Indium trichloride catalyzed glycosidation. An expeditious synthesis of 2,3-unsaturated glycopyranosides

Article abstract of DOI:10.1016/S0040-4039(99)02266-2

Treatment of tri-O-acetyl-D-glucal 1 with various alcohols and phenols in the presence of InCl₃/CH₂Cl₂ at ambient temperature gave the corresponding alkyl and aryl 2,3-unsaturated glycopyranosides in excellent yields with short reaction times and good anomeric selectivity. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02266-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1271–1274
Indium trichloride catalyzed glycosidation. An expeditious
synthesis of 2,3-unsaturated glycopyranosides†
Boga Sobhana Babu and Kalpattu Kuppuswamy Balasubramanian ∗
Department of Chemistry, Indian Institute of Technology, Madras Chennai, 600 036, India
Received 22 October 1999; accepted 7 December 1999
Abstract
Treatment of tri-O-acetyl-D-glucal 1 with various alcohols and phenols in the presence of InCl3/CH2Cl2 at
ambient temperature gave the corresponding alkyl and aryl 2,3-unsaturated glycopyranosides in excellent yields
with short reaction times and good anomeric selectivity. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: glycal; glycosides; indium; indium compounds; Ferrier rearrangement.
Indium trichloride, which is a relatively strong Lewis acid, has been used as a catalyst for a wide variety
of organic reactions viz., transmetallation with organotin compounds,1 Mukaiyama aldol reactions,2
imino Diels–Alder reactions3 and Barbier reactions involving addition of allyltin reagents to aldehydes
or aldoses to give adducts with high diastereoselectivity.4
Herein, we present our preliminary results on the interesting utility of InCl3 as an efficient catalyst for
the synthesis of alkyl and aryl 2,3-unsaturated glycopyranosides 2–11 via the Ferrier rearrangement.
When 1 equiv. of tri-O-acetyl-D-glucal 1 was treated with 1.2 equiv. of benzyl alcohol 5 and anhydrous
InCl3 in CH2Cl2 for 10 min at ambient temperature, benzyl 2,3-unsaturated glycopyranoside 15 was
obtained in 86% yield with the α-anomer as the major product. Likewise, other alcohols led to facile
glycosidation upon reaction with 1 in InCl3/CH2Cl2 affording the corresponding alkyl 2,3-unsaturated
glycopyranosides 12–17 in excellent yields (Scheme 1).
The reaction was extended to phenols which furnished the corresponding 2,3-unsaturated aryl glycopy-
ranosides 18–20 in moderate yields with the α-anomer as the major product. Extension of this reaction to
o-iodobenzyl alcohol 6 gave the corresponding α-glycoside 16 which is a potential precursor for chiral
isochroman type compounds (Table 1).
In the case of methyl 2,3,4-tri-O-methyl-α-D-glucopyranoside 11, within 1 h, the disaccharide 21 was
formed in 80% yield with the α-anomer (α:β 9:1) as the major product (Scheme 2).
∗
†
Corresponding author. Fax: 91-44-2350509; e-mail: kkbalu@hotmail.com (K. Kuppuswamy Balasubramanian)
Dedicated to Professor T. R. Govindachari, Advisor, Centre for Natural Products, SPIC Science Foundation, Chennai, India,
on the occasion of his 85th birthday.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02266-2
tetl 16194

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Scheme 1.
Table 1
InCl3 mediated glycosidation of alcohols and phenols with 1
Scheme 2.
To the best of our knowledge, this is the first report on InCl3 mediated Ferrier rearrangements. Several
Lewis acids have been employed to bring about the Ferrier rearrangement.5 Other reagents such as,
the environmentally more acceptable clay catalyst6 montmorillonite K-10, DDQ,7 (enabling neutral
conditions) and N-iodosuccinimide,8 (providing a non-acidic medium to effect Ferrier rearrangement
on 4-n-pentenoyl esters of glycals) are also known to bring about the Ferrier rearrangement under mild
conditions.
The efficacy of a few other catalysts viz., LiClO4, LiBF4, BF3·Et2O and SnCl4 was examined for the
Ferrier rearrangement of 1 with selected alcohols. It was observed that among these catalysts, InCl3 is
found to be the best (Table 2).
In all the cases studied, the reaction was fast with InCl3 as compared to other catalysts. Besides the
diastereoselectivity, the yield is greatest with InCl3. We have also examined a few other catalysts such as
TaCl5, PsCl3, LnCl3 in dichloromethane. However, none of these Lewis acids was found to catalyze the
Ferrier rearrangement.
In summary, we have observed that anhydrous InCl3 in CH2Cl2 is a useful catalyst for the rapid
synthesis of alkyl and aryl 2,3-unsaturated glycopyranosides in excellent yields with good anomeric

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Table 2
Study of various acid catalysts in the Ferrier rearrangement of 1 with alcohols
selectivity. Tandem ‘O’ to ‘C’ rearrangement of aryl 2,3-unsaturated glycopyranosides to form the 2,3-
unsaturated C-aryl glycosides is currently under investigation.
Typical experimental procedure: To a mixture of tri-O-acetyl-D-glucal 1 (1 mmol) and the aglycone
(1.1 mmol), was added anhydrous InCl3 (0.2 mmol; 20 mol%) in dry CH2Cl2 (1–2 mL) at ambient
temperature. The contents were stirred for the required time (Table 1) and the reaction monitored by
TLC. The reaction mixture was quenched by the addition of aqueous sodium hydrogen carbonate (10%,
25 mL), extracted with dichloromethane (3×25 mL), dried over anhydrous sodium sulphate, filtered
and concentrated. The residue was purified by flash column chromatography on silica gel to obtain the
products.
Acknowledgements
The authors thank: Department of Science and Technology, India, for financial support, and RSIC,
IIT, Chennai, SPIC Science Foundation, Chennai and Sun Pharmaceutical Advanced Research Centre,
Baroda for spectral data. One of us (B.S.B) also thanks Dr. K. Vijayakumaran, Director, R&D, Chimique
Laboratories, Chennai and Dr. Indrapal Singh Aidhen, IIT, Chennai for useful discussions.

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