Synthesis of nitrogen-bridged terthiophenes by tandem Buchwald-Hartwig coupling and their properties

Article abstract of DOI:10.1021/ol300887t

The first synthesis of nitrogen-bridged terthiophenes (NBTTs) has been achieved by a tandem Buchwald-Hartwig coupling of 3,3′,3″,4′- tetrabromo-2,2′:5′,2″-terthiophene. Several NBTT derivatives bearing aryl or alkyl moieties on the N-atoms could be synthesized. Their fundamental electrochemical characteristics and HOMO-LUMO levels were found to be influenced by the substituents on the N-atoms.

Full text of DOI:10.1021/ol300887t

ORGANIC
LETTERS
2012
Vol. 14, No. 11
2702–2705
Synthesis of Nitrogen-Bridged
Terthiophenes by Tandem
BuchwaldꢀHartwig Coupling
and Their Properties
Koichi Mitsudo,* Shuichi Shimohara, Jun Mizoguchi, Hiroki Mandai, and Seiji Suga*
Division of Chemistry and Biotechnology, Graduate School of Natural Science and
Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan
mitsudo@cc.okayama-u.ac.jp; suga@cc.okayama-u.ac.jp
Received April 6, 2012
ABSTRACT
The first synthesis of nitrogen-bridged terthiophenes (NBTTs) has been achieved by a tandem BuchwaldꢀHartwig coupling of 3,30,300,
40-tetrabromo-2,20:50,200-terthiophene. Several NBTT derivatives bearing aryl or alkyl moieties on the N-atoms could be synthesized. Their
fundamental electrochemical characteristics and HOMOꢀLUMO levels were found to be influenced by the substituents on the N-atoms.
Fused dithiophene skeletons, such as 4H-dithieno[3,2-b:
20,30-d]pyrrole (DTP),1 -thiophene,2 -silole,3 -borole,4 and
-phosphole,5 have received considerable attention as key
components of organic materials for use in optical and
electronic devices.
Beyond the more common fused bithiophenes, larger
heteroacenes with up to seven fused rings have also been
reported.6,7 In addition to the simple thienoacene series,7
these larger heteroacenes also contain numerous examples
containing multiple heteroatoms,6 although currently all
known examples also contain at least one benzene ring in
the heteroacene backbone. In this study, we report the
first example of a larger heteroacene consisting solely of
(1) (a) Ogawa, K.; Rasmussen, S. C. J. Org. Chem. 2003, 68, 2921–
2928. (b) Evenson, S. J.; Rasmussen, S. C. Org. Lett. 2010, 12, 4054–
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Trans. 1 1983, 2551–2554. (d) Koeckelberghs, G.; De Cremer, L.;
Vanormelingen, W.; Dehaen, W.; Verbiest, T.; Persoons, A.; Samyn,
C. Tetrahedron 2005, 61, 687–691. (e) Nozaki, K.; Takahashi, K.;
Nakano, K.; Hiyama, T.; Tang, H.-Z.; Fujiki, M.; Yamaguchi, S.;
Tamao, K. Angew. Chem., Int. Ed. 2003, 42, 2051–2053. (f) Patra, D.;
Sahu, D.; Padhy, H.; Kekuda, D.; Chu, C.-W.; Wei, K.-H.; Lin,
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Subramaniyan, S.; Kim, F. S.; Xin, H.; Jenekhe, S. A. Macromolecules
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1553–1554.
(6) For recent representative examples, see: (a) Balaji, G.; Valiyaveettil,
S. Org. Lett. 2009, 11, 3358–3361. (b) Qi, T.; Guo, Y.; Liu, Y.; Xi, H.;
Zhang, H.; Gao, X.; Liu, Y.; Lu, K.; Du, C.; Yu, G.; Zhu, D. Chem.
Commun. 2008, 6227–6229. (c) Qi, T.; Qiu, W.; Liu, Y.; Zhang, H.; Gao,
X.; Liu, Y.; Lu, K.; Du, C.; Yu, G.; Zhu, D. J. Org. Chem. 2008, 73,
4638–4643. (d) Balaji, G.; Phua, D. I.; Shim, W. L.; Valiyaveettil, S. Org.
Lett. 2010, 12, 232–235. (e) Gao, P.; Cho, D.; Yang, X.; Enkelmann, V.;
(3) (a) Kunai, A; Ohshita, J.; Iida, T.; Kanehara, K.; Adachi, A.;
Okita, K. Synth. Met. 2003, 137, 1007–1008. (b) Ohshita, J.; Lee, K.-H.;
Kimura, K.; Kuani, A. Organometallics 2004, 23, 5622–5625.
(c) Ohshita, J. Macromol. Chem. Phys. 2009, 210, 1360–1370.
(4) Iida, A.; Yamaguchi, S. J. Am. Chem. Soc. 2011, 133, 6952–6955.
(5) (a) Dienes, Y.; Durben, S.; Karpati, T.; Neumann, T.; Englert, U.;
Nyulaszi, L.; Baumgartner, T. Chem.;Eur. J. 2007, 13, 7487. (b)
Baumgartner, T.; Bergmans, W.; Karpati, T.; Neumann, T.; Nieger,
M.; Nyulaszi, L. Chem.;Eur. J 2005, 11, 4687–4699. (c) Baumgartner,
T.; Neumann, T.; Wirges, B. Angew. Chem., Int. Ed. 2004, 43, 6197–
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3318. (b) Xiao, K.; Liu, Y.; Qi, T.; Zhang, W.; Wang, F.; Gao, J.; Qiu,
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r
10.1021/ol300887t
Published on Web 05/17/2012
2012 American Chemical Society

