Deprotection of dithioacetals using the tantalum(V) chloride catalyzed oxidation of iodide ion by hydrogen peroxide

Article abstract of DOI:10.1016/j.tetlet.2005.06.170

Dithioacetals can be deprotected to afford carbonyl groups using the tantalum(V) chloride catalyzed oxidation of iodide ion by hydrogen peroxide under mild conditions.

Full text of DOI:10.1016/j.tetlet.2005.06.170

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6377–6380
Deprotection of dithioacetals using the tantalum(V)
chloride catalyzed oxidation of iodide ion by hydrogen peroxide
Masayuki Kirihara,* Aiko Harano, Hiroyuki Tsukiji, Ryu Takizawa,
Tomoyuki Uchiyama and Akihiko Hatano
Department of Materials and Life Science, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa, Fukuroi,
Shizuoka 437-8555, Japan
Received 16 June 2005; accepted 30 June 2005
Abstract—Dithioacetals can be deprotected to afford carbonyl groups using the tantalum(V) chloride catalyzed oxidation of iodide
ion by hydrogen peroxide under mild conditions.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Dithioacetals are widely used as a carbonyl protecting
group in organic synthesis due to their stability under
both acidic and basic conditions.1 Moreover, a cyclic
dithioacetal, such as 1,3-dithiane, is an important syn-
thetic reagent as an acyl anion equivalent.2 Although
many procedures have been developed for regeneration
of the carbonyl functionality,1,3 most of them have seri-
ous disadvantage. The most frequently used deprotec-
tion procedures involve using a stoichiometric amount
or an excess amount of heavy metals such as mercury.4
These procedures need to treat highly toxic and expen-
sive reagents, and produce undesirable wastes. Halo-
nium ion sources, such as N-bromosuccinimide, are
also utilized to deprotect dithioacetals,5 however, these
methods have drawbacks such as the use of an excess
amount of reagents, and require expensive silver salts
in the case of olefinic compounds.
toxic vanadium compound, a stoichiometric amount of
bromide, and dichloromethane as the solvent.
We recently found that tantalum(V) chloride (TaCl5)7
catalyzed the oxidation of bromide ion (BrÀ) into the
bromonium ion (Br+) equivalent with H2O2 and the
reaction can be used for the electrophilic bromination
of organic compounds.8 Iodide ion (IÀ) was also oxi-
dized into the iodonium ion (I+) equivalent with H2O2
in the presence of a catalytic amount of TaCl5 (Scheme
1).9
The TaCl5 catalyzed oxidation of halogen anions (XÀ)
into the halogen cation (X+) equivalents is expected to
be used as an environmentally benign dedithioacetaliza-
tion, because tantalum compounds are less toxic than
vanadium compounds. We now report that dithioacetals
(1) can be deprotected to afford carbonyl groups (2)
using the TaCl5 catalyzed oxidation of IÀ by H2O2 in
ethyl acetate–water under mild conditions (Scheme 2).
Khan and co-workers recently developed dethioacetali-
zation by employing the vanadium pentoxide (V2O5)
catalyzed oxidation of ammonium bromide (NH4Br)
by hydrogen peroxide (H2O2).6 The reaction conditions
of this method are very mild, and the reaction affords a
product in high yield with high chemoselectivity. How-
ever, there are still some problems such as the use of a
First, the dithioacetal (1a) derived from 2-acetonaph-
thone and 1,3-propanedithiol was used as the substrate,
and the reaction conditions were investigated. The sub-
strate (1a) was treated with BrÀ or IÀ, catalytic amounts
cat. TaCl5, H2O2
Br-
I-
"Br+"
"I+"
Keywords: Deprotection of dithioacetals; Tantalum(V) chloride; Iodide
ion; Hydrogen peroxide.
cat. TaCl5, H2O2
*
Corresponding author. Tel.: +81 538 45 0166; fax: +81 538 45
0110; e-mail: kirihara@ms.sist.ac.jp
Scheme 1.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.170

