SHORT PAPER
1741
A Mild and Efficient Oxidative Deprotection of THP Ethers with NBS in the
Presence of b-Cyclodextrin in Water
Mildand Efficient
O
xi
.
dative Depro
N
tection of THP Et
a
w
ithN
r
B
S
ender, M. Somi Reddy, K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
E-mail: drkrrao@yahoo.com
Received 9 February 2004; revised 3 May 2004
lowed by oxidation of free alcohol or by a direct method
one pot oxidative deprotection). The direct transforma-
tion of tetrahydropyranyl ethers to their carbonyl com-
Abstract: An efficient and user-friendly procedure has been devel-
oped for the oxidative deprotection of tetrahydropyranyl (THP)
ethers with N-bromosuccinimide (NBS) using b-cyclodextrin (b-
(
CD) in water. A series of tetrahydropyranyl ethers were oxidatively pounds is a useful practical achievement and only few
deprotected at room temperature in impressive yields.
reports are available.12
Key Words: oxidative deprotection, tetrahydropyranyl ethers, N- In continuation of our ongoing program to develop syn-
bromosuccinimide, b-cyclodextrin, water
thetic approaches for chemical reactions involving cyclo-
dextrins in water,13 we report herein for the first time a
novel, convenient and mild approach for one pot in situ
Protection and deprotection of alcohols play an essential oxidative deprotection of tetrahydropyranyl ethers using
1
role in synthetic strategy. Amongst various reagents used NBS in the presence of b-cyclodextrin (b-CD) with water
for protection of alcohols, 3,4-dihydro-2-pyran is em- as solvent (Scheme 1). This method has many advantages
ployed for the protection of alcohol group owing to the over the existing methodologies offering an environmen-
outstanding stability of tetrahydropyranyl ethers under a tally benign protocol with the practical convenience of not
variety of conditions in various organic syntheses includ- having to handle flammable and anhydrous organic sol-
ing peptide, nucleotide and carbohydrate chemistry. A va- vents.
riety of catalysts have been studied for the oxidative
deprotection of tetrahydropyranyl ethers such as PCC (py-
2
ridinium chlorochromate), CPCC (3-carboxy pyridinium
3
chlorochromate), (n-BuPPh ) S O (n-butyltriphenyl
3
2
4
2
8
phosphonium peroxodisulfate), AgBrO and NaBrO in
presence of AlCl tetramethylammonium chlorochro-
mate, benzyl triphenylphosphonium peroxymonosulfate
with bismuth chloride, iron(III) nitrate with clay and
montmorillonite K-10, and several reagents impregnated
on mineral supports such as chromium(VI) oxide. Many
3
3
5
3
,
6
Scheme 1
7
8
9
These reactions can be carried out effectively in impres-
sive yields in water (Table 1) without the generation of
any toxic waste products. No over oxidation products
have been detected. Here, the role of cyclodextrin appears
to be to activate the tetrahydrohydropyranyl ethers by hy-
drogen bonding facilitating the hydrolysis. The hydro-
lyzed product alcohol is further oxidized in situ to
carbonyl compounds with NBS. These reactions are effi-
ciently carried out with catalytic amounts of b-cyclodex-
trin (0.1 mmol of cyclodextrin per mmol of the substrate).
The cyclodextrin can also be recovered and reused. b-Cy-
clodextrin was used as a catalyst since it is easily accessi-
ble and inexpensive among various cyclodextrins. A
reaction was performed without NBS in the presence of b-
cyclodextrin. It was found that only deprotection takes
place without any formation of oxidized product. In the
absence of b-cyclodextrin, no deprotection takes place
and hence no oxidation occurs. The yields were compara-
of these methods have severe limitations such as use of
anhydrous organic solvents, Lewis acid catalysts, use of
expensive reagents, longer reaction times, lower yields,
tedious work up. Moreover, the oxidative transformations
with chromium(VI) reagents is compromised in many
ways due to their inherent toxicity, cumbersome prepara-
tion and potential danger (ignition) in handling its com-
plexes, difficulties in terms of product isolation and waste
disposal. They are corrosive and irritant for the skin and
sensitive parts of body such as eyes. Derivatives of chro-
mium (VI) in particular are well known carcinogens.10
Hence in the view of increasing environmental con-
straints, the design of new, less polluting, inexpensive re-
agents is still in demand and has become a priority for
1
1
chemical industry.
The oxidative deprotection can be carried out by either a
conventional two-step procedure, i.e. deprotection fol-
tively diminished when substituents such as NO , OTB-
2
DMS and OTHP were present in the aromatic ring
(
Table 1). However, when both functionalities like -OTB-
SYNTHESIS 2004, No. 11, pp 1741–1743
x
x.
x
x
.
2
0
0
4
DMS (phenolic) and -OTHP (alcoholic) were present in
Advanced online publication: 13.07.2004
DOI: 10.1055/s-2004-829148; Art ID: Z02704SS
Georg Thieme Verlag Stuttgart · New York
©
Narender
