The synthesis of head-to-tail (H-T) dimers of 3-substituted thiophenes by the hypervalent iodine(III)-induced oxidative biaryl coupling reaction

Article abstract of DOI:10.1039/b503058g

The head-to-tail (H-T) dimers could be obtained selectively by the oxidative coupling reaction of 3-substituted thiophenes using a combination of hypervalent iodine(III) reagents and trimethylsilyl trifluoromethanesulfonate. The Roval Society of Chemistry 2005.

Full text of DOI:10.1039/b503058g

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
The synthesis of head-to-tail (H–T) dimers of 3-substituted thiophenes
by the hypervalent iodine(III)-induced oxidative biaryl coupling reaction
Toshifumi Dohi, Koji Morimoto, Yorito Kiyono, Akinobu Maruyama, Hirofumi Tohma and Yasuyuki Kita*
Received (in Cambridge, UK) 3rd March 2005, Accepted 13th April 2005
First published as an Advance Article on the web 29th April 2005
DOI: 10.1039/b503058g
The head-to-tail (H–T) dimers could be obtained selectively by
the oxidative coupling reaction of 3-substituted thiophenes
using a combination of hypervalent iodine(III) reagents and
trimethylsilyl trifluoromethanesulfonate.
As previously reported, 3-hexylthiophene (1a) gave 2,29-bithio-
phenes (2a and 3a) in 68% yield as a mixture in the ratio 46:54
3 2
using a combination of PIFA and BF ?Et O at 278 uC (Table 1,
9
entry 1). The reaction conditions such as temperature or con-
centration did not effect this selectivity. Next, we examined the
1
1
Recently, the oligo- and poly-(3-alkylthiophene) derivatives have
received considerable attention due to their useful physical
behavior such as electrical conductivity, electroluminescence and
distribution of the reaction product using several hypervalent
iodine(III) reagents with different electrical and steric properties,
but they also gave almost the same result in selectivities and only
varied in product yields (Table 1, entries 2–4).
1
in organic thin film transistors (TFTs). 2,29-Bithiophenes are one
of the most important class of compounds for synthesizing oligo-
However, surprisingly, we found that Lewis acids, which were
originally added for the purpose of activating the hypervalent
iodine(III) reagents, remarkably affected the selectivity of the
dimers. Thus, by changing BF ?Et O to B(C F ) , the dimers were
and poly-thiophenes, which makes them attractive synthetic
2–4
targets in modern organic synthesis. Among them, the head-
to-tail (H–T) dimers of the 3-alkylthiophenes have been the focus
of much attention as useful precursors of high-quality electro-
conductive materials due to their excellent degree of co-planarity in
3
2
6 5 3
obtained in 66% yield with the slightly preferential formation of
the H–T dimer 2a (Table 1, entry 5). To confirm the difference
among the Lewis acids used, extensive numbers of Lewis acids
1,5,6
their oligomer forms.
A transition metal-catalyzed stepwise
12
methodology via the condensation of metallated thiophenes
and/or thienyl halides might be reliable for the selective construc-
tion of H–T dimers, despite the need for the pre-functionalization
of a reactive functionality such as a halogen or metal into the
were examined (Table 1, entries 6–10). Among them, the
relatively weak Lewis acid, TMSOTf, gave the best result in terms
of selectivity. Thus, the H–T dimer of 3-hexylthiophene was
obtained as almost the sole product (Table 1, entry 10). On the
other hand, the reaction was quite sluggish in the presence of
2,3
thiophenes. In contrast, relatively few examples have been
reported about the direct synthesis of the 2,29-bithiophenes
from thiophenes themselves, which provided no H–T dimers
3 2 4
Brønsted acids such as TfOH, CF CO H and HBF . By using 4d,
dimers were obtained in good yield with acceptable selectivity
(Table 1, entry 11).
4
but exclusively head-to-head (H–H) dimers. To the best of our
knowledge, no reports of the selective H–T dimer formation
have appeared.
