Scope and limitations of imidazolium-based ionic liquids as room temperature glycosylation promoters

Article abstract of DOI:10.1016/j.carres.2009.09.034

The scope and limitations of imidazolium-based ionic liquids as room temperature glycosylation promoters have been studied. Herein, we report the effects of modifying the structure of the imidazolium cation and how important the choice of counter ion becomes on model glycosylation reactions of thioglycosides at room temperature in the presence of N-iodosuccinimide (NIS).

Full text of DOI:10.1016/j.carres.2009.09.034

Carbohydrate Research 345 (2010) 45–49
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Scope and limitations of imidazolium-based ionic liquids as room
temperature glycosylation promoters
*
M. Carmen Galan , Kevin Jouvin, Dimitri Alvarez-Dorta
School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 August 2009
Received in revised form 28 September 2009
Accepted 29 September 2009
Available online 7 October 2009
The scope and limitations of imidazolium-based ionic liquids as room temperature glycosylation promot-
ers have been studied. Herein, we report the effects of modifying the structure of the imidazolium cation
and how important the choice of counter ion becomes on model glycosylation reactions of thioglycosides
at room temperature in the presence of N-iodosuccinimide (NIS).
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Oligosaccharide synthesis
Glycosylation at room temperature
Ionic liquids
1. Introduction
thiophenyl and trichloroacetimidate glycoside donors; the condi-
tions are mild, and compatible with a range of hydroxyl-protecting
Carbohydrates continue to be a central focus of research in
chemistry, biology and material science.1–3 Although many chem-
ical approaches have been developed, the synthesis of complex
oligosaccharides is still troublesome.4,5 Thus, there is great interest
in the development of novel and general strategies that will lead
to the efficient synthesis of complex carbohydrates. Factors includ-
ing the choice of leaving group at the anomeric position of the do-
nor, the selection of protecting groups in both the donor and
acceptor moieties, the solvent system, and the choice of promoter
need to be considered when carrying out the synthesis of glyco-
sides.6 Glycosidic bond formation is a crucial step in oligosaccha-
ride synthesis but despite many efforts, there is still a need to
identify a general, mild, and convenient glycosylation promoter.
Room temperature ionic liquids (RTILs) have recently emerged
as a new class of solvents for a wide range of organic reactions.
groups, such as acetates, benzyl ethers, acetals, and also amenable
to NH2 masking strategies, that is, phthalimide (Phth) and trichlo-
roethylcarbamate (Troc). We have also shown that 1a can selec-
tively promote activated (armed) trichloroacetimidate glycosyl
donors and thiophenyl glycosides in combination with NIS, while
less active (disarmed) donors required the addition of catalytic tri-
flic acid. Initial mechanistic studies suggest that 1a can facilitate
glycosylation reactions by the slow release of catalytic amounts
of triflic acid and that 1a also protects the newly formed glycosidic
linkage from hydrolysis.15
It is well established that ILs can be fine-tuned by changing the
anion or cation to produce derivatives with different physical and
chemical properties.9,16 With that in mind, we decided to explore
the scope of modified ILs by generating a series of imidazolium-
based ILs 1a–n, with differing R1 and R2 groups and different coun-
ter ions (Xꢀ) (Fig. 1) and testing their effectiveness in glycosylation
reactions to gain a better understanding of the IL-promoted glyco-
sylation and to find an optimum IL to carry out the reaction. We
focused on thioglycosides as a suitable glycosyl donor due to its
wide applicability and effectiveness on these types of reactions.17
Herein, we report the effects of modified ionic liquids on model
glycosylation reactions of thioglycosides at room temperature.
7–9
The high polarity of RTILs can provide strong accelerating ef-
fects to reactions involving cationic intermediates7 and in particu-
lar they have been shown to exhibit excellent solubilizing
properties, facilitating a wide range of chemical transformations,
including acetylation, ortho-esterification, benzylidenation, and
glycosylation reactions of carbohydrates.10–15
As part of our program to develop new methods and strategies
for oligosaccharide synthesis, we became interested in the applica-
tion of ionic liquids for glycosylation reactions. We have recently
reported the use of [bmim][OTf] 1a as a mild and versatile ionic li-
quid (IL) promoter for the room temperature glycosylation of both
2. Results and discussion
Previously, we demonstrated that triflate-based 1a was success-
fully used to catalyze the glycosylation reaction of thioglycosides,15
moreover the participation of triflated ionic liquids in the
reaction mechanism involving trichloroacetimidates has also been
* Corresponding author. Tel.: +44 1179287654; fax: +44 1179298611.
