Selective reduction of thioacetal to sulfide by gallium(II) chloride

Article abstract of DOI:10.1016/j.tetlet.2005.10.024

The reaction of dithioacetals with gallium(II) chloride followed by the acid treatment afforded sulfides in good yields.

Full text of DOI:10.1016/j.tetlet.2005.10.024

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8773–8775
Selective reduction of thioacetal to sulfide by gallium(II) chloride
Kei-ichiro Ikeshita,a Nobuhiro Kiharab,* and Akiya Ogawaa
aDepartment of Applied Chemistry, Faculty of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho,
Sakai, Osaka 599-8531, Japan
bDepartment of Chemistry, Faculty of Science, Kanagawa University, 2946 Tsuchiya, Hiratsuka 259-1293, Japan
Received 9 September 2005; revised 6 October 2005; accepted 11 October 2005
Available online 25 October 2005
Abstract—The reaction of dithioacetals with gallium(II) chloride followed by the acid treatment afforded sulfides in good yields.
Ó 2005 Elsevier Ltd. All rights reserved.
Group XIII elements are among the most useful metals
for synthetic organic chemistry. Yet, the use of gallium
compounds in organic chemistry has so far rarely been
studied. In a recent study, gallium(III) chloride was used
for thioacetal activation,1 vinylation reaction,2 isocya-
nide cycloaddition,3 allylation reaction,4 and acetal acti-
vation.5 However, the utilization of gallium(II) chloride
has mostly been limited to the reductive Friedel–Crafts
reaction.6 Since gallium(II) chloride has both Lewis
acidity and reducing ability, we further explored the
reaction of gallium(II) chloride.
carried out at reflux conditions in dichloromethane.
Therefore, the following reactions were carried out at
0 °C. When polar solvent was used, the yield decreased
considerably, indicating that the Lewis acidity of gal-
lium(II) chloride played an essential role in the reduc-
tion reaction. However, the reaction in cyclohexane
resulted in a low sulfide yield because of the low solubil-
ity of gallium(II) chloride in cyclohexane.
Under the above optimized conditions, the reduction of
various thioacetals was carried out.8 The results are
shown in Table 2. Both aromatic and aliphatic thioace-
tals reacted smoothly with gallium(II) chloride to afford
the corresponding sulfide in moderate to good yields. In
every case, the starting material was completely con-
sumed, and hydrocarbon was not observed, although
by-product was not clear. Although the ether group
was tolerated by the reaction conditions, the ester or
nitro group reacted with gallium(II) chloride to give a
low or poor product yield. Dithioketal gave the corre-
sponding sulfide in rather low yield. Since bis(phenyl-
thio)acetal was more reactive than bis(ethylthio)acetal,
the use of excess gallium(II) chloride decreased the
yield in certain cases. Further, cyclic dithioacetal also
reacted with gallium(II) chloride to give monoalkyl-
ated dithiol. However, when acetal or O,S-acetal was
used as the substrate, a complex mixture was obtained
probably because of the simultaneous Friedel–Crafts
reaction.
When benzaldehyde bis(ethylthio)acetal was treated
with gallium(II) chloride at 0 °C, benzyl ethyl sulfide
was obtained after treatment with concd hydrochloric
acid in 20% yield. Since the selective reduction of thio-
acetal to sulfide without the formation of hydrocarbon
is a rare transformation,7 we optimized the reduction
conditions for an efficient transformation to sulfide as
shown in Table 1.
1-Naphthaldehyde bis(ethylthio)acetal was used as the
substrate. A strongly acidic condition, that is, trifluoro-
acetic acid, 6 M sulfuric acid, and concd hydrochloric
acid, is essential for the work-up. When 2equiv of gal-
lium(II) chloride were used, sulfide was obtained in high
yield. It is not clear why 2equiv of gallium(II) chloride
was necessary.
Although the reaction proceeded even at lower tempera-
ture, the yield tended to decrease when the reaction was
A plausible reaction mechanism is illustrated in Scheme
1. Gallium(II) chloride acts as the double salt of gal-
lium(I) chloride and gallium(III) chloride.9 Gallium(III)
chloride, which is Lewis acid with high affinity to sulfur,
activates thioacetal. The insertion of gallium(I) chloride
*
Corresponding author. Tel.: +81 463 59 0411; fax: +81 463 58
9684; e-mail: kihara@kanagawa-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.024

