Programmed Site-Selective Palladium-Catalyzed Arylation of Thieno[3,2-b]thiophene

Article abstract of DOI:10.1002/asia.201700562

Mono-, di-, tri-, and tetraarylated thieno[3,2-b]thiophenes were synthesized by direct site-selective Pd-catalyzed C?H activation reactions with various aryl bromides in the presence of a phosphine-free Pd(OAc)₂/KOAc catalyst system in N,N-dimethylacetamide (DMAc). The arylation of 2-arylthieno[3,2-b]thiophene took place at the C3 position if the 2-aryl substituents possessed electron-withdrawing groups and at the C5 position if they were bulky and possessed electron-donating groups.

Full text of DOI:10.1002/asia.201700562

CHEMISTRY
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Accepted Article
Title: Programmed Site-selective direct Palladium Catalyzed Arylations
of Thieno[3,2-b]thiophene
Authors: Tung Thanh Dang, Thi Minh Ha Vuong, Hien Nguyen, Didier
Villemin, Thanh Tin Le, and Hung Huy Nguyen
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10.1002/asia.201700562
Chemistry - An Asian Journal
FULL PAPER
Programmed Site-selective Palladium Catalyzed Arylations of
Thieno[3,2-b]thiophene
T. M. Ha Vuong,a,b Didier Villemin,b Hung-Huy Nguyen,c Tin Thanh Le,d Tung T. Dang,*e Hien Nguyen,*f
a Faculty of Applied Sciences, Ton Duc Thang University, 19 Nguyen Huu Tho Street, Tan Phong Ward, District 7, Ho Chi Minh City,
Vietnam.
b LCMT, UMR 6507, ENSICAEN, Normandie Université France, 6 bd Maréchal Juin, 14000 Caen Cedex, France.
c Department of Chemistry, VNU - Hanoi University of Science, 19 Le Thanh Tong Street, Ha Noi, Viet Nam.
d Faculty of Chemistry, Hochiminh National University of Education, 280 An Duong Vuong, Hochiminh, Vietnam.
e COBRA UMR 6014 Batiment IRCOF, Normandie Université France,1 Rue Tesniere,76821 Mont St Aignan Cedex, France.
f Division of Organic Chemistry, Faculty of Chemistry, Hanoi National University of Education, 136 Xuan Thuy, Cau Giay, Ha Noi, Viet
Nam.
*Corresponding authors: tung-thanh.dang@univ-rouen.fr, hiennguyendhsphn@gmail.com
Abstract: Mono-, di-, tri- and tetra-arylated thieno[3,2-b]thiophenes
were synthesized by direct site-selective Pd-catalyzed C-H activation
reactions with various aryl bromides in the presence of a phosphine-
free Pd(OAc)2/KOAc catalyst system in DMAc. The arylation of 2-
arylthieno[3,2-b]thiophene took place at the C-3 position when the 2-
aryl substituents bear electron-withdrawing groups, and at the C-5
position when they are bulky and possess electron-donating groups.
building block have rapidly gained much attention. Thieno[3,2-
b]thiophene has been known as an important building block in
the structures of semiconductor polymers, molecular electronics
and electronic devices.7,8 Because of intermolecular sulfur–sulfur
interactions, organic materials containing thieno[3,2-b]thiophene
moiety may increase the electronic transport between
neighbouring molecules. In addition, the electronic properties,
the solubility and the molecular packing of various materials
could be significantly changed when substituents were
introduced into the core structure of the materials.7,8
!
!
INTRODUCTION
Scheme 1. Structures of polymers (pBTTT and pQT) and a pyrene-based
organic semiconductor containing the thieno[3,2-b]thiophene building block
Recently, the direct palladium-catalyzed arylation of arenes and
heteroarenes by C-H bond activation using aryl halides have
For the purpose of fine-tuning the electronic and physical
properties of thieno[3,2-b]thiophene-containing materials, many
synthetic methods have been developed, especially those using
conventional Pd-catalyzed cross-coupling reactions. The liquid-
crystalline semiconducting polymers pBTTT and pQT9-11
showed valuable high charge-carrier mobility for transistor
performance. The semiconductive polymers containing
thieno[3,2-b]thiophene (pBTTT and pQT) were prepared by the
palladium-catalyzed Stille cross-coupling reactions between 2,5-
dibromothieno[3,2-b]thiophene and various substituted 2-
thienylstannanes. Similarly, isoindigo-based low bandgap
conjugated polymers towards application in photovoltaic devices
were synthesized by the Stille cross-coupling reaction of 2,5-
been extensively developed.1,2 It has become
a powerful
methodology2 for rapid construction and diversification of highly
functionalized molecules. Until now, palladium-catalyzed
arylation method has found successful applications in the
synthesis of bioactive natural products, drugs, and fine
chemicals. In addition, it plays an essential role in agrochemical
industries as well as in material sciences. Compared with
classical cross-coupling reactions (Stille, Suzuki-Miyaura,
Neigishi, Kumada, etc.),3-6 the palladium-catalyzed C-H
functionalization shows several advantages concerning the
unnecessary pre-functionalization of the substrates and
preparation of organometallic reagents. In this context, direct C-
H bond activation has proved to be a straightforward and
efficient tool for chemists in terms of atom-economy, less
undesired waste, and more environmentally friendly reaction
conditions.
bis(trimethylstannyl)thieno[3,2-b]thiophene
and
6,6’-
dibromoisoindigo.12 The star-shaped organic semiconductor
1,3,6,8-tetera(thieno[3,2-b]thien-2-yl)pyrene13 obtained from the
In recent decades, a large number of research related to the
employment of functionalized thieno[3,2-b]thiophene as a basic
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Stille cross-coupling reaction of 1,3,6,8-tetrabromopyrene and
Doucet and co-workers have recently described an efficient
tributyl-(6-nonylthieno[3,2-b]thien-2-yl)-stannane
successsfully applied in the development of new light-emitting
was
phosphine-free
palladium-catalyzed
functionalization
of
thiophene.26-29 Their catalytic systems, composed of Pd(OAc)2
as catalyst and a base (K2CO3, KOAc, or Cs2CO3) in an organic
solvent (DMAc, DMF,…), are efficient for direct site-selective
arylation of functionalized thiophenes.
diodes (OLEDs). Several well-soluble thieno[3,2-b]thiophene-
based
oligomers14
and
2,5-di(2-azulenyl)thieno[3,2-
b]thiophenes,15 which were constructed via the Suzuki-Miyaura
cross-coupling reactions of 2,5-disubstituted thieno[3,2-
b]thiophenyl pinacolato boronic ester and 2-iodoazulene or 2-
bromo- or 2,5-dibromothieno[3,2-b]thiophene, showed high hole
mobilities, small transition energies, and high-order orientations
in the crystalline state. These p-channel organic field-effect
transistors (OFET) demonstrated promising performance due to
the presence of thieno[3,2-b]thiophene moiety.7,16,17 Fluorescent
boron-nitrogen heteroacenes18 containing the thieno[3,2-
b]thiophene building block were constructed by the Suzuki-
Table 1. Pd-catalyzed arylation of thieno[3,2-b]thiophene 1 with aryl bromides
2(a-q)a,b
.
Miyaura
b]thiophene
cross-coupling
isomers
reaction
of
dibromothieno[3,2-
and 2-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)benzenamine, followed by the insertion of
boron atoms with phenyldicholorborane.
