A practical and efficient procedure for the cleavage of acylals to aldehydes catalyzed by indium tribromide in water

Article abstract of DOI:10.1016/j.tetlet.2004.11.161

Indium tribromide (10 mol %) is an efficient catalyst for chemoselective cleavage of aryl acylals in refluxing water. A variety of acylals have been deprotected to give the corresponding parent aldehydes in high yield. The procedure presented is operationally simple, practical, and compatible with other sensitive functionalities such as methoxy, methyleneioxy, and benzyloxy groups present in the substrates.

Full text of DOI:10.1016/j.tetlet.2004.11.161

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 889–893
A practical and efficient procedure for the cleavage of acylals
to aldehydes catalyzed by indium tribromide in water
Zhan-Hui Zhang, Liang Yin, Yi Li and Yong-Mei Wang*
Department of Chemistry and the State Key Laboratory of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, PR China
Received 29 June 2004; revised 10 November 2004; accepted 15 November 2004
Available online 15 December 2004
Abstract—Indium tribromide (10 mol %) is an efficient catalyst for chemoselective cleavage of aryl acylals in refluxing water. A vari-
ety of acylals have been deprotected to give the corresponding parent aldehydes in high yield. The procedure presented is operation-
ally simple, practical, and compatible with other sensitive functionalities such as methoxy, methyleneioxy, and benzyloxy groups
present in the substrates.
ꢀ
2004 Elsevier Ltd. All rights reserved.
5
The toxic and volatile nature of many organic solvents,
particularly chlorinated hydrocarbons and benzene,
which are widely used in organic synthetic procedures,
has posed a serious threat to the environment. There
has been considerable research recently into replacing
the use of these volatile organic solvents with clean ones
nucleophiles and used as carbonyl surrogates for asym-
6
metric synthesis.
However, the final stages of chemical manipulation
require their cleavage so as to regenerate the parent
aldehydes. Although the conventional deprotection of
acylals is achieved under basic conditions by using either
sodiumhydroxide or potassiumcarbonate in aqueous
1
as reaction media. Performing organic reactions in
aqueous media has attracted much attention, because
water would be considerably safe, non-toxic, environ-
mentally friendly and cheap compared to organic
7
THF, the strong basic conditions make them inappro-
priate for base-sensitive substrates. A variety of reagents
for the removal of acylals have been developed to solve
this problem. These include the use of boron triiodide-
2
solvents. Moreover, when a water-soluble catalyst is
used, most products can be separated by simple decanta-
tion and the catalyst solution can be recycled. Therefore,
development of a catalyst system that is not only stable
toward water but also completely soluble in this solvent
seems highly desirable.
8
N,N-diethylaniline complex, ceric ammonium nitrate
9
coated on silica gel, neutral alumina under microwave
12
1
0
11
+
irradiation, CeCl Æ7H O/NaI, CBr4, [NO ÆCrown
3
14
2
À
1
13
4e
15
17
H(NO3)2 ], AlCl , zirconium(IV) chloride, BiCl3,
6
3
Sc(OTf)3, 2,6-dicarboxypyridiniumchlorochro ma te
1
8
The protection–deprotection of aldehyde functionalities
is important in synthetic organic chemistry, and a pleth-
ora of reagents and methods have been developed to this
end. In recent years, acylals have been introduced as a
and heterogeneous catalyst such as montmorillonite
1
9
20
21
clays, expansive graphite, zeolite, layered zirco-
2
2
ꢁ 23
niumsulfophenyl phosphonate,
Envirocat EPZG .
Many of these methods suffer one or more drawbacks,
such as the use of harmful volatile organic solvents,
unsatisfactory yields, expensive reagents, longer reaction
times, tedious work-up procedure or the use of an addi-
tional microwave oven. In this context there is a need
to devise a mild, efficient method with environmental
benign using water as a green solvent for the selective
cleavage of acylals in the presence of acid-sensitive
protecting groups. Scanning the literature, we have dis-
covered an unique use of water as solvent with b-cyclo-
3
suitable protection group for this purpose because of
their stability in mildly acidic and basic medium and
ease of chemoselective preparation in the presence of
4
ketone. In addition, they can be converted into other
useful functional groups by reaction with appropriate
Keywords: Acylals; Aldehydes; Deprotection; Indiumtribro mi de;
Protecting groups; Water.
*
Corresponding author. Tel.: +86 2223504439; fax: +86
223502654; e-mail: zhanhui@mail.nankai.edu.cn
2
4
2
dextrin for this conversion.
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.161