6378
M. Kirihara et al. / Tetrahedron Letters 46 (2005) 6377–6380
with 20.0 equiv of H2O2 quantitatively provided the de-
sired compound within a shorter time (run 5).
cat. TaCl5, cat. I-, H2O2
AcOEt-H2O
O
2
S
R1
S
R2
R1
R2
1
Several kinds of dithioacetals were treated with
0.1 equiv of NaI, 0.1 equiv of TaCl5 and 20.0 equiv of
H2O2 in AcOEt–H2O. These results are summarized in
Table 3. Most of the substrates quantitatively provided
the carbonyl compounds. We observed that the aro-
matic ring (entries 3–9), the double bond (entry 5), the
acetoxy group (entry 6), and the silyloxy group (entry
7) were inert under the given reaction conditions. The
dithioacetal (1j) having the tetrahydropyranyl (acetal)
group afforded the ketone in 56% yield accompanied
with the ketone lacking an acetal moiety, however, the
desired compound was quantitatively obtained when
Scheme 2.
Table 1.
O
S
S
MX, cat.TaCl5, H2O2 (4.0 eq.)
CH3CN-H2O (1:1)
1a
2a
Run MX (equiv) Catalyst (equiv) Time (h) Yield (%)
1
2
3
4
5
6
KBr (1.0)
KBr (1.0)
NaI (1.0)
NaI (0.1)
NaI (1.0)
––
TaCl5 (0.05)
TaCl5 (0.1)
TaCl5 (0.05)
TaCl5 (0.1)
––
48
19.5
25
20
90
20
42
80
82
93
Table 3.
O
0.1 eq. NaI, 0.1 eq. TaCl5, 20 eq. H2O2
AcOEt, H2O
No reaction
No reaction
S
S
R1 R2
2
R2
R1
TaCl5 (0.1)
1
Entry
Starting material
Time
Yield (%)
of TaCl5, and 4.0 equiv of H2O2 in water containing ace-
tonitrile (Table 1). The dithioacetal (1a) was efficiently
deprotected to afford 2-acetonaphthone in high yields.
Sodium iodide (NaI) is an excellent halogen anion
source, and only 0.1 equiv of the reagent was enough
to complete the reaction (run 4). In the absence of
TaCl5, the dedithioacetalization did not proceed at all
(run 5). The reaction also did not occur in the absence
of halogen anions (run 6). These results mean that both
a halogen anion and TaCl5 catalyst are essential for the
dedithioacetalization to occur.
S
S
1
4.5 h
Quant.
(CH2)8CH3
1b
S
2
3
5 h
89
S
1c
S
S
0.3 h
Quant.
We then examined the dedithioacetalization of 1 with
0.1 equiv of NaI, 0.1 equiv of TaCl5, and 4.0 equiv of
H2O2 in several solvent systems (Table 2). The best
result was obtained in a two-phase system using ethyl
acetate and water (AcOEt–H2O) (run 4). The product
was obtained in a high yield with a shorter reaction time.
It is notable that ethyl acetate is more environmentally
benign than a chlorinated hydrocarbon such as dichloro-
methane or chloroform. We also found that the reaction
1d
S
S
4
5
6
7
2.5 h
0.5 h
1.5 h
1.5 h
91
1e
S
S
Quant.
Ph
1f
Table 2.
S
S
O
0.1 eq. NaI, 0.1 eq. TaCl5,
4.0 eq. H2O2
S
S
O
94
O
solvent
1g
O
1a
2a
S
S
Run
Solvent
Time
Yield (%)
Me
tBu Si
Me
90
1
2
3
4
5a
6
CH3CN–H2O (1:1)
CH3OH–H2O (1:1)
Acetone–H2O (1:1)
AcOEt–H2O
AcOEt–H2O
CHCl3–H2O
19 h
96
90
81
85
Quant.
24
74
17.5 h
3 days
2 h
1 h
9 days
2 days
1h
S
S
8
0.5 h; 0.5 h
56; quant.a
7
CH2Cl2–H2O
O
O
a 20.0 equiv H2O2 was used.
1j

M. Kirihara et al. / Tetrahedron Letters 46 (2005) 6377–6380
6379
Table 3 (continued)
cat. TaCl5
I-
"I+"
H2O2
Entry
Starting material
Time
Yield (%)
Quant.
I
S
S
S
S
S
I S
S
S
9
1 h
R
R'
R
R'
R
R'
HO
1k
H2O
-H+
-H+
O
I-
+
OH
R'
I
S
S
R
R'
R
S
S
-
S S
10
1.5 h
95
Scheme 4.
1l
S
Ph
S
H
1m
compound (Scheme 4). Further details of this reaction
are currently under investigation.
11
12
92 h
68 h
82
85
The general experimental procedure for the deprotection
is as follows: A mixture of 1 (0.5 mmol), tantalum chlo-
ride (17.9 mg, 0.05 mmol), sodium iodide (7.5 mg,
0.05 mmol) and 30% hydrogen peroxide (1.15 mL,
10.0 mmol) in ethyl acetate (3 mL) and water (3 mL)
was stirred at room temperature. The reaction was moni-
tored by thin layer chromatography (TLC). After 1 dis-
appeared on TLC, saturated aqueous sodium thiosulfate
(2 mL) and saturated aqueous sodium bicarbonate
(2 mL) were added to the reaction mixture. The organic
layer was separated and the aqueous phase was
extracted with ethyl acetate (20 mL · 3). The combined
organic phase was washed with brine, dried over
anhydrous sodium sulfate, and evaporated. Chromato-
graphy on silica gel gave a pure product.
S
S
H
CH3(CH2)6
1n
S
S
H
13
6 days
81
1o
a Phosphate buffer (pH = 7.2) was used instead of water.
phosphate buffer (pH 7.2) was used as the part of sol-
vent instead of water (entry 8). Interestingly, the dithio-
acetals derived from aldehydes (1m–o) reacted more
slowly than the dithioacetals (1a–l) derived from
ketones. In the case of the equimolar mixture of 1a
and 1m, 1a was chemoselectively deprotected to afford
2a in 91%, and 80% of 1m was recovered (Scheme 3).
These results are in sharp contrast to the results of the
dedithioacetalization with V2O5–BrÀ–H2O2 reported
by Khan et al. They reported that the dithioacetals
derived from aldehydes quickly reacted to afford the
aldehydes.5
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S
S
H
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1a
1m
O
S
S
H
+
2a (91%)
1m (80%)
Scheme 3.

6380
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