Obviously, the functionalization of thieno[3,2-b]thiophene
building block plays a remarkable role in the development of
novel organic materials with promising electronic properties. In
2010, Knochel and Kunz reported the full functionalization of all
four positions of thieno[3,2-b]thiophene by selective multiple
magnesiations of 2,5-dichlorothieno[3,2-b]thiophene.19 Very
recently, Miura and co-workers20 published a study on a
convenient palladium-catalyzed direct alkenylation of thieno[3,2-
b]thiophene. This protocol gave a facile synthetic route to
achieve regioselectively mono- and di- alkenylated thieno[3,2-
b]thiophenes at the C-2 and/or C-5 positions. Multiarylated
thieno[3,2-b]thiophenes via sequential Suzuki-Miyaura cross-
coupling reactions between tetrabromothieno[3,2-b]thiophene
and various arylboronic acids were reported in our recent work.21
In this context, the direct arylation of thieno[3,2-b]thiophene via
site-selective C-H bond activation is straightforward since it
provides a more environmental-friendly and atom-economical
approach to multiarylated thieno[3,2-b]thiophene without the
!
aReaction conditions: 1 (0.2 mmol), 2(a-q) (0.1 mmol), Pd(OAc)2 (1 mol%),
b
employment of halogenated thieno[3,2-b]thiophenes
or
KOAc (0.2 mmol), DMAc (2 mL); isolated yields are given. PdCl(C3H5)dppb
preparation of corresponding organometallic reagents.
was used.
Herein, to the best of our knowledge, we wish to report a new
and efficient route for the synthesis of mono-, di-, tri- and
tetraarylated thieno[3,2-b]thiophenes with controllable site-
selectivity by the palladium-catalyzed direct arylation reactions
of thieno[3,2-b]thiophene with aryl bromides using low catalyst
loading.
In principle, the reactivities of thiophene and thieno[3,2-
b]thiophene are similar. Therefore, we applied Doucet’s protocol
for the direct arylation of thieno[3,2-b]thiophene with various aryl
bromides. As expected, the arylation of 1 was successfully
conducted with various commercially available bromoarenes in
the presence of Pd(OAc)2/KOAc as catalyst/base in DMAc.
The C-H arylation reactions of 1 (2.0 equiv) with various aryl
bromides (1.0 equiv) resulted in the site-selective formation of a
series of 2-Arylthieno[3,2-b]thiophenes 3a-q in moderate to good
yields (35 – 75%) (Table 1). After extensive screening with
regards to temperature, solvent, base, and water additive,
Pd(OAc)2 without ligand was found to be an efficient catalyst for
the direct arylation of thieno[3,2-b]thiophene. All reactions were
carried out at 120-150° C (Table 1, see SI). The optimized
reaction conditions were compatible with a wide range of
functional groups, such as nitro, dialkylamino, ester, cyano, or
heterocyclic substituents. Generally, the arylation reaction gave
RESULTS AND DISCUSSION
First, the starting material compound, thieno[3,2-b]thiophene 1
was synthesized using Fuller’s procedure.22
A pioneering work reported by Ohta et al.23 in 1990 for direct
arylation of thiophene, furan, and thiazole gave medium to good
yields using 5 mol% of Pd(PPh3)4 as catalyst. Since this high-
impact discovery, the direct arylation of heterocycles has been
studied thoroughly and proved to be a powerful tool for
construction of (hetero)biaryl frameworks.24,25 Noticeably,
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10.1002/asia.201700562
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better yields with aryl bromides bearing electron-withdrawing
groups (2e, 2h, 2k, 2n, and 2q) than with aryl bromides bearing
electron-donating groups (2i and 2o). However, 9-
bromoanthracene 2f and 3-bromonaphthalene 2g also afforded
the corresponding 2-substituted thieno[3,2-b]thiophene 3f and
3g in good yields. For the synthesis of compounds 3m and 3q,
dppb ligand was employed because the two corresponding aryl
bromides, 2m and 2p, did not work well under the present
phosphine-free palladium-catalyzed reaction condition.30
Interestingly, the direct C-H arylation of 2-Aryl1-thieno[3,2-
b]thiophenes 3e and 3h (1.0 equiv) with various aryl halides,
such as 2e and 2h (1.1 equiv), resulted in the abnormal site-
selective formation of 2-Aryl1-3-Aryl2thieno[3,2-b]thiophenes 5a-
c in 40 – 45% yields (Table 3). In an attempt to the structures
as well as the site-selectivity in the direct arylation of 3e and 3h,
the structure 5c was elucidated by NMR spectroscopic method
and X-ray crystal structure analysis (Figure 2).
Table 3. Synthesis of 2,3-diarylthieno[3,2-b]thiophenes 5a-c from 2-
arylthieno[3,2-b]thiophene 3e,h and aryl bromides 2e,h.
Table 2. Pd-catalyzed arylation of 2-Arylthieno[3,2-b]thiophenes 3f, m with
aryl bromidesa.
Ar3
H
S
S
H
H
Pd(OAc)2
Ar3Br
Ar1
Ar1
KOAc, DMAc
S
S
5a,b,c
3e,h
2e,h
NO2
CN
CN
S
S
S
S
S
S
NO2
CN
NO2
5b, 45%
5a, 42%
5c, 40%
aReaction conditions: 3(e,h) (0.2 mmol), 2 (0.22 mmol), Pd(OAc)2 (1 mol%),
KOAc (0.2 mmol), DMAc (2.5 mL); isolated yields are given.
!
aReaction conditions: 3(f,m) (0.1 mmol), 2 (0.11 mmol), Pd(OAc)2 (1 mol%),
KOAc (0.1 mmol), DMAc (1.5 mL); isolated yields are given.
In order to perform a second aryltion of 2-arylated thieno[3,2-
b]thiophenes, the C-H activation reactions of 2-Aryl1thieno[3,2-
b]thiophenes 3f or 3m (1.0 equiv.) with various aryl halides 2c,
2g, 2h, 2k, or 2l (1.1 equiv) resulted in the highly site-selective
formation
of
unsymmetrical
2-Aryl1-5-Aryl2thieno[3,2-
!
b]thiophenes 4a-f in acceptable yields (41 – 60%) (Table 1).
To confirm the site-selectivity at the C-2 and C-5 positions of
thieno[3,2-b]thiophene in our arylation reaction, the structure of
Figure 2. X-Ray crystal structure of 5c38
4a was well characterized by H NMR and 13C NMR spectra in
1
NO2
Br
combination with X-ray crystal structure analysis (Figure 1).
S
PdCl(C3H5)(dppb) 1 mol%
DMAc, 140°C, 24 h
S
NO2
S
2h
H
5c, 40%
or
NO2
Me
S
H
Br
1
S
O
PdCl(C3H5)(dppb) 1 mol%
DMAc, 140°C, 24 h
S
!
O
Me
5d, 35%
Figure 1. X-Ray crystal structure of 4a38
Me
2n
O
The similar site-selectivity in the direct arylation of thiophene and
thieno[3,2-b]thiophene is predictable since they share analogous
structural characteristics.
Figure 3. Synthesis of 2,3-diarylthieno[3,2-b]thiophenes 5c and 5d from 1 and
aryl bromides 2.
