SCHEME 1
P r otic Acid (HClO4 Su p p or ted on Silica
Gel)-Med ia ted Syn th esis of
2,3-Un sa tu r a ted -O-glu cosid es a n d a Ch ir a l
F u r a n Diol fr om 2,3-Glyca ls
Aditi Agarwal, Shikha Rani, and Yashwant D. Vankar*
16
BiCl3,14 ZnCl2,15 LiBF4
,
montmorillionite K-10,17 Dy-
Chemistry Department, Indian Institute of Technology,
Kanpur 208 016, India
(OTf)3,18 and ZrCl4.19 In addition to these Lewis acids,
oxidants such as DDQ,20 NIS,21 I2,22 I(Coll)2 ClO4,23 and
CAN24 have also been employed for the Ferrier reaction.
Recently, an interesting reagent system, viz., HClO4
supported on silica gel, has been introduced25 for convert-
ing alcohols to the corresponding acetates in an effective
manner. Glycals are known to react with alcohols in the
presence of protic acid catalysts such as MeOH‚HCl,26
cationic-exchange resin AG 50WX2,27 and Ph3P/HBr28 to
form the corresponding 2-deoxy-O-glycosides. It was
therefore of interest to us to find out the behavior of the
reagent system of HClO4 supported on silica gel, which
is cheap and moisture-insensitive, toward glycals in the
presence of alcohols. In this Note we wish to report that
HClO4 supported on column silica gel (200-400 mesh)29
allows the reaction of several alcohols, including primary,
secondary, and allylic alcohols, phenols, and thiophenol
with 3,4,6-tri-O-acetyl-D-glucal 1 to yield the correspond-
ing 2,3-unsaturated-O-glycosides in good to excellent
yields and in short reaction times with high R selectivity.
Further, it does not require any workup, as mere filtra-
tion of the catalyst followed by chromatographic purifica-
tion is sufficient. Our results are summarized in Table
1. All reactions were completed in less than 1 h except
with MeOH, EtOH, and cholesterol. Varying amounts of
vankar@iitk.ac.in
Received April 8, 2004
Abstr a ct: Perchloric acid supported on silica gel acts as
an excellent reagent system in converting glucals into 2,3-
unsaturated-O-glucosides in good to excellent yields in short
reaction time with good R selectivity. Primary, secondary,
and allylic alcohols, phenols, and thiols react with 3,4,6-tri-
O-acetyl glucal with equal ease. In addition to this, a chiral
furan diol is obtained from unprotected D-glucal or D-galactal
in good yields.
2,3-Unsaturated-O-glycosides are useful chiral inter-
mediates1 in the synthesis of biologically active com-
pounds such as glycopeptide building blocks,2 oligosac-
charides,3 and modified carbohydrates.4 They have also
been employed in the synthesis of some important
antibiotics5 and nucleosides.6 2,3-Unsaturated-O-glyco-
sides 2 (Scheme 1) are readily obtained from the corre-
sponding glycal derivatives 1 upon treatment with vari-
ous alcohols, generally in the presence of a Lewis acid
catalyst. This reaction was discovered by Ferrier in 1969
by using BF3‚Et2O as a Lewis acid catalyst and is
popularly known as the Ferrier reaction.7 Apart from
BF3‚Et2O,7,8 a large number of other Lewis acid catalysts
have been reported to effect the Ferrier reaction, which
include InCl3,9 SnCl4,10 Yb(OTf)3,11 Sc(OTf)3,12 FeCl3,13
(12) Yadav, J . S.; Reddy, B. V. S.; Murthy, C. V. S. R.; Kumar, G.
M. Synlett 2000, 1450.
(13) Masson, C.; Soto, J .; Bessodes, M. Synlett 2000, 9, 1281.
(14) Swami, N. R.; Venkateswarlu, A. Synthesis 2002, 598.
(15) Bettadaiah, B. K.; Srinivas, P. Tetrahedron Lett. 2003, 44, 7257.
(16) Babu, B. S.; Balasubramnaian, K. K. Synth. Commun. 1998,
29, 4299.
(17) (a) Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M. Synlett
1995, 306. (b) Shanmugasundaram, B.; Bose, A. K.; Balasubramanian,
K. K. Tetrahedron Lett. 2002, 43, 6795. (c) de Oliviera, R. N.; de Freitas,
J . R.; Srivastava, R. M. Tetrahedron Lett. 2002, 43, 2141.
(18) Yadav, J . S.; Subba Reddy, B. V.; Sunder Reddy, J . S. J . Chem.
Soc., Perkin Trans. 1 2002, 2390.
(19) Smitha, G.; Reddy, C. S. Synthesis 2004, 834.
(20) Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M.; Konoshita,
M. J . Chem. Soc., Chem. Commun. 1993, 704.
(21) Fraser-Reid, B.; Madsen, R. J . Org. Chem. 1995, 60, 3851.
(22) Koreeda, M.; Houston, T. A.; Shull, B. K.; Klemke, E.; Tuinman,
R. J . Synlett 1994, 90.
(23) Lo´pez, J . C.; Fraser-Reid, B. J . Chem. Soc., Chem. Commun.
1992, 94.
(24) Yadav, J . S.; Reddy, B. V. S.; Pandey, S. K. New J . Chem. 2001,
25, 538.
* To whom correspondence should be addressed. Fax: 0091-512-
259 7492.
(1) (a) Tolstikov, A. G.; Tolstikov, G. A. Russ. Chem. Rev. 1993, 62,
579. (b) Fraser-Reid, B. Acc. Chem. Res. 1985, 18, 347. (c) Ferrier, R.
J . Adv. Carbohydr. Chem. Biochem. 1969, 24, 199.
(2) (a) Winterfeld, G. A. Ph.D. Dissertion, University of Konstanz,
Germany, 2000. (b) Dorgan, B. J .; J ackson, R. F. W. Synlett 1996, 859.
(3) (a) Liu, Z. J . Tetrahedron: Asymmetry 1999, 10, 211 (b) See-
berger, P. H. Aldrichimica Acta 1997, 30, 75. (c) Danishefsky, S. J .;
Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 120, 13515.
(4) Schmidt, R. R.; Angerbauer, R. Angew. Chem., Int. Ed. Engl.
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(5) Williams, N. R.; Wander, J . D. The Carbohydrates in Chemistry
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M. R. Carbohydr. Res. 1998, 181, 308. (b) Schmidt, R. R.; Angerbauer,
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(29) HClO4 supported on silica gel was prepared as follows: 105.3
mg of HClO4 (0.125 mmol, as a 70% aqueous solution) was added to
the suspension of silica gel (2 g, 200-400 mesh) in Et2O. The mixture
was concentrated, and the residue was heated at 100 °C for 6 h to get
HClO4-SiO2 as a free flowing powder. The loading capacity of HClO4
on silica gel is 0.37 mmol H+/g. We thank the editor and the referee
for suggesting that we determine the loading capacity of HClO4 in this
reagent system.
(11) Takhi, M.; Abdel-Rahman; Adel, A. H.; Schmidt, R. R. Tetra-
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10.1021/jo049415j CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/31/2004
J . Org. Chem. 2004, 69, 6137-6140
6137