Novel dehydrative glycosidations of 1-hydroxy sugars using a heteropoly acid

Article abstract of DOI:10.1055/s-1999-2869

Novel and convenient dehydrative glycosidations of 1-hydroxy glycosyl donors have been developed. Several O-benzylated 1-hydroxy sugars are effectively cross-coupled with a variety of alcohols to give the corresponding O-glycosides in high yields with goo

Full text of DOI:10.1055/s-1999-2869

1420
LETTER
Novel Dehydrative Glycosidations of 1-Hydroxy Sugars Using a Heteropoly
Acid
Kazunobu Toshima,* Hideyuki Nagai, Shuichi Matsumura
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522,
Japan
Fax 045-563-0446; E-mail: toshima@applc.keio.ac.jp
Received 25 June 1999
O
Abstract: Novel and convenient dehydrative glycosidations of 1-
(BnO)n
OH
hydroxy glycosyl donors have been developed. Several O-benzylat-
ed 1-hydroxy sugars are effectively cross-coupled with a variety of
alcohols to give the corresponding O-glycosides in high yields with
good a-stereoselectivities by using the heteropoly acid,
H4SiW12O40.
Heteropoly acid
1-Hydroxy sugars 1~6
(H4SiW12O40
)
O
+
(BnO)n
OR
MeCN
R-OH
O-Glycosides
Alcohols 7~12
Key words: dehydrative glycosidation, 1-hydroxy sugar, O-glyco-
side, solid acid, heteropoly acid
OH
O
BnO
BnO
HO
OBn
7
8
1
A simple, practical and environmentally acceptable chem-
ical glycosidation protocol, which is synthetically impor-
tant for the preparation of both natural and unnatural
glycosides, is urgently needed both in the laboratory and
in industry.1 In this context, the direct and stereoselective
formation of a glycosidic bond from a 1-hydroxy sugar
has undoubtedly high efficiency, since the operation for
the introduction of a latent leaving group into a glycosyl
donor is not required.1,2 We now report novel and conve-
nient dehydrative glycosidations of several 1-hydroxy
sugars with a variety of alcohols using the heteropoly ac-
id, H4SiW12O40 (Figure 1).
HO
OBn
O
BnO
BnO
OH
OH
2
HO
O
BnO
BnO
9
3
HO
OBn
O
10
OH
BnO
BnO
OH
OBn
O
BnO
BnO
4
BnO
OMe
OBn
O
BnO
We anticipated that a suitably dried heteropoly acid3
would work well as both an activating reagent of the 1-hy-
droxy group of a glycosyl donor and a dehydrating agent
of water generated during a glycosidation because a het-
eropoly acid works as an acid in the hydrate form. In this
study, we selected one of the heteropoly acids,
H4SiW12O40, which has a high thermal and hydrolytic sta-
bility and low oxidation potential.3,4 We first examined
the glycosidations of the O-benzylated L-rhamnose (1)
and cyclohexylmethanol (7) using the heteropoly acid,
H4SiW12O40,5 along with other easily handling, nonvola-
tile and odorless solid acids such as Nafion-H®,6 montmo-
11
BnO
BnO
OH
OH
O
5
OBn
O
BnO
BnO
OBn
O
HO
N3
OBn
12
6
Figure 1
Our attention next turned to the generality and the limita-
tion of this novel dehydrative glycosidation. Therefore,
we examined the glycosidations of several O-benzylated
1-hydroxy sugars 2–6 with the alcohol 7 using
H4SiW12O40. These results are summarized in Table 2. It
was found that the glycosidations of the deoxy sugars 2
and 3 with 7 effectively proceeded using a small amount
of H4SiW12O40 (10 wt%) to afford the corresponding O-
glycosides in high yields with good a-stereoselectivity.
On the other hand, in the glycosidations of the fully ben-
zylated 1-hydroxy sugars 4–6, a larger amount of
H4SiW12O40 (100 wt%) is needed to obtain the corre-
sponding O-glycosides in good yields. These results
8
rillonite K-107 and SO4/ZrO2 in MeCN. It was found that
only H4SiW12O40 showed a sharp contrast to the other sol-
id acids and worked efficiently. As shown by the entry 1
result in Table 1, 1 was smoothly cross-coupled with 7 us-
ing 20 wt% H4SiW12O40 in MeCN9 at 25 °C for 15 h to
