Novel stereocontrolled glycosidations of 2-deoxyglucopyranosyl fluoride using a heterogeneous solid acid, sulfated zirconia (SO4[ZrO2)

Article abstract of DOI:10.1055/s-1999-2742

Novel stereocontrolled glycosidations of a 2-deoxy-α-D-glucopyranosyl fluoride using a heterogeneous and environmentally friendly solid acid, sulfated zirconia (SO₄/ZrO₂), have been developed. The glycosidations of the perbenzylated

Full text of DOI:10.1055/s-1999-2742

LETTER
813
Novel Stereocontrolled Glycosidations of 2-Deoxyglucopyranosyl Fluoride
Using a Heterogeneous Solid Acid, Sulfated Zirconia (SO4/ZrO2)
Kazunobu Toshima,* Ken-ichi Kasumi, Shuichi Matsumura
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522,
Japan
Received 23 March 1999
lack of an electron-withdrawing C-2 substituent.1c There-
Abstract: Novel stereocontrolled glycosidations of a 2-deoxy-a-D-
fore, the development of direct stereocontrolled glycosi-
dations of 2-deoxy sugar in an environmentally benign
manner is of particular interest. In this communication, we
glucopyranosyl fluoride using a heterogeneous and environmental-
ly friendly solid acid, sulfated zirconia (SO4/ZrO2), have been de-
veloped. The glycosidations of the perbenzylated 2-deoxy-a-D-
glucopyranosyl fluoride 1 and various alcohols using SO4/ZrO2 in wish to report the novel and direct stereocontrolled gly-
CH3CN at 25 °C for 1 h predominantly gave the corresponding 2-
cosidations of the totally benzylated 2-deoxy-a-D-glu-
deoxy-a-D-glucopyranosides. On the other hand, the corresponding
copyranosyl fluoride and alcohols using a heterogeneous
2-deoxy-b-D-glucopyranosides were selectively obtained by the
and environmentally friendly solid acid, sulfated zirconia
glycosidations of 1 and various alcohols employing SO4/ZrO2 in the
(SO4/ZrO2),4-6 for the selective syntheses of both the 2-
presence of molecular sieves 5A in Et2O at 0 °C for 1 h.
deoxy-a- and b-D-glucopyranosides (Figure 1).
Key words: glycosidation, carbohydrate, 2-deoxy sugar, solid acid,
We recently announced novel stereocontrolled glycosida-
tions of an a-D-mannopyranosyl fluoride and alcohols us-
ing SO4/ZrO2.2f Therefore, based on these results, we first
examined the glycosidations of the totally benzylated 2-
deoxy-a-glucopyranosyl fluoride (1)7 and cyclohexyl-
methanol (2) using SO4/ZrO2 with or without molecular
sieves 5A (MS 5A) under several conditions. These re-
sults are summarized in Table 1. It was found that the gly-
sulfated zirconia
Highly effective, simple and environmentally acceptable
glycosidations have attracted considerable attention in
current synthetic organic chemistry related to both bio-
molecules and functional materials.1 Some of the chal-
lenges for the greening of synthetic chemistry in the field
of glycosidations may include the use of a heterogeneous
and reusable solid acid as the activator.2 On the other
hand, deoxy sugars frequently appear in the glycosidic
components of the bioactive substances.3 Among them, 2-
deoxyglycoside is one of the most common and impor-
tant, and found in many biologically attractive natural
products such as aureolic acids, anthracyclines, angucy-
clines, avermectins, ethythromycins, concanamycins, and
recently discovered enediynes.3 However, the direct
stereocontrolled glycosidation of a 2-deoxy sugar, espe-
cially b-stereoselective glycosidation, is difficult due to
the lack of stereodirecting anchimeric assistance from the
C-2 position and the low stability of the glycosidic bond
of a 2-deoxyglycoside under acidic conditions due to the
8
cosidation of 1 and 2 using 5 wt% of SO4/ZrO2 in CH3CN
at 25 °C for 1 h smoothly proceeded to afford the corre-
sponding 2-deoxyglucopyranoside in high yield with high
a-stereoselectivity (entry 2 in Table 1). Moreover, the ste-
reoselectivity of the glycosidation was dramatically
changed by the solvent, and the corresponding 2-deoxy-b-
glucopyranoside was predominantly produced when Et2O
was used as the solvent.2f Furthermore, it was found that
the b-stereoselectivity was highly dependent on the reac-
tion temperature and the amount of MS 5A; the use of 500
wt% of MS 5A as an additive along with 100 wt% of SO4/
ZrO2 in Et2O at 0 °C led to the highest chemical yield and
stereoselectivity for the 2-deoxy-b-glucopyranoside (en-
try 7 in Table 1). Thus, the glycosidation of 1 and 2 using
5 wt% of SO4/ZrO2 in CH3CN at 25 °C for 1 h predomi-
OBn
O
OBn
O
OBn
O
SO4/ZrO2-MS 5A
Et2O
SO4/ZrO2
BnO
BnO
BnO
BnO
BnO
BnO
+
OR
R-OH
CH3CN
F
OR
2-Deoxy-α-D-glucopyranoside
2-Deoxy-α-D-glucopyranosyl
fluoride (1)
2-Deoxy-β-D-glucopyranoside
O
OH
O
OBn
O
MeO
MeO
HO
HO
HO
HO
MeO
OMe
HO
N3
2
3
4
5
6
7
Figure 1
Synlett 1999, No. 6, 813–815 ISSN 0936-5214 © Thieme Stuttgart · New York

