ORGANIC
LETTERS
2008
Vol. 10, No. 21
5075-5077
Regioselective Protection of Sugars
Catalyzed by Dimethyltin Dichloride
Yosuke Demizu, Yuki Kubo, Hiroko Miyoshi, Toshihide Maki,
Yoshihiro Matsumura, Noriaki Moriyama, and Osamu Onomura*
Graduate School of Biomedical Sciences, Nagasaki UniVersity, 1-14 Bunkyo-machi,
Nagasaki 852-8521, Japan
Received September 8, 2008
ABSTRACT
The first catalytic process for protection of hydroxyl groups in sugars has been developed. Highly regioselective protection was accomplished
along with high chemical yield. The regioselectivity of the benzoylation was realized as an intrinsic character of sugars based on a
stereorelationship among their hydroxyl groups. Furthermore, complete protection of r-methyl glucoside and ꢀ-methyl xyloside was accomplished.
Selective protection of hydroxyl groups in sugars is one of
the most fundamental techniques in sugar chemistry since it
is essential for selective functionalization of sugars including
glycosidation.1 For this purpose, some methods have been
developed based on regioselective complexation of hydroxyl
groups in sugars with tin or boron reagents.2 These methods,
however, require a stoichiometric amount of hazardous
reagents. We have developed selective monobenzoylation of
1,2-diols using a catalytic amount of dimethyltin dichloride.3
Also, the catalytic ability of dibutyltin reagent for activation
of 1,2-diols has been demonstrated.4 However, so far there
is no literature applying organotin catalysts to regioselective
protection of unprotected sugars.5
In this communication, we present the first catalytic
process for protection of hydroxyl groups of sugars6 in a
highly regioselective manner using dimethyltin dichloride
(Me2SnCl2) and its application to preparation of com-
pletely protected sugars.
We started off by treating sugars 1a-g with 1.2 equiv
of benzoyl chloride in the presence of DIPEA and 0.05
equiv of Me2SnCl2 in THF or aqueous THF to test their
benzoylation. The results are summarized in Table 1.
In all cases, monobenzoylated sugars 2a-g were
regioselectively obtained in high to excellent yields. The
monobenzoylation predominantly took place at the 1,2-
diol moiety except for ꢀ-methyl glucoside (2b) where the
primary hydroxyl group at the 6-position was selectively
benzoylated (entry 2). For 1a-d, anhydrous THF as a
solvent was better than aqueous THF (entries 1-4), while
aqueous THF (THF:H2O ) 9: 1) was more effective for
(1) Boons, G. J. Tetrahedron 1996, 52, 1095, and references cited
therein.
(2) (a) Wagner, D.; Verheyden, J. P. H.; Moffatt, J. G. J. Org. Chem.
1974, 39, 24. (b) Munavu, R. M.; Szmant, H. H. J. Org. Chem. 1976, 41,
1832. (c) Nashed, M. A.; Anderson, L. Tetrahedron Lett. 1976, 17, 3503.
(d) Tsuda, Y.; Haque, M. E.; Yoshimoto, K. Chem. Pharm. Bull. 1983, 31,
1612. (e) Nicolaou, K. C.; van Delft, F. L.; Conley, S. R.; Mitchell, H. J.;
Jin, Z.; Rodr´ıguez, R. M. J. Am. Chem. Soc. 1997, 119, 9057. (f) Tsuda, Y.
J. Synth. Org. Chem. Jpn. 1997, 55, 907. (g) Oshima, K.; Aoyama, Y. J. Am.
Chem. Soc. 1999, 121, 2315.
(3) (a) Maki, T.; Iwasaki, F.; Matsumura, Y. Tetrahedron Lett. 1998,
39, 5601. (b) Iwasaki, F.; Maki, T.; Onomura, O.; Nakashima, W.;
Matsumura, Y. J. Org. Chem. 2000, 65, 996.
(5) A preliminary result of this work was disclosed by us: Matsumura,
Y.; Maki, T.; Iwasaki, F. Jpn. Kokai tokkyo Koho 2001; JP 2001247592:
CA 135:242453, 2001.
(4) (a) Caddick, S.; McCarroll, A. J.; Sandham, D. A. Tetrahedron 2001,
57, 6305. (b) Burke, S. D.; Voight, E. A. Org. Lett. 2001, 3, 237. (c)
Martinelli, M. J.; Vaidyanathan, R.; Pawlak, J. M.; Nayyar, N. K.; Dhokte,
U. P.; Doecke, C. W.; Zollars, L. M. H.; Moher, E. D.; Khau, V. V.;
Kosˇmrlj, B. J. Am. Chem. Soc. 2002, 124, 3578.
(6) More recently, two excellent methods were reported. See: from per-
O-silylated sugars by TMSOTf: (a) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.;
Kulkarni, S. S.; Huang, Y.-W.; Lee, C.-C.; Cheng, K.-L.; Hung, S.-C. Nature
2007, 446, 896. By organocatalyst: (b) Kawabata, T.; Muramatsu, W.;
Nishio, T.; Shibata, T.; Schedel, H. J. Am. Chem. Soc. 2007, 129, 12890.
10.1021/ol802095e CCC: $40.75
Published on Web 10/10/2008
2008 American Chemical Society