ORGANIC
LETTERS
2004
Vol. 6, No. 21
3755-3758
Generation of Alkoxycarbenium Ion
Pools from Thioacetals and Applications
to Glycosylation Chemistry
Shinkiti Suzuki, Kouichi Matsumoto, Kohsuke Kawamura, Seiji Suga,* and
Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Nishikyo-ku, Kyoto 615-8510, Japan
Received July 28, 2004
ABSTRACT
Alkoxycarbenium ions have been generated and accumulated as “cation pools” by the low-temperature electrochemical oxidation of
-phenylthioethers. Although an unsuccessful attempt to accumulate glycosyl cations was made, a one-pot method for electrochemical
r
glycosylation, which involves anodic oxidation of thioglycosides to generate glycosyl cation equivalents followed by their reactions with
glycosyl acceptors, has been developed.
Glycosyl cations have received significant research attention
both from mechanistic chemists and those involved in the
synthesis of oligosaccharides.1 Studies on glycosyl cations
have been important for helping the design of inhibitors of
glycosidases by providing information on the transient
species present in the active site of the enzyme.2 After the
pioneering work by Crich3 on the characterization of glycosyl
triflate intermediates, glycosyl cation equivalents were
recognized as discrete intermediates with reasonable stability.
Although they are quite effective for glycosylation, they are
covalent rather than ionic species. Despite extensive effort
to observe ionic glycosyl cation intermediates, they have not
been detected spectroscopically.
Recently, we developed the “cation pool” method for
carbocation generation, in which carbocations are accumu-
lated in solution by low-temperature electrolysis.4 In the next
step, the carbocations are allowed to react with nucleophiles.
This one-pot method serves as a powerful method for
combinatorial synthesis. The method has since been suc-
cessfully applied to N-acyliminium ions5 and alkoxycarbe-
nium ions.6 Thus, we initiated the present project in which
glycosyl cations would be generated and accumulated by the
“cation pool” method with great anticipation.
(1) (a) PreparatiVe Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel
Dekker: New York, 1997. (b) Sears, P.; Wong, C.-H Science 2001, 291,
2344. (c) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40,
1576. (d) Seeberger, P. H.; Haase, W.-C. Chem. ReV. 2000, 100, 4349. (e)
Koeller, K. M.; Wong, C.-H. Chem. ReV. 2000, 100, 4465. (f) Herzner, H.;
Reipen, T.; Schltz, M.; Kunz, H. Chem. ReV. 2000, 100, 4495.
(2) For example: (a) Look, G. C.; Fotsch, C. H.; Wong, C.-H. Acc. Chem.
Res. 1993, 26, 182. (b) Winchester, B.; Fleet, G. W. J. Glycobiology 1992,
3, 199. (c) Bernotas, R. C.; Pezzone, M. A.; Ganem, B. Carbohydr. Res.
1987, 167, 305. (d) Papandreou, G.; Tong, M. K.; Ganem, B. J. Am. Chem.
Soc. 1993, 115, 11682. (d) Fotsch, C. H.; Wong, C.-H. Tetrahedron Lett.
1994, 35, 3481. (e) Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M.
Chem. ReV. 2002, 102, 515.
(4) Yoshida, J.; Suga, S. Chem. Eur. J. 2002, 8, 2650. For cation flow
method, see: Suga, S.; Okajima, M.; Fujiwara, K.; Yoshida, J. J. Am. Chem.
Soc. 2001, 123, 7941.
(5) (a) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.;
Fujiwara, K. J. Am. Chem. Soc. 1999, 121, 9546. (b) Suga, S.; Okajima,
M.; Yoshida, J. Tetrahedron Lett. 2001, 42, 2173. (c) Suga, S.; Suzuki, S.;
Yoshida, J. J. Am. Chem. Soc. 2002, 124, 30. (d) Suga, S.; Watanabe, M.;
Yoshida, J. J. Am. Chem. Soc. 2002, 124, 14824. (e) Suga, S.; Nagaki, A.;
Yoshida, J. Chem. Commun. 2003, 354. (f) Suga, S.; Nagaki, A.; Tsutsui,
Y.; Yoshida, J. Org. Lett. 2003, 5, 945.
(3) (a) Crich, D.; Sanxing, S. J. Am. Chem. Soc. 1997, 119, 11217. (b)
Crich, D.; Sun, S. J. Am. Chem. Soc. 1998, 120, 435. (c) Crich, D.; Cai,
W. J. Org. Chem. 1999, 64, 4926.
10.1021/ol048524h CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/18/2004