Novel stereocontrolled glycosidations using a solid acid, SO4/ZrO2, for direct syntheses of α- and β-mannopyranosides

Article abstract of DOI:10.1055/s-1998-1741

Novel stereocontrolled glycosidations using an environmentally friendly solid acid, sulfated zirconia (SO₄/ZrO₂), for direct syntheses of α- and β-mannopyranosides have been developed. The glycosidations of the totally benzylated mannopyranosyl fluoride 1 and various alcohols using SO₄/ZrO₂ in CH₃CN at 40°C for 15 h exclusively gave the corresponding α-mannopyranosides. On the other hand, the corresponding β-mannopyranosides were selectively obtained by the glycosidations of 1 and various alcohols employing SO₄/ZrO₂ in the presence of molecular sieves 5A? in Et₂O at 25°C for 15 h.

Full text of DOI:10.1055/s-1998-1741

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Novel Stereocontrolled Glycosidations Using a Solid Acid, SO /ZrO , for Direct Syntheses of
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α- and β-Mannopyranosides
Kazunobu Toshima,* Ken-ichi Kasumi, and Shuichi Matsumura
Department of Applied Chemistry, Faculty of Science and Technology,
Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223, Japan
Received 27 February 1998
Abstract: Novel stereocontrolled glycosidations using an
by only filtration and then reused. These results are summarized in Table
environmentally friendly solid acid, sulfated zirconia (SO /ZrO ), for
1. It was found that these glycosidations in CH CN at 25 °C for 15 h
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2
3
direct syntheses of α- and β-mannopyranosides have been developed.
The glycosidations of the totally benzylated mannopyranosyl fluoride 1
smoothly proceeded to afford the mannopyranoside 8 in high yields.
Furthermore, SO /ZrO was shown to be superior to the others with
4
2
and various alcohols using SO /ZrO in CH CN at 40 °C for 15 h
exclusively gave the corresponding α-mannopyranosides. On the other
hand, the corresponding β-mannopyranosides were selectively obtained
respect to both chemical yield and α-stereoselectivity. These results
4
2
3
9,10
clearly indicated that the solid acid, SO /ZrO ,
was very useful for
4
2
the environmentally acceptable glycosidation of the mannopyranosyl
by the glycosidations of 1 and various alcohols employing SO /ZrO in
fluoride 1.
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2
the presence of molecular sieves 5Å in Et O at 25 °C for 15 h.
2
Glycosubstances including glycolipids, glycoproteins and many
antibiotics continue to be the central focus of research both in chemistry
and biology. Since α- and β-mannopyranosides frequently appear in
many naturally occurring bioactive substances, the stereocontrolled
formation of α- and β-mannopyranosides is of considerable importance
1
in synthetic organic chemistry. The stereospecific and direct formation
of β-mannopyranoside has proved particularly difficult to achieve, in
spite of considerable effort, because the axial β-hydroxy group at the C2
1,2,3
position and the anomeric effect blocks access to the β-face.
On the
other hand, a practical and environmentally benign glycosidation
protocol without using a heavy metal or a Lewis acid, which is not
reusable and would make the reaction solvent dirty, is also needed both
4
in the laboratory and in industry. Therefore, a highly stereocontrolled
synthesis of α- and β-mannopyranosides by an environmentally friendly
manner is of particular interest. In this communication, we now report
the novel stereocontrolled glycosidations of a mannopyranosyl fluoride
Our attention next turned to the solvent effect on this novel
glycosidation. Therefore, we tested the glycosidations of 1 and 2 using
using an environmentally compatible solid acid, sulfated zirconia (SO /
4
ZrO ), for the direct syntheses of both α- and β-mannopyranosides in
2
SO /ZrO in various solvents. From the results shown in Table 2,
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2
high yields (Figure 1).
CH CN was found to be the best solvent to selectively obtain the α-
3
In our first experiments, we examined the glycosidations of the totally
mannopyranoside 8α, and the use of 5 wt% of the present activator was
sufficient to perform this reaction at 40 °C with quite satisfactory
chemical yield and α-stereoselectivity (entries 1 and 6 in Table 2).
Moreover, interestingly, the stereoselectivity of the glycosidation was
5
benzylated α-mannopyranosyl fluoride 1 and cyclohexylmethanol (2)
6
7
using several solid acids such as montmorillonite K-10, Nafion-H and
8
SO /ZrO , all of which could be recovered from the reaction mixture
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2

