Glycosylation in ionic liquids

Article abstract of DOI:10.1055/s-2003-41446

Glycosyl trichloroacetimidates react smoothly in the presence of trimethylsilyl trifluoromethanesulfonate as a catalyst with a variety of alcohols and monosaccharides in [bmim]PF₆ (1-butyl-3-methylimidazolium hexafluorophosphate) as a solvent to afford the corresponding glycosides or disaccharides.

Full text of DOI:10.1055/s-2003-41446

2074
PAPER
Glycosylation in Ionic Liquids
G
lycosylation in
b
Ionic
L
iqui
i
ds gniew Pakulski*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland
Fax +48(22)6326681; E-mail: pakul@icho.edu.pl
Received 22 April 2003; revised 24 June 2003
As expected, in the presence of trimethylsilyl trifluo-
romethanesulfonate (TMSOTf) only a-mannopyrano-
sides 2 and 3 were obtained (Figure 1, Table 1).
Formation of b-mannosides was not observed because of
a strong anomeric effect and the influence of the partici-
pating benzoyl group.12 A similar result was obtained for
methyl 6-hydroxyhexanoate which formed mannoside 410
in good yield. Reaction of trichloroacetimidate 1 with me-
thyl 2,3-O-isopropylidene-b-D-ribofuranoside (7) proced-
ed smoothly and methyl 2,3,4,6-tetra-O-benzoyl-a-D-
mannopyranosyl-(1→5)-2,3-O-isopropylidene-b-D-ribo-
furanoside (5) was obtained in 77% yield.
Abstract: Glycosyl trichloroacetimidates react smoothly in the
presence of trimethylsilyl trifluoromethanesulfonate as a catalyst
with a variety of alcohols and monosaccharides in [bmim]PF6 (1-
butyl-3-methylimidazolium hexafluorophosphate) as a solvent to
afford the corresponding glycosides or disaccharides.
Key words: glycosylation, ionic liquid, disaccharides
To date, most chemical reactions have been carried out in
volatile organic solvents (VOCs – volatile organic com-
pounds). However, the toxicity, hazardous properties of
many solvents and serious environmental issues prompted
chemists in the quest for novel reaction media. Recently
rediscovered ionic liquids (ILs) seem to be an excellent al-
ternative to VOCs and environmentally benign ‘green’
solvents. ILs possess several attractive properties. They
have no measurable vapor pressure, so they can emit no
VOCs, they are chemically and thermally stable, nonflam-
matory and in most cases water- and air-stable. Addition-
ally, chemical and physicochemical properties of ILs can
be easily switched by changing one of the components
(the anion or cation). In the recent decade several organic
reactions using ILs both as solvents and/or catalysts have
been described, e.g. Friedel–Crafts alkylation/acylation,
Heck reaction, Diels–Alder reaction, Pauson–Khand reac-
tion, hydroformylation, hydrogenation, and many others.1
Alkyl glycosides and oligosaccharides are important in-
termediates and products in the synthesis of biologically
active natural compounds and mimics. A variety of re-
agents are reported to promote formation of glycoside
bond which include classical glycosyl halides,2 thioglyco-
sides,3 pentenyl glycosides,4 anomeric trichloro-
acetimidates5 and others.6 The chemistry of the
saccharides in ionic liquids is almost unknown. Only O-
acetylation of carbohydrates7 and reaction of glycals with
simple alkyl and aryl alcohols in the presence of dyspro-
sium triflate8 have been described.
Figure 1 Structures of compounds 1–8
Reaction of 1 with glucofuranose derivative 8 afforded a
very thick, sticky suspension, which impeded the comple-
tion of the reaction. Disaccharide 6 was obtained in 48%
yield together with recovered furanose 8 (23%). Addition
of a small amount (20–40 vol%) of diethyl ether improved
the solubility of the product and afforded the disaccharide
6 in 53% yield and considerably decreased amount of un-
reacted 8 (10%, Table 1).