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NO2
NO2
second
arylation
1
S
7.28
ppm
H
2
3
6
S
To further investigate the abnormal site-selectivity of the direct
arylation of 2-substituted thieno[3,2-b]thiophene, we conducted
the diarylation reaction of thieno[3,2-b]thiophene 1 (1.0 equiv)
with 2h or 2n (3.0 equiv) (Figure 3). In our expectation, two
corresponding 2,3-diarylthieno[3,2-b]thiophenes, 5c and 5d,
were also obtained with 40% and 35% yields, respectively. In
these reactions, the more reactive catalyst, PdCl(C3H5)(dppb),
was employed instead of Pd(OAc)2 since the latter showed
sluggish conversion. Under this phosphine-supported condition,
the same site-selectivity at the C-2 and C-3 positions was
observed.
Considering the mechanism of the direct arylation via C-H bond
activation, three potential pathways have been proposed for the
C-C cross-coupling reactions.25,31,32 In our catalytic system, the
essential role of the base, KOAc, would support for the
concerted metalation deprotonation (CMD) pathway. This CMD
mechanism has been thoroughly studied and can be applied in
reactions of similar aromatic compounds.33,34 In an aromatic ring,
the more acidic proton is normally activated favourably.35
[Pd]
O
H
7.46
ppm
favoured
at C-3
S
4
5
H
S
H
7.66 ppm
O
CH3
Figure 4. Possible interpretation of selective formation of 2,3-diarylthieno[3,2-
b]thiophenes
Interestingly, the site-selectivity of the second and the third
direct arylations of 2-arylthieno[3,2-b]thiophenes 3f and 3g were
again observed at the C-5 and C6 positions on the other sites of
the thieno[3,2-b]thiophene scaffold (Figure 6). The more reactive
sites in these cases are still in good agreement with the CMD
mechanism.25 In fact, the arylation reaction of 3f or 3g (1.0
equiv) with 2h or 2l (3.0 equiv) furnished two corresponding 2-
Aryl1-5,6-(Aryl2)2thieno[3,2-b]thiophenes, 6a and 6b, with 20 and
32% yields, respectively (Figure 5). In these cases, the site-
selectivity of the third arylation results from the increased acidity
of the C-6 proton due to the EWG at the C-5 position. In addition,
the steric hindrance caused by the fused aromatic ring systems
at the C-2 position, namely, the anthracene and the naphthalene
substituents, also contributes to the observed site-selectivity.
Table 4. Resonances of C-3, C-5, and C-6 protons of several 2-arylthieno[3,2-
b]thiophenes*.
NO2
S
Compounds
H3, δ(ppm)
7.60
7.35
H5, δ(ppm)
7.44
7.36
H6, δ(ppm)
7.27
7.47
S
H
Pd(OAc)2
3e
3f
S
2h
KOAc, DMAc
S
H
3f
6a, 20%
3l
7.56
7.40
7.25
NO2
CF3
3n
3g
3h
3k
7.63
7.61
7.66
7.62
7.43
7.36
7.46
7.44
7.28
7.27
7.28
7.28
S
S
H
Pd(OAc)2
3l
S
KOAc, DMAc
S
H
6b, 32%
3g
*see supporting information for more details
CF3
Figure 5. Synthesis of 2,3,5-triarylthieno[3,2-b]thiophenes 6a-b from 2-
arylthieno[3,2-b]thiophene 3f or 3g and the aryl bromide 2h or 2l.
In order to get an insight into the site-selectivity of the arylation
of thieno[3,2-b]thiophene, the resonances of the related protons
on the thieno[3,2-b]thiophene moiety of several 2-arylthieno[3,2-
b]thiophene were compared (Table 4). In the 2-arylated
thieno[3,2-b]thiophene scaffolds, the electronic effect of a strong
electron-withdrawing group (EWG) on the C-2 atom may have
significant influence on the proton on the adjacent position, the
C-3 atom.
Indeed, the acidity of the proton at the C-3 position is higher
than that of the proton at the C-5 position as indicated by the
NMR data. Table 4 shows that when the 2-aryl substituent of a
2-Arylthieno[3,2-b]thiophene possesses an electron-withdrawing
group, such as cyano (3e), nitro (3k, 3h), trifluoromethyl (3l), or
acetyl (3n), especially at its para position, the resonance of the
C-3 proton is noticeably higher than that of the C-5 proton.
Obviously, this evidence reveals that the acidity of the C-3
proton in 2-(EWG-aryl)thieno[3,2-b]thiophenes is increased.
Hence, the subsequent direct arylation took place more
favourably at the C-3 position.
Figure 6. X-Ray crystal structure of 6a38
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The 2,3,5-triarylthieno[3,2-b]thiophenes 6c and 6d were also
directly synthesized from the arylation of thieno[3,2-b]thiophene
in 50% and 46% yields, respectively (Figure 7).
Interestingly, the sequential arylations of the 2-arylthieno[3,2-
b]thiophenes took place at predictable positions, either at the C-
3 or at the C-5 position in the thieno[3,2-b]thiophene skeleton,
depending on the nature and the size of the 2-aryl substituents.
In terms of low catalyst loading, simple reaction conditions, and
a wide range of functional group tolerance, to our opinion, this
current procedure is convenient and useful for further
applications in materials science.
Experimental Section
General: NMR spectra were recorded on a Bruker Avance
spectrometer (500 MHz for 1H and 125 MHz for 13C). MS
measurements were conducted with a Q-TOF Micro WATERS
instrument using ionization electrospray positive (ESI) method.
The intensities for the X-ray determination of 4a, 5c, and 6a
were collected on a D8 QUEST Bruker (Germany) instrument at
100 K with Mo Kα radiation (λ = 0.71073 Å) using a TRIUMPH
monochromator. Melting points were measured on a Stuart-
Scientific SMP3 apparatus without correction. THF were dried
and distilled over sodium benzophenone ketyl just before used.
Anhydrous DMAc and other commercially available reagents
were used without further purification. All C-H activation
reactions were performed in argon atmosphere.
Figure 7. Synthesis of 2,3,5-triarylthieno[3,2-b]thiophenes 6c and 6d from
thieno[3,2-b]thiophene 1 and aryl bromide 2k or 2n, respectively.
In summary, when the 2-arylsubstituent bearing an EWG, the
sequential direct arylations take place first at the C-3 position,
then at the C-5 position, and finally at the C-6 position due to the
activation of the corresponding C-H bonds (Figure 8).
General procedure for the synthesis of 2-arylthieno[3,2-
b]thiophene 3a-q
Procedure A: Thieno[3,2-b]thiophene 1 (2.0 equiv), KOAc (2.0
equiv), an aryl bromide 2 (1.0 equiv), and Pd(OAc)2 (0.01 equiv)
was dissolved in DMAc which was saturated with argon. The
resulting reaction mixture was heated at 120 – 150 oC under
argon atmosphere until TLC (n-hexane/ethyl acetate) showed
the complete consumption of the starting material. The reaction
mixture was cooled to room temperature and filtered to remove
insoluble impurities. The filtrate was diluted with ethyl acetate,
washed with water (3 times), dried over Na2SO4, and
concentrated under reduced pressure by rotary evaporation. The
residue was purified by SiO2-column chromatography (n-
hexane/ethyl acetate) to give the C-H activation cross-coupling
product.
!
Figure 8. Sequential direct arylations of 2-arylthieno[3,2-b]thiophenes.
The one-pot synthesis of 2,3,5,6-tetrarylthieno[3,2-b]thiophene 7
could be achieved from the direct arylation of thieno[3,2-
b]thiophene 1 with the aryl bromide 2n in 25% yield (Figure 9).