Selectivities were generally observed for various 3-substituted
thiophenes (Table 2).{ Similarly, alkyl thiophenes 1b and 1c having
a higher n-heptyl or n-octyl group also gave the desired H–T
dimers with no marked change in the selectivity (Table 2, entries 3
and 4). The smaller the alkyl substituent was, the lower the
selectivity (Table 2, entry 5). Bulkier substituents did not affect the
Oxidative biaryl coupling reactions using hypervalent iodine(III)
7
reagents are recognized as alternative methods to that using
8
heavy-metal oxidizers. We recently reported a phenyliodine
bis(trifluoroacetate) (PIFA)-induced oxidative biaryl coupling
9
reaction of thiophenes, in which its mild oxidation ability is
important for preventing any further undesired reaction of the
Table 1 Effect of the Lewis acids in oxidative biaryl coupling reaction
of 1a (eqn. (1))
10
products (eqn. (1)). Herein, we report the PIFA-induced
oxidative biaryl coupling reaction of various 3-substituted thio-
phenes using trimethylsilyl trifluoromethanesulfonate (TMSOTf)
as a Lewis acid, selectively enabling the direct formation of the
H–T dimers.
a
Entry ArI(OCOCF3)2
b
Lewis acid Time/h Yield (%) 2a:3a
c
1
2
3
4
5
6
7
8
9
0
1
Ar 5 C
Ar 5 C
Ar 5 4-MeC
6
H
5
(4a)
(4b)
BF
BF
(4c) BF
(4d) BF
3
3
3
3
?Et
?Et
?Et
?Et
2
2
2
2
O
O
O
O
6
3
3
3
3
1.5
68
74
34
73
66
48
71
—
19
41
46:54
52:48
45:55
44:56
62:38
89:11
64:36
—
6
F
5
6
H
H
4
4
Ar 5 2-MeC
6
4a
4a
4a
4a
4a
4a
4d
B(C
BBr
Bu BOTf 1.5
2
6
F
5
)
3
d
e
3
TMSBr
3
3
3
3
TBSOTf
TMSOTf
TMSOTf
82:18
94:6
81:19
(
1)
1
1
a
f
72 (90)
b
The molar ratio of 1a, 4a–d, and Lewis acids is 3:1:2. Isolated
c
yields based on 4a–d. Determined by H-NMR of the isolated
1
d
product mixture. The brominated 2,29-bithiophenes were also
e
obtained. No reaction. Isolated yield based on consumed 1a.
f
*kita@phs.osaka-u.ac.jp
2
930 | Chem. Commun., 2005, 2930–2932
This journal is ß The Royal Society of Chemistry 2005

View Article Online
Table 2 H–T dimer selective oxidative coupling reaction of
3-substituted thiophenes (1)
Scheme 2 Biaryl coupling reaction of 3-hexylthiophene with mesitylene.
a
1
R
b
Yield (%) Product
Entry
Substrate
In summary, we have developed an unprecedented oxidative
coupling reaction of alkyl thiophenes selectively leading to the
corresponding H–T dimer of 2,29-bithiophenes by choosing a
suitable Lewis acid and hypervalent iodine(III) reagent. This is the
first example for controlling the selectivity of the oxidative biaryl
coupling reaction products. It is postulated that the end-free 2,29-
bithiophenes could be easily functionalized at these end-free sites as
well as being converted to the corresponding high-quality oligo-
and poly-thiophenes. Therefore, the present reaction provides a
novel direct route to various 2,29-bithiophenes. Further applica-
tions of these products are currently under way in our laboratory.
This work was supported by a Grant-in-Aid for Scientific
Research (S) and for Encouragement of Young Scientists from the
Ministry of Education, Science, Sports and Culture, Japan. H. T.
also thanks the Industrial Technology Research Grant Program
from the New Energy and Industrial Technology Development
Organization (NEDO) of Japan.
c
1
1a
1a
1b
1c
1d
1e
1f
1h
1i
1j
n-Hexyl
n-Hexyl
n-Heptyl
n-Octyl
Methyl
n-Butyl
Isobutyl
41
2a + 3a (94:6)
d
2
3
4
72 (90)
52
30
72
88
2a + 3a (81:19)
2b + 3b (92:8)
2c + 3c (95:5)
2d + 3d (80:20)
2e + 3e (77:23)
2f + 3f (87:13)
2h + 3h (90:10)
2i + 3i (82:18)
2j + 3j (1:99)
b
c
5
6
7
98
c
8
Cyclohexyl 67
9
(CH
2
)
6
Br
62
46
10
SiMe
3
a
The molar ratio of 1, 4d and TMSOTf is 3:1:2. Isolated yield
based on consumed 4a,d. 4a was used instead of 4d. Isolated yield
based on consumed 1a.
c
d
yields of the products, while higher selectivities were generally
observed (Table 2, entries 7 and 8). The bromo group of 2i may
be useful for further functionalization of these dimers (Table 2,
13
entry 9). On the other hand, 3-trimethylsilylthiophene 1j selec-
tively gave the H–H dimer 3j rather than the H–T dimer 2j
Toshifumi Dohi, Koji Morimoto, Yorito Kiyono, Akinobu Maruyama,
Hirofumi Tohma and Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University,
1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan.
