Lewis acid-catalyzed reduction of dithioacetals by 1,4-cyclohexadiene

Article abstract of DOI:10.1016/j.tetlet.2007.02.119

Dithioacetals were reduced by 1,4-cyclohexadiene in the presence of a catalytic amount of Lewis acid to afford the corresponding sulfides in good yields.

Full text of DOI:10.1016/j.tetlet.2007.02.119

Tetrahedron Letters 48 (2007) 3025–3028
Lewis acid-catalyzed reduction of dithioacetals by
1,4-cyclohexadiene
Kei-ichiro Ikeshita,a Nobuhiro Kihara,b,* Motohiro Sonodaa and Akiya Ogawaa
aDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku,
Sakai, Osaka 599-8531, Japan
bDepartment of Chemistry, Faculty of Science, Kanagawa University, 2946 Tsuchiya, Hiratsuka 259-1293, Japan
Received 12 January 2007; revised 20 February 2007; accepted 26 February 2007
Available online 1 March 2007
Abstract—Dithioacetals were reduced by 1,4-cyclohexadiene in the presence of a catalytic amount of Lewis acid to afford the cor-
responding sulfides in good yields.
Ó 2007 Elsevier Ltd. All rights reserved.
The oxidation of 1,4-cyclohexadiene (1,4-CHD) deriva-
tives to afford benzene derivatives is a useful aromatiza-
tion method in organic reactions.1 Various oxidants
such as chloranil,1,2 DDQ,1,3 trityl salts,1,4 and oxygen5
have been used for this purpose. The oxidation of 1,4-
CHD after deprotonation by n-BuLi/N,N,N0,N0-tetra-
methylethylenediamine is also reported.1,6 Furthermore,
Pd/C is the effective catalyst for the aromatization of
1,4-CHD.1,3a,7 Although Lewis acid-catalyzed aromati-
zation of 1,4-CHD and related hydrocarbons has been
extensively studied, selective aromatization reactions
using Lewis acids are very limited.1,8 Since the aromati-
zation of 1,4-CHD formally leads to the concomitant
formation of two hydrogen atoms, 1,4-CHD may have
the potential usefulness as the reductant. However,
examples of the reduction using 1,4-CHD are rare.
For example, catalytic hydrogenation using 1,4-CHD
as hydrogen source is performed typically by Pd/C.9
1,4-CHD has also been used as the radical hydrogen
donor,10 especially in Bergmam cyclization.11 In this
Letter, we wish to report a novel finding that various
Lewis acids smoothly induce the dehydrogenation of
1,4-CHD, and more interestingly, 1,4-CHD acts as the
reductant for dithioacetal to monosulfide transforma-
tion in the presence of these Lewis acids.
ately disappeared, and the signals of benzene and
complex aliphatic hydrocarbons which might be formed
by cationic oligomerization accompanied with aromati-
zation appeared with the evolution of gas (Table 1, entry
1). The dehydrogenation proceeded even in the presence
of a catalytic amount of Lewis acids (entries 2 and 6).
When ethylaluminum dichloride and gallium(III) chlo-
ride were used, complex aromatic compounds were ob-
tained probably because of Friedel–Crafts reaction
(entries 3 and 5). Although indium(III) chloride, zinc(II)
chloride and zinc(II) iodide showed lower activity for
the aromatization, the selectivity was high (entries 7, 9
and 10).
Table 1. Aromatization of 1,4-CHD
Lewis acid
CDCl3, rt
Entry Lewis acid (mol %) Time
Yielda (%) Conv.a (%)
1
2
3
4
5
6
7
8
9
AlCl3 (100)
AlCl3 (12)
8 min 31
30 min 37
100
100
100
96
100
100
2
91
5
100
b
EtAlCl2 (100)
BF3ÆOEt2 (100)
GaCl3 (100)
GaCl3 (10)
InCl3 (100)
TiCl4 (91)
11 min
7 d
8 min
—
30
—
b
10 min 15
1,4-CHD was treated with aluminium(III) chloride at
room temperature in CDCl3, and the reaction was mon-
7 d
21 h
7 d
2
42
5
1
itored by H NMR. The signals of 1,4-CHD immedi-
ZnCl2 (140)
ZnI2 (100)
10
12 d
97
a Determined by 1H NMR.
b Complex aromatic compounds were observed.
*
Corresponding author. Tel.: +81 463 59 4111; fax: +81 463 58
9684; e-mail: kihara@kanagawa-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.02.119