E-mail address: M.C.Galan@bristol.ac.uk (M.C. Galan).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.09.034

46
M. C. Galan et al. / Carbohydrate Research 345 (2010) 45–49
Ionic Liquids
+
Thioglycoside Donors
X-
OR
OR
OR
N
N
O
O
R1
RO
RO
2
R2
SPh
SPh
RO
OR
OR
1a R =Me, R =H, X=OTf
2a
1
2
R=Bn
2b R=Ac
3a R=Bn
1b
R =Me, R =H, X=N(Tf)
3b R=Ac
1
2
2
1c R =Me, R =H, X=BF
1
2
4
6
1d R =Me, R =H, X=PF
1
1
2
2
2
2
Glycoside Acceptor
1e
1f
R =Me, R =H, X=Br
R =Me, R =H, X=Cl
1
OH
O
O
1g R =Me, R =H, X=AlCl
1
4
3
1h R =Me, R =H, X=HSO
1
2
O
1i
1j R =CH COOH, R =H, X=OTf
R =CH COOH, R =H, X=BF
1
2
2
4
O
O
4
1
2
2
O
1k
R =
1
, R =H, X=OTf
2
1l R =Me, R =Me, X=OTf
1
2
1m
1n
R =Me, R =Ph, X=OTf
1
2
R =Me, R =Ph, X=N(Tf)
1
2
2
Figure 1. Ionic liquids, thioglycoside donors, and model acceptor used in this study.
reported.18 In order to study the effect of the counter ion, a series of
commercial ILs were screened for their ability to promote glycosyl-
ation reactions. These ILs contained 1-butyl-3-methylimidazolium
as the cation with a variety of counter ions. In brief, anions such as
bis(trifluoromethylsulfonyl)imide (NðTfOÞ2ꢀ) 1b and PF6ꢀ 1d, which
are widely used in catalytic applications and grant hydrophobic
properties to the IL.19–21 Hydrophilic ILs with counter ions such as,
Table 1
Summary of glycosylation reactions with thioglycoside donor 2a and model acceptor 4
in the presence of different IL promoters at room temperature to yield disaccharide 5a
4
2a
5a
Promoter
NIS (2 equiv), DCM
BF4 1c, Brꢀ 1e and Clꢀ 1f and acidic IL 1g containing chloroalumi-
ꢀ
Entry
Promoter
Yield (%)
Ratio
a
/b
Reaction time (h)
nate (ClꢁAlCl3ꢀ) as the anion, which have been successfully used as
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
TMSOTf
75
77
86
0.02/1
3
3
6
a
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
0.40/0.60
0.52/0.48
—
a
dual Lewis acid catalyst/solvent in the sulfamoylation of
arenes.22,23 Finally, hydrogen sulfate (HSO4ꢀ) containing 1h, a Bron-
sted acidic IL.24 For the purpose of the study, a series of glucose- and
galactose-based thioglycoside donors were prepared following
reported procedures. Thus phenyl 2,3,4,6,-tetra-O-benzyl-1-
s.m.
<5 + s.m.
s.m.
s.m.
<10 + s.m.
s.m.
s.m.
65
24
24
24
24
24
24
24
3
3
2
1
6
N.D.
—
—
N.D.
—
—
thio-b-
thio-b-
D
-glucopyranoside 2a,25 phenyl 2,3,4,6,-tetra-O-acetyl-1-
-glucopyranoside 2b,26 phenyl 2,3,4,6,-tetra-O-benzyl-
D
1-thio-b-
yl-1-thio-b-
and reacted with commercial 1,2:3,4-di-O-isopropylidene-
D
-galactopyranoside 3a27 and phenyl 2,3,4,6,-tetra-O-acet-
0.52/0.48
0.55/0.45
0.54/0.46
0.58/0.43
0.53/0.47
D
-galactopyranoside 3b25 were obtained in good yields
71
77
97
80
a-D-
galactopyranose 4 as model acceptor in the presence of the different
ILs 1a–n (Fig. 1) to yield the corresponding disaccharides (Fig. 2).
