Environmentally benign deprotection of dithioacetals using 30% hydrogen peroxide catalyzed by Fe(acac)3 and sodium iodide

Article abstract of DOI:10.1016/j.tetlet.2013.07.130

The reaction of dithioacetals with 30% hydrogen peroxide in the presence of catalytic amounts of iron(III) acetylacetonate and sodium iodide efficiently produced the corresponding carbonyl compounds in high yields.

Full text of DOI:10.1016/j.tetlet.2013.07.130

Tetrahedron Letters 54 (2013) 5477–5480
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Environmentally benign deprotection of dithioacetals using 30%
hydrogen peroxide catalyzed by Fe(acac)3 and sodium iodide
⇑
Masayuki Kirihara , Satoshi Suzuki, Yuki Ishizuka, Kento Yamazaki, Ryoji Matsushima, Takaya Suzuki,
Toshiaki Iwai
Department of Materials and Life Science, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa, Fukuroi, Shizuoka 437-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of dithioacetals with 30% hydrogen peroxide in the presence of catalytic amounts of iron(III)
Received 13 May 2013
Revised 19 July 2013
Accepted 26 July 2013
Available online 2 August 2013
acetylacetonate and sodium iodide efficiently produced the corresponding carbonyl compounds in high
yields.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Deprotection of dithioacetals
Tantalum(V) chloride
Iodide ion
Hydrogen peroxide
Dithioacetals are widely used as carbonyl protecting groups1 or
desired carbonyl compounds, the catalysts (TaCl5 and NbCl5) are
expensive. To remedy this limitation, in this Letter, much more
inexpensive iron(III) acetylacetonate [Fe(acac)3]–NaI is shown to
effectively catalyze the deprotection of dithioacetals with 30%
H2O2 to produce carbonyl compounds (Scheme 1).
First, a dithioacetal was prepared for use as the substrate from
2-acetonaphthone and 1,3-propanedithiol according to the litera-
ture,9 and various iron catalysts were investigated (Table 1). The
substrate was treated with 0.1 equiv of the iron compound,
0.2 equiv of sodium iodide, and 4.0 equiv of 30% H2O2 (Table 1).
All of the iron compounds tested, except for ferrocene, exhibited
catalytic activity, and the desired 2-acetonaphthone was obtained
as acyl anion equivalents2 in organic synthesis. However deprotec-
1,3
tion of dithioacetals to regenerate the carbonyl functionality
is
not particularly easy because dithioacetals are quite stable under
a variety of reaction conditions including acid or base catalyzed
hydrolysis. Although many procedures for dedithioacetalyzation
have been developed, most of them have serious disadvantages.
The most reliable and frequently used deprotection procedures in-
volve using a stoichiometric amount or an excess amount of heavy
metals such as mercury.4 These procedures need to treat highly
toxic and expensive reagents, and produce undesirable wastes.
Halonium ion sources, such as N-bromosuccinimide, are also uti-
lized to deprotect dithioacetals,5 however, these methods have
drawbacks, such as the necessity of an excess amount of reagents,
and the requirement of expensive silver salts in the case of olefinic
compounds.
Environmentally-benign methods for dithioacetal-deprotection
mediated by hydrogen peroxide (H2O2) have been developed re-
cently by several research groups, in which nontoxic water is the
sole waste product of these reactions.5
We have been exploring the use of these reactions for organic
syntheses,6 and have found that dithioacetal deprotection can be
achieved smoothly by reaction with 30% H2O2 catalyzed by tanta-
lum(V) chloride (TaCl5)–sodium iodide (NaI)7,8 or niobium(V) chlo-
ride (NbCl5)–NaI.7 Although, this procedure efficiently provides the
Previous Work
NbCl5 (0.02 eq.), NaI (0.1 eq.),
30% H2O2 (4 eq.)
AcOEt-H2O = 1 : 1, r.t.
O
S
R
S
R'
R
R'
TaCl5 (0.1 eq.), NaI (0.1 eq.),
30% H2O2 (20 eq.)
quant~49%
AcOEt-H2O = 1 : 1, r.t.
This Work
Fe(acac)3 (0.1 eq.), NaI (1.0 eq.),
30% H2O2 (4.0 eq.)
O
S
R
S
R'
R
R'
AcOEt-H2O = 1 : 1, r.t.
99~78%
⇑
Corresponding author. Tel.: +81 538 45 0166; fax: +81 538 45 0110.
E-mail address: kirihara@ms.sist.ac.jp (M. Kirihara).
Scheme 1.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.130