Glycosylation of 2,3,4,6-tetra-O-acetyl-a,b-D-glucopyra-
nosyl trichloroacetimidate (9) with allyl and benzyl alco-
hols proceeded smoothly to afford the corresponding allyl
and benzyl glucopyranosides. In both cases, column chro-
matography of the crude reaction product gave two frac-
tions. The faster moving fraction contained peracetylated
a,b-glycosides, 10 or 12, respectively, whereas the slower
moving fraction comprised a mixture of the a- and b-glu-
copyranosides deacetylated at the O-2 position, 11 or 13,
respectively (Figure 2). Structures of compounds 11 and
13 were confirmed by 1H NMR spectroscopy. The specif-
ic movements to the higher field position of the 1H NMR
In the course of our studies directed towards the synthesis
of oligosaccharides9,10 we would like to report that
[bmim]PF6 is a useful solvent in the formation of the gly-
cosidic bond.
The first trial employed 2,3,4,6-tetra-O-benzoyl-a-D-
mannopyranosyl trichloroacetimidate (1)11 as glycosyl
donor and allyl and benzyl alcohols as glycosyl acceptors.
Synthesis 2003, No. 13, Print: 18 09 2003. Web: 28 08 2003.
Art Id.1437-210X,E;2003,0,13,2074,2078,ftx,en;P03503SS.pdf.
DOI: 10.1055/s-2003-41446
© Georg Thieme Verlag Stuttgart · New York

PAPER
Glycosylation in Ionic Liquids
2075
Table 1 Reaction of 1 with Glycosyl Acceptors in the Presence of
TMSOTf in [bmim]PF6 as a Solvent
Glycosylation of 9 with methyl ribofuranoside 7 afforded
disaccharide 15 in 49% yield. In this case, small amounts
of methyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside,
methyl 5-O-acetyl-2,3-O-isopropylidene-b-D-ribofurano-
side and 2,3-O-isopropylidene-D-ribofuranose were also
detected in the reaction mixture. This suggests that migra-
tion of the acetyl group under reaction conditions is pos-
sible. On the other hand, the presence of methyl glucoside
and 2,3-O-isopropylidene-D-ribofuranose indicated par-
tial hydrolysis of methyl ribofuranoside 7 and subsequent
methylation of 9.
Acceptor
Product
Yield (%)a
CH2=CHCH2OH
2
3
4
5
6
93
PhCH2OH
68
HO(CH2)5CO2Me
70b
77
7
8
53c
a Isolated and unoptimized yields.
The results of the reactions of 2,3,4,6-tetra-O-acetyl-a,b-
D-galactopyranosyl trichloroacetimidate (16) with allyl
and benzyl alcohols and methyl 6-hydroxyhexanoate are
summarized in Table 3. In all cases mixtures of a- and b-
anomers were obtained and products of deacetylation at
the O-2 positions were not observed. By comparison, dis-
accharide 20 was formed exclusively as the b-galactoside
(Figure 3).
b After two steps. Isolated as 5-(methoxycarbonyl)pentyl-a-D-man-
nopyranoside (see Ref.10 for explanation). 2,3,4,6-Tetra-O-benzoyl-
a,b-D-mannopyranose (16%) was also isolated.
c Recovered acceptor 8 (10%) was also isolated.
signals for H-2 protons proved deacetylation at the O-2
position. A similar reaction with methyl 6-hydroxyhex-
anoate yielded peracetylated a,b-glucosides 14 as the only
products (Table 2).
For all glycosides described above the a/b ratios were de-
termined on the basis of integration of the anomeric or
other well separated protons in the 1H NMR spectra.
Figure 3 Structures of compounds 16–20
1
All isolated compounds gave H and 13C NMR spectra
Figure 2 Structures of compounds 9–15
consistent with the indicated structures and in agreement
with literature data (if available). For selected compounds
1
the H-coupled 13C NMR spectra showed C-1, H-1 cou-
Table 2 Reaction of 9 with Glycosyl Acceptors in the Presence of
TMSOTf in [bmim]PF6 as a Solvent
pling constants of J = 159.5–164.7 Hz for anomeric car-
bon atoms, which are indicative of b-glycosides (Table 4).
