Facile and selective deallylations of esters under 'aqueous' free-radical conditions

Article abstract of DOI:10.1055/S-2008-1072727

The conversion of allyl esters into carboxylic acids using radical initiators has been achieved in high yields in aqueous media. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-2008-1072727

LETTER
1233
Facile and Selective Deallylations of Esters under ‘Aqueous’ Free-Radical
Conditions
Selective
D
eallylat
.
ions of
E
ster
T
s
amara Perchyonok,*a,b Sarah J. Ryan,b Steven J. Langford,b Milton T. Hearn,a Kellie L. Tuck*b
a
Centre for Green Chemistry, Monash University, Clayton 3800, Australia
School of Chemistry, Monash University, Clayton 3800, Australia
b
Fax +61(3)99054597; E-mail: kellie.tuck@sci.monash.edu.au; E-mail: tamara.perchyonok@sci.monash.edu.au
Received 1 February 2008
AIBN
(10% wt)
O
O
Abstract: The conversion of allyl esters into carboxylic acids using
radical initiators has been achieved in high yields in aqueous media.
R'
O
R'
OH
solvent
Key words: deallylation, esters, radical, selective, aqueous
Scheme 1 General deallylation reaction
MeO
Functional group protection and deprotection strategies
are quite often a necessary part of organic syntheses.1 The
acyl group is one of the most important functional groups
and its controlled protection and deprotection is of great
value in synthetic organic chemistry. Protection of acyl
groups as the allyl ester are often employed because of
their ease of preparation and stability under a wide variety
of reaction conditions.2 Although there are a number of
methods for the selective cleavage of allyl esters, there are
significant drawbacks to most of these procedures, for ex-
ample, the use of heavy metals leads to problems with tox-
icity and waste removal.3–13 As a result, there is a need to
develop general and selective methods for the cleavage of
allyl esters and which occur under environmentally be-
nign conditions. Of the types of reactions possible, radical
reactions hold promise since they occur under mild reac-
tion conditions and show broad functional tolerance, but
more importantly new synthetic methodologies have
emerged that show radical reactions are complementary to
ionic processes.14–16 Here we report on the novel selective
deallylations of a series of carboxylic esters under free-
1 R' =
O
Figure 1
radical conditions in aqueous media (Scheme 1, Figure 1,
Table 1).
The mechanism proposed to account for the formation of
the major product observed under the experimental condi-
tions is shown in Scheme 2.17 Hydrogen abstraction from
1 by the isobutyronitryl radical (formed via thermal de-
composition of AIBN) leads to the formation of the stabi-
lized oxyallyl radical 2, which undergoes reaction with
residual oxygen to produce peroxyl radical 3. Radical 3
abstracts hydrogen from a second molecule of 1, which
leads to the generation of another radical species 2, and
the formation of the corresponding hydroperoxide 4. Sub-
sequently, ester 4 undergoes facile transacylation to pro-
OH
initiator
O
O
O
R
R
O
O
R
O
4
O
O2
1
O
O
O
H
O
R
O
R
O
3
1
2
O
OH
O
O
O
O
O
transacylation
fragmentation
H2O
O
R
R
OH
R
O
HO
6
7
4
5
Scheme 2 Proposed mechanism for the deprotection of the allyl ester
SYNLETT 2008, No. 8, pp 1233–1235
x
x.
x
x.
2
0
0
8
Advanced online publication: 16.04.2008
DOI: 10.1055/s-2008-1072727; Art ID: G04808ST
© Georg Thieme Verlag Stuttgart · New York

1234
V. T. Perchyonok et al.
LETTER
Table 1 Radical Deprotection of Allyl Ester 1 under Various Con-
Table 2 Radical Deprotection of Various Allyl Esters in the Pres-
ditions
ence of AIBN (10 wt%) in Water or Benzene
Entry
Additive
AIBN
Solvent
C6H6
H2O
Yield (%)a
96
Entry
1
R¢ of substrate
Solvent
Yield (%)
1
2
3
4
5
6
7
H2O
C6H6
75
quant
AIBN
83
V-501b
H2O
93
n.r.c
n.r.c
n.r.c
n.r.c
H2O
C6H6
70
quant
none
C6H6
H2O
2
3
none
O
O
AIBN, PhOHd
AIBN, PhOHd
C6H6
H2O
H2O
C6H6
quant
quant
a Yields were determined by 1H NMR analysis of the crude reaction
mixture after evaporation of the solvent.
b 4,4¢-Azobis(4-cyanopentanoic acid).
c No reaction; only starting material present.
d A stoichiometric amount of phenol was added to the reaction mix-
ture.
H2O
C6H6
91
86
4
5
duce corresponding acylperoxide 5, which subsequently
fragments into the corresponding acid 6, acrolein 7, and
water. The proposed mechanism is supported by experi-
mental evidence and several important literature prece-
dences.18–21
H2O
C6H6
78
quant
O
In conclusion we have established a facile, efficient free-
radical method for the selective deallylation22 of esters in
aqueous media. This method represents an environmen-
tally friendly alternative to existing methodologies.
H2O
C6H6
quant
quant
6
HN
Fmoc
General Procedure
H2O
C6H6
65
quant
To the allyl ester (0.2 mmol) in nondegassed H2O (5 mL) was added
AIBN (10 wt%) and the reaction mixture was stirred at 65–70 °C
for 3 h or until completion of the reaction as indicated by TLC anal-
ysis. After completion the solvent was removed in vacuo and the re-
action analyzed by H NMR spectroscopy. ESI-MS was used to
confirm formation of the deallylated product.
7
8
O
1
H2O
C6H6
76
quant
Acknowledgment
We wish to thank the Australian Research Council and Monash’s
Centre of Green Chemistry for their support. Funding support of the
CSIRO Food Futures Flagship is also gratefully acknowledged.
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References and Notes
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J. Chem. Soc., Perkin Trans. 2 1988, 1643.
Synlett 2008, No. 8, 1233–1235 © Thieme Stuttgart · New York

LETTER
Selective Deallylations of Esters
1235
(14) (a) Davis, M. E. Acc. Chem. Res. 1993, 26, 11.
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(16) For excellent review on the cleavage of allylic and
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(17) Authors are grateful to the referees for the suggestion of a
plausible mechanism and valuable insight into the kinetics of
the acyl radicals.
(18) Recent references on generation of acyl radicals from
aldehydes: (a) Esposti, S.; Dondi, D.; Fagnoni, M.; Albini,
A. Angew. Chem. Int. Ed. 2007, 46, 2531. (b) Nambu, H.;
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(22) Competition experiments with a 1:1 mixture of the methyl
ester and allyl ester of 2-(4-isobutylphenyl)propanoic acid
(Table 2, entry 4) under our general reaction conditions
revealed no consumption of the methyl ester. The
corresponding acid, formed by reaction at the allyl ester, was
formed in 86% and 91% in benzene and H2O, respectively.
Synlett 2008, No. 8, 1233–1235 © Thieme Stuttgart · New York

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