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LETTERS
SYNLETT
dramatically changed by the solvent, and β-mannopyranoside 8β was
predominately produced when Et O was used as the solvent (entry 5 in
2
11
Table 2). Furthermore, it was found that the use of molecular sieves
5Å (MS 5Å) as an additive in the glycosidation in Et O led to the high
12
2
chemical yield and stereoselectivity for β-mannopyranoside 8β (entry 8
in Table 2). Thus, the glycosidation of 1 and 2 using 5 wt% of SO /ZrO
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2
in CH CN at 40 °C for 15 h exclusively gave the α-mannopyranoside
3
8α, while the glycosidation employing 100 wt% of the same activator in
the presence of equal amounts of MS 5Å in Et O at 25 °C for 15 h
2
afforded the β-mannopyranoside 8β in high yield with high
stereoselectivity.
To enhance the synthetic utility of this novel and unusual reaction, the
glycosidations using other primary and secondary alcohols 3~8 were
next examined. Based on the results summarized in Table 3, all
glycosidations of 1 and 3~8 using 5 wt% of SO /ZrO in CH CN at 40
4
2
3
°C for 15 h, as well as that of 2, effectively proceeded to give the
corresponding α-mannopyranosides 9α~13α, respectively, in high
yields with high stereoselectivity. On the other hand, stereoselective
syntheses of the corresponding β-mannopyranosides by the present
glycosidation are outlined in Table 4. Although only β-
mannopyranoside 13β was produced in moderate yield with low
stereoselectivity, other β-mannopyranosides 9β~12β were obtained in
high yield with good stereoselectivity by the glycosidations of 1 and 3~6
under the conditions similar to that for 8β.
alcohol using an environmentally acceptable solid acid. Moreover, the
results including the simple protocol, high yield and stereoselectivity
should be instructive for further research that employs solid acids in
glycosidation reactions. Further studies along this line are currently
underway.
General experimental protocols for the preparations of the α- and β-
13
mannopyranosides: α-Mannopyranosides: To a stirred solution of the
glycosyl fluoride 1 (0.5 mmol) and a glycosyl acceptor (1.0 mmol) in
dry CH CN (5.0 ml) was added SO /ZrO (5 wt% to the glycosyl donor
3
4
2
References and Notes
1). After stirring for 15 h at 40 °C, the mixture was filtered and the
filtrate was concentrated in vacuo. Purification of the residue by flash
column chromatography gave mannopyranosides which predominately
contained its α-anomer. β-Mannopyranosides: To a stirred solution of 1
(1) For a recent review, see: Toshima, K.; Tatsuta, K. Chem. Rev.
1993, 93, 1503-1531.
(2) For recent selective and direct syntheses of β-mannnopyranosides,
see: (a) Kim, W.-S.; Sasai, H.; Shibasaki, M. Tetrahedron Lett.
1996, 37, 7797-7800. (b) Crich, D.; Sun, S. J. Org. Chem. 1996,
61, 4506-4507. (c) Crich, D.; Sun, S. J. Org. Chem. 1997, 62,
1198-1199. (d) Tatsuta, K.; Yasuda, S. Tetrahedron Lett. 1996, 37,
2453-2456. (e) Hodosi, G.; Kovac, P. J. Am. Chem. Soc. 1997,
119, 2335-2336. (f) Crich, D.; Sun, S. J. Am. Chem. Soc. 1998,
120, 435-436.
(0.5 mmol) and a glycosyl acceptor (1.0 mmol) in dry Et O (5.0 ml)
2
were added powdered MS 5Å (100 wt% to 1) and SO /ZrO (100 wt%
4
2
to 1). After stirring for 15 h at 25 °C, the similar workup and
purification mentioned above gave mannopyranosides which included
its β-anomer as a major product. In conclusion, we have presented a
novel and stereocontrolled strategy for the direct synthesis of both α-
and β-mannopyranosides from a mannopyranosyl fluoride and an