Acceptor
Product
a:b
Yield (%)a
CH2=CHCH2OH
10
11
1: 6
1: 2.1
62
21
Table 3 Reaction of 16 with Glycosyl Acceptors in the Presence of
TMSOTf in [bmim]PF6 as a Solvent
PhCH2OH
12
13
1: 8
1: 1.8
50
13
Acceptor
Product
17
a:b
Yield (%)a
CH2=CHCH2OH
PhCH2OH
HO(CH2)5CO2Me
7
1:7.6
1:6.4
1:10.6
b
67
60
66
52b
HO(CH2)5CO2Me
14
15
1: 3.2
52
18
7
b
49b
19
a Isolated and unoptimized yields.
b Contains traces of methyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
20
side.
a Isolated and unoptimized yields.
b Contains traces of methyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyra-
noside.
Synthesis 2003, No. 13, 2074–2078 © Thieme Stuttgart · New York

2076
Z. Pakulski
PAPER
Table 4 Configurational Assignments of Glucopyranosides 10–15 and Galactopyranosides 17–20 by 1H and 13C NMR Data; d, J (Hz)
Product
H-1
C-1
1J(C-1, H-1) (Hz) Configuration
Observed
Reported
Observed
Reported
–
10
11
12
13
14
4.45
-
4.5913
5.1113
99.57
94.87
–
–
–
–
–
b
a
4.40
4.95
–
101.87
97.61
–
b
a
4.55
-
4.5514
5.1314
99.30
99.3214
95.1614
b
a
4.43
5.04
–
101.70
97.91
–
b
a
4.49
5.05
–
100.79
95.68
–
b
a
15
17
4.51
–
100.47
–
–
164.7
160.4
b
4.52
-
4.5215
100.09
95.34
b
a
18
19
20
4.51
–
99.82
95.40
–
–
b
a
4.45
ca. 5
4.4516
–
101.31
96.12
101.316
–
161.2
b
a
4.50
101.11
159.5 (C-1¢,H-1)
b
Glycosylation Reaction in [Bmim]PF6; Allyl 2,3,4,6-Tetra-O-
benzoyl-a-D-mannopyranoside (2); Typical Procedure
To a solution of 1 (0.5 mmol) and allyl alcohol (1.0 mmol) in
[bmim]PF6 (0.7–2.0 mL, for the synthesis of disaccharides 20–40
vol% of Et2O was added for improving the solubility) was added
TMSOTf (0.05 mmol) under argon and the reaction mixture was
stirred vigorously at r.t. for 15–30 min. The product was extracted
with toluene (6 × 3 mL) and the organic solvent was removed in
vacuo. Column chromatography of the residue gave 2; amorphous
glass; [a]D20 –54.5 (c = 0.86, CHCl3).
As known, for a-anomers these values are approximately
10 Hz higher.17
The ionic liquid could be easily recovered as follows: Af-
ter extraction of the products, ionic liquid was additional-
ly washed with toluene, and water, dissolved in acetone
and filtered through a pad of Celite. All volatiles were re-
moved by evaporation and the residue was dried at 70 °C
under reduced pressure. Recovered [bmim]PF6 has been
used in the preparation of allyl mannoside 2 which was
formed in 82% yield.
1H NMR (CDCl3): d = 6.12 (t, 1 H, J3,4 = J4,5 = 10.0 Hz, H-4), 6.00
(m, 1 H, =CH), 5.95 (dd, 1 H, J2,3 = 3.3 Hz, H-3), 5.72 (dd, 1 H,
J1,2 = 1.8 Hz, H-2), 5.40 and 5.27 (2 m, 2 H, =CH2), 5.15 (d, 1 H,
In summary, a practical method for the synthesis of glyco-
sides or disaccharides by use of an ionic liquid as a solvent
is presented. Reactions are performed at room tempera-
ture in a small volume of ionic liquid. The reuse of the
molten salt is possible and efficient. Separation of the
products is simple. Although a/b selectivities are general-
ly similar to the selectivities found for ‘classical’ condi-
tions, the volume of volatile organic solvent used as the
reaction medium is drastically lowered.
