleophilicity of the acceptor alcohol
mation of various by-products rather than the desired glycosides.
However metal carbonates of lower basicity, particularly those of
the d-Block elements, served the purpose very well and the results
are presented herein.
2. Results and discussion
In our attempts to generate libraries of carbohydrate-based
click macrocycles a need was felt for propargyl mono- and disac-
charide glycosides in substantial quantities. Therefore our initial
efforts were directed towards preparing the desired propargyl gly-
cosides in multi-gram quantities. Acetobromo-a-D-glucose (1) was
chosen to serve as the glycosyl donor substrate and thus it was co-
ground in a planetary ball mill with propargyl alcohol (2 mol
equiv) and K2CO3 (2.2 mol equiv) under the conditions optimized
for the synthesis of acetylated phenyl b-D-glucopyranoside 2 in
our earlier work.11 In less than 30 min at 600 rpm complete disap-
pearance of the bromide 1 occurred (TLC, EtOAc:Hex, 1:1). But un-
like in the preparation of the phenyl glycoside 2,11 the product
obtained was a mixture of several compounds with partially/fully
de-O-acetylated sugar skeleton. Importantly, the desired propargyl
glycoside 4 was not obtained. Clearly, the low nucleophilicity of
propargyl alcohol while preventing the desired glycosylation reac-
tion from happening, resulted instead in side reactions, to varying
extents, leading to facile base-catalysed removal of acyl residues
present on the sugar substrate. Besides, elimination of HBr giving
3 with random loss of the acyl protection had also occurred. The
reaction was therefore attempted in the presence of relatively
weaker metal carbonates. Thus, when K2CO3 was replaced with
CaCO3, the reaction indeed culminated in the formation of the
⇑
Corresponding author. Tel.: +91 172 229 2028; fax: +91 172 2214692.
E-mail address: rkartha@niper.ac.in (K.P. Ravindranathan Kartha).
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.06.018

56
M. Tyagi et al. / Carbohydrate Research 379 (2013) 55–59
desired glycoside 4 which was obtained pure after chromato-
graphic purification on a short column of silica gel (eluent, EtOA-
c:Hex, 1:20) in a yield of 63% (Table 1, entry 1).
ble 1, entry 2) the yield of 4 was found to be poorer and was only to
an extent of 45% best. However glycosylation tried under the con-
ventional Koenigs–Knorr promoter silver carbonate (though is
light and heat sensitive) gave the desired product 4 in an isolated
yield of 65% (Table 1, entry 3). The commercially available MnCO3
(Table 1, entry 4) on the other hand gave, after a 4 h reaction, 4 in a
yield of 69%. Use of basic metal carbonates such as those of Ni, Cu
and Zn (Table 1, entries 5–7, respectively) gave the product in the
range 61–76%, the higher yield being in the case of zinc carbonate.
Best result, though, was forthcoming from the use of CdCO3 (Ta-
ble 1, entry 8), namely, 83% yield of 4 in 2 h of grinding under
otherwise identical conditions as above (Table 1, entry 8). Thus,
it was possible to conclude that use of either Zn- or Cd-based car-
bonates could serve to promote solvent-free mechanochemical
glycosylation of acetobromoglucose (1) with only poorly nucleo-
philic propargyl alcohol in which the former will be the promoter
of choice from the green chemistry perspective. The structure of 4
was confirmed by 1H NMR spectroscopic analysis [anomeric proton
signal at d 4.78 ppm with coupling constant J1,2 = 8.0 Hz as well as
the aglycon-centred OCH2 protons at d 4.37 ppm (d, J = 2.4 Hz) and
the terminal OCH of the propargyl residue at 2.47 ppm (J = 2.4 Hz)]
and comparison of its physical constants with literature values.16 It
may be recalled that use of CdCO3 was reported as an improved
Koenigs–Knorr catalyst specifically for the preparation of steroidal
glycosides by Conrowan and Bernstein in 197117 but surprisingly
has not since been found applied to other examples, either in con-
ventional solution-phase or under solvent-free glycosylation
reactions.