E-mail: kita@phs.osaka-u.ac.jp; Fax: +81-6-6879-8229;
Tel: +81-6-6879-8225
(
Table 2, entry 10). This is probably due to the electronic character
of the silyl group.
A plausible reaction mechanism is as follows (Scheme 1): cation
radical B is initially formed from 1 with 4d-Lewis acid via the
1
4
CT-complex A during the reaction. The radical B is thought
15
to be confined in the coordination sphere of iodine(III). Then, B
reacts with a neutral molecule of 1 followed by the one-electron
oxidation and deprotonation to give a mixture of the H–T dimer 2
and H–H dimer 3.
Notes and references
{ Typical experimental procedure is as follows: TMSOTf (0.36 mL,
2.0 mmol) and PIFA (430 mg, 1.0 mmol) were sequentially added to a
stirred solution of 3-hexylthiophene (1a) (0.5 g, 3.0 mmol) in CH Cl
2 2
The selectivities of products are determined in the last step.
The selective couplings of the 2-position of the cation radical
intermediate B and the 5-position of 1 accounts for the formation
of the observed H–T linked 2,29-bithiophene products. The
following experiment and our previous results on the function-
(
2.5 mL) at 278 uC under a nitrogen atmosphere. The mixture was stirred
for 3 h under the same reaction condition. An aqueous work-up with
saturated NaHCO at 0 uC followed by column chromatography (SiO /
3
2
n-hexane) gave the corresponding 2,29-bithiophenes 2a and 3a in 41% yield.
Identification and isolation of the two regioisomers, H–T and H–H, were
11
performed by a previously reported procedure.
16
alization of thiophenes support this explanation. Thus, during
the biaryl coupling reaction of 3-hexylthiophene 1a and mesitylene,
the C–C bond formation preferentially occurred at the 2-position
of 3-hexylthiophene (Scheme 2).
1
Recent reviews, see: (a) J. Roncali, Chem. Rev., 1992, 92, 711; (b)
Electronic Materials: The Oligomer Approach, ed. K. M u¨ llen and
G. Wegner, Wiley-VCH, Verlag GmbH, 1998; (c) R. D. McCullough,
Adv. Mater., 1998, 10, 93; (d) R. L. Elsenbaumer, K.-Y. Jen,
G. G. Miller, H. Eckhardt, L. W. Shacklette and R. Jow, Electronic
Properties of Conjugated Polymers, ed. H, Kuzmany, M. Mehring and
S. Roth, Springer Series in Solid State Sciences, Springer-Verlag, Berlin,
1987, vol, 76, p. 400; (e) N. J. L. Guernion and W. Hayes, Curr. Org.
Chem., 2004, 8, 637.
2
3
4
Pre-treatment with strong bases: (a) J. Kagan and S. K. Arora,
Heterocycles, 1983, 20, 1937; (b) H. Higuchi, T. Nakayama, H. Koyama,
J. Ojima, T. Wada and H. Sasabe, Bull. Chem. Soc. Jpn., 1995, 68, 2363,
and references cited therein.
Transition metal-catalyzed coupling of thienyl halide: (a) J. M. Tour,
Chem. Rev., 1996, 96, 537; (b) J. Hassan, M. S e´ vignon, C. Gozzi,
E. Schulz and M. Lemaire, Chem. Rev., 2002, 102, 1359, and references
cited therein.
Palladium-catalyzed direct homocoupling of thiophene: (a) T. Itahara,
M. Hashimoto and H. Yumisashi, Synthesis, 1984, 255; (b) K. Masui,
H. Ikegami and A. Mori, J. Am. Chem. Soc., 2004, 126, 5074.
Scheme 1 Reaction mechanism.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 2930–2932 | 2931

View Article Online
5
(a) R. D. McCullough, R. D. Lowe, M. Jayaraman and D. L. Anderson,
J. Org. Chem., 1993, 58, 904; (b) R. D. McCullough and S. P. Williams,
J. Am. Chem. Soc., 1993, 115, 11608; (c) R. S. Loewe, P. C. Ewbank,
J. Liu, L. Zhai and R. D. McCullough, Macromolecules, 2001, 34,
(g) Hypervalent Iodine Chemistry, ed. T. Wirth, Springer-Verlag,
Berlin–Heidelberg, 2003.