J1,2 = 1.8 Hz, H-1), 4.69 (dd, 1 H, J5,6 = 2.5 Hz, J6,6¢ = 11.9 Hz, H-
6), 4.51 (dd, 1 H, J5,6¢ = 4.5 Hz, H-6¢), 4.46 (m, 1 H, H-5), 4.34 (m,
1 H, OCHH), 4.17 (m, 1 H, OCHH).
13C NMR (CDCl3): d = 118.46 (=CH2), 96.78 (C-1), 70.59, 70.09,
69.00, 68.97 (CH2), 67.03, 62.94 (CH2).
HRMS (ESI): m/z calcd for C37H32O10Na [M + Na]+: 659.1888;
found: 659.1913.
Benzyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranoside (3)
Amorphous glass; [a]D20 –37.2 (c = 0.49, CHCl3).
The solvents were purified and dried according to literature meth-
ods. TLC was performed on silica gel HF-254 and column chroma-
tography on silica gel 230–400 mesh (Merck). NMR spectra were
recorded with a Varian Mercury 400BB (400 MHz) and a Bruker
AM-500 (500 MHz) spectrometers in CDCl3 with Me4Si as internal
standard. High resolution mass spectra (HRMS) were measured
with a Mariner mass spectrometer. Optical rotations were measured
with a Jasco DIP-360 automatic polarimeter. [Bmim]PF6 was pre-
pared according to the literature method.18
1H NMR (CDCl3): d = 6.12 (t, 1 H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.96
(dd, 1 H, J2,3 = 3.3 Hz, H-3), 5.76 (dd, 1 H, J1,2 = 1.8 Hz, H-2), 5.18
(d, 1 H, J1,2 = 1.8 Hz, H-1), 4.86 and 4.71 (ABq, 2 H, J = 11.9 Hz,
PhCH2), 4.66 (dd, 1 H, J5,6 = 2.4 Hz, J6,6¢ = 11.9 Hz, H-6), 4.49 (dd,
1 H, J5,6¢ = 4.5 Hz, H-6¢), 4.45 (m, 1 H, H-5).
13C NMR (CDCl3): d = 96.94 (C-1), 70.51, 70.16, 70.00 (CH2),
69.10, 67.00, 62.88 (CH2).
HRMS (ESI): m/z calcd for C41H34O10Na [M + Na]+: 709.2044;
found: 709.2065.
Synthesis 2003, No. 13, 2074–2078 © Thieme Stuttgart · New York

PAPER
Glycosylation in Ionic Liquids
2077
Methyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1∆ 5)-
2,3-O-isopropylidene-b-D-ribofuranoside (5)
13C NMR (CDCl3): d = 101.70 (C-1b), 97.91 (C-1a), 74.64 (C-3b),
73.72 (C-3a), 72.42 (C-2b), 72.17 (C-5b), 71.53 (b-PhCH2), 71.11
(C-2a), 70.71 (a-PhCH2), 68.74 (C-4b), 68.22 (C-4a), 68.12 (C-
5a), 62.38 (C-6b), 62.12 (C-6a).
HRMS (ESI): m/z calcd for C19H24O9Na [M + Na]+: 419.1313;
found: 419.1307.
Amorphous glass; [a]D20 –51.2 (c = 0.56, CHCl3).
1H NMR (CDCl3): d = 6.11 (t, 1 H, J3,4 = J4,5 = 10.0 Hz, H-4¢), 5.92
(dd, 1 H, J2,3 = 3.3 Hz, H-3¢), 5.74 (dd, 1 H, J1,2 = 1.8 Hz, H-2¢), 5.12
(d, 1 H, H-1¢), 4.99 (s, 1 H, H-1), 4.80 (d, 1 H, J2,3 = 6.0 Hz, H-2),
4.69 (dd, 1 H, J5,6 = 2.2 Hz, J6,6¢ = 11.9 Hz, H-6¢), 4.64 (d, 1 H,
J2,3 = 6.0 Hz, H-3), 4.45–4.52 (m, 3 H, H-5¢,6¢,5), 3.88 (dd, 1 H
5-(Methoxycarbonyl)pentyl 2,3,4,6-Tetra-O-acetyl-a,b-D-glu-
copyranoside (14)
J4,5 = 5.4 Hz, J4,5¢ = 10.2 Hz, H-4), 3.63 (dd, 1 H, J5,5¢ = 8.7 Hz, H-
5), 3.31 (s, 3 H, OCH3), 1.52 and 1.37 [2 s, 6 H, C(CH3)2].