OAc
OAc
O
OR
O
O
AcO
AcO
AcO
AcO
RO
OR
RO
AcO
AcO
Br
RO
3 R = Ac/H
1
2 R = Phenyl
4 R = Propargyl
Structures of compounds 1 - 4
To be applicable on a multi-gram scale thus promoters giving
better overall yields were desired and therefore screening some
of the other commercially available metal carbonates became nec-
essary. When CaCO3 was substituted by BaCO3 in the reaction (Ta-
Table 1
Optimization of conditions for metal carbonate-promoted solvent-free glycosylation
in a planetary ball milla
M2(CO3)x
OAc
(1.5 mol
equiv)
OAc
O
O
AcO
AcO
AcO
AcO
O
OH
AcO
Br
AcO
1
Ball-mill
600 rpm
4
Under the optimized reaction conditions when acetobromo-
Entry
Metal carbonate
Time (h)
Yield (%)
a-D-galactopyranose (5) was treated with propargyl alcohol the
1
2
3
4
5
6
7
8
CaCO3
BaCO3
Ag2CO3
MnCO3
NiCO3Á2Ni(OH)2ÁxH2O
CuCO3ÁCu(OH)2
ZnCO3ÁZn(OH)2
CdCO3
4
10
3
4
4
5
3.5
2
63
45
65
69
61
62
76
83
desired 1,2-trans-linked galactoside 6 was again obtained in good
isolated yield (79%, entry 1, Table 2). The higher reactivity of bromide
5 compared to the analogous 1 can be seen from a shorter reaction
time observed for the former. Likewise, the acetobromopentose 7
also reacted smoothly to give the corresponding pentoside 8 in
very good yield (87%, entry 2, Table 2). Benzobromoanalogue of 1
(9, entry 3, Table 2) also reacted efficiently giving the correspond-
ing glycoside 10 in 85% yield. As a typical disaccharide-derived
glycosyl halide lactosyl bromide 11 (Table 2, entry 4) was also tried
a
Compound 1 (1 mmol), propargyl alcohol (2 mmol) and the metal carbonate
(1.5 mmol) were homogenized in the ball mill. The yield reported is that of the
isolated pure product.
Table 2
Metal–carbonate-promoted solvent-free synthesis of various propargyl mono- and disaccharide glycosidesa
Entry
Substrate
Product
Time (h)
1.5
Yield (%)
79
AcO
OAc
O
AcO
OAc
O
1
AcO
O
AcO
AcO
AcO
Br
5
6
AcO
AcO
O
O
AcO
AcO
AcO
AcO
2
3
2
5
8
85
87
78
Br
O
7
8
OBz
O
OBz
O
BzO
BzO
BzO
BzO
O
BzO
BzO
Br
9
OAc
O
10
OAc
O
RO
AcO
RO
AcO
4
5
O
AcO
Br
AcO
12
11
R = 2,3,4,6-tetra-O-acetyl-b-
D
-galacto-pyranosyl
a
Substrate (1 mmol), propargyl alcohol (2 mmol) and the metal carbonate (1.5 mmol) were homogenized in the ball mill. The yield reported is that of the isolated pure
product.

M. Tyagi et al. / Carbohydrate Research 379 (2013) 55–59
57
Table 3
as a substrate for the reaction and the corresponding glycoside 12
Application of solvent-free glycosylation to a variety of alcohol acceptorsa
could also be isolated in a yield of 78%. It may be pointed out that
in none of the above cases presence of any orthoester by-product,
which occasionally accompanies the traditional Koenigs–Knorr
reaction, was noticed. In order to exclude any possibility of evad-
ing-detection (because of overlapping Rf value on TLC or possible
hydrolytic instability under silica gel column chromatography) of
the orthoester, its absence in the product was confirmed from
NMR spectroscopic analysis in which the H-1 (in the 1H NMR spec-
trum) and the C-1 and the tertiary orthoester carbon (in the 13C
NMR spectrum) are expected to have characteristic chemical shift
distinguishable clearly from the H-1 of the desired glycoside
product.
