An efficient deprotection of dithioacetals to carbonyls using Oxone-KBr in aqueous acetonitrile

Article abstract of DOI:10.1016/j.tetlet.2006.09.138

A simple and efficient method has been developed for the chemoselective dethioacetalization of dithioacetals to aldehydes and ketones using Oxone-KBr in aqueous acetonitrile at room temperature.

Full text of DOI:10.1016/j.tetlet.2006.09.138

Tetrahedron Letters 47 (2006) 8559–8561
An efficient deprotection of dithioacetals to carbonyls using
Oxone–KBr in aqueous acetonitrile
a,
a
a
b
b
*
U. V. Desai, D. M. Pore, B. V. Tamhankar, S. A. Jadhav and P. P. Wadgaonkar
a
Department of Chemistry, Shivaji University, Kolhapur 416 004, India
Polymer Science and Engineering Division, National Chemical Laboratory, Pune 411 008, India
b
Received 1 August 2006; revised 13 September 2006; accepted 22 September 2006
Available online 17 October 2006
Abstract—A simple and efficient method has been developed for the chemoselective dethioacetalization of dithioacetals to aldehydes
and ketones using Oxone–KBr in aqueous acetonitrile at room temperature.
Ó 2006 Elsevier Ltd. All rights reserved.
Protection and deprotection of functional groups is a
common tactic in multistep organic syntheses. As a
carbonyl protecting group, the S,S-acetal function has
found wide use in organic synthesis due to its easy
R1
1
S
S
R
Oxone-KBr
H O-CH CN, RT
O
R2
( )
n
R2
2
3
1
2
1
access and high stability towards both acidic and basic
R1 = alkyl, aryl
2
conditions. In addition, S,S-acetals are often used as
;
R = H, alkyl
2
acyl anion equivalents in C–C bond forming reactions.
Scheme 1.
A large number of efficient methods are available for
3
,4
deprotection of dithioacetals to carbonyls.
Some
recently introduced methods include the use of
and deprotective transformations15 is well documented.
In fact, Oxone supported on alumina and an organic
5
6
9
reagents such as ZrCr O , Dess–Martin periodinane,
15a
2
7
7
8
Bi(OTf)3,
TABCO–DMSO,
FeCl –KI, benzyltriphenylphosphonium peroxymono-
sulfate, TBHP and silica chloride–DMSO. How-
ever, many of these methods suffer from serious
drawbacks such as the use of expensive catalysts,
NaNO –CH COCl,
2 3
solvent soluble derivative of Oxone, benzyltriphenyl-
1
0
11
3
phosphonium peroxymonosulfate, (BTPP) in the pres-
1
1
12
13
ence of AlCl have already been reported for demasking
3
12
dithioacetals. As with TBHP, the use of Oxone or
6
,7,11
BTPP for demasking of dithioacetals proceeds via con-
version to the corresponding disulfoxide followed by
attack of water to generate the carbonyl group. This
necessitates either the use of a large excess (5 equiv) of
5
,8,9,13
toxic reagents
and in a few cases, more than stoi-
chiometric amounts required of the reagents.
1
1,12
Hence,
improved methods for dethioacetalization using cheap
and less toxic reagents coupled with simple reaction con-
ditions and easier work-up procedures are required.
15a
Oxone or the initial preparation of expensive, benzyl-
triphenyl phosphonium peroxymonosulfate. To avoid
these drawbacks and due to our continued interest in
In this letter, we report a very simple and efficient
approach for the chemoselective dethioacetalization of
dithioacetals using Oxone–KBr in aqueous acetonitrile
16a–c
the chemistry of Oxone,
we envisioned a simple ap-
proach for dethioacetalization using Oxone in combina-
tion with an alkali metal bromide. We earlier reported
the combination of Oxone–KBr in aqueous acetonitrile
(
Scheme 1).
1
6b
medium for the bromination of activated arenes
as
Oxone is a stable 2:1:1 ternary composite of K SO ,
16c
2
4
well as in the synthesis of azo-bis-nitriles. From these
experiences, we surmised that the Br ion generated by
1
4
+
KHSO and KHSO and its use in various oxidative
4
5
the combination of Oxone–KBr would be attacked by
the dithiane, making it a good leaving group with a
subsequent attack by a water molecule leading to the
carbonyl (Scheme 2). However, this concept was
Keywords: Oxone; Dethioacetalization; Deprotection.
*
Corresponding author. Tel.: +91 231 2690571; fax: +91 231
692333; e-mail: uprabhu_desai@rediffmail.com
2
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.138