5478
M. Kirihara et al. / Tetrahedron Letters 54 (2013) 5477–5480
Table 1
Fe(acac)3 (0.1 eq.),
NaBr or NaCl (0.2 eq.),
30% H2O2 (4.0 eq.)
S
S
No Reaction
Fe cat. (0.1 eq.),
NaI (0.2 eq.),
S
O
AcOEt-H2O = 1 : 1
r.t., ~8 h
S
30% H2O2 (4.0 eq.)
AcOEt-H2O = 1 : 1
r.t.
Scheme 2.
Run
Catalyst
FeCl3
Fecl2Á4H20
Fe(OAc)2
Fe(acac)3
Time
Yield (%)
The deprotection of several dithioacetals derived from alde-
hydes was then examined under the same reaction conditions (Ta-
ble 4). The reactions proceeded much more slowly than those
involving dithioacetals derived from ketones. In addition, large
amounts of H2O2 were required to complete the reaction, because
simple decomposition of H2O2 predominates over the deprotection
of the dithioacetals.
1
2
3
4
5
0.6 h
0.3 h
0.4 h
1.0 h
2 days
90
88
92
91
NR
Cp2Fe (ferrocene)
Table 2
Fe(acac)3 (0.1 eq.),
Table 3
O
NaI (x eq.),
S
S
30% H2O2 (4.0 eq.)
Fe(acac)3 (0.1 eq.), NaI (1.0 eq.),
AcOEt-H2O = 1 : 1
r.t.
O
30% H2O2 (>4.0 eq.)
S
R1
S
R2
R1
R2
AcOEt-H2O = 1 : 1, r.t.,
Run
Nai (equiv)
Time (h)
Yield (%)
Entry Substance
30% H2O2 (equiv)
4.0
Time (h)
3.6
Yield (%)
99
1
2
3
4
5
6
0.1
0.2
0.4
1.0
2.0
4.0
7.7
1.0
0.3
0.4
7.0
7.0
5
91
89
93
25
5
S
S
Me
1
2
Me(CH2)8
S
S
8.0
4.0
2.8
0.3
97
93
in high yield (runs 1–4). With iron(III) chloride (FeCl3), iron(II)
chloride (FeCl2), and iron(II) acetate [Fe(OAc)2], the reaction solu-
tion became acidic, whereas it was effectively neutral (slightly
weak acidic) in the presence of iron(III) acetylacetonate [Fe(acac)3].
It is preferable to carry out the deprotection under a milder condi-
tion, therefore, Fe(acac)3 was used as the iron-catalyst for the fur-
ther investigation.
Since the amount of NaI to dithioacetal is a crucial factor in
obtaining the desired carbonyl compound in NbCl5–NaI catalyzed
dedithioacetalyzation with 30% hydrogen peroxide,8 reactions with
varying several amounts of NaI were examined (Table 2).
The dedithioacetalyzation efficiently proceeded to afford the
desired 2-acetonaphthone in high yields with between 0.2 and
1.0 equiv of NaI. Conversely, the reaction proceeded very slow
and the ketone was obtained in poor yields in the presence of
0.1 equiv or more than 2.0 equiv of NaI. These results are similar
to those of NbCl5–NaI catalyzed dedithioacetalyzation with 30%
hydrogen peroxide.8
Variation of the halogen anion in the catalysts was then exam-
ined. The dedithioacetalyzation did not proceed at all in the pres-
ence of either NaBr or NaCl-containing catalysts (Scheme 2).
Based on these results, several dithioacetals prepared from ke-
tones were reacted with 30% hydrogen peroxide in the presence
of 0.1 equiv of Fe(acac)3 and 1.0 equiv of NaI in AcOEt/H2O (1:1,
v/v) at room temperature (Table 3).10 The results are similar to
those of the deprotections catalyzed by TaCl5–NaI7,8 or NbCl5–
NaI.8 The corresponding ketones were obtained in high yields in
all cases. The aromatic ring (entries 3–11), the double bond (entry
5), the acetoxy group (entry 7), and the silyloxy group (entry 8)
were inert to the deprotection. The dithioacetal having a tetrahy-
dropyranyl (acetal) group afforded the desired ketone in only
43% yield accompanied by the ketone lacking the acetal moiety.
Fortunately, the desired compound was quantitatively obtained
when a phosphate buffer (pH 7.2) was used instead of water as part
of the solvent (entry 9).
S
S
3
4
5
S
S
Me
8.0
4.0
20
97
95
S
S
Me
0.2
S
S
6
7
8
4.0
8.0
4.0
0.3
20.4
0.5
90
90
97
Me
HO
S
S
Me
AcO
TBSO
S
S
Me
S
S
Me
8.0
8.0
1.6
0.3
43
9
93a
THPO
S
S
Me
10
11
8.0
8.0
18.4
18.4
92
99
N2O
S
S
a
Phosphate buffer (pH 7.2) was used instead of water.