Procedure B: Procedure B was similar to procedure A except
that the phosphine-based complex [PdCl(C3H5)dppb] (dppb:
bis(diphenylphosphino)butane) (0.01 equiv) was used as
catalyst instead of Pd(OAc)2.30,36,37
Figure 9. Synthesis of 2,3,5,6-tetra(4-acetylphenyl)thieno[3,2-b]thiophene 7
from 1 and 4-bromoacetophenone 2n.
2-(4-Nitrophenyl)thieno[3,2-b]thiophene 3h: Following procedure
A, from thieno[3,2-b]thiophene (28 mg, 0.2 mmol, 2.0 equiv), 1-
bromo-4-nitrobenzene (20 mg, 0.1 mmol, 1.0 equiv), Pd(OAc)2
(0.5 mg, 0.02 mmol, 0.01 equiv), KOAc (19.6 mg, 0.2 mmol, 2.0
equiv), DMAc (2.0 mL), 3h was obtained as a pale yellow
needles (18.8 mg, 72%). Mp 110-112 oC; 1H NMR (500 MHz,
CDCl3): δ 8.25 (2 H, d, J = 8.5 Hz), 7.75 (2 H, d, J = 8.5 Hz),
7.66 (1 H, s), 7.47 (1 H, d, J = 5.0 Hz), 7.29 (1 H, d, J = 5.5 Hz);
13C NMR (125 MHz, CDCl3): δ 146.8, 143.1, 141.0, 140.4, 128.9,
125.9, 124.5, 119.7, 117.9. HRMS-ESI: m/z calcd for
C12H7NO2S2Na [M+Na]+ 283.9816, found 283.9833.
Conclusions
In conclusion, we have developed an efficient and
straightforward method for the direct site-selective palladium-
catalyzed arylation reactions of simple thieno[3,2-b]thiophene.
This versatile method allows the synthesis of a large number of
mono-, di-, tri- and tetraarylated thieno[3,2-b]thiophenes under
phosphine-free conditions with controllable site-selectivity.
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7-Diethylaminocoumarin-3-ylthieno[3,2-b]thiophene
3q:
s); 13C NMR (CDCl3, 125 MHz): δ 145.1, 139.3, 136.3, 134.4,
131.2, 130.8, 130.6, 128.2, 126.4, 125.9, 119.4, 118.6, 21.1.
3j: White solid (31.8 mg, 35%). Mp 147-148 oC; 1H NMR (500
MHz, CDCl3): δ 7.73 (1 H, s), 7.47 (1 H, d, J = 5.5 Hz), 7.30 (1 H,
d, J = 5.0 Hz).
Following procedure B, from 1 (70 mg, 0.5 mmol, 2.0 equiv) and
7-diethylaminocoumarin-3-yl bromide 2q (74 mg, 0.25 mmol, 1.0
equiv), 3q was isolated as orange crystals (66 mg, 75%). Mp
o
1
132-133 C; H NMR (CDCl3, 500 MHz): δ 7.95 (1 H, s), 7.82 (1
H, s), 7.35 (1 H, d, J = 5.5 Hz), 7.30 (1 H, d, J = 9.0 Hz), 7.22 (1
3k: Pale yellow solid (37 mg, 71%). Mp 122-123 oC; 1H NMR
H d, J = 5.0 Hz), 6.59 (1 H, dd, J = 9.0 Hz and 2.5 Hz), 6.50 (1 H, (500 MHz, CDCl3): δ 8.46 (1 H, m), 8.13 (1 H, dq, J = 8.5 Hz
d, J = 2.5 Hz), 3.40 (4 H, q, J = 7.0 Hz), 1.22 (6 H, t, J = 7.0 Hz);
13C NMR (CDCl3, 125 MHz): δ 160.1, 155.5, 150.6, 140.0, 139.8,
138.7, 136.8, 128.9, 127.3, 119.4, 117.8, 114.8, 109.3, 108.7,
97.0, 44.8, 12.5; HRMS-ESI: m/z calcd for C19H18NO2S2 [M+H]+
356.0778, found 356.0789.
and 1.5 Hz), 7.91 (1 H, dq, J = 8.0 Hz and 1.0 Hz), 7.62 (1 H, s),
7.56 (1 H, t, J = 8.0 Hz), 7.44 (1 H, d, J = 5.5 Hz), 7.28 (1 H, d, J
= 5.0 Hz); 13C NMR (125 MHz, CDCl3): δ 148.8, 143.0, 140.1,
139.5, 136.5, 131.3, 129.9, 128.3, 122.1, 120.3, 119.6, 117.1;
HRMS-ESI: m/z calcd for C12H7NO2S2Na [M+Na]+ 283.9816,
3a: White solid (23.7 mg, 55%). Mp 68-70 oC; 1H NMR (500 MHz, found 283.9832.
CDCl3): δ 7.62 (2 H, d, J = 8.0 Hz), 7.48 (1 H, s), 7.39 (2 H, t, J =
8.0 Hz), 7.35 (1 H, d, J = 5.5 Hz), 7.28 (1 H, t, J = 8.0 Hz), 7.24
(1 H, d, J = 5.0 Hz); 13C NMR (125 MHz, CDCl3): δ 146.3, 143.0,
138.5, 131.0, 128.9, 127.8, 126.8, 125.8, 119.6, 115.3.
3b: Colorless liquid (23 mg, 40%). 1H NMR (500 MHz, CDCl3): δ
8.11 (1 H, d, J = 2.0 Hz), 7.93 (1 H, dd, J = 8.0 Hz and 2.0 Hz),
7.38 (1 H, d, J = 5.0 Hz), 7.37 (1 H, d, J = 8.0 Hz), 7.28 (1 H, d,
J = 5.0 Hz), 7.25 (1 H, d, J = 6.0 Hz, overlapped by CHCl3
residue).
3l40: White solid (31.2 mg, 55%). Mp 136-137 oC; 1H NMR (500
MHz, CDCl3): δ 7.71 (2 H, d, J = 8.5 Hz), 7.64 (2 H, d, J = 8.5
Hz), 7.56 (1 H, s), 7.41 (1 H, d, J = 5.5 Hz), 7.26 (1 H, d, J = 5.0
Hz); 13C NMR (125 MHz, CDCl3): δ 144.3, 140.1, 139.4, 138.2,
129.4 (q, J = 32.6 Hz, C-CF3), 127.9, 126.0 (q, J = 3.3 Hz, C-C-
CF3), 125.9, 124.1 (q, J = 270.5 Hz, CF3), 119.6, 116.7.
3m: Yellow solid (45.6 mg, 67%). Mp 184-185 oC; 1H NMR (500
MHz, CDCl3): δ 8.54 (1 H, d, J = 9.0 Hz), 8.09 (8 H, m), 7.52 (1
H, s), 7.43 (1 H, d, J = 5.0 Hz), 7.35 (1 H, d, J = 5.0 Hz).
3n: Yellow solid (36.2 mg, 70%). Mp 116-117 oC; 1H NMR (500
MHz, CDCl3): δ 7.98 (2 H, d, J = 8.0 Hz), 7.72 (2 H, d, J = 8.5
Hz), 7.63 (1 H, s), 7.43 (1 H, d, J = 5.0 Hz), 7.28 (1 H, d, J = 5.0
Hz), 2.62 (3 H, s); 13C NMR (125 MHz, CDCl3): δ 197.2, 144.7,
140.2, 139.6, 139.2, 136.0, 129.2, 128.1, 125.6, 119.6, 116.8,
26.5.
