ORGANIC
LETTERS
2008
Vol. 10, No. 5
725-728
Direct C-Glycosylation by
Indium-Mediated Alkynylation on Sugar
Anomeric Position
Nade`ge Lubin-Germain,*,† Jean-Pierre Baltaze,‡ Alexis Coste,† Agne`s Hallonet,†
Hugo Laure´ano,† Gre´gory Legrave,† Jacques Uziel,*,† and Jacques Auge´†
Laboratoire de Synthe`se Organique Se´lectiVe et Chimie Organome´tallique, Unite´
CNRS-UCP-ESCOM 8123, 5 mail Gay-Lussac, NeuVille-sur-Oise,
95031 Cergy-Pontoise, France, and ICMMO-UMR 8182 Baˆtiment 420, UniVersite´
Paris-Sud XI, 15 rue Georges Cle´menceau, 91405 Orsay Cedex, France
Received December 4, 2007
ABSTRACT
Indium-mediated alkynylation reaction was studied for the direct preparation of C-glycosides. Easily available starting sugar derivatives with
an acetyl group at the anomeric position were tested as electrophiles toward alkynylindium reagents under Barbier conditions. Good yields
and stereoselectivities were observed during the reaction. The alkynylation was applied to the synthesis of an
of isomaltoside.
r-(1f6)-C-disaccharide analogue
Over the last couple of years, indium has been receiving an
increasing interest,1 due to its smooth reactivity and its ease
of use. Even though indium is particularly used in allylation
reactions in polar solvents, we looked into its potential to
catalyze alkynylation reactions of carbonyl compounds under
Barbier conditions2 and investigated new methods3 to prepare
C-glycosides. These nonhydrolyzable carbohydrate isosteres
have become of great interest since they were found to have
potent biological properties and to be useful building blocks.
Thus, we successfully applied this reaction to C-glycosides
synthesis,4 using formylglucoses as electrophiles. We also
demonstrated the possibility of accessing various function-
alized C-glycosides after transformation of the resulting
propargylic alcohols. The creation of the C-C bond by direct
alkynylation, starting from more simple carbohydrate deriva-
tives, represents a significant achievement. Such an alkyny-
lation was previously carried out by the addition of ethy-
nylmagnesium bromide and ethynylaluminium derivatives
on D-glucopyranosyl bromide, which led to byproducts.5
Organotin acetylides which are softer nucleophiles, were also
used with sugar bromides,6 but the application was limited
by the toxicity of tin reagents which need to be prepared
first. As a matter of fact, the most frequently used method
is the addition of an organometallic reagent onto a sugar
lactone.7 The diastereoselectivity is controlled during the
subsequent reduction of the lactol, leading to â isomers. An
alternative to this approach is the addition of organometallic
reagents to glycal epoxides. The control of the anomeric
stereoselectivity is then dependent on the metal.8 As sug-
gested by our previous results on the indium-mediated Ferrier
† University of Cergy-Pontoise.
(5) (a) Zelinski, R.; Meyer, R. J. Org. Chem. 1957, 23, 810. (b) Tolstikov,
G. A.; Prokhorova, N. A.; Spivak, A.; Khalilov, L. M.; Sultamuratova, V.
R. J. Org. Chem. USSR (Engl. Transl.) EN 27, 1991, 10, 1858.
(6) Zhai, D.; Zhai, W.; Williams, R. M. J. Am. Chem. Soc. 1988, 110,
2501.
(7) (a) Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104,
4976. (b) Lancelin, J.-M.; Amvam Zollo, P. H.; Sinay¨, P. Tetrahedron Lett.
1983, 24, 4833. (c) Dondoni, A.; Mariotti, G.; Marra, A.; Massi, A. Synthesis
2001, 2129. (d) Gomez, A. M.; Uriel, C.; Valverde, S.; Jarosz, S.; Cristobal
Lopez, J. Tetrahedron Lett. 2002, 43, 8935.
‡ University of Paris-Sud.
(1) (a) Nair, V.; Ros, S.; Jayan, C. N.; Pillai, B. S. Tetrahedron 2004,
60, 1959. (b) Auge´, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739.
(2) Auge´, J.; Lubin-Germain, N.; Seghrouchni, L. Tetrahedron Lett. 2003,
44, 819.
(3) Ousmer, M.; Boucard, V.; Lubin-Germain, N.; Uziel, J.; Auge´, J.
Eur. J. Org. Chem. 2006, 1216.
(4) Picard, J.; Lubin-Germain, N.; Uziel, J.; Auge´, J. Synthesis 2006,
979.
10.1021/ol7029257 CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/06/2008