June 1998
SYNLETT
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(3) For elegant syntheses of β-mannnopyranosides by intramolecular
approaches, see: (a) Barresi, F.; Hindsgaul, O. J. Am. Chem. Soc.
1991, 113, 9376-9377. (b) Barresi, F.; Hindsgaul, O. Synlett 1992,
759-761. (c) Stork, G.; Kim, G. J. Am. Chem. Soc. 1992, 114,
1087-1088. (d) Stork, G.; La Clair, J. J. Am. Chem. Soc. 1996,
118, 247-248. (e) Ito, Y.; Ogawa, T. Angew. Chem. 1994, 106,
1843-1845; Angew. Chem., Int. Ed. Engl. 1994, 33, 1765-1767. (f)
Dan, A.; Ito, Y.; Ogawa, T. J. Org. Chem. 1995, 60, 4680-4681.
(g) Ziegler, T.; Lemanski, G.; Rakoczy, A. Tetrahedron Lett. 1995,
36, 8973-8976. (h) Crich, D.; Sun, S.; Brunckova, J. J. Org. Chem.
1996, 61, 605-615. (i) Crich, D.; Hwang, J.-T.; Yuan, H. J. Org.
Chem. 1996, 61, 6189-6198. (j) Iimori, T.; Ohtake, H.; Ikegami, S.
Tetrahedron Lett. 1997, 38, 3415-3418.
(6) Montmorillonite K-10 was purchased from Aldrich Chemical
Company, Inc. and dried at 200 °C/1 mmHg for 12 h before using.
®
(7) 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.
(8) SO /ZrO was purchased from Wako Pure Chemical Industries,
4
2
Ltd. and dried at 200 °C/1 mmHg for 12 h before using.
(9) The study on glycosidation using SO /ZrO -CaCl has been quite
4
2
2
recently announced. Nishimura, S.; Matsuda, M. The Abstract of
XIXth Japanese Carbohydrate Symposium, A3-10, 1997.
(10) 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.
(4) For glycosidations using a reusable solid acid, see: (a) Florent, J.-
C.; Monneret, C. J. Chem. Soc., Chem. Commun. 1987, 1171-
1172. (b) Fukase, K.; Winarno, H.; Kusumoto, S. Chem. Express
1993, 8, 409-411. (c) Toshima, K.; Ishizuka, T.; Matsuo, G.;
Nakata, M. Synlett 1995, 306-308. (d) Toshima, K.; Miyamoto,
N.; Matsuo, G.; Nakata, M.; Matsumura, S. Chem. Commun.
1996, 1379-1380.
(11) For a pioneering work on β-mannosylation using a heterogenic
catalyst, see; Paulsen, H.; Lockhoff, O. Chem. Ber. 1981, 114,
3102.
(12) MS 5Å was shown to be slightly superior to other MS such as MS
3Å and MS 4Å.
(5) The fluoride 1 was prepared from the corresponding 2,3,4,6-tetra-
O-benzyl-α-D-mannopyranose and DAST as previously described
in the literature, see; Posner, G. H.; Haines, S. R. Tetrahedron Lett.
1985, 26, 5-8.
(13) All mannopyranosides were purified by silica gel column
chromatography and were fully characterized by spectroscopic
means. The anomeric configuration is assigned in each case with
1
the aid of H-NMR analysis and confirmed by comparison with
the authentic samples which were reported in ref. 2 or 3.