Initial screen of glycosylation was performed with armed thio-
glycoside donor 2a, (Table 1). Reactions with 1b as the promoter,
which contains a bistriflimide-based counter ion, (Table 1, entry
3), gave the corresponding disaccharide 6a28 (Fig. 2) in yields com-
parable to those of the reaction carried out in the presence of 1a at
room temperature15 or TMSOTf at low temperatures (Table 1, en-
N.D. not determined.
s.m. starting material.
a
The reaction was performed in DCM with TMSOTf (0.2 equiv) at ꢀ40 °C.
entries 4–10) resulted in no reaction or degradation of the starting
materials. These results clearly highlight the importance of the
choice of counter ion in the IL and further emphasizes the role of
triflate- and triflimide-based anions for catalyzing these types of
glycosylation reactions.
tries 1 and 2). An increase in the a-linked disaccharide was noted
for 1b when compared to the reaction carried out with TMSOTf,
which was also observed in reactions promoted by 1a. On the other
hand, reactions carried out with more hydrophilic ILs 1c–i (Table 1,
Having demonstrated the significance of the counter ion, we
next studied the effect that substituents on the imidazolium moi-
ety will induce in the glycosylation reaction. To that end, tethered
OR
OR
O
OR
O
imidazolium carboxylic acid 1i29 was prepared and BF4 was cho-
ꢀ
RO
RO
O
O
RO
sen as an inert counter ion, so that any glycosylation product ob-
served could only be attributed to the modification at R1.
Nonetheless, no reaction was observed and the starting material
was recovered. When 1j,29 which contains a OTfꢀ as counter
ion was used, the reactivity of the IL toward promoting glycosyla-
tion was restored, confirming the importance of the counter ion
(Table 1, entries 10 and 11).
OR
OR
O
O
O
O
5a R=Bn
5b R=Ac
6a R=Bn
6b R=Ac
O
O
O
O
O
O
Figure 2. Structures of glycoside products 6–7.

M. C. Galan et al. / Carbohydrate Research 345 (2010) 45–49
47
Table 2
Chiral ILs (CILs) have become very popular in the recent years as
a source for novel chiral solvents that can influence the outcome of
asymmetric reactions.30 In particular, camphor derivatives have
proved to be excellent chiral auxiliaries due to their special steric
demands and more recently, they have been used to some success,
in controlling the diastereoselectivity in Diels–Alder reactions, as
either the anion or cation of the IL.31,32 Camphor-derived imidazo-
lium triflate 1k, was prepared by a modified literature procedure.31
In brief, treatment of (1S)-(+)-camphorsulfonic acid 8 with iodine
in the presence of triphenylphosphine yielded the 10-iodo cam-
phor intermediate 9, which was further reacted with N-methylim-
idazole applying microwave conditions to afford the imidazolium
salt 10. Anion metathesis with KOTf afforded 1k in a 48% overall
yield. (Scheme 1). When 1k was used as a promoter in the glyco-
sylation reaction of 2a with 4 (Table 1, entry 12), the reaction pro-
ceeded in good yields at room temperature, however no change in
Summary of glycosylation reactions of thioglycoside donors 3a, 2b, and 3b with
model acceptor 4
O
O
Donor
Donor
4
PO
PO
OR
SPh
Promotera
NIS (2 equiv), DCM
Product
Entry
Promoter
Yield (%)
Product
Ratio
Reaction
time (h)
a/b
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
2b
2b
2b
2b
3b
3b
3b
3b
TMSOTfb
75
97
90
72
70
80
6a
6a
6a
6a
5b
5b
—
5b
6b
6b
—
0.02/1
0.78/1
0.75/1
0.67/1
Only b
Only b
—
Only b
Only b
Only b
—
3
3
2
1
3
1a
1l
1m
b
TMSOTf
1a, TMSOTf
3
1l
1m
s.m.
10 + s.m.
83
24
24
3
3
24
24
b
the diastereoselectivity was observed when comparing the
a/b
TMSOTf
10
11
12
1a, TMSOTf
95
ratio of the reaction with those obtained for active ILs 1a and 1b
(Table 1, entries 2, 3 and 12).
1l
1m
s.m.
20 + s.m.
6b
Only b
In our previous studies, 1-butyl-2,3-dimethyl imidazolium tri-
flate 1l was synthesized and used to investigate the role of the
H-2 of the imidazolium moiety in 1a in the activation of the glyco-
syl donor.15 (Table 1, entry 13) Interestingly, the reaction with 1l
yielded the corresponding glycosyl products in good yields and
the reaction time was shortened, suggesting that substitution at
R2 of the imidazolium ring had an effect on the rate of the reaction.
