An efficient biomimetic cleavage of gem-diacetates to aldehydes by β-cyclodextrin under neutral conditions in aqueous medium

Article abstract of DOI:10.1081/SCC-120002012

The cleavage of gem-diacetates to aldehydes, a widely used protecting group in organic synthesis, has been achieved for the first time under neutral conditions in aqueous medium using β-cyclodextrin as catalyst. The main advantage of the present methodology is that it can be used with compounds having a variety of functional groups since the cleavage is carriedout under neutral conditions in aqueous medium.

Full text of DOI:10.1081/SCC-120002012

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
AN EFFICIENT BIOMIMETIC CLEAVAGE OF GEM-
DIACETATES TO ALDEHYDES BY β-CYCLODEXTRIN
UNDER NEUTRAL CONDITIONS IN AQUEOUS
MEDIUM*
M. Arjun Reddy , L. Rajender Reddy , N. Bhanumathi & K. Rama Rao
To cite this article: M. Arjun Reddy , L. Rajender Reddy , N. Bhanumathi & K. Rama Rao
(2002) AN EFFICIENT BIOMIMETIC CLEAVAGE OF GEM-DIACETATES TO ALDEHYDES BY
β-CYCLODEXTRIN UNDER NEUTRAL CONDITIONS IN AQUEOUS MEDIUM*, Synthetic
Communications, 32:2, 273-277, DOI: 10.1081/SCC-120002012
To link to this article: http://dx.doi.org/10.1081/SCC-120002012
Published online: 16 Aug 2006.
Submit your article to this journal
Article views: 32
View related articles
Citing articles: 9 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [The UC San Diego Library]
Date: 02 February 2017, At: 07:34

SYNTHETIC COMMUNICATIONS, 32(2), 273–277 (2002)
AN EFFICIENT BIOMIMETIC
CLEAVAGE OF GEM-DIACETATES
TO ALDEHYDES BY b-CYCLODEXTRIN
UNDER NEUTRAL CONDITIONS
IN AQUEOUS MEDIUM*
M. Arjun Reddy, L. Rajender Reddy,
N. Bhanumathi, and K. Rama Raoy
Organic Chemistry Division-I, Indian Institute of
Chemical Technology, Hyderabad, 500 007, India
ABSTRACT
The cleavage of gem-diacetates to aldehydes, a widely used
protecting group in organic synthesis, has been achieved for
the first time under neutral conditions in aqueous medium
using b-cyclodextrin as catalyst. The main advantage of the
present methodology is that it can be used with com-
pounds having a variety of functional groups since the
cleavage is carriedout under neutral conditions in aqueous
medium.
*IICT Communication No. 4655.
yCorresponding author. E-mail: ramaraok@iict.ap.nic.in
273
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
274
ARJUN REDDY ET AL.
Selective protection and deprotection of carbonyl groups are of great
significance in organic synthesis especially in multistep synthesis of natural
products.1 Amongst various protecting groups, gem-diacetates have been
recognized as the method of choice due to their easy installation and
removal and their stability in a variety of reaction conditions. Apart from
this, these gem-diacetates are useful synthetic intermediates in various
organic transformations.2,3 However, most of the general methods used
for the cleavage of these diacetates include various acidic reagents such as
K10 clay,4 hydrochloric acid,5 sulfuric acid,6 BI3-N,N-dimethyl aniline com-
plex7 etc. as well as basic reagents such as sodium and potassium hydro-
xide.8 However, these are some severe limitations with the literature
methods such as use of strong acidic or basic conditions, lower yields,
longer reaction times etc. Keeping in viewthe limitations of the existing
procedures, we felt the need to develop an alternate and mild approach
under neutral conditions using water as the solvent, which is an environ-
mentally benign one. In our effort to develop biomimetic approaches for
chemical reactions involving cyclodextrins in water,9 we report herein, for
the first time, a practical and efficient method for the cleavage of gem-
diacetates to aldehyde catalysed by b-cyclodextrin under neutral conditions
in aqueous medium.
Cyclodextrins (CDs) which are cyclic oligosaccharides with hydropho-
bic cavities exert microenvironmental effect leading to selective reactions.
They catalyse reactions involving supramolecular catalysis through non-
covalent bonding as seen in enzymes. These biomimetic reactions can be
effectively carried out in water under neutral conditions without generating
any toxic waste products. Thus, mimicking of biochemical selectivity which
involves supramolecular catalysis with the reactions being carried out in
water will be superior to chemical selectivity. This has prompted us to
attempt the cleavage of gem-diacetates using CDs, as this is one of the
most useful synthetic transformations (scheme).
Scheme.
The reactions were carried out by dissolving b-cyclodextrin in water
followed by the addition of gem-diacetate. The yields of the products were