14; b-Anomer
1H NMR (CDCl3): d = 5.20 (t, 1 H, J = 9.5 Hz, H-3), 5.08 (t, 1 H,
13C NMR (CDCl3): d = 112.58 [C(CH3)2], 109.57 (C-1), 98.27 (C-
1¢), 85.23, 84.67, 82.06, 70.35, 69.96, 69.66 (C-5), 69.14, 66.87,
62.76 (C-6¢), 55.01 (OCH3), 26.48 and 25.02 [C(CH3)2].
HRMS (ESI): m/z calcd for C43H42O14Na [M + Na]+: 805.2467;
found: 805.2496.
J = 9.5 Hz, H-4), 4.98 (dd, J2,3 = 9.6 Hz, H-2), 4.49 (d, 1 H, J1,2
=
8.0 Hz, H-1), 4.25 (dd, 1 H, J5,6 = 4.8 Hz, J6,6¢ = 12.3 Hz, H-6), 4.14
(dd, 1 H, J5,6¢ = 2.5 Hz, H-6¢), 3.86 (dt, 1 H, J = 6.3, 9.6 Hz, OCHH),
3.69 (m, 1 H, H-5), 3.66 (s, 3 H, OCH3), 3.48 (dt, 1 H, J = 6.9, 9.6
Hz, OCHH).
13C NMR (CDCl3): d = 100.79 (C-1), 72.86 (C-3), 71.77 (C-5),
71.34 (C-2), 69.75 (OCH2), 68.49 (C-4), 61.98 (C-6), 51.43
(OCH3), 33.90 (CH2), 29.03 (CH2), 25.35 (CH2), 24.52 (CH2).
2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1∆ 5)-3-O-ben-
zyl-1,2-O-isopropylidene-6-O-(tert-butyldiphenylsilyl)-a-D-glu-
cofuranose (6)
Mp 184–185 °C (heptane–EtOAc); [a]D20 –40.4 (c = 0.3, CHCl3).
14; a-Anomer
1H NMR (CDCl3): d = 6.06 (t, 1 H, J3,4 = J4,5 = 10.0 Hz, H-4¢), 5.95
(dd, 1 H, J2,3 = 3.1 Hz, H-3¢), 5.96 (d, 1 H, J1,2 = 3.7 Hz, H-1), 5.71
(dd, 1 H, J1,2 = 1.8 Hz, H-2¢), 5.18 (d, 1 H, H-1¢), 4.81 (dd, 1 H,
J5,6 = 3.1 Hz, J6,6¢ = 9.0 Hz, H-6¢), 4.72 and 4.65 (ABq, 2 H, PhCH2),
4.69 (d, 1 H, J1,2 = 3.7 Hz, H-2), 4.46 (m, 1 H, H-5¢), 4.29 (d, 1 H,
1H NMR (CDCl3): d = 5.47 (dd, 1 H, J = 9.4, 10.1 Hz, H-3), 5.05
(m, 2 H, H-1,4), 4.86 (dd, J2,3 = 3.7 Hz, H-2), 4.25 (dd, 1 H), 4.08
(dd, 1 H, J5,6¢ = 2.4 Hz, H-6¢), 4.01 (m, 1 H, H-5).
13C NMR (CDCl3): d = 95.68 (C-1), 70.91 (C-2), 70.23 (C-3), 68.65
(C-4), 68.39 (OCH2), 67.18 (C-5), 61.95 (C-6), 51.45 (OCH3),
28.91 (CH2), 25.56 (CH2), 24.55 (CH2).
J3,4 = 3.2 Hz, H-3), 4.14 and 4.02 (2 m, 4 H, H-6¢,5,6,6), 3.94 (dd, 1
H, J4,5 = 12.5 Hz, H-4), 1.55 and 1.37 [2 s, 6 H, C(CH3)2], 1.19 (s, 9
H, t-C4H9).