8560
U. V. Desai et al. / Tetrahedron Letters 47 (2006) 8559–8561
..
..
water to the reaction mixture containing KBr. Thus the
Br ion formed would participate chemoselectively in
the dethioacetalization reaction.
R1
1
1
R
+
S
R
S
+
Br
S+
S
+
2
2
2
R
S
R
S
R
..
Br
.
.
O
Br
H
To check the feasibility of this procedure, the dithioac-
etal of anisaldehyde was selected as a model compound.
Thus, to an equimolar (10 mmol, each) mixture of the
dithioacetal of anisaldehyde and KBr in aqueous aceto-
nitrile (3:1, v/v, 7 mL), was added dropwise with stir-
ring, a solution of Oxone (10 mmol) in water (18 mL)
and the stirring was continued until completion of the
reaction (TLC). Work-up of the reaction mixture
furnished anisaldehyde as the sole product1 (89%),
there was no formation of either the ring bromination
product or the over-oxidation product. To determine
the functional group compatibility and to investigate the
chemoselectivity in this deprotection, a series of dithio-
acetals derived from substituted aromatic, conjugated
as well as aliphatic aldehydes were successfully dethio-
acetalized employing the present reaction conditions.
The interesting points to note are the non formation
H
1
1
R
R
S
S
HBr
+
O
2
2
R
O
R
Br
H
9
Scheme 2.
associated with the serious drawback of probable ring
bromination
as the formation of a-bromoketones. To overcome this
problem, we planned to avoid the presence of excess Br
1
6b,17
in the case of activated arenes as well
1
8
+
in the system by slow addition of a solution of Oxone in
Table 1. Deprotection of dithioacetals using Oxone–KBr in aqueous acetonitrile
a,b
Yield (%)
Entry
Substrate
n
Time (min)
S
(
)n
S
1
R'''
R'
R''
0
0
0
0
00
000
(
(
(
(
(
(
(
(
(
(
(
a) R = R = R = H
2
2
1
1
1
1
1
1
1
1
1
20
20
25
20
25
20
15
20
15
20
15
91
89
89
92
79
82
80
78
93
87
84
00
000
b) R = Me, R = R = H
00
000
c) R = OMe, R = R = H
00
000
d) R = CH(Me)
2
, R = R = H
0
00
000
e) R = NO
2
, R = R = H
0
00
000
f) R = N(Me)
2
, R = R = H
00
00
0
0
000
g) R = OH, R = R = H
000
h) R = OH, R = OMe, R = H
0
00
000
000
i) R = R = H, R = Me
0
00
j) R = R = Me, R = H
0
00
000
k) R = OMe, R = H, R = Me
S
2
S
H
—
15
78
S
S
3
4
—
—
120
120
81
65
S
S
MeO
S
5
S
—
60
72
a
1
All products are known compounds and were characterized by H NMR spectroscopy.
Yields refer to pure isolated products.
b