814
K. Toshima et al.
LETTER
Table 2. α-Stereoselective glycosidations of 1 and several
alcoholsa
nantly gave the corresponding 2-deoxy-a-glucopyrano-
side, while the glycosidation employing 100 wt% of the
same activator in the presence of 5 times the amount of
MS 5A in Et2O at 0 °C for 1 h afforded the corresponding
2-deoxy-b-glucopyranoside in high yield with high
stereoselectivity. These optimized conditions for selec-
tively obtaining both the 2-deoxy a- and b-glycosides in-
cluding the reaction temperature and time, and the ratio of
SO4/ZrO2 and MS 5A significantly differed from those for
the previously reported stereocontrolled mannosylations2f
probably due to the higher reactivity of the 2-deoxyglyc-
osyl donor compared to that of the mannosyl donor.
SO4/ZrO2 (5 wt%)
+
2~7
1
2-Deoxy glucopyranosides
CH3CN
25 °C, 1 h
Alcohol
Entry
Yield (%)b
α/β Ratioc
2
3
4
5
6
7
1
2
3
4
5
6
98
92
92
97
90
80
88 : 12
84 : 16
83 : 17
82 : 18
82 : 18
80 : 20
Table 1. Glycosidations of 1 and 2 by SO4/ZrO2 under several conditionsa
SO4/ZrO2
+
2
2-Deoxy glucopyranosides
1
1 h
a All reactions were carried out by use of 2.0 equiv. of the
alcohol to 1. b Isolated yields after purification by column
chromatography. c α:β Ratios were determined by 1H-NMR
(270 MHz) spectroscopy and / or isolation of pure isomers.
Entry
Wt% of
Temp. (°C) Yield (%)b α/β Ratioc
Solvent
Wt% of
MS 5A
SO4/ZO2
CH3CN
CH3CN
Et2O
5
5
0
0
1
2
3
45
25
25
74
98
90
85 : 15
88 : 12
50 : 50
100
100
Table 3. β-Stereoselective glycosidations of 1 and several
alcoholsa
Et2O
Et2O
Et2O
Et2O
Et2O
100
100
100
100
100
100
200
4
5
6
7
8
0
0
0
0
0
98
97
98
98
96
24 : 76
25 : 75
21 : 79
19 : 81
18 : 82
SO4/ZrO2 (100 wt%)
300
MS 5A (500 wt%)
+
500
2~7
1
2-Deoxy glucopyranosides
Et2O
0 °C, 1 h
1000
a All reactions were carried out by use of 2.0 equiv. of 2 to 1. b Isolated yields
after purification by column chromatography. c α:β Ratios were determined by
1H-NMR (270 MHz) spectroscopy and / or isolation of pure isomers.
Yield (%)b
α/β Ratioc
Alcohol
Entry
2
3
4
5
6
7
1
2
3
4
5
6
98
96
97
99
85
56
19 : 81
15 : 85
20 : 80
19 : 81
27 : 73
33 : 67
To enhance the synthetic utility of this novel and environ-
mentally benign reaction, the glycosidations using other
primary and secondary alcohols 3-7 were next examined.
Based on the results summarized in Table 2, all the gly-
cosidations of 1 and 3-7 using 5 wt% of SO4/ZrO2 in
CH3CN at 25 °C for 1 h, as well as that of 2, effectively
proceeded to afford the corresponding 2-deoxy-a-glu-
copyranosides in high yields with high stereoselectivities.
a All reactions were carried out by use of 2.0 equiv. of the
alcohol to 1. b Isolated yields after purification by column
chromatography. c α:β Ratios were determined by 1H-NMR
(270 MHz) spectroscopy and / or isolation of pure isomers.
On the other hand, the stereoselective syntheses of the
corresponding 2-deoxy-b-glucopyranosides by the
present glycosidation are outlined in Table 3. Although
only entry 6 using 7 as the alcohol showed moderate yield
and stereoselectivity, the other 2-deoxy-b-glucopyrano-
sides were obtained in high yield with good to high stereo-
selectivities by the glycosidations of 1 and 3-6 as well as
that of 2.
was filtered and the filtrate was concentrated in vacuo. Pu-
rification of the residue by flash column chromatography
gave the 2-deoxyglucopyranosides which predominantly
contained the a-anomer. 2-Deoxy-b-glucopyranosides:
To a stirred solution of 1 (0.5 mmol) and an alcohol (1.0
mmol) in dry Et2O (5.0 ml) were added powdered MS 5A
(500 wt% to 1) and SO4/ZrO2 (100 wt% to 1). After stir-
ring for 1 h at 0 °C, a similar workup and purification as