HR-MS (ESI): m/z calcd for C21H32NaO12 [M + Na]+: 499.1786;
found: 499.1794.
13C NMR (CDCl3): d = 111.94 [C(CH3)2], 105.17 (C-1), 98.93 (C-
1¢), 82.26, 81.69, 77.58, 77.57, 71.74 (PhCH2), 70.62, 70.12, 68.88,
66.57, 63.81 (C-6), 62.12 (C-6¢), 27.06 (CCH3), 26.86 and 26.46
[C(CH3)2], 19.82 (CCH3).
Methyl 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-(1∆ 5)-2,3-
O-isopropylidene-b-D-ribofuranoside (15)19
1H NMR (CDCl3): d = 5.16 (t, J3,2 = J3,4 = 9.5 Hz, H-3¢), 5.04 (t,
J4,5 = 9.6 Hz, H-4¢), 4.95 (dd, J2,1 = 8.0 Hz, H-2¢), 4.90 (s, 1 H, H-
1), 4.61 (br d, 1 H, J = 6.0 Hz, H-3), 4.51 (m, 2 H, H-1¢,2), 4.22 (m,
H-4,6¢), 4.10 (m, H-6¢), 3.74 (dd, 1 H, J5,4 = 8.8 Hz, J5,5¢ = 10.6 Hz,
H-5), 3.66 (m, H-5¢), 3.57 (dd, 1 H, J5,4 = 6.2 Hz, H-5), 3.26 (s,
OCH3), 2.05 (s, 3 H, CH3), 2.01 (s, 3 H, CH3), 1.98 (s, 3 H, CH3),
1.96 (s, 3 H, CH3), 1.42 (s, 3 H, CH3), 1.26 (s, 3 H, CH3).
MS (ESI): m/z = 1149.4, 1150.4, 1151.4 [M + Na]+.
Anal. Calcd for C66H66O15Si (1127.34): C, 70.32; H, 5.90. Found:
C, 70.38; H, 5.98.
Allyl 3,4,6-Tri-O-acetyl-a,b-D-glucopyranoside (11)
1H NMR (CDCl3): d = 5.90 (m, =CH), 5.30 (m, =CHH), 5.23
(m, =CHH, H-3a), 5.10 (t, J3,2 = J3,4 = 9.5 Hz, H-3b), 5.00 (m, H-
4a,4b), 4.95 (d, J1,2 = 3.9 Hz, H-1a), 4.40 (d, J1,2 = 7.8 Hz, H-1b),
4.36 (m, b-OCHH), 4.23 (m, H-a-OCHH, H-6a,6b), 4.13 (m, b-
OCHH), 4.08 (m, a-OCHH, H-6a,6b), 3.97 (m, H-5a), 3.66 (m, H-
2a,5b), 3.58 (m, H-2b).
13C NMR (CDCl3): d = 112.25 [C(CH3)2], 109.35 (C-1), 100.47 (C-
1¢), 84.91 (C-2), 84.47 (C-4), 81.71 (C-3), 72.70 (C-3¢), 71.80 (C-
5¢), 71.06 (C-2¢), 69.81 (C-5), 68.32 (C-4¢), 61.81 (C-6¢), 54.69
(OCH3), 26.31, 24.81.
HRMS (ESI): m/z calcd for C23H34O14Na [M + Na]+: 557.1841;
found: 557.1831.
11; a-Isomer
13C NMR (CDCl3): d = 133.25 (=CH), 118.78 (=CH2), 97.61 (C-1),
73.66 (C-3), 71.04 (C-2), 69.33 (OCH2), 68.26 (C-4), 68.00 (C-5),
62.21 (C-6).
Benzyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranoside (18)
1H NMR (CDCl3): d = 5.36 (dd, 1 H, J4,3 = 3.5 Hz, J4,5 = 1.2 Hz, H-
4), 5.26 (dd, 1 H, J1,2 = 8.0 Hz, J2,3 = 10.4 Hz, H-2), 4.98 (dd, 1 H,
J
3,2= 10.4 Hz, J3,4= 3.5 Hz, H-3), 4.90 and 4.63 (ABq, 2 H, J = 12.3
11; b-Isomer
Hz, CH2Ph), 4.51 (d, 1 H, J1,2 = 8.0 Hz, H-1), 4.16 (m, 2 H, H-6,6¢),
3.88 (m, 1 H, J5,6 = J5,6¢ = 6.7 Hz, H-5).
