Stepwise construction of head-to-tail-type oligothiophenes via iterative palladium-catalyzed CH arylation and halogen exchange

Article abstract of DOI:10.1021/ol900622h

The well-defined head-to-tail oligothiophenes were synthesized via palladium-catalyzed CH arylation and halogen exchange sequentially through the 2-halothiophene derivatives.

Full text of DOI:10.1021/ol900622h

ORGANIC
LETTERS
2009
Vol. 11, No. 11
2297-2300
Stepwise Construction of
Head-to-Tail-Type Oligothiophenes via
Iterative Palladium-Catalyzed CH
Arylation and Halogen Exchange
Naoyuki Masuda,† Shunsuke Tanba,† Atsushi Sugie,† Daiki Monguchi,†
Nagatoshi Koumura,‡ Kohjiro Hara,‡ and Atsunori Mori*,†
Department of Chemical Science and Engineering, Kobe UniVersity, 1-1 Rokkodai,
Nada, Kobe 657-8501, Japan, and National Institute of AdVanced Industrial Science
and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan,
amori@kobe-u.ac.jp
Received March 25, 2009
ABSTRACT
The well-defined head-to-tail oligothiophenes were synthesized via palladium-catalyzed CH arylation and halogen exchange sequentially through
the 2-halothiophene derivatives.
As demand increases for oligothiophenes and polythiophenes
as advanced electronic and photonic materials, such as
organic TFT, liquid crystals, photovoltaic cells, etc.,1,2
preparative methodologies of oligothiophenes have become
a significant issue in organic synthesis.3,4 We have recently
shown that palladium-catalyzed homocoupling of bro-
mothiophene derivatives, which occurs at the carbon-
hydrogen bond of thiophene adjacent to the sulfur atom and
the carbon-bromine bond is completely intact, is a highly
efficient synthetic pathway for well-defined oligothiophenes,
and indeed has prepared several oligomers bearing 2-8
thiophene units.5 Although the method is effective for the
head-to-head (HH) or tail-to-tail (TT) type oligomers,
synthetic design of head-to-tail (HT) oligothiophene that
(2) (a) Takahashi, T.; Matsuoka, K.; Takimiya, K.; Otsubo, T.; Aso, Y.
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† Kobe University.
‡ National Institute of Advanced Industrial Science and Technology.
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Takimiya, K. Bull. Chem. Soc. Jpn. 2001, 74, 1789. (h) Funahashi, M.;
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10.1021/ol900622h CCC: $40.75
Published on Web 05/07/2009
 2009 American Chemical Society