On successful completion of the application of the method
developed for the synthesis of propargyl glycosides of various
mono- and disaccharides described above, the method was ex-
tended to other important acceptor alcohols with a view to testing
the generality of its acceptance in the context of preparing various
other glycosides of high synthetic value. Thus, besides the propar-
gyl glucoside derivative 4 (Table 3, entry 1), various other glycoside
derivatives such as allyl, (13, entry 2, Table 3), 4-pentenyl (14, en-
try 3, Table 3), 2-(trimethylsilyl)ethyl (15, entry 4, Table 3), n-octyl
(16, entry 5, Table 3), n-hexadecyl (17, entry 6, Table 3), menthyl
(18, entry 7, Table 3), 1-(3-O-tosyl)glyceryl (19, entry 8, Table 3),
3b-cholesteryl (20, entry 9, Table 3) and benzyl (21, entry 10, Ta-
M2(CO3)x
(1.5 mol
equiv)
R-OH
Ball-mill
OAc
O
OAc
O
AcO
AcO
AcO
AcO
OR
AcO
AcO
12-22
Br
1
600 rpm
Entry
1b
Substrate
Time (h)
Product (yield %)
4 (87)
2
OH
OH
2
3
4
5
2.5
3
13 (82)
14 (87)
15 (88)
16 (88)
OH
OH
Me3SiO
3
OH
3
6
3
17 (85)
OH
10
OH
7
9
18 (74)
HO
8
8
19 (72)
TsO
OH
ble 3) b-D-glucopyranosides were also successfully synthesized in
excellent yields, except in the case of 20 where the isolated yield
obtained was only 35% (though comparable to the value of 24%
obtainable by the literature method).18 In the case of the partially
tosylated glycerol (Table 3, entry 8) the regioselectively glycosyl-
ated product 19 was interestingly obtained as the sole product,
in spite of the presence of the base-labile Ts group in the molecule
with possibility for base-catalysed intramolecular substitution
reaction.
9
15
20 (35)
21 (85)
H
H
H
HO
OH
10
4
a
Compound 1 (411 mg, 1 mmol), the desired alcohol (2 mmol) and the metal
carbonate (1.5 mmol) were homogenized in the ball mill. The yield reported is that
of the isolated pure product.
2.1. One-pot preparation of b-hydroxy triazoles by ball-milling
b
The reaction was carried out at 20 g scale.
During the foregoing work it became amply evident that even
the crude glycosylation products obtained on completion of the
reaction with the respective alcohol were fairly neat and hence
their further transformation must be possible if desired. Thus we
found an attractive opportunity to extend this method for the
one-pot synthesis of b-hydroxy triazoles, known for their medici-
nal application in HIV-protease inhibitors.19,20 In an attempt to
demonstrate this possibility the pentenyl glycoside 14 obtained
above was epoxidized under solvent-free conditions by using m-
chloroperbenzoic acid (m-CPBA) in the ball-mill (600 rpm, 2 h)
and was then subjected to epoxide ring opening by NaN3 by wet
grinding (55 min) in the presence of PEG-400 in the same pot, after
which the click reaction was also performed in the same pot
(30 min). The click product could then be isolated in 85% yield by
chromatographic filtration (Scheme 1).