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K. Ikeshita et al. / Tetrahedron Letters 48 (2007) 3025–3028
The Lewis acids that were active in aromatization were
H H
H MX3
generally effective in reduction. The highest yield was
obtained with ethylaluminum dichloride (entry 7). The
yield increased at the higher temperature (entries 6, 14
and 15). Since the reaction proceeded even at lower tem-
perature, further experiments were carried out at room
temperature. Sulfide was obtained in high yield when
nonpolar solvent was used (entries 16–18). Since the
acidity of a Lewis acid is suppressed in a polar solvent,
the Lewis acidity of the catalyst seems to be the essential
factor in this reduction.
+ H2 + MX3
H H
H
MX3
Scheme 1. Plausible reaction mechanism of aromatization.
Plausible mechanism of this aromatization is shown in
Scheme 1. Lewis acid abstracts hydride8b,12 from 1,4-
CHD to form intermediary hydride complex and cyclo-
hexadienyl cation. The deprotonation of the cation by
the hydride affords benzene. We were prompted to use
intermediary hydride complex as the reductant.
The reduction of various thioacetals was investigated
with 1,4-CHD in the presence of ethylaluminum dichlo-
ride or gallium(III) chloride. The results are summarized
in Table 3.16,17 Aromatic thioacetals were reduced
smoothly to afford the corresponding sulfide in good
to excellent yields (entries 1–3 and 6). For the reduction
of less reactive thioacetals such as aliphatic thioacetal,
cyclic thioacetal, and thioketal, the use of gallium(III)
chloride instead of ethylaluminum dichloride provided
better results (entries 4, 5, 7–9). Surprisingly, in the case
of cyclic thioacetal (entry 8), 1,3-bis(benzylthio)propane
was obtained as the major product while 3-(benzyl-
thio)propane-1-thiol was not detected. It can be deduced
that facile acetal exchange reaction was accompanied
with the reduction. Gallium(III) chloride was also effec-
tive when dimethylacetal was used as the substrate (en-
tries 10–12).
Since we previously reported the reduction of thioacetals
by gallium(II) chloride,13 we tried to use the above aro-
matization system for the reduction of thioacetals.
When 1-naphthaldehyde bis(ethylthio)acetal was treated
with 2.0 equiv of 1,4-CHD in the presence of 10 mol %
of aluminium(III) chloride, ethyl (1-naphthyl)methyl
sulfide was obtained in 84% yield. Since the selective
reduction of thioacetal to sulfide without the formation
of hydrocarbon is a rare transformation,14 we optimized
the reduction conditions for the efficient transformation
of thioacetals to sulfides. The results are shown in Table
2. First, the reduction was carried out using various
unsaturated hydrocarbons. Hydrocarbons with 1,4-
CHD structure showed reducing activity, and 1,4-
CHD was the most effective reductant (entries 1–3).
Reduction proceeded effectively by even 1.0 equiv of
1,4-CHD.15 1,3-CHD did not work at all because cat-
ionic polymerization of 1,3-CHD preferentially occurred
(entry 4). Lewis acid greatly affected the yield of sulfide.
A
plausible reaction mechanism is illustrated in
Scheme 2. Lewis acid has two roles: activation of
thioacetal and abstraction of hydride from 1,4-CHD
to form hydride complex. Sulfide is obtained by the
Table 2. Optimization of the reaction conditions
EtS
SEt
SEt
Lewis acid
hydrocarbon
solvent
temp., time
Entry
Lewis acid (mol %)
Hydrocarbon (1.0 equiv)
Solventa
Temperature (°C)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
AlCl3 (10)
AlCl3 (10)
AlCl3 (10)
AlCl3 (10)
AlCl3 (10)
AlCl3 (5)
EtAlCl2 (5)
Et2AlCl (5)
BF3ÆOEt2 (5)
GaCl3 (5)
InCl3 (5)
1,4-CHD
c-Terpinene
9,10-DHAc
1,3-CHD
Cyclohexene
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
1,4-CHD
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
PhH
AN
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
80
0
6
6
6
6
6
5
5
5
5
5
5
5
5
5
5
5
5
5
94
60
65
Trace
2
81
94
33
73
82
50
72
1
TiCl4 (5)
ZnCl2 (5)
AlCl3 (5)
AlCl3 (5)
AlCl3 (5)
AlCl3 (5)
AlCl3 (5)
95
63
81
2
rt
rt
rt
THF
Trace
a DCE: 1,2-dichloroethane; PhH: benzene; AN: acetonitrile; THF: tetrahydrofuran.
b Determined by 1H NMR.
c 9,10-DHA: 9,10-dihydroanthracene.