13C NMR (CDCl3): d = 99.82 (C-1), 70.93, 70.74, 70.72 (CH2Ph),
68.88, 67.08, 61.32 (C-6); a-Isomer: d = 95.39 (C-1), 69.95
(CH2Ph), 68.10, 68.06, 67.64, 66.49, 61.66 (C-6).
13C NMR (CDCl3): d = 133.56 (=CH), 118.60 (=CH2), 101.87 (C-
1), 74.69 (C-3), 72.34 (C-2), 72.07 (C-5), 70.75 (OCH2), 68.72 (C-
4), 62.34 (C-6).
HRMS (ESI): m/z calcd for C15H22O9Na [M + Na]+: 369.1156;
found: 369.1170.
HRMS (ESI): m/z calcd for C21H26O10Na [M + Na]+: 461.1418;
Benzyl 3,4,6-Tri-O-acetyl-a,b-D-glucopyranoside (13)
found: 461.1431.
1H NMR (CDCl3): d = 5.24 (t, J3,2 = J3,4 = 9.7 Hz, H-3a), 5.09 (t,
J3,2 = J3,4 = 9.4 Hz, H-3b), 5.04 (m, H-1a,4a,4b), 4.92 and 4.65
(ABq, J = 11.7 Hz, b-PhCH2), 4.74 and 4.60 (ABq, J = 11.7 Hz, a-
Methyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl-(1∆5)-2,3-
O-isopropylidene-b-D-ribofuranoside (20)
PhCH2), 4.43 (d, J1,2 = 7.8 Hz, H-1b), 4.27 (dd, J6,5 = 5.0 Hz, J6,6¢
=
1H NMR (CDCl3): d = 5.38 (dd, 1 H, J4,3 = 3.4 Hz, J4,5 = 0.8 Hz, H-
4¢), 5.20 (dd, 1 H, J2,1 = 8.0 Hz, J2,3 10.5 Hz, H-2¢), 5.01 (dd, 1 H,
12.3 Hz, H-6b), 4.23 (dd, J6,5 = 4.8 Hz, J6,6¢ = 12.6 Hz, H-6a), 4.14
(dd, J6,5 = 2.4 Hz, H-6¢b), 3.97 (m, H-5a,6¢a), 3.60–3.72 (m, H-
2a,2b,5b).
J
3,2 = 10.5, J3,4= 3.4 Hz, H-3¢), 4.93 (s, 1 H, H-1), 4.64 (d, J3,2 = 6.0
Hz, H-3), 4.55 (d, 1 H, H-2), 4.50 (d, 1 H, J1,2 = 8.0 Hz, H-1¢), 4.26
Synthesis 2003, No. 13, 2074–2078 © Thieme Stuttgart · New York

2078
Z. Pakulski
PAPER
(4) Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottosson, H.;
Merritt, J. R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett
1992, 927.
(5) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212.
(6) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(7) Forsyth, S. A.; MacFarlane, D. R.; Thomson, R. J.; von
Itzstein, M. Chem. Commun. 2002, 714.
(8) Yadav, J. S.; Subba Reddy, B. V.; Sunder Reddy, J. S. J.
Chem. Soc., Perkin Trans. 1 2002, 2390.
(9) (a) Pakulski, Z.; Zamojski, A.; Holst, O.; Zähringer, U.
Carbohydr. Res. 1991, 215, 337. (b) Nepogodev, S. A.;
Pakulski, Z.; Zamojski, A.; Holst, O.; Brade, H. Carbohydr.
Res. 1992, 232, 33.