alternating thiophene and pyrrole rings, nitrogen-bridged
terthiophenes (NBTTs).
Scheme 1. Retrosynthesis of NBTT
To clarify the effect of π-conjugation on fused oligothio-
phenes, DFT calculations of nitrogen-bridged thiophenes
1Aꢀ3A and thienoacenes 1Bꢀ3B at the B3LYP/6-31G(d)
level of theory were conducted (Figure 1). To investigate
the energy level for each skeleton, nitrogen-bridged thio-
phenes that did not bear any substituents on the N-atoms
were used. The band gap of NBTT (2A, dithieno[2,3-
d:20,30-d0]thieno[3,2-b:30,20-b0]dipyrrole, 3.92 eV) was smal-
ler than that of dithienopyrrole 1A (4.58 eV), and further
extension of thiophene units led to a smaller band gap. A
similar tendency was observed in the case of 1Bꢀ3B. The
band gap of nitrogen-bridged thiophene 2A was close to
that of pentathienoacene 2B (3.83 eV), which exhibited
p-type semiconductivity.6b These results prompted us to
synthesize NBTT derivatives and clarify their optical and
electrochemical characteristics.
dichloro[1,10-bis(diphenylphosphino)ferrocene]palladium
(Pd(dppf)Cl2, 6 mol %), the coupling reaction of tetrabro-
mothiophene and 3-bromo-2-thienylzinc chloride (3 equiv)
proceeded smoothly to afford 4 in 84% yield.
We next carried out a Pd-catalyzed tandem Buchwaldꢀ
Hartwig coupling for the synthesis of NBTT using
p-toluidine as an amine (Table 1). In the presence of
Pd2(dba)3•CHCl3 (10 mol % of 4), tri(tert-butyl)-
phosphine (P(t-Bu)3, 0.2 mmol), and NaOtBu (8 mmol),
4 (0.5 mmol) was treated with p-toluidine (1.2 mmol) at
110 °C for 12 h to give the desired N,N0-di(p-tolyl)-
dithieno[2,3-d:20,30-d0]thieno[3,2-b:30,20-b0]dipyrrole (di-p-
tolyl-NBTT, 2a) in 16% yield (entry 1). To increase
the yield, screening of the ligands was carried out
(entries 2ꢀ5). With BINAP, the yield of 2a slightly in-
creased to 29% (entry 2). Alkylene diphospines such as
1,2-bis(diphenylphosphino)ethane (dppe) and 1,4-bis-
(diphenylphosphino)butane (dppb) were unsuitable for
the reactions (entries 3 and 4). With dppf, the reaction
was terminated within 6 h and the yield of 2a increased to
48% (entry 5). Finally, the Pd source was optimized
(entries 6ꢀ9). Pd(dba)2 and [PdCl(η3-C3H5)]2 were found
to be suitable Pd sources for the reactions, and 2a was
obtained in 54% yield in each case (entries 6 and 7).
Palladium acetate was not a good Pd source for the
reaction. With Pd(OAc)2, 2a was obtained in only a 12%
yield (entry 8). The use of Pd(dppf)Cl2 instead of the set
of Pd(dba)2 and dppf gave 2a in lower yield (18% yield,
entry 9).
Figure 1. Comparison of the KohnꢀSham HOMO and LUMO
energy levels of nitrogen-bridged multithiophenes and thienoacenes
at the B3LYP/6-31G(d) level of theory.
The strategy for the synthesis of NBTT derivatives is
described in Scheme 1. We designed 3,30,300,40-tetrabromo-
2,20:50,200-terthiophene (4), which could be prepared from
2,3-dibromothiophene and tetrabromothiophene, as a key
precursor of NBTT. The Pd-catalyzed tandem Buch-
waldꢀHartwig coupling of 4 and a primary amine would
give 2. We report here the first synthesis of 4 and the first
construction of NBTT 2. X-ray crystallographic analysis
and fundamental studies on the electrochemical and op-
tical properties of 2 were also conducted.
Scheme 2. Synthesis of 4
First, we attempted to synthesize 4 by Pd-catalyzed
KumadaꢀTamaoꢀCorriu coupling between tetrabromo-
thiophene and a (3-bromothiophen-2-yl)magnesium ha-
lide under several conditions. However, complex mixtures
were obtained in all cases, since a bromideꢀmagnesium
exchange occurred between tetrabromothiophene and the
(3-bromothiophen-2-yl)magnesium halide. After further
optimization, we found that Negishi coupling was suitable
for the synthesis of 4 (Scheme 2). In the presence of
Under the optimized conditions, coupling reactions
between 4 and several amines were carried out (Table 2).
First, substituted anilines were used in the reactions.
Org. Lett., Vol. 14, No. 11, 2012
2703