generally shows a higher performance than other regio
isomers has been difficult.
diversity efficiently, is intriguing.10 In addition, recent
progress of the HT-type oligothiophenes as materials for
organic dye-sensitized11,12 and thin-film13 photovoltaic bat-
teries as well as organic TFTs1c prompted us to develop facile
synthetic strategies for such materials. We herein report
stepwise synthesis of HT regioregular oligothiophenes via
iterative palladium-catalyzed CH arylation and halogen
exchange reactions leading to the oligomers bearing 2-4
thiophene units.
On the other hand, transition metal-catalyzed C-H func-
tionalization reactions are of great interest in organic
synthesis since the reaction shows advantages in atom
efficiency compared with related cross coupling with orga-
nometallic compounds.6 The reaction of heteroaromatic
compounds is particularly important because of their wide
utilities in the synthesis of biologically active molecules and
advanced organic materials.7 The catalytic carbon-carbon
bond-forming reaction via C-H functionalization has been
achieved by the reaction of aryl halides.8,9
Synthesis of the HT-type oligothiophene based on the CH
arylation of a 2-bromothiophene derivative at the CH bond
is illustrated in Scheme 1. Since palladium-catalyzed CH
Thereby, a new synthetic strategy for HT oligothiophenes
based on the CH coupling, which improves synthetic
Scheme 1
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arylation of heteroaromatic compounds we have shown
selectively takes place with an aryl iodide, cross coupling
of iodothiophene 2 and bromothiophene 1 forms HT
bithiophene 3 bearing a C-Br bond. Halogen exchange of
3 into iodide 2′ and following coupling with 1 bring about
an additional extension of a thiophene unit and the iterative
reactions would lead to HT oligothiophenes.
We first performed the synthesis of oligothiophene bearing
a carbazole moiety at the end group. Introduction of the
carbazole group was performed by the palladium-catalyzed
CH arylation of 2-bromo-3-hexylthiophene 4 with N-ethyl-
3-iodocarbazole 5 in the presence of silver nitrate/KF to
obtain the corresponding product 6 in 75% yield. Transfor-
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bromine-lithium exchange with butyllithium and following
treatment of iodine at -78 °C afforded 7 in 90% yield.
The CH coupling reaction of thus obtained 7 with
bromothiophene 4 was carried out in the presence of the
palladium catalyst and AgNO3/KF to obtain bithiophene 8
(66% yield). Transformation into the iodide of 8 similarly
proceeded (91%).
derivatives, the exchange reaction proceeded in moderate to
good yields to afford the corresponding iodide 13. Although
the reaction was efficient and facile, it was found to be
difficult to achieve complete conversion of bromide 4 into
iodide 13, which caused troubles in chromatographic puri-
fication of 13 due to the similar polarity between bromide
and iodide. The reaction with complete conversion was
successful when the reaction with excess amounts of CuI/
LiI was employed, which was a modified method reported
by Yamashita (use of excess CuI in DMSO under hetero-
geneous conditions).15 The reaction proceeded in a homo-
geneous manner in DMSO at 150 °C and resulted in almost
complete conversion after stirring for 24 h. The correspond-
ing iodide 13 was isolated in 97% yield (Scheme 3).
As shown in Scheme 2, further extension of the thiophene
unit was similarly successful to afford up to the correspond-
Scheme 2
Scheme 3
Synthesis of HT-type oligothiophene bearing an ester
group was carried out with palladium-catalyzed CH arylation
and copper-mediated halogen exchange protocols. Scheme
4 shows the synthetic pathway of the head-to-tail oligothio-
phene bearing four thiophene units and (4-ethoxycarbon-
yl)phenyl group at the end group. The reaction of ethyl
4-iodobenzoate 14 with bromothiophene 4 in the presence
of PdCl2(PPh3)2 (5 mol %) and AgNO3/KF proceeded
smoothly to afford the bromothiophene bearing the aryl group
15 in an excellent yield. The obtained bromothiophene
derivative was subjected to the halogen exchange reaction,
whose conditions were optimized in the model study, to
afford iodothiophene 16 in 91% yield. The CH arylation
reaction of 16 with 4 was performed in a similar manner to
the reaction of 14 to afford the corresponding HT bithiophene
17. Since CH arylation with aryl iodide bearing an electron-
donating substituent has been shown to proceed with inferior
yield to that with electron-deficient arenes, thienyl iodide
that is recognized as an electron-enriched substrate would
result in a lower yield.9d Indeed, the arylation reaction of
16 under similar conditions to that for 14 resulted in a lower
yield (26%). However, a slight modification of the conditions
by reducing amount of the solvent and repeating addition of
AgNO3/KF improved the yield of 17 to 70%. By the iterative
halogen-exchange reaction and palladium-catalyzed CH
arylation in a similar manner, synthesis of HT-type oligoth-
iophenes up to the tetramer 19 was successfully achieved.
In summary, we showed that the several well-defined head-
to-tail oligothiophenes were synthesized efficiently with
ing trimer 10, which was subjected to protonolysis and CH
arylation with thienyl aldehyde 11 to give the tetramer 12a.
The obtained 12a was identical with a intermediate of the
dye molecule 12b available as a dye-sensitized solar cell on
the electrode of titanium oxide nanoparticle, which showed
remarkably high efficiency as an organic dye.12 Transforma-
tion of 12a was shown to be performed by Knoevenagel
reaction of the formyl group with cyanoacetic acid lead to
12b as reported.11a We then examined the synthesis of a
head-to-tail oligothiophene bearing an ester moiety at the
end group.
Since strong base or nucleophile can not be employed for
the halogen exchange reaction from bromine to iodine, a
copper-mediated protocol reported by Buchwald14 for halo-
gen exchange was examined by using the reaction of
2-bromo-3-hexylthiophene 4 as a model study. When the
reaction of 4 was carried out with 2 equiv. of NaI in the
presence of a catalytic amount of CuI with several diamine
(15) Yamashita, Y.; Suzuki, K.; Tomura, M. Synth. Met. 2003, 133-134,
341.
(16) The authors thank Nara Institute of Science and Technology, Kyoto-
Advanced Nanotechnology Network, supported by MEXT for measurements
of high resolution mass spectra.
(14) Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844.
Org. Lett., Vol. 11, No. 11, 2009
2299

Scheme 4
repeating palladium-catalyzed CH arylation and halogen
“Advanced Molecular Transformation of Carbon Resources”
by Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan.
exchange sequentially with 2-bromo-3-hexylthiophene. Fur-
ther oligomers of well-defined structure would be prepared
in a similar manner. With these methodologies, introduction
of a thiophene unit bearing a different substituent would also
be possible by the stepwise methodology.
Supporting Information Available: Experimental de-
tails.16 This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research on Priority Areas,
OL900622H
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Org. Lett., Vol. 11, No. 11, 2009