M. Kirihara et al. / Tetrahedron Letters 54 (2013) 5477–5480
5479
Table 4
I
S
S
I
Fe(III), H2O2
Fe(acac)3 (0.1 eq.), NaI (1.0 eq.),
30% H2O2 (>8.0 eq.)
I-
"I+"
R
R'
O
S
R1
S
H
B
R1
H
AcOEt-H2O = 1 : 1, r.t.,
30% H2O2 (equiv)
8.0
I
S
R
S
R
S
I S
S
S
R'
Entry
1
Substance
Time (h)
20.6
Yield (%)
93
R
R'
R'
A
H2O
-H+
-H+
O
S
S
H
I-
+
I
S
S
OH
R'
R
R'
-
R
S
S
S
S
H
2
8.0
48.3
94
Scheme 3.
A
plausible reaction mechanism is shown in Scheme 3.
S
S
H
3
4
12.0
16.0
27.5
77.3
81
62
Fe(acac)3 catalyzes the hydrogen peroxide oxidation of IÀ to the
I+ equivalent, and the reactive I+ equivalent then reacts with the
dithioacetal to form an iodosulfonium complex (A), which is finally
hydrolyzed by water to generate the carbonyl compound. When an
excess of IÀ is present, an iodosulfonium complex further reacts
with the I+ equivalent to form a bisiodosulfonium complex (B),
which is inactive toward hydrolysis.
S
S
H
Me(CH2)6
In contrast, the deprotection of dithioacetals prepared from
aldehydes proceeded more rapidly when the 30% H2O2 was slowly
added to the reaction mixture using a syringe pump (4 equiv over
30 min) (Table 5, entries 1–3).11 This procedure is also effective for
the dithioacetals prepared from ketones. The dithioacetals which
were deprotected rather slowly in Table 3 (entries 4, 7, 10, and
11) rapidly reacted to produce the corresponding ketones (Table 5,
entries 4–7).
This reaction is applicable for a preparation of an acylsilane
which is easily oxidized. In the case of syntheses of 4-chlorophenyl
trimethylsilyl ketone from dedithioacetalyzation of 2-(4-chloro-
phenyl)-2-(trimethylsilyl)-1,3-dithiane, other methods (for exam-
ple, HgCl2,12 N-bromosucusinimide,12 or 30% H2O2 catalyzed by
NbCl5–NaI13) provide the desired acylsilane in low yields accompa-
nied with the corresponding carboxylic acid as a by-product. In
contrast, the reaction of 2-(4-chlorophenyl)-2-(trimethylsilyl)-
Table 5
Fe(acac)3 (0.1 eq.), NaI (1.0 eq.)
30%H2O2 (4.0 eq. / 30 min )
O
S
R
S
R'
AcOEt : H2O = 1 : 1 , r.t.
R
R'
Entry
1
Substance
Total amount of 30% H2O2 (equiv)
8.0
Time (h)
1.3
Yield (%)
98
S
S
H
S
S
H
2
3
4
8.0
16.0
12.0
1.3
2.6
3.0
98
78
89
S
S
H
Me(CH2)6
S
S
Me
S
S
Me
5
4.0
0.75
90
AcO
NO2
S
S
Me
6
7
12.0
8.0
2.0
2.0
91
S
S
Quant