8774
K. Ikeshita et al. / Tetrahedron Letters 46 (2005) 8773–8775
Table 1. Reduction of 1-naphthaldehyde bis(ethylthio)acetal
EtS SEt
SEt
1) Ga2Cl4
2) H+
solvent
Entry
Ga2Cl4 (equiv)
Solvent
CH2Cl2
H+
Temp (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
1
H2O
0
0
0
0
0
4
5
4
4
5
4
5
8
4
3
4
3
277
4
3.5
5
4
9
58
56
84
4
89
88
90
81
11
15
1
2Cl2 CH
CH3COOH
CF3COOH
6 M HCl
1
1
2
2
2
2
2
CH2Cl2
CH2Cl2
2Cl2
CH
CH
CH
CH
CH
CF3COOH
1 M H2SO4
6 M H2SO4
6 M H2SO4
6 M H2SO4
6 M H2SO4
CF3COOH
3COOH
2Cl2
2Cl2
2Cl2
2Cl2
2Cl2
3CN
0
0
À48
9
rt
10
11
122
13
14
15
16
17
2CH
2CH
Reflux
0
0
0
0
0
0
0
THF
CF
2PhCl
2ClCH
2CHCl
2CCl
CF
3COOH
2CH2Cl
CF3COOH
CF3COOH
CF3COOH
3COOH
64
33
33
41
3
4
2Cyclohexane
CF
4
Table 2. Reduction of various acetals
1) 2 eq. Ga2Cl4
2) 6 M H2SO4
SR'
SR'
SR'
R
R
CH2Cl2
Entry
1
Substrate
Temp (°C)
Time (h)
5
Yield (%)
SEt
SEt
SEt
SEt
0
73
2
3
4
5
6
0
7
5
56
52
57
SEt
SEt
0
MeO
Cl
SEt
SEt
rt
rt
rt
4
MeO
O
SEt
SEt
1217
24
SEt
SEt
Complex mixture
0
O2N
SEt
SEt
7
8
0
2
52
SEt
SEt
rt
1268
Ph SEt
SEt
9
rt
0
10
5
27
79
SPh
10a
SPh
PhS SPh
11a
0
0.5
32

K. Ikeshita et al. / Tetrahedron Letters 46 (2005) 8773–8775
8775
Table 2 (continued)
Entry
Substrate
Temp (°C)
Time (h)
Yield (%)
94
SPh
SPh
12
rt
24.5
S
S
13a
rt
4.5
30b
OEt
OEt
14
15
0
0
4.5
7
Complex mixture
Complex mixture
O
S
a Ga2Cl4 1 equiv.
b 1-NpCH2SCH2CH2SH.
+
3. (a) Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.; Murai, S.
J. Am. Chem. Soc. 2003, 125, 7812; (b) Oshita, M.;
Yamashita, K.; Tobisu, M.; Chatani, N. J. Am. Chem.
Soc. 2005, 127, 761.
SEt
SEt
SEt
SEt
GaCl3
SEt
SEt
-
Cl3Ga
Cl3Ga
4. Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. Org.
Lett. 2005, 7, 3577.
5. Yoshioka, S.; Oshita, M.; Tobisu, M.; Chatani, N. Org.
Lett. 2005, 7, 3697.
6. (a) Hashimoto, Y.; Hirata, K.; Kihara, N.; Hasegawa, M.;
Saigo, K. Tetrahedron Lett. 1992, 33, 6351; (b) Hashimoto,
Y.; Hirata, K.; Kagoshima, H.; Kihara, N.; Hasegawa, M.;
Saigo, K. Tetrahedron 1993, 49, 5969.
SEt
SEt
GaCl
HX
Ga SEt
Cl GaCl3
Scheme 1.
7. (a) Kunishima, M.; Nakata, D.; Hioki, K.; Tani, S. Chem.
Pharm. Bull. 1998, 46, 187; (b) Krief, A.; Kenda, B.;
Barbeaux, P. Tetrahedron Lett. 1991, 32, 2509; (c) Ikehira,
H.; Tanimoto, S.; Oida, T. J. Chem. Soc., Perkin Trans. 1
1984, 1223; (d) Kikugawa, Y. J. Chem. Soc., Perkin Trans.
1 1984, 609.
8. Typical procedures for the reduction of 1-naphthaldehyde
bis(ethylthio)acetal: Under a nitrogen atmosphere, 1-naph-
thaldehyde bis(ethylthio)acetal (87.7 mg, 0.334 mmol) in
dichloromethane (4.00 ml) was added to a suspension of
gallium(II) chloride (190 mg, 0.675 mmol) in dichlorometh-
ane (4.00 ml) at room temperature, and the mixture was
stirred at the temperature for 4 h. After 6 M sulfuric acid
(10.0 ml) was added, the mixture was stirred for about
10 min. The organic materials were extracted with chloro-
form. The organic layer was washed with satd. CuSO4 aq,
brine, dried over MgSO4, and concentrated. The residue
was purified by column chromatography (hexane/chloro-
form = 4/1) to give ethyl 1-naphthylmethyl sulfide
(60.7 mg, 0.300 mmol, 90%).
into the activated C–S bond affords organogallium
intermediate, which is then converted to sulfide by the
protonation of the C–Ga bond. Because of the low
polarity of the C–Ga bond, highly acidic conditions
are necessary for hydrolysis.
In summary, we have developed a novel method for
the reduction of thioacetal to sulfide by the action of
gallium(II) chloride. The application of intermediary
organogallium species is in progress.
References and notes
1. Saigo, K.; Hashimoto, Y.; Kihara, N.; Umehara, H.;
Hasegawa, M. Chem. Lett. 1990, 831.
2. Yamaguchi, M.; Kido, Y.; Hayashi, A.; Hirama, M.
Angew. Chem., Int. Ed. 1997, 36, 1313.
9. Garton, G.; Powell, H. M. J. Inorg. Nucl. Chem. 1957, 4, 84.