To further exploit that observation, ILs 1m and 1n, which bear a
phenyl substituent at R2 and a ꢀOTf or ꢀN(Tf)2, respectively, as
counter ions, were prepared from 2-phenylimidazole 11 following
a literature procedure33 and tested in the glycosylation reaction of
glycosyl donor 2a with acceptor 4. Reactions proceeded in excel-
lent yields, at room temperature and in a third of the time. In addi-
tion, no change in the stereoselectivity was noted when comparing
s.m. starting material.
a
Unless indicated otherwise, reactions were carried out at room temperature.
The reaction was performed in DCM with TMSOTf (0.2 equiv) at ꢀ40 °C.
b
1–4). Furthermore, an increase in the a/b ratio was also observed
for reactions promoted at room temperature by ILs in this screen,
as it was shown in the glucoside series (Table 1). It is important
to note that reactions with 1m (R2 = Ph) as co-solvent/promoter
with ‘armed’ donor 3a and 3b, proceeded faster, reactions were
complete within 1 h, while reactions with 1l (R2 = Me) were com-
plete after 2 h and 1a (R2 = H) 3 h, as determined by TLC. These re-
sults suggest that by introducing hydrophobic groups at the R2
position of the imidazolium cation, we can increase the reactivity
of the IL toward promoting this type of glycosylation reactions.
Previously, we reported that peracetylated thioglycoside do-
nors, which are electronically deactivated species (disarmed)34
could not be efficiently activated by 1a, but that the addition of cat-
alytic triflic acid (0.2 mol %) was sufficient to carry out the reac-
tions while still at room temperature and in good yields.15 With
that in mind, reactions of peracetylated thioglycoside donors 2b
and 3b with model acceptor 4 were carried out with the more reac-
tive 1m and 1l. However only starting material was recovered for
reactions with 1m (Table 2, entries 7 and 11) and only small
amounts of product (10% 5b and 20% 6b) were detected for reac-
tions carried out with 1l after 16 h (Table 2, entries 8 and 12). In
terms of the reactivity of the IL, the results are encouraging and ef-
forts are underway to find a more reactive IL that could activate
‘disarmed’ glycosides by finding the optimum substitution at R2
of the imidazolium cation.
it with the a/b ratios obtained for reactions with 1a or 1b (Table 1,
entries 2, 3, 14 and 15).
Encouraged by these results, we decided to extend our studies
to other common thiophenyl glycosides. Activated perbenzylated
galactopyranoside 3a and disarmed peracetylated thioglycosides
2b and 3b were tested with IL promoters 1a, 1l, and 1m, which
showed the best reactivities in the initial screening, with model
glycosyl acceptor 4 (Table 2).
In general, conversion yields for activated glycoside 3a were
good with all of the tested ILs at room temperature in comparison
to the reaction carried out at ꢀ40 °C with TMSOTf (Table 2, entries
7
N-methyl-
imidazole,
4
I2, PPh3
MW, 130°C
5
3
1
2
6
PhMe, 56%
10
O
O
N
O
SO3H
X-
N
I
9
3. Summary
8
10 X= I-
1j X= -OTf
In summary, we have shown that imidazolium-based ILs bear-
ing triflate or triflimide counter ions serve as room temperature
selective glycosylation promoters for activated (armed) thiophenyl
glycosyl donors, thus we have further demonstrated the impor-
tance of the choice of counter ion when choosing an IL to promote
these types of glycosidic bond-forming reactions. Furthermore,
substitutions at R1 of the imidazolium cation do not have an effect
on the reactivity or diastereoselectivity of thioglycoside glycosyla-
tions, while modifications at R2 have an effect in the rate of glyco-
sidic bond-forming reactions. The stereoselectivity of the
glycosylation reactions is significantly affected by the IL, with an
KOTf, CH3CN
85% (2 steps)
a) MeI, Tol
NaOH, H2O,
TBAI
Ph
Ph
X-
N
N
N
N
b)
Br
11
120°C, MeCN
-
12
X= I
1l X= -OTf
KOTf or KN(Tf)2, CH3CN
75-77% (3 steps)
1m X=
-N(OTf)2
increase in the amount of
a glycoside products. The ability to
recycle the IL promoter is also very attractive in terms of green
Scheme 1. Preparation of ionic liquids 1k–m.

