ORGANIC
LETTERS
2002
Vol. 4, No. 12
2039-2042
Solution-Phase Hexasaccharide
Synthesis Using Glucosyl Iodides
Son N. Lam and Jacquelyn Gervay-Hague*
Department of Chemistry, UniVersity of California DaVis, DaVis, California 95616
Received March 18, 2002
ABSTRACT
Oligosaccharides composed of 1,6-glucosyl residues have been prepared from glucosyl iodides. The reactions are highly stereoselective,
giving the r-glycosides as the only isolated products in yields ranging from 84% to 94%. Oligomer synthesis can take place in an iterative
1 + 1 + 1 fashion or in a convergent manner where dimer iodides serve as donors for higher order acceptors.
Many strategies are available for the construction of O-
glycosidic linkages as a result of the early work of Fischer,1
Ko¨enigs and Knorr,2 Helferich and Olst,3 Lemieux,4 and
Paulsen5 and the more recent work of Schmidt,6 Kahne,7
Danishefsky,8 Seeberger,9 and others.10 Glycosyl halides are
among the most useful donors; however, they have not been
widely employed in the construction of higher order oligo-
saccharides. Because recent studies11,12 have shown that
iodide donors offer advantages over bromides in terms of
reaction times, efficiencies, and stereochemical outcomes,
we decided to probe the utility of glycosyl iodides in solution-
phase oligosaccharide synthesis.
We have found that the most practical way of generating
glycosyl iodides is through the reaction of glycosyl acetates
with iodotrimethylsilane.13 The byproduct, trimethylsilyl
acetate, can be removed through rotoevaporation, yielding
the iodide without need of further purification. However, the
emergence of glycosyl iodides as viable glycosyl donors has
prompted other groups to devise new preparative methods
including the use of solid supported diphenylphosphine and
molecular iodine12c or in situ generation of anhydrous
hydroiodic acid from thiolacetic acid and molecular iodine.14
Our glycosylation studies involve a modification of the
in situ anomerization conditions established for glycosyl
bromides in the pioneering work of Lemieux and co-
workers.15 A combination of glycosyl iodide and tetrabutyl-
(1) Fischer, F. Chem. Ber. 1893, 26, 2400.
(2) Ko¨enigs, W.; Knorr, E. Chem. Ber. 1901, 34, 957.
(3) Helferich, B.; Ost, W. Chem. Ber. 1962, 95, 2612.
(4) Lemieux, R. U.; Hendricks, K. B.; Stick, R. V.; James, K. J. Am.
Chem. Soc. 1975, 97, 4056.
(5) Paulsen, H.; Kolar, C. Chem. Ber. 1981, 114, 306.
(6) Schmidt, R. R.; Michel, J. Angew. Chem. 1980, 92, 763. Schmidt,
R. R.; Kinzy, W. AdV. Carbohydr. Chem. Biochem. 1994, 50, 21-123.
(7) Kahne, D.; Walker, S.; Cheng, Y.; Van Engen, D. J. Am. Chem. Soc
1989, 111, 6881.
(8) Danishefsky, S. J.; McClure, K. F.; Randolph, J. T.; Ruggeri, R. B.
Science 1993, 260, 1307.
(9) (a) Plante, O. J.; Palmacci, E. R.; Andrade, R. B.; Seeberger, P. H.
J. Am. Chem. Soc. 2001, 123, 9545. (b) Hewitt, M. C.; Seeberger, P. H. J.
Org. Chem. 2001, 66, 4233. (c) Plante, O. J.; Andrade, R. B.; Seeberger,
P. H. Org. Lett. 1999, 1, 211. (d) Plante, O. J.; Seeberger, P. H. J. Org.
Chem. 1998, 63, 9150.
(10) Garegg, P. I. AdV. Carbohydr. Chem. Biochem. 1997, 52, 179-
205. Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong,
C.-H. J. Am. Chem. Soc. 1999, 121, 734. Barresi, F.; Hindsgaul, O. J.
Carbohydr. Chem. 1995, 14, 1043. Ernst, B., Hart, G. W., Sina¨y, P., Eds.;
Carbohydrates in Chemistry and Biology; Part I, Chemistry of Saccharides;
Volume 1, Chemical Syntheses of Glycosides and Glycomimetics; Wiley-
VCH: Weinheim, 2000.
(11) (a) Bhat, A. S.; Gervay-Hague, J. Org. Lett. 2001, 3, 2081. (b) Hadd,
M. J.; Gervay, J. Carbohydr. Res. 1999, 320, 61. (c) Gervay, J. Org.
Synth.: Theory Appl. 1998, 4, 121-153. (d) Gervay, J.; Hadd, M. J. J.
Org. Chem. 1997, 62, 6961.
(12) (a) Schmid, U.; Waldmann, H. Liebigs Ann./Relc. 1997, 2573. (b)
Tanaka, H.; Sakamoto, H.; Sano, A.; Nakamura, S.; Nakajima, M.;
Hashimoto, S. Chem. Commun. 1999, 1259. (c) Caputo, R.; Kunz, H.;
Dominico, M.; Palumbo, G.; Pedatella, S.; Solla, F. Eur. J. Org. Chem.
1999, 3147.
(13) Thiem, J.; Meyer, B. Chem. Ber. 1980, 113, 3075.
10.1021/ol025887d CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/17/2002