9 H. Tohma, M. Iwata, T. Maegawa, Y. Kiyono, A. Maruyama and
Y. Kita, Org. Biomol. Chem., 2003, 1, 1647.
4
324.
(a) T. -A. Chen and R. D. Rieke, J. Am. Chem. Soc., 1992, 114, 10087;
b) T.-A. Chen and R. D. Rieke, Synth. Met., 1993, 60, 175; (c)
10 (a) R. M. Souto Maior, K. Hinkelmann, H. Eckert and F. Wudl,
Macromolecules, 1990, 23, 1268; (b) K. Yoshino, S. Nakajima and
R. Sugimoto, Jpn. J. Appl. Phys., 1987, 26, L1038; (c) L. Juli a´ ,
A. G. Davies, D. R. Rueda and F. J. B. Calleja, Chem. Ind., 1989, 78; (d)
J. Tormo, F. J. Moreno, J. Ruiz, L. Fajar ´ı and L. Juli a´ , J. Org. Chem.,
1997, 62, 878; (e) F. Barbosa, L. Eberson, G. Gescheidt, S. Gronowitz,
A. H o¨ rnfeldt, L. Juli a´ and O. Persson, Acta. Chem. Scand., 1998, 52, 1275.
11 H. Higuchi, N. Hayashi, H. Koyama and J. Ojima, Chem. Lett., 1995,
1115.
6
7
(
T.-A. Chen, X. Wu and R. D. Rieke, J. Am. Chem. Soc., 1995, 117, 233.
(a) Y. Kita, M. Gyoten, M. Ohtsubo, H. Tohma and T. Takada, Chem.
Commun., 1996, 1481; (b) T. Takada, M. Arisawa, M. Gyoten,
R. Hamada, H. Tohma and Y. Kita, J. Org. Chem., 1998, 63, 7698; (c)
M. Arisawa, S. Utsumi, M. Nakajima, N. G. Ramesh, H. Tohma and
Y. Kita, Chem. Commun., 1999, 469; (d) H. Tohma, H. Morioka,
S. Takizawa, M. Arisawa and Y. Kita, Tetrahedron, 2001, 57, 345; (e)
H. Hamamoto, G. Anilkumar, H. Tohma and Y. Kita, Chem.
Commun., 2002, 450; (f) H. Hamamoto, G. Anilkumar, H. Tohma
and Y. Kita, Chem. Eur. J., 2002, 8, 5377; (g) H. Tohma, M. Iwata,
T. Maegawa and Y. Kita, Tetrahedron Lett., 2002, 43, 9241.
3 3 4 4 2 3 2
12 Lewis acids such as AlCl , GaCl , TiCl , SnCl , ZnBr , FeCl , Cu(OTf)
and MgBr did not produce any 2,29-bithiophenes.
2
13 (a) K. K. Stokes, K. Heuze and R. D. McCullough, Macromolecules,
2003, 36, 7114; (b) M. Schaeferling and P. Baeuerle, J. Mater. Chem.,
2004, 14, 1132.
8
(a) P. J. Stang and V. V. Zhdankin, Chem. Rev., 1996, 96, 1123; (b)
Y. Kita, T. Takada and H. Tohma, Pure Appl. Chem., 1996, 68, 627; (c)
A. Varvoglis, Hypervalent Iodine in Organic Synthesis, Academic Press,
San Diego, CA, 1997; (d) T. Kitamura and Y. Fujiwara, Org. Prep.
Proc. Int., 1997, 29, 409; (e) T. Wirth and U. H. Hirt, Synthesis, 1999,
14 Y. Kita, H. Tohma, K. Hatanaka, T. Takada, S. Fujita, S. Mitoh,
H. Sakurai and S. Oka, J. Am. Chem. Soc., 1994, 116, 3684.
15 M. Kameyama, N. Kamigata and M. Kobayashi, J. Org. Chem., 1987,
52, 3312, and references cited therein.
16 T. Dohi, K. Morimoto, Y. Kiyono, H. Tohma and Y. Kita, Org. Lett.,
2005, 7, 537.
1271; (f) V. V. Zhdankin and P. J. Stang, Chem. Rev., 2002, 102, 2523;
2
932 | Chem. Commun., 2005, 2930–2932
This journal is ß The Royal Society of Chemistry 2005