it environment friendly.3b,c Our current efforts have been aimed
at meeting the requirements of preparing various orthogonally
protected sugars and related building blocks in a fashion that
minimizes the reaction steps including the final workup.
Tandem Acetalation-Acetylation of Sugars and
Related Derivatives with Enolacetates under
Solvent-Free Conditions
Acetonide formation is the most commonly used protection
for 1,2 (cis)- and 1,3-diols, which has extensively been used in
carbohydrate chemistry to selectively mask the hydroxyls of
different sugars. These reactions are generally effected either
with a free carbonyl4 (e.g., aldehyde, ketone) or a masked
carbonyl (e.g., acetals,5 ketals,6 enolethers7) in the presence of
a variety of catalysts such as mineral acid,8 formic acid,9
CuSO4,10 ZnCl2,11 p-toluenesulfonic acid,12 camphorsulfonic
acid,13 iodine,14 etc. The protection of alcohols with an acetyl
group is another common transformation in organic synthesis.
The process is sluggish in the absence of an appropriate catalyst.
Though a number of methods are available, their use in
carbohydrate chemistry has limitations. In almost all the cases
acetic anhydride is used as the acetylating agent, generally in
the presence of pyridine,15 sodium acetate,16 Sc(OTf)3,17 Et3N-
DMAP,18 I2,19 ZnCl2,20 or InCl3.21 Perchloric acid22 and sulfuric
acid23 immobilized on silica have been used as promoters for
acetalation and subsequent acetylation of sugar glycosides in
good yield, though the acidic conditions during reactions can
lead to cleavage of acid-sensitive groups in the sugar ring.
Debaraj Mukherjee, Bhahwal Ali Shah, Pankaj Gupta, and
Subhash Chandra Taneja*
Bioorganic Chemistry Section, Indian Institute of IntegratiVe
Medicine (CSIR), Canal Road, Jammu Tawi, India 180001
ReceiVed February 22, 2007
Molecular iodine catalyzes acetalation and acetylation of
reducing sugars and sugar glycosides with stoichiometric
amounts of enol acetates under solvent-free conditions,
thereby facilitating the synthesis of various types of orthogo-
nally protected sugar derivatives in short time and good
yields. The outcome of the reaction can be controlled by
variation in temperature. Thus at lower temperature, it is
possible to obtain the acetonide acetate as a single product
whereas peracetate is the major product at higher tempera-
ture.
In recent years, molecular iodine has emerged as an inex-
pensive, nontoxic, nonmetallic, and readily available catalyst
for various organic transformations carried out with high
selectivity. Molecular iodine-catalyzed acetonide formation14 and
acetylation19 with acetone and acetic anhydride, respectively,
are known in sugar chemistry. The regioselective acetylation
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Carbohydrates are useful chiral synthons in natural product
synthesis.1 They contain an abundance of hydroxy groups and
it is often necessary to react only one (or some) of these groups
at a time. This is generally possible by choosing suitable
protecting group/s, which may be manipulated under different
reaction conditions.2 The introduction of such orthogonal
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Recently Wang et al. have reported a highly regioselective one-
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of a monosaccharide unit by using a single catalyst TMSOTf.3a
However, during the development of such strategies, one has
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* Address correspondence to this author. Fax: +91-191-2569111-333.
Phone: +91-191-2569000-006 (ext 210, 236).
(18) Nicolaou, K. C.; Pfefferkorn, J. A.; Roecker, A. J.; Cao, G.-Q.;
Barluenga, S.; Mitchell, H. J. J. Am. Chem. Soc. 2000, 122, 9939-9953.
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(2) Wang, Y.; Ye, X.-S.; Zhang, L.-H. Org. Biomol. Chem. 2007, 5,
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(3) (a) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Kulkarni, S. S.; Huang, Y.-
W.; Lee, C.-C.; Chang, K.-L.; Hung, S.-C. Nature 2007, 446, 896-899.(b)
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
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10.1021/jo070363i CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/16/2007
J. Org. Chem. 2007, 72, 8965-8968
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