Selective deprotection of tetrahydropyranyl ethers catalysed by
b-cyclodextrin in water¤
M. Arjun Reddy, L. Rajender Reddy, N. Bhanumathi and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical T echnology, Hyderabad 500 007,
India. E-mail: ramaraok=iict.ap.nic.in
L e t t e r
Received (in Montpellier, France) 13th November 2000, Accepted 22nd December 2000
First published as an Advance Article on the web 13th February 2001
The hydrolysis of tetrahydropyranyl ethers to alcohols catalysed
This methodology is also very e†ective in deprotecting the
THP group in the presence of other sensitive functionalities
such as acetonide, methylenedioxy, O-methyl, O-benzyl,
N-Boc, formyl, silyl and ester groups. Here, the role of CD
appears to be to activate the THP ether by hydrogen bonding,
as shown in Scheme 2, thus facilitating the hydrolysis.
In conclusion, this methodology involving cyclodextrin in
water is the Ðrst of its kind for deprotecting THP ethers and
has several advantages over the existing methodologies.
by b-cyclodextrin proceeds in water under neutral conditions.
Selective protection and deprotection of functional groups is
of great signiÐcance in organic synthesis. Amongst these pro-
cedures, tetrahydropyranylation of hydroxyl groups has been
recognised as a method of choice for the protection of alco-
hols and phenols due to the ease of installation and stability
in the presence of most nonacidic reagents of the tetra-
hydropyranyl group.1 However, most of the general methods
used for the cleavage of tetrahydropyranyl (THP) ethers
involve a variety of catalysts, such as MgBr , Me AlCl,
2
2
(NCSBu Sn) O,
MeOHÈHCl,
NaBH CNÈBF É OEt ,
2
2
3
3
2
Ph PBr, DDQ, etc.2 There are also examples that, under
neutral conditions in aqueous or non-aqueous media, involve
Scheme 1
3
expensive and toxic reagents.2f, h,3 Apart from this, some of
these methods produce considerable amounts of side products.
Keeping in view the range of catalysts and the complexity of
procedures involved, we felt there was a need to develop an
alternate and mild approach for the selective removal of the
THP group in the presence of other sensitive functional
groups, preferably under neutral conditions. The best choice
would be through supramolecular catalysis, but this still
remains a goal yet to be attained.
In our e†orts to develop biomimetic approaches for chemi-
cal reactions involving cyclodextrins in water,4 we report
herein a simple methodology for the deprotection of THP
ethers catalysed by b-cyclodextrin (b-CD) in water (Scheme 1).
Cyclodextrins, which are cyclic oligosaccharides, exert a
microenvironmental e†ect that can lead to selective reactions.
They catalyse reactions by supramolecular catalysis through
non-covalent bonding, as seen in enzymes. These reactions
can be carried out e†ectively in water, which is an environ-
mentally benign solvent under neutral conditions, and also do
not generate any toxic waste products. This supramolecular
catalysis involving cyclodextrins has been applied to the de-
protection of THP ethers. It was carried out by dissolving b-
cyclodextrin in water, followed by addition of the THP ether.
The yields of the products obtained were in the range 70È90%
(Table 1). Though this reaction takes place in the presence of
a-CD also, b-CD will be the preferred catalyst due to its easy
accessibility and low cost. These reactions can be efficiently
carried out with only a catalytic amount of the cyclodextrin
(0.1 mol of CD per mol of the substrate). The cyclodextrin can
also be recovered and reused. These reactions, when carried
out in the absence of cyclodextrin, show no deprotection of
THP ethers. The fact that the deprotection of THP ethers
does not take place in the presence of other carbohydrates
such as glucose conclusively proves the role of cyclodextrin.
Scheme 2
Experimental
The substrate tetrahydropyranyl ethers (Table 1) were made
as reported in the literature.2j,l b-Cyclodextrin was procured
from Sterling Organics Ltd., U.K. Typical procedure is the
following: b-cyclodextrin (0.1 mmol) was dissolved in water
(25 ml) at 60 ¡C; tetrahydropyranyl ether (1 mmol) in meth-
anol (1 ml) was added slowly with stirring. The stirring was
continued at 50 ¡C for the speciÐed time (Table 1). It was
cooled to room temperature, extracted with ethyl acetate
(2 ] 30 ml), dried over anhydrous sodium sulfate and the
solvent was removed in vacuo. The crude product was puriÐed
by silica gel column chromatography using ethyl acetateÈ
hexane (3 : 7) as eluent. All the products were characterized by
1H NMR and mass spectral data and compared with the data
reported in the literature for the authentic samples.2a,b,d,ihm
Acknowledgements
M. A. R. and L. R. R. thank CSIR, New Delhi, India, for the
award of research fellowships.
¤ IICT Communication no. 4528.
DOI: 10.1039/b009187l
New J. Chem., 2001, 25, 359È360
359
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001
Arjun Reddy