give the corresponding O-rhamnoside in 99% yield with
excellent a-stereoselectivity (a/b = 92/8). This result
clearly indicated that the heteropoly acid, H4SiW12O40,
worked well as both an activating reagent for the 1-hy-
droxy group and a dehydrating agent of water generated
during the reaction as we expected.
Synlett 1999, No. 9, 1420–1422 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Novel Dehydrative Glycosidations of 1-Hydroxy Sugars Using a Heteropoly Acid
1421
Table 3 Glycosidations of 1 with several alcoholsa
Table 1 Glycosidations of 1 and 7 by several solid acidsa
H4SiW12O40
(20 Wt%)
Solid acid
+
7
O-Glycosides
1
+
7~12
1
O-Glycosides
α/β Ratioc
MeCN
MeCN
25 °C, 15 h
25 °C, 15 h
Entry
Yield (%)b α/β Ratioc
Solid acid
Wt% of
solid acid
Alcohol
Entry
Yield (%)b
H4SiW12O40
20
20
20
1
2
3
99
20
0
92 : 8
69 : 31
-
Nafion-H®
7
8
1
90
97
76
78
76
82
97 : 3
97 : 3
97 : 3
97 : 3
>99 : 1
>99 : 1
Montmorillonite K-10
2
SO4/ZrO2
20
4
0
-
9
3
10
11
12
4
a All reactions were carried out by use of 2.0 equiv. of 7 to
b
5
1. Isolated yields after purification by column
chromatography. cα:β Ratios were determined by 1H-NMR
6d
(270 MHz) spectroscopy and / or isolation of pure isomers.
a All reactions were carried out by use of 1.5 equiv. of
b
the alcohol to 1. 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. d 3.0 equiv. of the alcohol was used.
showed that deoxylated 1-hydroxy sugars were effective-
ly cross-coupled with an alcohol by this novel dehydrative
glycosidation protocol to give the corresponding a-glyco-
sides in good to high yields.
sides were obtained in good to high yields with good a-
stereoselectivities by the glycosidations of 2 with 8–12 us-
ing 10 wt% H4SiW12O40 in MeCN at 25 °C for 1 h as well
as that of 7. Since the configuration of the anomeric posi-
tion was isomerized by the exposure of the isolated single
b-anomer of the O-glycoside to the reaction conditions,
the predominant a-stereoselectivity observed in these gly-
cosidations must arise from the thermodynamic anomeric
effect.10
a
Table 2 Glycosidations of 1~6 with 7 using H4SiW12O40
H4SiW12O40
+
O-Glycosides
7
1~6
MeCN
Entry
Sugar
Wt% of
Temp. (°C)
Time (h)
Yield (%)b α/β Ratioc
H4SiW12O40
1
2
3
20
10
10
15
1
1
2
3
25
25
25
90
91
83
97 : 3
86 : 14
84 : 16
1
Table 4 Glycosidations of 2 with several alcoholsa
4
5
6
100
100
100
5
15
15
4
5
6
40
25
25
72
75
80
73 : 27
97 : 3
70 : 30
H4SiW12O40
(10 Wt%)
+
7~12
2
O-Glycosides
α/β Ratioc
MeCN
25 °C, 1 h
a All reactions were carried out by use of 1.5 equiv. of 7 to the
b
glycosyl donor. Isolated yields after purification by column
chromatography. c α:β Ratios were determined by 1H-NMR (270
Alcohol
Entry
Yield (%)b
MHz) spectroscopy and / or isolation of pure isomers.
7
8
1
91
88
84
71
74
82
86 : 14
82 : 18
82 : 18
82 : 18
86 : 14
90 : 10
2
To enhance the synthetic utility of this novel and conve-
nient glycosidation, the glycosidations of the deoxylated
1-hydroxy sugars 1 and 2 with other primary and second-
ary alcohols 8–12 were next examined. Based on the re-
sults summarized in Table 3, all the glycosidations of 1
with 8–12 using 20 wt% H4SiW12O40 in MeCN at 25 °C
for 15 h, as well as that of 7, effectively proceeded to af-
ford the corresponding O-rhamnosides in good to high
yields with excellent a-stereoselectivities.
9
3
10
11
12
4
5d
6d
a All reactions were carried out by use of 1.5 equiv. of
b
the alcohol to 1. 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. d 3.0 equiv. of the alcohol was used.
The stereoselective syntheses of the corresponding 2-
deoxyglucopyranosides by the present glycosidation are
outlined in Table 4. Thus, several 2-deoxyglucopyrano-
Synlett 1999, No. 9, 1420–1422 ISSN 0936-5214 © Thieme Stuttgart · New York