48
M. C. Galan et al. / Carbohydrate Research 345 (2010) 45–49
chemistry, and in general the ability of ILs to promote glycosyla-
tion reactions at room temperature is amenable to cost effective
automated oligosaccharide synthetic protocols where no strict
control of low temperatures will be required.
silica gel chromatography (gradient hexane/ethyl acetate, 3:1 to
1:1, v/v) to yield the corresponding oligosaccharides 5a and 6a.
4.2.1.2. (B) For deactivated thiophenyl donors 2b and 3b with
glycosyl acceptors
(0.2 equiv) was added to
4
.
Trimethylsilyl trifluoromethanesulfonate
stirred suspension of 1-butyl-3-
a
4. Experimental
4.1. General
methyl imidazolium triflate 1a, thioglycoside donor (1.5 equiv),
glycosyl acceptor (1 equiv), and NIS (2 equiv) in dry dichloro-
methane (3–10 mL). The mixture was left stirring at rt for 6 h.
TLC (hexane/ethyl acetate, 1:1, v/v) indicated completion of the
reaction. The mixture was neutralized with triethylamine
(2 equiv) and concentrated under reduced pressure. The syrup
mixture was then washed with diethyl ether (4 ꢂ 30 mL) to ex-
tract the product from the ionic liquid, which was monitored
by TLC to ensure the product was in the ether phase. Interest-
ingly, NIS showed preferential solubility in the [bmim][OTf]
phase and it did not extract into the ether portion. The washes
were then collected and after evaporation of the solvent, the res-
idue was further purified by flash silica gel chromatography (gra-
dient hexane/ethyl acetate, 3:1 to 1:1, v/v) to yield the
corresponding oligosaccharides 5b and 6b.
Chemicals were purchased from Aldrich and Fluka and used
without further purification. Molecular sieves were activated at
350 °C for 3 h and cooled under vacuum. Dry solvents, where
necessary, where obtained by distillation using standard proce-
dures or by passage through a column of anhydrous alumina
using equipment from Anhydrous Engineering (University of
Bristol) based on Grubbs’ design. Reactions requiring anhydrous
conditions were performed under an atmosphere of dry nitrogen;
glassware, syringes, and needles were either flame dried immedi-
ately prior to use or placed in an oven (150 °C) for at least 2 h
and allowed to cool either in a desiccator or under an atmo-
sphere of dry nitrogen; liquid reagents, solutions or solvents
were added via syringe or cannula through rubber septa; solid
reagents were added via Schlenk type adapters. Typical reactions
were carried out in 40–50 mg scale. Reactions were monitored by
TLC on Kieselgel 60 F254 (Merck). Detection was by examination
under UV light (254 nm) and by charring with 10% sulfuric acid
in methanol. Flash chromatography was performed using silica
4.2.2. Typical TMSOTf-promoted glycosylation procedures
4.2.2.1. (C) For thiophenyl donors 2b and 3b with glycosyl
acceptors 4. Trimethylsilyl trifluoromethanesulfonate (0.4 equiv)
was added to a stirred suspension of thiophenyl donor (1.5 equiv),
glycosyl acceptor (1 equiv), NIS (2 equiv) and freshly activated
powdered molecular sieves 4 Å (50–200 mg) in dry dichlorometh-
ane (3–10 mL). The mixture was left stirring at ꢀ40 °C for 3 h and
then let stir at room temperature for another hour. TLC (hexane/
ethyl acetate, 1:1, v/v) indicated completion of the reaction. The
mixture was neutralized with triethylamine (2 equiv) and then fil-
tered over Celite. The filtrate washings were combined and con-
centrated under reduced pressure. The residue was then diluted
in dichloromethane (30 mL), washed successively with a saturated
aqueous solution of NaHCO3 (10 mL), water (2 ꢂ 10 L), and brine
(10 mL), followed by drying over MgSO4. After evaporation of the
solvent, the residue was purified by flash silica gel chromatography
(gradient hexane/ethyl acetate, 3:1 to 1:1, v/v) to yield the corre-
sponding oligosaccharides 5b and 6b.
gel [Merck, 230–400 mesh (40–63 lm)], the crude material was
applied to the column as a solution in CH2Cl2 or by pre-adsorp-
tion onto silica, as appropriate. Extracts were concentrated under
reduced pressure using both a Büchi rotary evaporator (bath
temperatures up to 40 °C) at a pressure of either 15 mmHg (dia-
phragm pump) or 0.1 mmHg (oil pump), as appropriate, and a
high vacuum line at room temperature. 1H NMR and 13C NMR
spectra were measured in the solvent stated at 400 or 600 MHz
on JOEL JNM-GX400, JOEL Eclipse 400 or Varian INOVA 600
instruments, respectively. Chemical shifts quoted in parts per
million from SiMe4 and coupling constants (J) given in hertz.