3. Experimental
3.1. General
All reagents and chemicals were purchased from Aldrich Chem-
ical Co. (Milwaukee, WI, USA). Reactions were monitored by TLC,
which was performed on 0.2 mm Merck pre-coated silica gel 60
F254 aluminium sheets. Compounds were detected by dipping
the TLC plates in an ethanolic solution of sulfuric acid (5% v/v)
and thereafter heating them. Melting points were recorded on a
capillary melting point apparatus. Specific rotations were obtained
on Rudolph Research Autopol IV polarimeter at 20 °C. IR spectra
were recorded on a Nicolet FT-IR Impact 410 instrument either
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
a
O
c
O
b
O
AcO
AcO
AcO
22
1
2
Br
OAc
O
OAc
O
AcO
AcO
OH
N3
O
d
AcO
AcO
OH
O
AcO
AcO
23
N
N
24
N
Scheme 1. One-pot preparation of b-hydroxy triazoles from n-pentenyl glycosides by grinding. Reagents and conditions: (a) 4-penten-1-ol, M2(CO3)x, Ball-mill (600 rpm),
2 h; (b) m-CPBA (1.1 equiv), Ball-mill (600 rpm), 2 h; (c) NaN3 (1.1 equiv), PEG-400, Ball-mill (600 rpm), 55 min; (d) CuSO4Á5H2O (0.4 mol equiv)/sodium ascorbate, Ball-mill
(600 rpm), 30 min.

58
M. Tyagi et al. / Carbohydrate Research 379 (2013) 55–59
as neat or KBr pellets. 1H and 13C NMR spectra were referenced to
the internal standard tetramethylsilane, in the respective deuter-
ated solvents. Coupling constants (J) are reported in Hertz. High
resolution mass spectra (HRMS) were recorded on a Bruker Maxis
spectrometer. Data for compounds 2 and 24 only are listed below;
those for others can be found in the Supplementary data.
co-grinding with added 4-ethynyltoluene (1 mmol), CuSO4
(0.4 mmol) and sodium ascorbate (0.8 mmol)] in the same pot for
another 30 min which led to the complete conversion of the
in situ-formed azide derivative into the desired triazole derivative
24. The mixture was dissolved in EtOAc, and, after washing succes-
sively with aqueous sodium carbonate and water, it was concen-
trated to dryness under reduced pressure to give crude 24. It was
then purified by column chromatography to yield analytically pure
product. The spectral data were in accordance with the expected
structure.
3.2. General procedure for the metal carbonate-assisted
glycoside synthesis by planetary ball-milling as typical for
propargyl glycoside
The glycosyl bromide (1 mmol), propargyl alcohol (or another
acceptor alcohol desired, 2 mmol) and CdCO3/ZnCO3 (1.5 mmol)
were allowed to mix in a stainless steel (SS) jar (capacity, 50 mL)
containing 10 SS balls (10 mm o.d.) for 2 h (or until the reaction
is complete by TLC, depending upon the glycosyl bromide em-
ployed as substrate as in Table 2) in a planetary ball mill (Retsch
PM-100, Retsch GmbH, Germany) at 600 rpm. The reaction mixture
was dissolved in CH2Cl2 (or EtOAc, preferred as a greener alterna-
tive, is equally effective) and filtered through a Celite-bed and was
concentrated under reduced pressure to afford the respective
crude propargyl glycoside, which was purified by column chroma-
tography to yield analytically pure product. The spectral data were
in accordance with the expected structure and in agreement with
the literature values. The optimized method was also used for
the large scale (50 mmol-scale) preparation of propargyl 2,3,4,6-
3.3.1. 4-Hydroxy-5-[(4-p-tolyl-1,2,3-triazol)-1-yl]-pentyl 2,3,4,6-
tetra-O-acetyl-b-D-glucopyranoside (24)
Colourless syrup; dH (400 MHz, CDCl3); 7.83 (1H, 2s, CH Tria-
zole), 7.59 (2H, d, J 7.9 Hz, ArH), 7.17 (2H, d, J 8.0 Hz, ArH), 5.18
(1H, 2t, J 9.4 Hz, J 9.4 Hz, H-4), 4.95 (1H, t, J 8.0 Hz, H-2), 4.52–
4.42 (2H, m, H-1 & 1H of pentenyl residue), 4.22 (2H, m, H-6a &
1H of pentyl residue), 4.12 (2H, m, H-6a & 1H of pentyl residue),
3.91 (1H, m, 1H of pentyl residue), 3.67 (1H, m, H-5), 3.55 (1H,
m, 1H of pentyl residue), 2.35 (3H, s, ArCH3), 2.06–1.98 (12H, m,
4 Â OCOCH3), 1.24 (5H, s, 5H of pentyl residue); dC (100 MHz,
CDCl3); 175.21, 170.80, 170.77, 170.28, 169.65, 169.57, 169.47,
147.36, 139.26, 137.94, 137.92, 129.46, 127.46, 125.48, 120.98,
114.06, 100.74, 100.68, 69.89, 69.85, 69.78, 69.67, 68.36, 68.34,
61.82, 60.43, 56.14, 53.73, 33.80, 31.90, 31.72, 31.41, 31.11,
30.15, 29.67, 29.63, 29.59, 29.53, 29.48, 19.34, 19.19, 19.13,
18.92, 25.43, 25.37, 22.67, 21.26, 20.74, 20.69, 20.58, 14.11; IR
tetra-O-acetyl-b-
D-glucopyranoside (4) which was obtained in an
isolated yield of 87% after column chromatography.