U. V. Desai et al. / Tetrahedron Letters 47 (2006) 8559–8561
8561
of, (i) ring brominated products in the case of aldehydes
containing ring activating groups (Table 1, entries:
5. Firouzabadi, H.; Iranpoor, N.; Hassani, H.; Sabhani, S.
Synth. Commun. 2004, 34, 1967–1972.
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b–d,f–h); (ii) dibrominated product in the case of a
5, 575–578.
conjugated aldehyde (entry 2), and (iii) over-oxidation
products. The results of the present study are summa-
rized in Table 1.
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The non formation of ring brominated products and
over-oxidation products has also been reported by Khan
et al.2 in their Br mediated protocol to effect chemose-
lective dethioacetalization. We next turned our attention
towards the dethioacetalization of dithioacetals of
ketones. The results obtained during studies with three
representative compounds, viz. cyclohexanone, (entry
0
+
10. Chavan, S. P.; Soni, P. B.; Kale, R. R.; Pasupathy, K.
Synth. Commun. 2003, 33, 879–883.
1
1
1
1
1. Hajipour, A. R.; Mallakpour, S. E.; Bartork, I. M.; Adibi,
H. Molecules 2002, 7, 674–680.
2. Wakharkar, R. D.; Mahajan, V. A.; Shinde, P. D.;
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3. Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H.; Karimi,
B. J. Org. Chem. 2002, 67, 2572–2576.
3
) p-methoxy acetophenone (entry 1k) and 6-methoxy-
tetralone (entry 4) showed neither the formation of, (i)
a-brominated cyclohexanone nor (ii) the ring bromi-
nated derivatives with p-methoxy acetophenone or 6-
methoxytetralone.
4. (a) Webb, K. S.; Ruszkay, S. J. Tetrahedron 1998, 54, 401–
4
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285; (c) Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. Synlett 1999, 6, 777–779.
We have developed a very simple and efficient protocol
for chemoselective dethioacetalization using Oxone–
KBr in water acetonitrile at room temperature. The pro-
tocol avoids the use of Oxone in large excess and also
avoids the initial conversion of Oxone to BTPP to effect
dethioacetalization. These studies have revealed that the
present protocol can be used for the chemoselective
dethioacetalization to carbonyls.
15. (a) Ceccherelli, P.; Curini, M.; Marcrotullio, M. C.;
Epifano, F.; Rosati, O. Synlett 1996, 767–768; (b)
Marcotullio, M. C. Recent Trends in Organic Synthesis
2
003, 10, 21–45.
1
6. (a) Kulkarni, P. P.; Kadam, A. J.; Desai, U. V.; Mane, R.
B.; Wadgaonkar, P. P. J. Chem. Res. (S) 2000, 184–185;
(
b) Tamhankar, B. V.; Desai, U. V.; Mane, R. B.;
Wadgaonkar, P. P.; Bedekar, A. V. Synth. Commun.
001, 31, 2021–2027; (c) Tamhankar, B. V.; Desai, U. V.;
2
Mane, R. B.; Kulkarni, P. P.; Wadgaonkar, P. P. Synth.
Commun. 2002, 32, 3643–3646.
Acknowledgements
17. Narender, N.; Srinivasu, M.; Prasad, R.; Kulkarni, S. J.;
Raghavan, K. V. Synth. Commun. 2002, 32, 2313–2318.
1
1
8. Kim, E.-H.; Koo, B.-S.; Song, C.-E.; Lee, K.-J. Synth.
Commun. 2001, 31, 3627–3632.
One of the authors (U.V.D.) wishes to thank UGC,
New Delhi, for financial assistance [F.30-72/2004(SR)],
and B.V.T. thanks UGC authorities for the award of
Teacher Fellowship under the faculty improvement
programme.
9. Typical procedure: To a well stirred solution of the
dithioacetal (10 mmol) and KBr (10 mmol) in aqueous
acetonitrile (3:1, v/v, 7 mL) was added dropwise a solution
of Oxone (10 mmol) in water (18 mL). Stirring was
continued at room temperature until completion of the
reaction (TLC). The reaction mixture was extracted with
ether (30 mL) and the ether extract washed with water,
References and notes
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