Multiplicities are abbreviated as: br (broad),
s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet) or combinations
thereof. Negative ion matrix assisted laser desorption ionization
time-of-flight (MALDI-TOF) mass spectra were recorded using a
HP-MALDI instrument using gentisic acid matrix. Water content
measure by Karl Fisher titration in a Metrohm 756 KF Coulome-
ter equipped with a diaphragm free cell and 703 Titration Stand.
The KF reagent is Hydranal-Coulomat AG from Riedel-deHaen.
4.2.3. 1-Methyl-3-[(1S,4R)-(2-oxo-7,7-dimethylbicyclo[2.2.1]hept-
1-yl)methyl]imidazolium trifluoromethanesulfonate (1k)
10-Iodocamphor 5 (100 mg, 0.39 mmol) and N-methylimidaz-
ole (40 mg, 0.50 mmol) were added in a microwave vial in EtOAc
(80 lL) and sealed under N2. Irradiation at 130 °C for 5 h at 50 W.
The immiscible layer of ionic liquid was then separated from the
EtOAc and the crude ionic mixture was dissolved in dry acetonitrile
(0.5 mL) and KOTf added (75 mg, 0.4 mmol). The mixture was stir-
red under N2 for 24 h. Inorganic salts were filtered over a short pad
of Celite. The filtrate was evaporated to dryness and washed with
hexane and EtOAc. The solid was then dried under high vacuum
to yield 1k (109 mg, 0.33 mmol). dH (400 MHz, CDCl3) 9.52 (s, 1H,
NCHN), 7.61 (s, 1H, NCHCHN), 7.45 (s, 1H, NCHCHN), 4.22 (d, 1H,
J14.2 Hz, H-10), 3.93 (3H, s, CH3N), 2.31 (1H, ddd, J 18.7, 4.6,
1.8 Hz, H-3a), 2.25-2.12 (m, 3H, H-4, H-6a, H-5a), 1.85 (d, 1H, J
18.7 Hz, H-3b), 1.33-1.18 (m, 2H, H-6b, H-5b), 1.13 (s, 3H, H-8),
0.84 (s, 3H, H-9). dC (100.26 MHz, CDCl3) 216.3 (C, C-2), 137.3
(CH, NCHN), 123.6 (CH, NCHCHN), 123.2 (CH, NCHCHN), 60.9 (C,
C-1), 47.2 (CH2, C-10), 46.4 (CH3, C-7), 43.6 (CH3), 41.4 (CH2, C-
3), 36.5 (CH, C-4), 25.3 (CH2, C-5), 25.3 (CH2, C-6), 19.6 (CH3, C-8
or C-9), 19.4 (CH3, C-8 or C-9). dF (283 MHz, CDCl3) ꢀ77.07 (s, 3F,
OSO2CF3)) HRMS-FAB: m/z calcd for C14H21N2O: 233.1654; found:
233.1657.
4.2. General protocols for glycosylation reactions
4.2.1. Typical IL (1a–f) promoted glycosylation procedures
4.2.1.1. (A) For activated thiophenyl donors 2a and 3a with
glycosyl acceptors 4. IL (1a–n) (300 lL) was added to a stirred sus-
pension of thioglycoside donor (1.5 equiv), glycosyl acceptor
(1 equiv), and NIS (2 equiv) in dry dichloromethane (3–10 mL).
The mixture was left stirring at rt or 1–16 h. TLC (hexane/ethyl ace-
tate, 1:1, v/v) indicated completion of the reaction. The mixture
was neutralized with triethylamine (2 equiv) and concentrated un-
der reduced pressure. The sirup mixture was then washed with
diethyl ether (4 ꢂ 30 mL) to extract the product from the ionic li-
quid, which was monitored by TLC to ensure the product was in
the ether phase. Interestingly, NIS shows preferential solubility
in the ionic liquid phase for 1a–b and 1l–n, thus it did not extract
into the ether portion. The washes were then collected and after
evaporation of the solvent, the residue was further purified by flash

M. C. Galan et al. / Carbohydrate Research 345 (2010) 45–49
49
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We gratefully acknowledge financial support from EPSRC and
The Royal Society and thank Dr. Craig Butts and Dr. Gregory M.
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