(dd, 1 H, J4,5 = 8.7 Hz, J4,5¢ = 6.3 Hz, H-4), 4.18 (dd, 1 H, J6,5 = 6.6
Hz, J6,6¢ = 11.3 Hz, H-6¢), 4.11 (dd, 1 H, J6¢,5 = 6.9 Hz, H-6¢), 3.89
(m, 1 H, H-5¢), 3.78 (dd, 1 H, J5,5¢ = 10.6 Hz, H-5), 3.60 (dd, 1 H,
J5,4 = 6.3 Hz, J5,5’ = 10.6, H-5), 3.30 (s, 3 H, OCH3), 2.15 (s, CH3),
2.06 (s, CH3), 2.04 (s, CH3), 1.97 (s, CH3), 1.46 (s, CCH3), 1.30 (s,
CCH3).
13C NMR (CDCl3): d = 112.35 [C(CH3)2], 109.43 (C-1), 101.11 (C-
1¢), 85.00 (C-2), 84.64 (C-4), 81.81 (C-3), 70.88 (C-3¢), 70.76 (C-
5¢), 69.94 (C-5), 68.67 (C-2¢), 67.00 (C-4¢), 61.24 (C-6¢), 54.78
(OCH3), 26.40 (CCH3), 24.95 (CCH3).
HRMS (ESI): m/z calcd for C23H34NaO14 [M + Na]+: 557.1841;
found: 557.1843.
(10) Furneaux, R. H.; Pakulski, Z.; Tyler, P. C. Can. J. Chem.
2002, 80, 964.
(11) Becker, B.; Furneaux, R. H.; Reck, F.; Zubkov, O. A.
Carbohydr. Res. 1999, 315, 148.
(12) (a) Lemieux, R. U. Pure Appl. Chem. 1971, 25, 527.
(b) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem.
Biochem. 1994, 50, 21.
Acknowledgment
I am grateful to Prof. Aleksander Zamojski for helpful discussions
and to Dr. Halszka Stepowska for a sample of compound 8.
(13) Klotz, W.; Schmidt, R. R. Liebigs Ann. 1993, 683.
(14) (a) Matsui, M.; Okada, M. Chem. Pharm. Bull. 1970, 18,
2129. (b) Utamura, T.; Kuromatsu, K.; Suwa, K.; Koizumi,
K.; Shingu, T. Chem. Pharm. Bull. 1986, 34, 2341.
(15) RajanBabu, T. V.; Fukunaga, T.; Reddy, G. S. J. Am. Chem.
Soc. 1989, 111, 1759.
(16) Ye, X.-S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410.
(17) (a) Bock, K.; Lundt, I.; Pedersen, C. Tetrahedron Lett. 1973,
1037. (b) Bock, K.; Pedersen, C. J. Chem. Soc., Perkin
Trans. 2 1974, 293. (c) Bock, K.; Pedersen, C. Acta Chem.
Scand. 1975, B29, 258.
References
(1) Recent reviews on ionic liquids: (a) Dupont, J.; de Souza, R.
F.; Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667. (b) Zhao,
H.; Malhotra, S. V. Aldrichimica Acta 2002, 35, 75.
(c) Zhao, D.; Wu, M.; Kou, Y.; Min, E. Catal. Today 2002,
74, 157. (d) Olivier-Bourbigou, H.; Magna, L. J. Mol. Catal.
A: Chem. 2002, 182-183, 419. (e) Sheldon, R. Chem.
Commun. 2001, 2399. (f) Gordon, C. M. Appl. Catal. A
2001, 222, 101. (g) Earle, M. J.; Seddon, K. R. Pure Appl.
Chem. 2000, 72, 1391. (h) Wasserscheid, P.; Keim, W.
Angew. Chem. Int. Ed. 2000, 39, 3773. (i) Welton, T. Chem.
Rev. 1999, 99, 2071.
(18) Huddleston, J. D.; Willauer, H. D.; Swatloski, R. P.; Visser,
A. E.; Rogers, R. D. Chem. Commun. 1998, 1765.
(19) Ogawa, T.; Matsui, M. Carbohydr. Res. 1976, 51, C13.
(2) Paulsen, H. Angew. Chem., Int. Ed. Engl 1982, 21, 155.
(3) Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1988, 177, C13.
Synthesis 2003, No. 13, 2074–2078 © Thieme Stuttgart · New York