3c: Yellow solid (28.4 mg, 65%). Mp 87-89 oC; 1H NMR (500
MHz, CDCl3): δ 8.62 (1 H, d, J = 2.0 Hz), 8.24 (1 H, dd, J = 5.0
Hz and 1.5 Hz), 7.59 (1 H, dt, J = 7.5 Hz and 2.0 Hz), 7.12 (1 H,
d, J = 5.5 Hz), 7.04 (1 H, d, J = 8.0 Hz and 5.0 Hz), 6.99 (1 H, s),
6.98 (1 H, d, J = 5.0 Hz); 13C NMR (125 MHz, CDCl3): δ 148.7,
146.8, 142.1, 140.1, 139.2, 132.8, 130.8, 127.8, 123.7, 119.5,
116.4. Structure of 3c was independently determined by X-Ray
analysis (data not shown).
3o: White solid (20.5 mg, 35%). Mp 65-66 oC; 1H NMR (500
MHz, CDCl3): δ 7.67 (2 H, d, J = 8.0 Hz), 7.60 (4 H, m), 7.51 (1
H, s), 7.42 (2 H, t, J = 7.5 Hz), 7.34 (2 H, d, J = 5.0 Hz), 7.24 (1
H, d, J = 5.5 Hz).
3d: Yellow solid (29 mg, 67%). Mp 82-83 oC; 1H NMR (500 MHz,
CDCl3): δ 8.58 (1 H, dt, J = 5.0 Hz and 1.5 Hz), 7.78 (1 H, s),
7.69 (2 H, m), 7.41 (1 H, d, J = 5.5 Hz), 7.28 (1 H, d, J = 5.5 Hz),
o
1
3p: Yellow solid (35.8 mg, 35%). Mp 142-143 C; H NMR (500
7.16 (1 H, m); 13C NMR (125 MHz, CDCl3): δ 152.8, 149.7, 146.7, MHz, CDCl3): δ 7.38 (1 H, s), 7.36 (1 H, d, J = 5.5 Hz), 7.23 (1 H,
140.7, 139.8, 136.6, 128.1, 122.9, 119.9, 118.7, 116.8; HRMS-
d, J = 5.0 Hz).
ESI: m/z calcd for C11H8NS2 [M+H]+ 218.0098, found 218.0109.
o
1
3e40: White solid (36.2 mg, 75%). Mp 94-95 C; H NMR (500
MHz, CDCl3): δ 7.69 (2 H, d, J = 8.0 Hz), 7.65 (2 H, d, J = 8.5
Hz), 7.59 (1 H, s), 7.45 (1 H, d, J = 5.5 Hz), 7.27 (1 H, d, J = 5.5
Hz); 13C NMR (125 MHz, CDCl3): δ 143.6, 140.2, 139.9, 139.1,
132.8, 128.6, 125.9, 119.6, 118.8, 117.3; 110.8; HRMS-ESI: m/z
calcd for C13H7NS2Na [M+Na]+ 263.9918, found 263.9926.
General procedure for the synthesis of 2,5-diarylthieno[3,2-
b]thiophene 4a-e: Procedure for the synthesis of 2,5-
diarylthieno[3,2-b]thiophenes 4a-e was similar to that of 2-
arylthieno[3,2-b]thiophenes 3: from thieno[3,2-b]thiophene 1 (1.0
equiv), an aryl bromide 2 (3.0 equiv), Pd(OAc)2 (0.02 equiv), and
KOAc (4.0 equiv), or from a 2-arylthieno[3,2-b]thiophene 3 (1.0
equiv), an aryl bromide 2 (1.1 equiv), Pd(OAc)2 (0.01 equiv), and
o
1
3f40: White solid (46.1 mg, 75%). Mp 133-134 C; H NMR (500
MHz, CDCl3): δ 8.54 (1 H, s), 8.03 (2 H, d, J = 8.5 Hz), 7.97 (2 H, KOAc (1.0 equiv).
d, J = 8.5 Hz), 7.47 (3 H, m), 7.41 (2 H, m), 7.35 (2 H, m); 13C
NMR (125 MHz, CDCl3): δ 141.0, 140.4, 139.2, 131.8, 131.2,
128.5, 128.4, 128.3, 126.7, 126.5, 126.1, 125.3, 121.6, 119.5.
2-(Anthracene-9-yl)-5-(4-nitrophenyl)thieno[3,2-b]thiophene 4e:
From 2-(anthracene-9-yl)thieno[3,2-b]thiophene 3f (31.6 mg,
0.10 mmol, 1.0 equiv), 1-bromo-4-nitrobenzene 2h (22.1 mg,
0.11 mmol, 1.1 equiv), and Pd(OAc)2 (2.2 mg, 0.01 mmol, 0.01
equiv), 4e was isolated as an orange solid (26 mg, 60%). Mp
3g40: White solid (40 mg, 75%). Mp 115-116 C; H NMR (500
MHz, CDCl3): δ 8.06 (1 H, d, J = 1.0 Hz), 7.85 (2 H, d, J = 8.0
Hz), 7.82 (1 H, d, J = 7.5 Hz), 7.75 (1 H, dd, J = 8.5 Hz and 2.0
Hz), 7.61 (1 H, s), 7.47 (2 H, m), 7.37 (1 H, d, J = 5.0 Hz), 7.27
(1 H, d, J = 5.5 Hz); 13C NMR (125 MHz, CDCl3): δ 146.4, 140.2,
138.7, 133.6, 132.9, 132.2, 128.7, 128.1, 127.8, 127.0, 126.7,
126.1, 124.2, 124.1, 119.6, 115.7.
o
1
1
178-180 oC; H NMR (CDCl3, 500 MHz): δ 8.58 (1 H, s), 8.29 (2
H, d, J = 8.5 Hz), 8.06 (2 H, d, J = 8.0 Hz), 7.95 (2 H, d, J = 8.5
Hz), 7.83 (2 H, d, J = 9.0 Hz), 7.77 (1 H, s), 7.49 (2 H, t, J = 7.5
Hz), 7.44 (2 H, t, J = 7.5 Hz), 7.38 (1 H, s); 13C NMR (CDCl3, 125
MHz): δ 146.6, 142.8, 142.4, 141.3, 140.9, 140.2, 131.6, 131.0,
128.6, 128.3, 127.6, 126.2, 126.1, 125.8, 125.3, 124.4, 121.2,
118.0; HRMS-ESI: m/z calcd for C26H15NO2S2Na [M+Na]+
460.0442, found 460.0438.
3i: White solid (18.4 mg, 40%). Mp 52-53 oC; 1H NMR (CDCl3,
500 MHz): δ 7.43 (1 H, d, J = 8.0 Hz), 7.36 (1 H, d, J = 5.0 Hz),
7.27 (2 H, m), 7.23 (1 H, dd, J = 7.0 Hz and 2.0 Hz), 7.21 (1 H,
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o
1
4a: White solid (23 mg, 52%). Mp 184-185 C; H NMR (CDCl3,
7.41 (2 H, d, J = 8.5 Hz), 7.34 (1 H, d, J = 5.0 Hz), 2.63 (3 H, s),
500 MHz): δ 8.56 (1 H, s), 8.14 (1 H, s), 8.05 (2 H, d, J = 8.5 Hz), 2.59 (3 H, s); 13C NMR (CDCl3, 125 MHz): δ 197.6, 197.5, 139.9,
8.01 (2 H, d, J = 8.5 Hz), 7.90 (2 H, d, J = 8.5 Hz), 7.83 (2 H, t, J
= 8.0 Hz), 7.72 (1 H, s), 7.45 (6 H, m), 7.37 (1 H, s); 13C NMR
(CDCl3, 125 MHz): δ 145.9, 141.3, 140.8, 138.6, 133.7, 132.9,
132.3, 131.9, 131.2, 128.7, 128.5, 128.4, 128.5, 127.8, 126.7,
139.1, 137.7, 136.3, 136.1, 130.6, 130.4, 129.4, 129.2, 129.0,
128.7, 127.5, 119.9, 26.7, 26.5; HRMS-ESI: m/z calcd for
C22H17O2S2 [M+H]+ 377.0670, found 377.0668.