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M. Kirihara et al. / Tetrahedron Letters 54 (2013) 5477–5480
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S
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3
3
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1
2
3
HgCl2, H2O
NBS, H2O
NbCl5 (0.1 equiv), NaI (0.1 equiv)
30% H2O2 (20 equiv)
Fe(acac)3 (0.1 equiv), NaI (1 equiv)
30% H2O2 (50 equiv)
2512
2712
0a,13
4
90
a
The corresponding carboxylic acid (4-chlorobenzoic acid) was obtained in 75%
yield.
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10. General procedure for the deprotection of dithioacetals with 30% H2O2 catalyzed by
1,3-dithiane with 30% H2O2 catalyzed by Fe(acac)3–NaI produced
the desired acylsilane in high yield (Table 6).
In conclusion, a combination of Fe(acac)3 and NaI is the ideal
inexpensive, environmentally-benign catalyst for the deprotection
of dithioacetals using 30% H2O2. Further details and applications of
this reaction for syntheses of acylsilanes are currently under
investigation.
Fe(acac)3–NaI:
A mixture of a dithioacetal (2.0 mmol), Fe(acac)3 (70.6 mg,
0.20 mmol), sodium iodide (300 mg, 2.0 mmol), and 30% hydrogen peroxide
(0.91 ml, 8.0 mmol) in ethyl acetate (6 ml) and water (6 ml) was stirred at
room temperature. The reaction progress was monitored via thin layer
chromatography (TLC). After the dithioacetal disappeared from the TLC,
saturated aqueous sodium thiosulfate (4 ml), was added to the reaction
mixture. The organic layer was separated and the aqueous phase was extracted
with ethyl acetate (10 ml  3). The combined organic phase was washed with
brine, dried over anhydrous sodium sulfate, and evaporated. Chromatography
on silica gel gave a pure product.
References and notes
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11. General procedure for the deprotection of dithioacetals with 30% H2O2 (the slow
addition using a syringe pump) catalyzed by Fe(acac)3–NaI: A mixture of a
dithioacetal (2.0 mmol), Fe(acac)3 (70.6 mg, 0.20 mmol) and sodium iodide
(300 mg, 2.0 mmol) in ethyl acetate (6 ml) and water (6 ml) was stirred at
room temperature. To this mixture, 30% H2O2 was added slowly using a syringe
pump (4 ml/30 min). The reaction was monitored by thin layer
chromatography via TLC. After the dithioacetal disappeared from the TLC,
saturated aqueous sodium thiosulfate (4 ml), was added to the reaction
mixture. The organic layer was separated and the aqueous phase was extracted
with ethyl acetate (10 ml  3). The combined organic phase was washed with
brine, dried over anhydrous sodium sulfate, and evaporated. Chromatography
on silica gel gave a pure product.
´
12. Patrocınio, A.; Moran, P. J. S. J. Organomet. Chem. 2000, 603, 220–224.
13. Kirihara, M.; Suzuki, S.; Ishizuka, Y. unpublished result.