ORDER
REPRINTS
CLEAVAGE OF GEM-DIACETATES TO ALDEHYDES
275
Table 1. Selective Cleavage of gem-Diacetates to Aldehydes Catalysed by
b-Cyclodextrin

ORDER
REPRINTS
276
ARJUN REDDY ET AL.
impressive (up to 95%) and these reactions can be efficiently carried out with
only catalytic amount of cyclodextrin (0.1 mole of CD per mole of the
substrate). The cyclodextrin can also be recovered and reused. These reac-
tions do no take place in the absence of CD. This methodology apart from
having the advantage of neutral conditions and aqueous medium is also
compatible in the presence of various other functional groups such as
OMe, O-Bn, O-Allyl, methylene dioxy, OAc and N-Boc. However, the
yields with aliphatic and heterocyclic gem-diacetates, are comparatively
lower. Here, the role of CD appears to be to activate the acetyl group by
hydrogen bonding, thus facilitating its cleavage in the presence of water.
Though, this reaction takes place in the presence of a-CD also, b-CD will
be the most preferred catalyst due to its easy accessibility and economic
viability.
In conclusion, this biomimetic methodology is the first of its kind to be
applied for the cleavage of gem-diacetates, one of the most commonly used
protecting groups in organic synthesis, under neutral conditions in aqueous
medium in the presence of b-cyclodextrin. This method is also compatible in
the presence of other functional groups.
EXPERIMENTAL
1H NMR spectra were recorded on Gemini-200 MHz spectrometer
and mass spectra were observed on VG Autospect M. The IR spectra
were recorded on NICOLET FT-IR. Spectrometer.
General Procedure for the Cleavage of gem-Diacetates in Aqueous
Medium Using b-Cyclodextrin: In a typical procedure, to b-cyclodextrin
(0.1 mmol) dissolved in 20 ml of water by heating at 60ꢀC, was added
gem-diacetate (1 mmol) in methanol (1 ml) and stirred at this temperature
for the required length of time (table). The reaction mixture was cooled
to room temperature and extracted with ethylacetate (3 Â 20 ml). The
combined organic extract was washed with water (2 Â 10 ml), dried over
anhydrous sodium sulphate and evaporated under reduced pressure to
give the product. This was further purified by column chromatography on
silica gel (100–200) using hexane: ethylacetate (90:10). The yields were in the
range of (60–95%).
ACKNOWLEDGMENT
MAR and LRR thank CSIR, NewDelhi, India, for the award of
research fellowships.

ORDER
REPRINTS
CLEAVAGE OF GEM-DIACETATES TO ALDEHYDES
277
REFERENCES
1. a) Kocienski, P.J.; Protecting Groups, Georg. Theieme Verrlag Stuttgart:
NewYork, 1994. b) Green, T.W.; Wuts, P.G.M. Protective Groups in
Organic Synthesis, Wiley: NewYork, 2nd ed., 1991.
2. a) Sridher, B.B.; Amin, S.G. Synth. Commun. 1978, 8, 117. b) Bankas,
R.E.; Miller, J.A.; Nunn, M.J.; Stanley, P.; Weakley, T.J.R. Ullah, Z.
J. Chem. Soc. Perkin Trans 1 1981, 1096.
3. a) Sandberg, M.; Sydnes, L.K. Tetrahedron Lett. 1998, 39, 6361. b)
Heerden, F.R.; Huyser, J.J.; Willams B.D.G.; Holzapfel, C.W.
Tetrahedron Lett. 1998, 39, 5281.
4. Li, T.-S.; Zhang, Z.-H.; Fu, C.-G. Tetrahedron Lett. 1997, 38, 3285.
5. Tsaug, S.M.; Wood, E.H.; Johnson, J.R. Org. Syn. 1955, coll. vol. 3,
141.
6. Lieberman, S.V.; Cannon, R. Org. Syn. 1951, Coll. vol 3. 441.
7. Narayana, C.; Padmanabhan, S.; Kabalka, G.W. Tetrahedron Lett.
1990, 31, 6977.
8. Kochhar, K.S.; Bal. B.S.; Deshpande, R.P.; Rajadhyaksha, S.N.;
Pinnick, H.W. J. Org. Chem. 1983, 48, 1765.
9. a) Rama Rao, K.; Sattur, P.B. J. Chem. Soc. Chem. Commun. 1989,
342. b) Rama Rao, K.; Sampath Kumar, H.M. Synth. Commun. 1993,
23, 1877. c) Rama Rao, K.; Bhanumathi, N.; Rajender Reddy, L. Synth.
Commun. 1999, 29, 1703. d) Rajender Reddy, L.; Arjun Reddy, M.;
Bhanumathi, N.; Rama Rao, K. Synlett 2000, 339.
Received in the UK November 16, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120002012