Dimethylsulfoxide-iodine catalysed deprotection of allyl carboxylic esters

Article abstract of DOI:10.1016/j.tetlet.2005.11.130

A convenient method for deprotection of allyl carboxylic esters has been developed by using the inexpensive and environmentally friendly reagent dimethylsulfoxide-iodine. A variety of carboxylic esters were deprotected to the carboxylic acids. This method is more efficient and operationally simple in comparison to methods using transition metal complexes.

Full text of DOI:10.1016/j.tetlet.2005.11.130

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 643–646
Dimethylsulfoxide–iodine catalysed deprotection of
allyl carboxylic esters
Kiran N. Taksande, Sachin S. Sakate and Pradeep D. Lokhande*
The Center for Advanced Studies, Department of Organic Chemistry, University of Pune, Pune 411 007, India
Received 16 October 2005; revised 16 November 2005; accepted 24 November 2005
Abstract—A convenient method for deprotection of allyl carboxylic esters has been developed by using the inexpensive and envi-
ronmentally friendly reagent dimethylsulfoxide–iodine. A variety of carboxylic esters were deprotected to the carboxylic acids. This
method is more efficient and operationally simple in comparison to methods using transition metal complexes.
Ó 2005 Elsevier Ltd. All rights reserved.
Carboxylic acids can be protected as anhydrides,1
amides2 or esters.3 Allyl esters are particularly useful
as protecting groups in carboxylic acids.4 The allyl
group has frequently been used in peptide synthesis as
a protecting group due to its stability under basic, acidic
and reduction conditions.5 The allyl group for carbox-
ylic acid protection is now generally used in the liquid
or solid phase synthesis of a wide range of natural and
synthetic products.6
There has been a search for mild and chemo-selective
reagents for the cleavage of allylic carboxylic esters.
Schmidt reported that methyl, crotyl and cinnamyl
esters were cleaved in refluxing formic acid whereas
simple allyl esters were recovered unchanged under
similar experimental conditions.13 Iodine in cyclohexane
at room temperature cleaved a prenyl protecting group
but it did not cleave an allyl protecting group.14 Similar
observations were reported by Gajare et al., in the
deprotection of allyl esters by K-10 clay under micro-
wave irradiation.15 This led us to utilise the inexpensive,
readily available reagent iodine in dimethylsulfoxide for
the deprotection of the allyl esters. The DMSO–I2
reagent has been used in the oxidative cyclisation of
20-hydroxychalcones to flavones16 and the oxidation of
flavanones to flavones,17 isoxazolines to isoxazoles18
and pyrazolines to pyrazoles.19
Common allyl deprotection methods are two-step proce-
dures that include isomerisation to the more labile
1-propenyl group with a variety of reagents. The most
frequently employed conditions are treatment of the
allyl carboxylic ester with palladium complexes7 and
the use of a stoichiometric amount of a nucleophile.8
Complexes of nickel,9 ruthenium10 and rhodium11 have
also been used in deallylation procedures. The use of an
excess of nucleophile, however, decreases the atom
efficiency and sometimes causes problems during
work-up. Most of these processes are slow. Palladium
complexes have been reported to bring about decarboxyl-
ation–allylation in a-substituted b-keto-carboxylic acids
and malonic, nitro and cyano acetic acids.12a Reaction
of allyl a-fluoro-b-keto carboxylate with a Pd-complex
gave a-fluoro ketones.12b
Earlier we reported our previous results on the deallyl-
ation of 20-allyloxychalcones to afford flavones20 (Scheme
1) in excellent yields. The deprotection products, 20-
hydroxychalcones, were not isolated since these com-
pounds were immediately oxidised to flavones under
these conditions.21 In continuation of this effort, the
present investigation describes a facile cleavage of allyl
esters using the dimethylsulfoxide–iodine reagent
(Scheme 2).
The method is applicable to allyl esters of both aromatic
and aliphatic carboxylic acids. Allylic esters were pre-
pared using conventional techniques (K2CO3, allyl bro-
mide, DMF) in high yields. The allyl esters were then
subjected to cleavage conditions, which involved heating
Keywords: Allyl ester; Iodine; Deprotection.
*
Corresponding author. Tel.: +91 020 25896199; fax: +91 20
25691728; e-mail: pdlokhande@chem.unipune.ernet.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.130