1
5a: White solid (28.7 mg, 42%). Mp 134-135 oC; H NMR (CDCl3,
126.5, 126.2, 126.1, 125.3, 124.3, 124.2, 121.9, 115.8 Missing
500 MHz): δ 7.69 (2 H, d, J = 8.5 Hz), 7.58 (2 H, d, J = 8.5 Hz),
1
4b: Orange solid (24 mg, 55%). Mp 154-155 oC; H NMR (CDCl3, 7.53 (2 H, d, J = 8.5 Hz), 7.46 (1 H, d, J = 5.5 Hz), 7.38 (2 H, d,
500 MHz): δ 8.57 (1 H, s), 8.54 (1 H, d, J = 2.0 Hz), 8.16 (1 H, dt, J = 8.5 Hz), 7.34 (1 H, d, J = 5.5 Hz); 13C NMR (CDCl3, 125
J = 8.0 Hz and 1.0 Hz), 8.06 (2 H, d, J = 8.5 Hz), 8.00 (1 H, dt, J
= 7.5 Hz and 1.0 Hz), 7.95 (2 H, d, J = 8.0 Hz), 7.74 (1 H, s),
7.62 (1 H, t, J = 8.0 Hz), 7.49 (2 H, t, J = 8.0 Hz), 7.44 (2 H, t, J
= 7.5 Hz), 7.38 (1 H, s); 13C NMR (CDCl3, 125 MHz): δ 167.8,
148.9, 142.4, 142.2, 141.2, 139.3, 136.5, 137.1, 131.3, 131.1,
130.8, 130.0, 128.7, 128.6, 128.3, 127.8, 126.3, 126.2, 126.0,
125.3, 122.1. 121.7, 120.3, 117.2.
MHz): δ 145.1, 145.9, 141.3, 139.3, 138.6, 138.2, 132.9, 132.6,
129.8, 129.7, 128.0, 119.9, 118.4, 111.9, 111.7; HRMS-ESI: m/z
calcd for C20H10N2S2Na [M+Na]+ 365.0183, found 365.0198.
5c: Yellow solid (30.6 mg, 40%). Mp 192-193 oC; 1H NMR
(CDCl3, 500 MHz): δ 8.27 (2 H, d, J = 9.0 Hz), 8.17 (2 H, d, J =
9.0 Hz), 7.60 (2 H, d, J = 9.0 Hz), 7.50 (1 H, d, J = 5.0 Hz), 7.45
(2 H, d, J = 9.0 Hz), 7.37 (1 H, d, J = 5.0 Hz); 13C NMR (CDCl3,
125 MHz): δ 147.3, 138.5, 130.0, 129.9, 129.8, 128.4, 124.5,
124.2, 120.0.
4c: Orange solid (17.7 mg, 45%). Mp 142-143 oC; 1H NMR
(CDCl3, 500 MHz): δ 8.98 (1 H, s), 8.56 (2 H, m), 8.04 (2 H, d, J
= 8.5 Hz), 7.96 (2 H, d, J = 8.5 Hz), 7.92 (2 H, dt, J = 8.0 Hz and
1.5 Hz), 7.62 (1 H, s), 7.49 (2 H, t, J = 7.0 Hz), 7.44 (2 H, t, J =
6.5 Hz), 7.35 (2 H, m); 13C NMR (CDCl3, 125 MHz): δ 148.7,
146.9, 141.7, 141.5, 141.2, 139.1, 132.9, 131.8, 131.1, 130.9,
General
procedure
for
the
synthesis
of
2,3,5-
triarylthieno[3,2-b]thiophene 6a-d: Procedure for the synthesis
of 2,3,5-triarylthieno[3,2-b]thiophenes 6a-d was similar to that of
2-arylthieno[3,2-b]thiophenes 3: from thieno[3,2-b]thiophene 1
128.6, 128.4, 128.0, 126.4, 126.2, 125.4, 123.8, 121.8, 116.6.
1
4d: White solid (18.9 mg, 41%). Mp 166-167 oC; H NMR (CDCl3, (1.0 equiv), an aryl bromide 2 (4.5 equiv), [PdCl(C3H5)dppb]
500 MHz): δ 8.57 (1 H, s), 8.05 (2 H, d, J = 8.0 Hz), 7.97 (2 H, d,
(0.02 equiv), and KOAc (6.0 equiv), or from a 2-arylthieno[3,2-
J = 8.5 Hz), 7.79 (2 H, d, J = 8.0 Hz), 7.68 (2 H, m), 7.62 (1 H, s), b]thiophene 3 (1.0 equiv), an aryl bromide 2 (3.0 equiv),
7.49 (2 H, t, J = 8.0 Hz), 7.43 (2 H, t, J = 8.0 Hz), 7.36 (1 H, s);
13C NMR (CDCl3, 125 MHz): δ 143.7, 141.9, 141.2, 139.3, 138.2,
131.8, 131.2, 129.5 (q, J = 35.7 Hz, C-CF3), 128.6, 128.3, 126.4,
126.2, 126.0 (q, J = 35.7 Hz, C-C-CF3), 125.9, 125.4, 121.8,
116.9.
General procedure for the synthesis of 2,3-diarylthieno[3,2-
b]thiophene 5a-d: Procedure for the synthesis of 2,3-
diarylthieno[3,2-b]thiophenes 5a-d was similar to that of 2-
arylthieno[3,2-b]thiophenes 3: from thieno[3,2-b]thiophene 1 (1.0
equiv), a 4-EWG-aryl bromide 2 (3.0 equiv), [PdCl(C3H5)dppb]
(0.01 equiv), and KOAc (4.0 equiv), or from a 2-(4-EWG)-
arylthieno[3,2-b]thiophene 3 (1.0 equiv), an aryl bromide 2 (1.1
equiv), Pd(OAc)2 (0.01 equiv), and KOAc (2.0 equiv).
Pd(OAc)2 (0.02 equiv), and KOAc (4.0 equiv).
2-(Anthracene-9-yl)-5,6-di(4-nitrophenyl)thieno[3,2-b]thiophene
6a: From 2-(anthracene-9-yl)thieno[3,2-b]thiophene 3f (63.2 mg,
0.20 mmol, 1.0 equiv), 1-bromo-4-nitrobenzene 2h (120.5 mg,
0.60 mmol, 3.0 equiv), and Pd(OAc)2 (0.9 mg, 0.004 mmol, 0.02
equiv), 6a was obtained as a pale yellow solid (22.3 mg, 20%).
