ORGANIC
LETTERS
2004
Vol. 6, No. 22
3913-3915
A Novel Stereospecific Synthesis of
Glycosyl Cyanides from 1,2-O-Sulfinyl
Derivatives
Abdelhafid Benksim, Daniel Beaupe`re, and Anne Wadouachi*
Laboratoire des Glucides, FRE 2779 UniVersite´ de Picardie Jules Verne,
33 rue Saint-Leu, F-80039 Amiens, France
Received July 9, 2004 (Revised Manuscript Received September 20, 2004)
ABSTRACT
An efficient synthesis of 1,2-trans-glycosyl cyanides via 1,2-O-sulfinyl monosaccharides is described. Such SN2-type displacements at the
anomeric center are stereospecific and are best performed with sodium cyanide in the presence of ytterbium triflate. Significantly, the resulting
1,2-trans-glycosyl cyanides have a free hydroxyl group at C-2 ready for further modification.
The stereoselective synthesis of functionalized C-glycosides
has become an important area of carbohydrate research, as
many naturally occurring C-glycosides have shown useful
antibacterial, antiviral, and antitumor properties.1 One of the
most important types of C-glycoside intermediates are
glycosyl cyanides, as such compounds can be readily
converted to the corresponding C-1 aminomethyl (as gly-
cosidase inhibitor) and carboxylic acid derivatives.2,3
Generally, the direct cyanation of per-O-benzyl-protected
electrophilic substrates yields mainly or exclusively the 1,2-
cis cyanoglycosides.8
The corresponding acylated donors, however, give the 1,2-
trans-glycosyl cyanides.9
In previous work, we have shown that O-sulfinyl monosac-
charide derivatives are useful substrates for stereoselective
N-glycosylation reactions to form glycosyl azides and 1,2-
cyclic carbamates10,11 and for O-glycosylations aimed at
obtaining aryl glycosides.12 Given our past successes with
these substrates, we became interested in studying their
reactivity toward C-nucleophiles, and in this paper, we
describe a new procedure for cyanoglycosylation that com-
mences from 1,2-O-sulfinylglycose derivatives. We have
In this regard, they have served as important intermediates
in the synthesis of a wide variety of sugar derivatives such
as C-glycosyl R-glycines, cyclopeptides containing a sugar
amino acid moiety, C-nucleoside derivatives, and C-glycoside
heterocycles.4-7
(1) (a) Fischer, C.; Lipata, F.; Rohr, J. J. Am. Chem. Soc. 2003, 125,
7818-7819. (b) Faizi, S.; Ali, H. Planta Med. 1999, 65, 383-385.
(2) (a) Lai, W.; Martin, O. R. Carbohydr. Res. 1993, 250, 185-193. (b)
BeMiller, J. N.; Gilson, R. J.; Myers, R. W., Santoro, M. M.; Yadav, M. P.
Carbohydr. Res. 1993, 250, 93-100. (c) Bhat, A. S.; Gervay-Hague, J.
Org. Lett. 2001, 3, 2081-2084.
(8) (a) Mukaiyama, T.; Kobayashi, S.; Shoda, S. Chem. Lett. 1984, 1529-
1530. (b) Hoffman, M. G.; Schmidt, R. R. Liebigs Ann. Chem. 1985, 2403-
2419.
(9) (a) Myers, R. W.; Lee, Y. C. Carbohydr. Res. 1984, 132, 61-82.
(b) Kini, G. D.; Petrie, C. R.; Hennen, W. J.; Dalley, N. K.; Wilson, B. E.;
Robins, R. K. Carbohydr. Res. 1987, 159, 81-94. (c) Maity, S. K.; Dutta,
S. K.; Banerjee, A. K.; Achari, B.; Singh, M. Tetrahedron 1994, 50, 6965-
6974. (d) Phisivongsa, P.; Gallagher, J.; Cher, C. N.; Jones, P. R.; Samoshin,
V. V.; Gross, P. H. Org. Lett 2002, 4, 4587-4590.
(3) BeMiller, J. N., Yadav, M. P.; Kalabokis, V. N., Myers, R. W.
Carbohydr. Res. 1990, 200, 111-126.
(4) Pochet, S.; Allard, P.; Huynh-Dinh, T.; Igolen, J. J. Carbohydr. Chem.
1983, 1, 277-288.
(5) Stoeckle, M.; Voll, G.; Guenther, R., Lohof, E., Locardi, E.; Gruner,
S.; Kessler, H. Org. Lett. 2002, 4, 2501-2504.
(10) El Meslouti, A.; Beaupe`re, D.; Demailly, G.; Uzan, R. Tetrahedron
Lett. 1994, 35, 3913-3916.
(6) (a) Albrecht, H. P.; Repke, D. B.; Moffatt, J. G. J. Org. Chem. 1973,
38, 1836-1840. (b) Poonian, M. S.; Nowosniat, E. F. J. Org. Chem. 1980,
45, 203-208. (c) El Khadem, H. S.; Kawai, J. Carbohydr. Res. 1986, 153,
271-283.
(11) (a) Beaupe`re, D.; El Meslouti, A.; Lelie`vre, P.; Uzan, R; Tetrahedron
Lett. 1995, 36, 5347-5348. (b) Roussel, F.; Wadouachi, A.; Beaupe`re, D.
Carbohydr. Lett. 2000, 3, 397-404.
(7) Osz, E.; Czifrak, K.; Deim, T.; Szilagyi, I.; Benyei, A.; Somsak, L.
Tetrahedron 2001, 57, 5429-5434.
(12) Aouad, M. E. A.; El Meslouti, A.; Uzan, R.; Beaupe`re, D.
Tetrahedron Lett. 1994, 35, 6279-6282.
10.1021/ol0486829 CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/05/2004