644
K. N. Taksande et al. / Tetrahedron Letters 47 (2006) 643–646
R
O
I2 - DMSO
O
R
R
R
130 0C, 30 min
O
O
2
1
Scheme 1. Deallylation of 20-allyloxychalcone.
while allyl p-nitrobenzoate was deallylated in 20 min. A
control experiment with ethyl benzoate demonstrated no
cleavage under the reaction conditions, while allyl-
methyl salicylates and allyl aspirin ester resulted in the
formation of salicylic acid. The effects of acid catalyst
were also briefly investigated. In the presence of sulfuric
acid (a catalytic amount), the reaction was found to be
fast and was complete at 60 °C. This may be due to
the inevitable presence of hydroiodic acid in the experi-
ment, which hydrolysed the ester very rapidly. The allyl
ester of ibuprofen was also cleaved smoothly. Protected
allyl glycine, allyl phenyl glycine and allyl p-acetanilide
carboxylate were also tested with this reagent and found
to be deallylated smoothly.
O
O
I2 - DMSO
OH
O
R
R
130 0C, 10 - 30 min
3
4
Scheme 2. Deallylation of allylcarboxyl esters.
in dimethylsulfoxide with a catalytic amount of iodine
and monitoring the reaction by TLC. The results are
summarised in Table 1. The reactions were complete in
10–30 min at 130 °C. The allyl benzoates reacted slowly
Table 1.
Entry
Reactant
Product
Time (min)
30
Yield (%)
71
O
OH
1
O
O
O
O
O
OH
2
20
95
O2N
O2N
O
OH
3
4
8
73
87
O
O
O
O
20
O
OH
O
O
5
30
90
O
O
OH
O
6
7
8
30
30
12
85
80
76
O
O
OH
O
O
O
OH
O
O
O
O
OH
Cl
Cl

K. N. Taksande et al. / Tetrahedron Letters 47 (2006) 643–646
645
Table 1 (continued)
Entry
Reactant
Product
Time (min)
Yield (%)
OH
O
9
30
82
O
OH
O
O
OH
O
O
O
10
11
30
30
84
78
OH
O
O
O
O
OH
H
O
H
N
N
CH3
O
CH3
O
O
N
N
N
O
OH
OH
12
30
65
H
H
H
O
O
N
13
14
15
30
30
20
63
75
77
O
H
O
O
O
OH
MeO
Me
MeO
Me
O
O
O
OH
O
OH
16
17
20
—
69
—
O
O
O
O
O
O
A range of various functional groups such as –NO2,
–OMe, Cl, ACH@CHA were compatible with the
reagent. Groups like pyran,22 methoxymethyl, b-meth-
oxymethyl and methylthiomethyl were reported to be
inert to iodine deprotection23 and TBDMSCl24 did not
undergo deprotection in the presence of iodine under
appropriate reaction conditions. In solvents other than
dimethylsulfoxide including methanol, ethanol, diethyl
ether, dichloromethane and benzene, the starting allyl
esters were recovered. Thus the presence of both reagents,
iodine in catalytic amount and dimethylsulfoxide, were
necessary for the conversion of an allyl ester into a free
carboxyl group. At temperatures higher than 155 °C it
was observed that the >C@C< bond of 20-allyloxychal-
cone was oxidatively cleaved to benzaldehyde. There-
fore, the addition of an excess amount of iodine at
higher temperature had to be avoided. In the absence
of sulfuric acid at 100 °C, the reaction did not proceed.

646
K. N. Taksande et al. / Tetrahedron Letters 47 (2006) 643–646
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Iodine is a soft nucleophile and prefers to react at
the allylic position rather than at a carbonyl carbon.
Sandhu and co-workers25 reported that AlI3 efficiently
cleaved allyl carboxylic esters to carboxylic acids with
iodine acting as a soft nucleophile. Iodine has been
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The present work provides an efficient and inexpensive
deallylation procedure for a variety of allylic carboxylic
esters. The reaction proceeds using a weak oxidising
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protection of carboxylic acids along with allyl phenol
ethers.
The typical experimental procedure is as follows:
To a solution of allyl ester (207 mg, 1 mmol) in dimethyl-
sulfoxide (3 ml) was added a catalytic amount of iodine.
The reddish reaction mixture was heated in an oil bath
at 130 °C for 30 min. After cooling, the reaction mixture
was diluted with ice-cold water and the iodine was
removed by the addition of a saturated solution of
sodium thiosulfate and washing with water and brine.
The product was extracted with ethyl acetate and
washed with water. The organic layer was treated with
a saturated solution of sodium bicarbonate solution,
which dissolved the deprotected compound with strong
effervescence. On neutralisation with dilute hydrochloric
acid, the solid acid was isolated and purified by recrys-
tallisation from a suitable solvent.
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Pune, 2003.
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