Mp 195-196 oC; 1H NMR (CDCl3, 500 MHz): δ 8.59 (1 H, s), 8.25
(2 H, d, J = 9.0 Hz), 8.22 (2 H, d, J = 8.5 Hz), 8.07 (2 H, d, J =
8.0 Hz), 7.94 (2 H, d, J = 8.5 Hz), 7.68 (2 H, d, J = 9.0 Hz), 7.54
(2 H, d, J = 9.0 Hz), 7.50 (2 H, t, J = 7.0 Hz), 7.45 (1 H, s), 7.43
(2 H, t, J = 7.0 Hz); 13C NMR (CDCl3, 125 MHz): δ 147.4, 147.3,
142.5, 142.3, 141.3, 140.5, 138.6, 138.4, 134.3, 131.7, 131.1,
130.2, 130.0, 129.9, 129.5, 128.9, 128.5, 127.3, 126.4, 126.1,
125.4, 124.5, 124.3, 122.1, 114.1; HRMS-ESI: m/z calcd for
C32H18N2O4S2Na [M+Na]+ 581.0600, found 581.1100.
2-(4-Nitrophenyl)-3-(4-cyanophenyl)thieno[3,2-b]thiophene 5b:
From 2-(4-nitrophenyl)thieno[3,2-b]thiophene 3h (52.2 mg, 0.20
mmol, 1.0 equiv) and 1-bromo-4-cyanobenzene 2e (40 mg, 0.22
2,3,5-Tri(4-acetylphenyl)thieno[3,2-b]thiophene
6d:
From
mmol, 1.1 equiv), 5b was isolated as a white solid (32.5 mg,
thieno[3,2-b]thiophene 1 (70.0 mg, 0.5 mmol, 1.0 equiv), 4-
1
45%). Mp 187-189 oC; H NMR (CDCl3, 500 MHz): δ 8.16 (2 H, d, bromoacetophenone 2n (445.5 mg, 2.25 mmol, 4.5 equiv),
J = 9.0 Hz), 7.70 (2 H, d, J = 8.5 Hz), 7.54 (2 H, d, J = 8.0 Hz),
7.49 (1 H, d, J = 5.0 Hz), 7.45 (2 H, d, J = 9.0 Hz), 7.35 (2 H, d,
J = 5.0 Hz); 13C NMR (CDCl3, 125 MHz): δ 147.2, 140.6, 139.4,
138.8, 138.4, 132.9, 132.6, 130.4, 129.9, 129.8, 129.7, 128.3,
128.1, 124.4, 124.1, 119.9, 118.3, 112.1; HRMS-ESI: m/z calcd
for C19H10N2O2S2Na [M+Na]+ 385.0081, found 385.0095.
[PdCl(C3H5)dppb] (6.1 mg, 0.01 mmol, 0.02 equiv), 6d was
obtained as a pale yellow solid (113.6 mg, 46%). Mp 178-180
oC; 1H NMR (CDCl3, 500 MHz): δ 8.00 (4 H, d, J = 8.5 Hz), 7.88
(2 H, d, J = 8.5 Hz), 7.72 (2 H, d, J = 8.0 Hz), 7.67 (1 H, s), 7.56
(2 H, d, J = 8.0 Hz), 7.42 (2 H, d, J = 8.5 Hz), 2.64 (3 H, s), 2.63
(3 H, s), 2.60 (3 H, s); 13C NMR (CDCl3, 125 MHz): δ 197.4,
197.3, 197.1, 144.6, 141.7, 140.5, 139.5, 138.6, 138.5, 136.6,
136.3, 129.4, 129.3, 129.2, 129.1, 128.8, 125.6, 117.1, 26.6,
26.5 (br); HRMS-ESI: m/z calcd for C30H23O3S2 [M+H]+ 495.1089,
found 495.1053.
2,5-Di(4-acetylphenyl)thieno[3,2-b]thiophene
5d:
From
thieno[3,2-b]thiophene 1 (70.0 mg, 0.5 mmol, 1.0 equiv), 4-
bromoacetophenone 2n (297 mg, 1.5 mmol, 3.0 equiv), and
[PdCl(C3H5)dppb] (3 mg, 0.05 mmol, 0.01 equiv), 5d was
o
o
1
isolated as a pale yellow solid (65.8 mg, 35%). Mp 166-168 C;
6b: Pale yellow solid (35.5 mg, 32%). Mp 184-185 C; H NMR
1H NMR (CDCl3, 500 MHz): δ 7.97 (2 H, d, J = 8.5 Hz), 7.88 (2 H, (CDCl3, 500 MHz): δ 8.10 (1 H, s), 7.91 (1 H, d, J = 9.0 Hz), 7.87
d, J = 8.0 Hz), 7.54 (2 H, d, J = 8.0 Hz), 7.45 (1 H, d, J = 5.0 Hz),
(2 H, t, J = 6.5 Hz), 7.79 (1 H, dd, J = 8.5 Hz and 2.0 Hz), 7.71
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FULL PAPER
(5)
(6)
Negishi, E.-i. Angew. Chem., Int. Ed. 2011, 50, 6738.
(2 H, m), 7.62 (2 H, d, J = 8.5 Hz), 7.59 (2 H, d, J = 8.5 Hz), 7.53
(1 H, d, J = 9.0 Hz), 7.51 (1 H, d, J = 9.0 Hz), 7.47 (2 H, d, J =
8.5 Hz); 13C NMR (CDCl3, 125 MHz): δ 146.4, 140.6, 138.9,
138.5, 133.5, 133.0, 131.6, 130.1, 129.5, 129.3, 128.8, 128.1,
127.8, 126.9, 126.4, 126.0 (q, J = 3.75 Hz, C-C-CF3), 125.7 (q, J
= 3.75 Hz, C-C-CF3), 124.4, 123.8, 115.9.
Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, V. Angew. Chem., Int. Ed. 2012, 51, 5062.
Mei, J.; Diao, Y.; Appleton, A. L.; Fang, L.; Bao, Z. J. Am. Chem. Soc.
2013, 135, 6724.
(7)
(8) Cinar, M. E.; Ozturk, T. Chem. Rev. 2015, 115, 3036.
(9) Fei, Z.; Pattanasattayavong, P.; Han, Y.; Schroeder, B. C.; Yan, F.; Kline,
R. J.; Anthopoulos, T. D.; Heeney, M. J. Am. Chem. Soc. 2014, 136,
15154.
o
6c: Pale yellow solid (125.8 mg, 46%). Mp 201-202 C; 1H NMR
(CDCl3, 500 MHz): δ 8.49 (1 H, d, J = 1.5 Hz), 8.34 (1 H, s), 8.25
(1 H, d, J = 9.0 Hz), 8.21 (1 H, s), 8.18 (2 H, d, J = 8.5 Hz), 7.94
(1 H, d, J = 8.0 Hz), 7.74 (1 H, d, J = 7.5 Hz), 7.71 (1 H, s), 7.61
(3 H, m), 7.50 (1 H, t, J = 8.0 Hz); 13C NMR (CDCl3, 125 MHz): δ
148.9, 148.8, 148.6, 143.6, 141.0, 139.3, 138.6, 135.8, 135.2,
135.0, 134.9, 131.4, 130.3, 130.2, 130.0, 129.4, 124.0, 123.7,
123.3, 123.1, 122.7, 120.5, 117.4.
(10) McCulloch, I.; Heeney, M.; Bailey, C.; Genevicius, K.; MacDonald, I.;
Shkunov, M.; Sparrowe, D.; Tierney, S.; Wagner, R.; Zhang, W.;
Chabinyc, M. L.; Kline, R. J.; McGehee, M. D.; Toney, M. F. Nat. Mater.