that mentioned above gave the 2-deoxyglucopyranosides
which selectively included the b-anomer.
General experimental protocols for the preparations of the
2-deoxy-a- and b-glucopyranosides:9 2-Deoxy-a-glu-
copyranosides: To a stirred solution of the glycosyl fluo-
ride 1 (0.5 mmol) and an alcohol (1.0 mmol) in dry
CH3CN (5.0 ml) was added SO4/ZrO2 (5 wt% to the glyc-
osyl donor 1). After stirring for 1 h at 25 °C, the mixture
Synlett 1999, No. 6, 813–815 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Novel Stereocontrolled Glycosidations of 2-Deoxyglucopyranosyl Fluoride
815
Matsumura, S. Tetrahedron Lett. 1997, 38, 7375. (f) Toshima,
K.; Kasumi, K.; Matsumura, S. Synlett 1998, 643.
(3) Jütten, P.; Greven, R. in Polysaccharides in Medicinal
Applications, (Ed.: Dumitriu, S), Marcel Dekker, New York,
1996, pp. 339-410.
In conclusion, we have presented the novel and stereocon-
trolled glycosidations of a 2-deoxy sugar and alcohols us-
ing an environmentally acceptable solid acid, SO4/ZrO2.
Moreover, the results including the simple protocol, high
yield and stereoselectivity should find wide application in
the synthesis of biologically important natural products
which possess a 2-deoxy sugar as a glycosidic component.
Further studies along this line are currently underway.
(4) (a) Arata, K. Adv. Catal. 1990, 37, 165. (b) Arata, K.; Hino,
M. Mater. Chem. Phys. 1990, 26, 213.
(5) The study on glycosidation using SO4/ZrO2-CaCl2 has been
announced. Nishimura, S.; Matsuda, M. The abstract of XIXth
Japanese Carbohydrate Symposium, A3-10, 1997.
(6) For the use of zirconia species for glycosidations of glycosyl
fluorides, see; (a) Matsumoto, T.; Maeta, H.; Suzuki, K.;
Tsuchihashi, G. Tetrahedron Lett. 1988, 29, 3567. (b) Suzuki,
K.; Maeta, H.; Suzuki, T.; Matsumoto, T. Tetrahedron Lett.
1989, 30, 6879.
(7) We found that the a-fluoride 1 was stereoselectively prepared
in 92% yield by the treatment of 1-O-acetyl-3,4,6-tri-O-
benzyl-2-deoxy-a-D-glucopyranose with HF/Py in dry
CH2Cl2 at -30 - -20 °C for 30 min, see: Hayashi, M.;
Hashimoto, S.; Noyori, R. Chem. Lett. 1984, 1747.
(8) SO4/ZrO2 was purchased from Wako Pure Chemical
Industries, Ltd. and dried at 200 °C/1 mmHg for 12 h before
using.
Acknowledgement
Financial support by Grant-in-Aid for Encouragement of Young
Scientists from the Ministry of Education, Science, Sports and Cul-
ture is gratefully acknowledged.
References and Notes
(1) For some reviews on O-glycosidations, see: (a) Schmidt, R. R.
Angew. Chem. Int. Ed. Engl. 1986, 25, 212. (b) Sinaÿ, P. Pure
Appl. Chem. 1991, 63, 519. (c) Toshima, K.; Tatsuta, K.
Chem. Rev. 1993, 93, 1503. (d) Boons, G.-J. Tetrahedron
1996, 52, 1095. (e) Preparative Carbohydrate Chemistry,
Hanessian, S. (Ed.), Marcel Dekker, New York, 1977,
Chapters 12-22.
(2) For glycosidations using a reusable solid acid, see: (a) Florent,
J.-C.; Monneret, C. J. Chem. Soc., Chem. Commun. 1987,
1171. (b) Fukase, K.; Winarno, H.; Kusumoto, S. Chem.
Express 1993, 8, 409. (c) Toshima, K.; Ishizuka, T.; Matsuo,
G.; Nakata, M. Synlett 1995, 306. (d) Toshima, K.; Miyamoto,
N.; Matsuo, G.; Nakata, M.; Matsumura, S. Chem. Commun.
1996, 1379. (e) Toshima, K.; Ushiki, Y.; Matsuo, G.;
(9) All 2-deoxyglucopyranosides were purified by silica-gel
column chromatography and were fully characterized by
spectroscopic means. The configurations of the anomeric
centers were clearly confirmed by the coupling constants
between H-1 and H2-2 in the 1H-NMR analyses.
Article Identifier:
1437-2096,E;1999,0,06,0813,0815,ftx,en;Y07099ST.pdf
Synlett 1999, No. 6, 813–815 ISSN 0936-5214 © Thieme Stuttgart · New York