Facile one-pot synthesis of 2,3-thienoimides via formal [3+2] annulation reaction of 1,4-dithiane-2,5-diol and N-substituted imides

Article abstract of DOI:10.1016/j.tetlet.2015.04.097

A formal [3+2] annulation reaction of 1,4-dithiane-2,5-diol and N-substituted imides through one-pot metal-free strategy has been developed. This method could furnish 2,3-thienoimides in good to high yields.

Full text of DOI:10.1016/j.tetlet.2015.04.097

Tetrahedron Letters xxx (2015) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Facile one-pot synthesis of 2,3-thienoimides via formal [3+2]
annulation reaction of 1,4-dithiane-2,5-diol and N-substituted
imides
⇑
⇑
⇑
Wenjuan Shi, Shaofa Sun , Yimin Hu, Tao Gao, Yanhong Peng, Minghu Wu, Haibing Guo , Jian Wang
Hubei Collaborative Innovation Centre for Non-Power Nuclear Technology, College of Chemistry and Biological Sciences, Hubei University of Science and Technology, Hubei
Province 437100, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A formal [3+2] annulation reaction of 1,4-dithiane-2,5-diol and N-substituted imides through one-pot
Received 1 April 2015
Revised 21 April 2015
Accepted 23 April 2015
Available online xxxx
metal-free strategy has been developed. This method could furnish 2,3-thienoimides in good to high
yields.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
[3+2]-Cycloaddition
1,4-Dithiane-2,5-diol
Imide
Thiophene
Thiophenes have received much attention in the last few
decades due to their wide applications in pharmaceuticals and
material science.1–10 Substituted thiophenes have exhibited a wide
spectrum of biological activities, ranging from antianxiety,11
antibacterial,12,13 antiprotozoal,14 antivirus,15 antiproliferative,16
LIMK1 inhibitors,17 DPP-IV inhibitors,18 antioxidant,19 and insecti-
cidal herbicide.20–23 Moreover, polymeric thiophenes are also
broadly utilized as thin-film transistors,24,25 organic light-emitting
transistors (OLET),26 organic field-effect transistors,27–29 chemical
sensors,30,31 and solar cells.32,33 As outlined in Figure 1,
DTS(TTPD)2 was identified to be an highly efficient electron donor
in solar cells.34 T4DIM had been recognized as organic thin film
transistors (OTFT) and organic light emitting transistors (OLET).35
DTTDI exhibited a potency to become latent n-channel organic
semiconductors.36
O
O
n-C8H17
S
n-C8H17
S
Si
n-C8H17
n-C8H17
N
N
S
S
S
S
O
O
DTS(TTPD)2
O
N
R
O
O
N
S
S
O
S
O
S
S
S
O
S
N
R
N
O
T4DIM
O
DTTDI
Despite these significant progresses in applications, to our
knowledge, very few reliable and effective approaches to access
this important class of 2,3-thienoimides (structure highlighted in
Fig. 1) have been reported yet. Briefly, literature reported methods
for the synthesis of the core structure thieno[3,4-c]pyrrole-4,6-
dione mainly relied on the reaction of thieno[2,3-c]furan-4,6-dione
with primary amines in thionyl chloride.34,35,37 However, the
preparation of thieno[2,3-c]furan-4,6-dione in itself was a time-
Figure 1. Typical examples of oligomeric and polymeric thiophenes.
consuming process.38,39 On the other hand, 1,4-dithiane-2,5-diol
has also been found to be an attractive synthon for the assembly
of tetrahydrothiophene or thiophene derivatives.40–44 As part of
our continued interest in the development of organocatalytic
method for the construction of aromatic heterocyles,45 we
described herein a formal [3+2] annulation reaction between 1,4-
dithiane-2,5-diol and N-substituted imide, which provided a new
⇑
Corresponding authors.
E-mail addresses: 1047470997@qq.com, wangjian1999@hotmail.com (J. Wang).
http://dx.doi.org/10.1016/j.tetlet.2015.04.097
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Shi, W.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.04.097