1422
K. Toshima et al.
LETTER
(g) Takeuchi, K.; Higuchi, S.; Mukaiyama, T. Chem Lett.
A typical experimental protocol :11 To a stirred solution of
the 1-hydroxy sugar 1 (0.5 mmol) and an alcohol (0.75
mmol) in dry MeCN (5.0 ml) was added H4SiW12O40 (20
wt% of the glycosyl donor 1). After stirring for 15 h at
25 °C, the mixture was quenched with sat. NaHCO3 (aq).
The resultant mixture was then extracted with EtOAc. The
extract was washed with sat. NaCl (aq), dried over anhy-
drous Na2SO4, and concentrated in vacuo. Purification of
the residue by flash column chromatography gave the cor-
responding O-rhamnosides which predominantly con-
tained the a-anomer.
1997, 969; (h) Uchiro, H.; Miyazaki, K.; Mukaiyama, T.
Chem Lett. 1997, 403; (i) Inanaga, J.; Yokoyama, Y.;
Hanamoto, T. J. Chem. Soc., Chem. Commun. 1993, 1090; (j)
Susaki, H. Chem. Pharm. Bull. 1994, 42, 1917; (k) Garcia, B.
A.; Poole, J. L.; Gin, D. Y. J. Am. Chem. Soc. 1997, 119, 7597;
(l) Hirooka, M.; Koto, S. Bull. Chem. Soc. Jpn. 1998, 71,
2893; (m) Wakao, M.; Nakai, Y.; Fukase, K.; Kusumoto, S.
Chem. Lett. 1999, 27. (n) Jyojima, T.; Miyamoto, N.; Ogawa,
Y.; Matsumura, S.; Toshima, K. Tetrahedron Lett. 1999, 40,
5023.
(3) For recent reviews on heteropoly acids, see: (a) Kozhevnikov,
I. V. Chem. Rev. 1998, 98, 171; (b) Mizuno, N.; Misono, M.
Chem. Rev. 1998, 98, 199.
(4) The studies on glycosidations of 1-OAc and 1-OMe sugars
using heteropoly acids have been announced. (a) Kiromura,
K.; Kitazawa, S.; Takata, Y.; Sakakibara, T. U. S. Patent
4,874,852, 1988; (b) Kitazawa, S.; Okunura, M.; Kinomura,
K.; Sakakibara, T. Chem. Lett. 1990, 1733.
In conclusion, we have presented the novel and stereose-
lective dehydrative glycosidations of 1-hydroxy sugars
and alcohols using an easily handling, nonvolatile and
odorless heteropoly acid, H4SiW12O40. Moreover, the re-
sults including the convenient protocol, high yield and
good stereoselectivity should find wide application in the
synthesis of many types of O-glycosides which were
found in biomolecules and functional materials. Further
studies along this line are currently underway.
(5) H4SiW12O40 was purchased from Merck KGaA and dried at
25 °C/1 mmHg for 2 h before using.
(6) Nafion-H® was purchased from Wako Pure Chemical
Industries, Ltd. as Nafion® NR-50 and dried at 25 °C/1 mmHg
for 2 h before using.
(7) Montmorillonite K-10 was purchased from Aldrich Chemical
Company, Inc. and dried at 200 °C/1 mmHg for 12 h before
using.
(8) SO4/ZrO2 was purchased from Wako Pure Chemical
Industries, Ltd. and dried at 200 °C/1 mmHg for 12 h before
using.
Acknowledgment
Financial support by a Grant-in-Aid for Encouragement of Young
Scientists from the Ministry of Education, Science, Sports and Cul-
ture, Japan is gratefully acknowledged.
(9) MeCN was shown to be superior to other solvents such as
CH2Cl2, PhMe, THF and Et2O with respect to the chemical
yield and the stereoselectivity in the glycosidation.
(10) (a) The anomeric Effect and Related Stereoelectron Effects at
Oxgen, Kirby, A. J. (Ed.), Springer-Verlag, New York, 1983;
(b) Stereoelectronic Effects in Organic Chemistry,
Deslongchmps, P. (Ed.), Pergamon Press, Oxford, 1983.
(11) All obtained O-glycosides 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 H-2 and the chemical shift of H-1 in the 1H-
NMR analyses.
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 recent glycosidations of 1-hydroxy sugars, see:
(a) Mukaiyama, T.; Suda, S. Chem. Lett. 1990, 1143; (b) Suda,
S.; Mukaiyama, T. Chem. Lett. 1991, 431; (c) Mukaiyama, T.;
Matsubara, K.; Suda, S. Chem. Lett. 1991, 981;
(d) Mukaiyama, T.; Matsubara, K.; Hora. M. Synthesis 1994,
1368; (e) Uchiro, H.; Mukaiyama, T. Chem. Lett. 1996, 79;
(f) Uchiro, H.; Mukaiyama, T. Chem. Lett. 1996, 271;
Article Identifier:
1437-2096,E;1999,0,09,1420,1422,ftx,en;Y12499ST.pdf
Synlett 1999, No. 9, 1420–1422 ISSN 0936-5214 © Thieme Stuttgart · New York