2006, 5, 328.
(11) Gasperini, A.; Bivaud, S.; Sivula, K. Chem. Sci. 2014, 5, 4922.
(12) Zhang, G.; Fu, Y.; Xie, Z.; Zhang, Q. Macromolecules. 2011, 44, 1414.
(13) Sonar, P.; Soh, M. S.; Cheng, Y. H.; Henssler, J. T.; Sellinger, A. Org.
Lett. 2010, 12, 3292.
Procedure
acetylphenyl)thieno[3,2-b]thiophene
for
the
synthesis
of
7:
2,3,5,6-tetra(4-
(14) Tang, W.; Singh, S. P.; Ong, K. H.; Chen, Z.-K. J. Mat. Chem. 2010, 20,
1497.
Thieno[3,2-
(15) Yamaguchi, Y.; Maruya, Y.; Katagiri, H.; Nakayama, K.-i.; Ohba, Y. Org.
Lett. 2012, 14, 2316.
b]thiophene 1 (70.0 mg, 0.5 mmol, 1.0 equiv), KOAc (294 mg,
3.0 mmol, 6.0 equiv), and 4-bromoacetophenone 2n (495 mg,
2.5 mmol, 5.0 equiv) were dissolved in DMAc (5.0 mL) which
was saturated with argon. To the resulting solution was added
PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol, 0.02 equiv). The reaction
mixture was heated at 140 oC under argon atmosphere until TLC
(n-hexane/ethyl acetate, 95:5 v/v) showed the nearly complete
consumption of the starting material (32 h). The reaction mixture
was cooled to room temperature and filtered to remove insoluble
impurities. The filtrate was diluted with ethyl acetate, washed
with water (3 times), dried over Na2SO4 and concentrated under
reduced pressure by rotary evaporation. The residue was
purified by SiO2-column chromatography (n-hexane/ethyl
acetate, 98:2 v/v) to give 7 as a pale yellow solid (76.5 mg, 25%).
Mp 221-223 C; H NMR (CDCl3, 500 MHz): δ 8.00 (2 H, d, J =
8.0 Hz), 7.88 (2 H, d, J = 8.5 Hz), 7.56 (2 H, d, J = 8.0 Hz), 7.41
(2 H, d, J = 8.0 Hz), 2.64 (3 H, s), 2.59 (3 H, s); 13C NMR (CDCl3,
125 MHz): δ 197.4, 197.3, 139.8, 139.6, 139.2, 138.5, 136.6,
136.4, 130.8, 129.3, 129.2, 129.1, 128.8, 26.7, 26.6; HRMS-ESI:
m/z calcd for C38H29O4S2 [M+H]+ 613.1507, found 613.1547.
(16) Ahmed, M. O.; Wang, C.; Keg, P.; Pisula, W.; Lam, Y.-M.; Ong, B. S.;
Ng, S.-C.; Chen, Z.-K.; Mhaisalkar, S. G. J. Mat. Chem. 2009, 19, 3449.
(17) Wang, C.; Zang, Y.; Qin, Y.; Zhang, Q.; Sun, Y.; Di, C.-a.; Xu, W.; Zhu,
D. Chem. Eur. J. 2014, 20, 13755.
(18) Wang, X.; Zhang, F.; Gao, J.; Fu, Y.; Zhao, W.; Tang, R.; Zhang, W.;
Zhuang, X.; Feng, X. J. Org. Chem. 2015, 80, 10127.
(19) Kunz, T.; Knochel, P. Chem. Eur. J. 2011, 17, 866.
(20) Morita, T.; Satoh, T.; Miura, M. Org. Lett. 2015, 17, 4384.
(21) Nguyen, H.; Nguyen, D. X.; Tran, T. Q.; Vo, B. N.; Nguyen, T. H.; Vuong,
T. M. H.; Dang, T. T. Synlett 2014, 25, 93.
(22) S. Fuller, L.; Iddon, B.; A. Smith, K. J. Chem. Soc., Perkin Trans. 1 1997,
3465.
(23) Ohta, A. Y. A.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.;
Nakata, T.; Tani, N.; Aoyagi Y. Heterocycles 1990, 31, 1952.
(24) C. B. Bheeter, L. Chen, J.-F. Soulé, H. Doucet, Cat. Sci. Technol. 2016,
6, 2005.
o
1
(25) Tang, S.-Y.; Guo, Q.-X.; Fu, Y. Chem. Eur. J. 2011, 17, 13866.
(26) Bheeter, C. B.; Bera, J. K.; Doucet, H. J. Org. Chem. 2011, 76, 6407.
(27) Roger, J.; Požgan, F.; Doucet, H. J. Org. Chem. 2009, 74, 1179.
(28) Roger, J.; Doucet, H. Org. Biomol. Chem. 2008, 6, 169.
(29) Bheeter, C. B.; Bera, J. K.; Doucet, H. RSC Adv. 2012, 2, 7197.
(30) Dang, T. T.; Bonneau, M.; Gareth Williams, J. A.; Le Bozec, H.; Doucet,
H.; Guerchais, V. Eur. J. Inorg. Chem. 2015, 2015, 2956.
Compound
acetylphenyl)thieno[3,2-b]thiophene
7
can also be synthesized from 2,3,5-tri(4-
6d and 4-
(31) Gómez-Gallego, M.; Sierra, M. A. Chem. Rev. 2011, 111, 4857.
(32) Ackermann, L. Chem. Rev. 2011, 111, 1315.
bromoacetophenone 2n with comparable yield based on the
same procedure as for 2-arylthieno[3,2-b]thiophenes 3.
(33) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496.
(34) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130,
10848.
(35) Gorelsky, S. I. Coord. Chem. Rev. 2013, 257, 153.
ACKNOWLEDGMENT
(36) Cantat, T.; Génin, E.; Giroud, C.; Meyer, G.; Jutand, A. J. Organomet.
Chem. 2003, 687, 365.
This research is funded by “Vietnam National Foundation for Science
and Technology Development” (NAFOSTED) under the grant
number 104.01-2012.26.
(37) Chen, L.; Roger, J.; Bruneau, C.; Dixneuf, P. H.; Doucet, H. J. Chem.
Soc., Chem. Commun. 2011, 47, 1872.
(38) These crystal structures was deposed at the Cambridge Crystallographic
Data Centre and have been assigned to the deposition number (CCDC
1508675 : 4a, CCDC 1508674 : 5c, CCDC 1519729 : 6a). They can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.
(40) For further arylations, these compounds were synthesized with high
scale and obtained similar yield as small scale. Particularly, scale of 3e
is 0.28 g, 3g is 0.3 g, 3l is 0.45 mg, and 3f is 0.5 mg.
ACKNOWLEDGMENT
(1)
(2)
Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5, 369.
Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem., Int. Ed.
2012, 51, 8960.
Keywords: Pd catalyst • C-H Functionalization • thieno[3,2-
b]thiophenes • Site-selective • CMD
(3)
(4)
Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704.
Suzuki, A. Angew. Chem., Int. Ed. 2011, 50, 6722.
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T. M. Ha Vuong, Didier
Villemin, Hung-Huy Nguyen,
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Hien Nguyen*
H
S
Ar2
Page No. – Page No.
S
H
S
H
Programmed Site-selective
Palladium Catalyzed
Arylation of Thieno[3,2-
b]thiophene
EDG
+ArBr Pd(OAc)2
Ar2
KOAc, DMAc
S
S
H
R
S
EWG
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