2
W. Shi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
Table 1
Optimization of reaction conditionsa
O
O
O
OH
S
S
2
OH
1) solvent, cat. (20 mol% )
Ph
N
Ph
N
Ph N
HO
S
S
2) SiO2, DDQ, MnO2, µw
O
O
O
1a
3a
3a'
Entry
Cat.
Solvent
T (h)
Yield of 3ab (%)
1
2
3
4
5
6
7
8
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
CH2Cl2
CHCl3
Cl(CH2)2Cl
THF
0.5
0.5
0.5
0.5
2
8
8
8
0.5
1
1
2
2
2
2
2
85
84
80
81
75
40
32
37
86
80
70
74
55
72
37
0
CH3CN
Benzene
Toluene
Et2O
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
DIPEA
Pyridine
DEA
10
11
12
13
14
15
16
NaOAc
NaHCO3
K2HPO4
NaOH
c
—
a
Reaction conditions: a mixture of 1a (0.40 mmol), 2 (0.24 mmol), cat. (0.08 mmol) in solvent (1 mL) was stirred at room temperature for a certain period of time. The
solvent was then removed and obtained solid was ground with silica gel (20 equiv, w/w), DDQ (3.0 equiv), and MnO2 (6.0 equiv) in a mortar followed by irradiation in a
laboratory microwave for 15 min.
b
Yield of isolated product.
No catalyst.
c
and efficient route to generate 2,3-thienoimides followed by a sub-
sequent dehydration and aromatization sequence.
Table 2
Substrate scope
We began with an initial experiment of 1-phenyl-1H-pyrrole-
2,5-dione 1a and 1,4-dithiane-2,5-diol 2 catalyzed by trimethy-
lamine (TEA). The reaction was proceeded smoothly to form an
intermediate 3-hydroxyl-tetrahydrothienoimide 3a0 in DCM at
room temperature. Build upon intermediate 3a0, we then
attempted to covert 3a0 into the desired 2,3-thienoimide 3a. In
terms of the structure of 3a0, we proposed a subsequent dehydra-
tion and oxidation cascade reaction. Several oxidants (e.g., MnO2,
sulfuric acid, Oxones, DDQ) were tested independently, but all gave
poor conversion (<10%). For example, the reaction mixture was
directly treated with trifluoroacetic anhydride and DDQ heating
at reflux for 2 days, but no desired product 2,3-thienoimide 3a
was observed. In view of high temperature might be good for dehy-
dration and oxidation reaction, we replaced the dichloromethane
with a high boiling solvent acetic acid and refluxed the reaction
at 120 °C for 5 h. However, the isolated yield of 3a was only 30%.
Finally, a combination silica gel/DDQ/MnO2/Microwave was found
to be the most efficient toll to promote this reaction and afforded
the desired product 3a in 85% yield (Table 1, entry 1, 0.5 h).
To examine the generality of substrate scope, a wide range of N-
substituted imides 1 were investigated. As described in Table 2, all
reactions proceeded smoothly, providing the corresponding 2,3-
thienoimides 3 in good yields. The electronic nature and the posi-
tion of the substituents on the aryl ring of N-substituted imides
had no obvious influence on the formation of the desired product
3. Electron-withdrawing (3b–c, 3e–g, and 3j), -donating (3d, 3i,
and 3h), and -neutral (3a, 3l) substituents all gave good to high
chemical yields. It was also noteworthy that N-aliphatic substi-
tuted imides were well tolerated and afforded the corresponding
products in good yields (3m and 3n).
O
O
S
OH
1) DCM, TEA (20 mol% )
R
N
R N
S
2) SiO2, DDQ, MnO2, µw
HO
S
O
1
O
2
3
Product
R
Yielda
(%)
Product
R
Yielda
(%)
CH3
3a
3b
3c
3d
85
3h
3i
78
73
78
75
OCH3
82
80
76
F
F
3j
Cl
3k
Cl
CH3
H3CO
Br
3e
3f
75
80
78
3l
70
78
67
F
3m
3n
Cl
3g
a
Our postulated reaction mechanism is illustrated in Scheme 1.
1,4-Dithiane-2,5-diol 2 yields intermediate mercaptoacetaldehyde
Isolated yield after column chromatography.
Please cite this article in press as: Shi, W.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.04.097

W. Shi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
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Financial support from China Hubei Collaborative Innovation
2011 Project and National Natural Science Foundation of China
(21202136) are greatly appreciated.
Supplementary data
Supplementary data (experimental procedures and compound
characterization data) associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.04.
097.
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Please cite this article in press as: Shi, W.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.04.097