K. Ikeshita et al. / Tetrahedron Letters 48 (2007) 3025–3028
3027
Table 3. Reduction of thioacetals
Lewis acid
1.0 equiv 1,4-CHD
SR'
SR'
SR'
R
R
DCE
Entry
Substrate
Lewis acid (mol %)
Temperature (°C)
Time (h)
Yielda (%)
1
2
3
4
5
6
PhCH(SEt)2
EtAlCl2 (5)
EtAlCl2 (5)
EtAlCl2 (5)
EtAlCl2 (5)
GaCl3 (5)
rt
rt
rt
80
80
rt
5.5
9
5.5
24
24
3
88
87
96
29b
61b
77
p-MeOC6H4CH(SEt)2
p-ClC6H4CH(SEt)2
Me(CH2)10CH(SEt)2
Me(CH2)10CH(SEt)2
PhCH(SPh)2
EtAlCl2 (5)
S
7
EtAlCl2 (5)
GaCl3 (10)
80
24
0
Ph
S
S
8
80
40
44b,c
Ph
S
9
10
11
12
PhC(Me)(SEt)2
PhCH(OMe)2
PhCH(OMe)2
PhCH(OMe)2
EtAlCl2 (5)
EtAlCl2 (5)
GaCl3 (5)
GaCl3 (5)
80
rt
rt
20
5
10
21
55b
0
28d
92b,d
80
a Determined by 1H NMR.
b 2.0 equiv of 1,4-CHD was used.
c The product is PhCH2S(CH2)3SCH2Ph.
d The product is PhCH2OMe.
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SR'
MXn
SR'
R
RS MXn
H MXn
R
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H H
H
H MXn
SR'
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MXn
R
R
RS MXn
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Chem. 2003, 68, 8272; (b) Tanaka, H.; Ikeno, T.; Yamada,
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+
+
MXn
RSH
H
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Scheme 2. Plausible reaction mechanism for the reduction of thio-
acetal by 1,4-CHD.
attack of the hydride complex to the activated thio-
acetal. The cyclohexadienyl cation reacts with thiolate
complex to afford thiol and benzene with regenerating
the Lewis acid.
In summary, we have developed a novel method for the
reduction of thioacetal to sulfide using 1,4-CHD. The
application of reduction system using 1,4-CHD is in
progress.
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15. In every case, the formation of the complex hydrocarbons
was not observed even when ethylaluminum dichloride or
gallium(III) chloride was used as the Lewis acid. Although
the formation of benzene was not confirmed because of its
volatility, 4-isopropyl-1-methylbenzene and anthracene
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16. In every case, the starting material was almost consumed and
no hydrocarbon (over-reduction product) was observed,
although the structures of by-products were not clear.
17. Typical procedure for the reduction of dithioacetals: Under a
nitrogen atmosphere, 0.96 M ethylaluminum dichloride in
n-hexane (50.0 lL, 48.0 lmol) was added to a solution of 1-
naphthaldehyde bis(ethylthio)acetal (251 mg, 0.959 mmol)
and 1,4-CHD (77.5 mg, 0.967 mmol) in 1,2-dichloroethane
(7.00 mL) at room temperature, and the mixture was
stirred at the temperature for 5 h. After water was added,
the organic materials were extracted with chloroform. The
organic layer was washed with brine, dried over MgSO4,
and concentrated. The residue was purified by column
chromatography (hexane/chloroform = 4/1) to give ethyl
(1-naphthyl)methyl sulfide (182 mg, 0.904 mmol, 94%).
The yields determined by 1H NMR were based on
triphenylmethane as an internal standard.
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