(Neat) mmax; 1752, 1499, 1424, 1366, 1264, 1218, 1036, 896, 799,
732, 702; HRMS: m/z calculated for C28H37N3O11: 591.2428 Found
3.2.1. Propargyl 2,3,4,6-tetra-O-acetyl-b-
D
-glucopyranoside (2)16
614.2343 (M+Na)+.
Compound 2 was prepared by the general procedure described
above in 83% yield as white crystalline solid; mp 113–114 °C (lit.16
4. Conclusions
118–119 °C); [
a]
À48.4 (c 2, CHCl3) (lit.16 À50.5); dH (400 MHz,
D
CDCl3); 5.24 (1H, d, J 9.5 Hz, H-3), 5.10 (1H, t, J 9.6 Hz, H-4), 5.01
(1H, t, J 8.0 Hz, H-2), 4.78 (1H, d, J 8.0 Hz, H-1), 4.37 (2H, d, J
2.4 Hz, propargyl OCH2), 4.28 (1H, dd, J 4.6 Hz, J 12.3 Hz, H-6a),
4.14 (1H, dd, J 2.4 Hz, J 12.3 Hz, H-6b), 3.74 (1H, m, H-5), 2.09,
2.06, 2.03, 2.01 (12H, s, 4 Â OCOCH3), 2.47 (1H, t, J 2.4 Hz, propar-
gyl CH); dC (100 MHz, CDCl3); 170.60, 170.20, 170.09, 169.37,
98.09, 78.09, 75.53, 72.72, 71.87, 70.92, 68.26, 61.72, 55.91,
20.68, 20.64, 20.56; IR (Neat) mmax 3444, 2936, 1744, 1652, 1372,
1226, 1125, 1045; HRMS: m/z calculated for C17H22O10: 386.1213
Found 409.1110 (M+Na)+.
It has been successfully demonstrated that Zn and Cd carbon-
ates can be used to promote O-glycosylation of a range of poorly
nucleophilic alcohols by solvent-free homogenization of a mixture
of the desired acetobromosugar and the respective alcohol by
ball-milling. The product obtained is pure enough that successive
reactions in the same pot can lead to useful glycoconjugates of
potential biological activity.
Acknowledgement
Financial support by the Council of Scientific and Industrial
Research (CSIR), New Delhi (to M.T.) is gratefully acknowledged.
3.2.2. Propargyl 2,3,4-tri-O-acetyl-b-
L-arabinopyranoside (8)
Colourless syrup; [
a
]
D
À7.4 (c 2, CHCl3); dH (400 MHz, CDCl3);
5.27 (1H, m, H-4), 5.19 (1H, m, H-2), 5.07 (1H, m, H-3) 4.68 (1H,
d, J 6.8 Hz, H-1), 4.36 (2H, d, J 2.1 Hz, propargyl OCH2), 4.03 (1H,
m, H-5a), 3.66 (1H, m, H-5b), 2.46 (1H, t, J 2.3 Hz, propargyl CH),
2.13, 2.08, 2.03 (9H, s, 3 Â OCOCH3); dC (100 MHz, CDCl3);
170.30, 170.14, 169.57, 98.42, 78.34, 75.23, 70.04, 68.84, 67.54,
63.20, 55.61, 20.91, 20.81, 20.68; IR (Neat) mmax 3444, 2936,
1744, 1652, 1372, 1226, 1125, 1045; HRMS: m/z calculated for
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2013.