890
Z.-H. Zhang et al. / Tetrahedron Letters 46 (2005) 889–893
Table 1. Cleavage of a,a-diacetoxytoluene using InBr
3
in water
OAc
RCH
OAc
InBr3 (10 mol%)
water
a
Yield (%)
RCHO
Entry Catalyst load (mol %) Temp (ꢂC) Time
2
1
2
3
4
5
6
100
100
1
rt
100
100
100
60
24 h
—
1
10 min 96
80 min 95
30 min 96
60 min 93
20 min 96
Scheme 1.
5
10
10
Recently, indiumtribromide has been discovered to be a
new type of water-soluble green Lewis acid imparting
high regio-, chemo- and stereoselectivity in various
100
a
Isolated yield.
2
5
chemical transformations. As a continuation of these
2
6
studies and in an effort to investigate on organic reac-
tions in water, we first report in this letter a selective and
convenient procedure for the deprotection of acylals
in a longer reaction period (Table 1, entry 5). We have
also investigated the efficiency of the catalyst in less than
stoichiometric amount. The deprotected benzaldehyde
using a catalytic amount of InBr in aqueous media
3
was obtained using 10 mol % of the InBr in high yield.
3
(
Scheme 1).
Lower catalyst loading could be used with only a mar-
ginal drop in reaction rate (Table 1, entries 3 and 4).
The catalytic activity of indiumtribro mi de was first
tested for the deprotection of acylals in water. Initially,
the cleavage of a,a-diacetoxytoluene in the presence of
Having established the preferred reaction conditions,
the deprotection of several representative acylals was
performed to demonstrate the versatility and uniqueness
of the present reaction conditions (Table 2). Aromatic
acylals were converted to the parent aldehydes in
impressive yield. 2-Furanylmethanediol diacetate (entry
15) also was converted to its corresponding aldehydes
1
equiv InBr in water was first investigated at room
3
temperature, no deprotected product was obtained even
the mixture was stirred for 24 h. To our satisfaction,
rapid conversion was observed when the reaction was
carried out with reflux at 100 ꢂC in water. In these cases,
lower temperature could also be applied but to result
without polymerization in the presence of InBr . a,b-
3
3
Table 2. Cleavage results of acylals using InBr in refluxing water
a,b
Yield (%)
Entry
Substrate
Product
Time (min)
20
1
CH(OAc)2
CH(OAc)2
CHO
CHO
96
Me
Me
2
20
94
3
4
5
Me
CH(OAc)2
Me
CHO
18
15
15
93
92
94
OMe
CH(OAc)2
OMe
CHO
MeO
CH(OAc)2
CH(OAc)2
MeO
CHO
O
O
O
O
CHO
6
7
8
9
30
18
20
35
95
94
94
92
BnO
F
CH(OAc)2
CH(OAc)2
BnO
F
CHO
CHO
Cl
Cl
CH(OAc)2
CHO
Cl
Cl
Cl
Cl
1
1
0
1
35
50
86
95
CH(OAc)2
CHO
CH(OAc)2
CHO

Z.-H. Zhang et al. / Tetrahedron Letters 46 (2005) 889–893
891
Table 2 (continued)
a,b
Yield (%)
Entry
Substrate
NO2
Product
Time (min)
180
NO2
1
2
3
95
CH(OAc)2
CHO
O N
O N
2
2
1
200
93
CH(OAc)2
CH(OAc)2
CHO
c
90
14
15
16
17
O N
O N
CHO
240
25
2
2
90
89
CH(OAc)2
CHO
O
O
CH(OAc)2
CHO
40
d
93 (96 )
AcO
MeO
AcO
CH(OAc)2
CH(OAc)2
AcO
MeO
AcO
CHO
CHO
15
d
95 (98 )
1
1
8
9
20
CH
3
(CH
2
)
8
CH(OAc)
2
CH (CH
3
2
)
8
CHO
5 h
Trace
90
CH(OAc)2
CHO
20
4 h
OCH CH(OAc)2
OCH CH(OAc)2
2
2
a
b
c
Yield refers to pure isolated products.
All products are known, and spectral data identical with authentic samples.
Two milliliters of methanol was added.
Based on GC analysis.
d
Unsaturated acylals (entry 16) were also proved amica-
ble to this methodology. The presence of electron-donat-
ing and electron-withdrawing groups on the aromatic
ring made obvious difference for the deprotection of
acylals according to the reaction rates. The substitution
of the electron-withdrawing group onto the aromatic
ring severely retards the deprotection. The reaction with
CH(OAc)2
+
InBr3 (10 mol%)
water, 20min
C H19CH(OAc)
9 2
CH3
H C
3
CHO + C H19CH(OAc)2
9
9
5%
94%
(
4-methylphenyl)methanediol diacetate (entry 3) was
completed within 18 min whereas with 2-, 3- and 4-
nitrobenzylidene diacetates (entries 12–14) the reaction
time was extended to 3–4 h. We have also tried the reac-
tion of 1,1-diacetoxydecane (entry 19) as an example of
an aliphatic aldehyde acylal in refluxing water for 5 h in
the presence of the catalyst. Only trace of decanal was
obtained. Removal of an aromatic acylal group from
double protected aldehydes was achieved with high
selectivity (entry 20). To stress the selectivity of this
method, we have also performed a competitive reaction
between 4-methylphenylmethanediol diacetate and 1,1-
diacetoxydecane in the presence of 0.1 molar ratio of
Scheme 2.
phenyl) methanediol (entry 18) with InBr gave only
3
the cleavage product of acylals in more than 90% yield
in short reaction time. These results have demonstrated
that such reaction conditions allow for selective cleavage
of aryl aldehyde acylals in the presence of phenolic ace-
tate. Moreover, the reaction conditions are sufficiently
mild not to affect the methyl (entries 2 and 3), methoxy
(entries 4 and 5), methyleneioxy (entry 6), benzyloxy
(entry 7) and chloro (entries 9–11) functionalities.
InBr and observed the following conversion (Scheme
3
2
). Such selectivity can be applied in synthetic sequences
After removal of the reaction product by ethyl acetate
extraction of the aqueous reaction mixture, the mother
liquor could be reused and subjected to a second run
of the cleavage process by charging with the same sub-
strate. The results of the first experiment and four sub-
sequent runs were almost consistent in yield (96%,
in which two acylal groups must be deprotected at differ-
ent stages of the synthesis.
It should be noted that the treatment of (4-acetoxyphen-
yl) methanediol (entry 17) and (4-acetoxy-3-methoxy-

892
Z.-H. Zhang et al. / Tetrahedron Letters 46 (2005) 889–893
95%, 93%, 94%) for the cleavage of a,a-diacetoxytolu-
ene, but the complete conversion of substrate required
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