06.018.
References
C
14H18O8: 314.1002 Found 337.0902 (M+Na)+.
1. Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900–1934.
2. Galonic, D. P.; Gin, D. Y. Nature 2007, 446, 1000–1007.
3. Toshima, K. Carbohydr. Res. 2006, 341, 1282–1297.
4. Demchenko, A. V. Synlett 2003, 1225–1240.
3.3. General procedure for one-pot preparation of the b-hydroxy
triazoles under ball-milling conditions
5. Jensen, K. J. J. Chem. Soc., Perkin Trans. 1 2002, 2219–2233.
6. Davis, B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137–2160.
7. Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21–123.
8. Stolle, A.; Szuppa, T.; Leonhardt, S. E. S.; Ondruschka, B. Chem. Soc. Rev. 2011, 40,
2317.
Pentenyl glycoside (1 mmol) and m-CPBA (1.1 mmol) were
ground in a stainless steel (SS) jar (capacity, 50 mL) containing
10 SS balls (10 mm o.d.) for 2 h in a planetary ball mill (Retsch
PM-100, Retsch GmbH, Germany) at 600 rpm. After completion
of the epoxidation NaN3 (1.1 mmol) and PEG-400 (1 mL/100 mg
of substrate) were added to the same pot and the mixture was
ground until the disappearance of the epoxide was complete
(about 55 min). It was then subjected to click reaction by further
ˇ ´
9. James, S. L.; Adams, C. J.; Bolm, C.; Braga, D.; Collier, P.; Frišcic, T.; Grepioni, F.;
Harris, K. D. M.; Hyett, G.; Jones, W.; Krebs, A.; Mack, J.; Maini, L.; Orpen, A. G.;
Parkin, I. P.; Shearouse, W. C.; Steed, J. W.; Waddell, D. C. Chem. Soc. Rev. 2012,
41, 413–447.
10. Kaupp, G. Top. Curr. Chem. 2005, 254, 95–183.
11. Patil, P. R.; Kartha, K. P. R. Green Chem. 2009, 11, 953–956.

M. Tyagi et al. / Carbohydrate Research 379 (2013) 55–59
59
12. Hotha, S.; Kashyap, S. J. Am. Chem. Soc. 2006, 128, 9620–9621.
13. Wang, P.; Haldar, P.; Wang, Y.; Hu, H. J. Org. Chem. 2007, 72, 5870–5873.
14. Nicolaou, K. C.; Seitz, S. P.; Papahatjis, D. P. J. Am. Chem. Soc. 1983, 105, 2430–
2434.
15. Lipshutz, B. H.; Pegram, J. J.; Morey, M. C. Tetrahedron Lett. 1981, 22, 4603–
4606.
17. Conrowan, R. B.; Bernstein, D. S. J. Org. Chem. 1971, 36, 863–870; Reviewed in
Pellissier, H. Tetrahedron 2004, 60, 5123–5162.
18. Goto, J.; Suzaki, K.; Nambara, T. Chem. Pharm. Bull. 1979, 27, 1926–1931.
19. Brik, A.; Muldoon, J.; Lin, Y.-C.; Elder, J. H.; Goodsell, D. S.; Olson, A. J.; Fokin, V.
V.; Sharpless, K. B.; Wong, C.-H. ChemBioChem 2003, 4, 1246–1248.
20. Brik, A.; Alexandratos, J.; Lin, Y.-C.; Elder, J. H.; Olson, A. J.; Wlodawer, A.;
Goodsell, D. S.; Wong, C.-H. ChemBioChem 2005, 6, 1167–1169.
16. Mesires, R.; Gonzaljzz, A.; Santamaria, C. Carbohydr. Res. 1972, 22, 457–459.