colorless, air-stable solids that were easy to handle under
aerobic conditions. With methylamine hydrochloride, di-
methyl-NBTT (2g) was obtained in 51% yield (entry 6).
2g was slowly oxidized under aerobic conditions to give a
polymerized blue solid.
Table 1. Pd-Catalyzed Tandem BuchwaldꢀHartwig Coupling
between 4 and p-Toluidine under Various Conditionsa
The crystal structures of 2aꢀ2c and 2eꢀ2g were exam-
ined via X-ray crystallography. As expected from the DFT
calculations, their terthiophene skeletons were in the same
plane. The bond lengths of NBTT skeletons were quite
similar to those of DTP.1a However, the SꢀC bonds of 2
were slightly longer than those of DTP.8
time
(h)
yield
(%)b
entry
Pd
ligand
1
2
3
4
5
6
7
8
9
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd(dba)2
P(t-Bu)3
BINAP
dppe
dppb
dppf
12
12
12
12
6
16
29
3
0
48
54
54
12
18
dppf
6
[PdCl(η3-C3H5)]2
Pd(OAc)2
dppf
6
dppf
6
Pd(dppf)Cl2
ꢀ
6
a Reaction conditions: 4 (0.5 mmol), p-toluidine (1.2 mmol), Pd
source (10 mol % Pd based on 4), ligand (0.2 mmol), NaOtBu (8 mmol),
toluene (3.5 mL), 110 °C. b Isolated yield.
Figure 2. UVꢀvis spectra of 2aꢀg and n-butyl-DTP measured in
CH2Cl2 (1.0 ꢁ 10ꢀ5 M).
Table 2. Pd-Catalyzed Tandem BuchwaldꢀHartwig Coupling
between 4 and Several Aminesa
yield
entry
R
2
(%)b
1
p-Bu-C6H4
2b
2c
2d
2e
2f
66
74
77
44
74
51
2
p-MeO-C6H4
3c
4
Bn
Oct
Bu
Me
5c
6c,d
2g
a Reaction conditions: 4 (0.5 mmol), amine (1.2 mmol), Pd(dba)2
(0.05 mmol), dppf (0.20 mmol), NaOtBu (16 equiv), toluene (7 mL), 110 °C.
b Isolated yield. c Reaction was performed at 90 °C. d MeNH2•HCl was used
as an amine source.
Figure 3. Cyclic voltammogram of 2a.
We next investigated the optical and electrochemical
properties of NBTTs. The UVꢀvis absorption spectra of
2aꢀg and n-butyl-DTP are shown in Figure 2. Compounds
2aꢀg all exhibited two absorption maxima (λmax) at
around 339ꢀ357 nm, which are longer wavelengths than
those of n-butyl-DTP (309 and 298 nm). These results
suggest that their optical characteristics were independent
Withp-butylaniline, tandem BuchwaldꢀHartwig coupling
gave the corresponding coupling product 2b in 66% yield
(entry 1). Similarly, the reaction with p-methoxyaniline
afforded 2c in 74% yield (entry 2). Alkylamines could also
be used in the reactions. The tandem coupling reaction
with benzylamine afforded dibenzyl-substituted NBTT 2d
in good yield (77%, entry 3). With octylamine and buty-
lamine, corresponding dialkyl-substituted NBTT 2e and 2f
were obtained in 44% and 74% yields, respectively (entries
4 and 5). These diaryl-NBTTs and dialkyl-NBTTs were
(8) For data for DFT calculations and X-ray analyses, see Support-
ing Information.
(9) For details of cyclic voltammetry, see Supporting Information.
2704
Org. Lett., Vol. 14, No. 11, 2012

on the N-atoms. For instance, that of 2g was 0.08 eV
(vs Fc/Fcþ). The growth of redox peaks was observed
during sequential potential cycling. This result suggests the
formation of an electroactive film on the surface of the
working electrode. Indeed, a black film was observed on
the surface of the electrode.
Table 3. Electrochemical and Optical Data for NBTTs and
DTPa
Eonset
EHOMO
λmax
λonset
ELUMO
2
(V)
(eV)
(nm)
log ε
(nm)
(eV)
The combined electrochemical and optical data for
NBTTs are illustrated in Table 3 along with the data for
n-butyl-DTP for comparison. Compounds 2aꢀg all had
higher HOMO levelsthanDTP. Inparticular, the values of
EHOMO for 2f and 2g were ꢀ5.05 and ꢀ5.03 eV, respec-
tively. As expected, both EHOMO and ELUMO were influ-
enced by thesubstituents onthe N-atoms. Forinstance, the
HOMO energies were slightly stabilized by the aryl sub-
stituents on the N-atoms. The tendency was similar to that
of DTP reported by Rasmussen and co-workers.11
In conclusion, we have developed a synthetic strategy
that leads to NBTTs, which belong to a new class of fused
thiophenes. X-ray single-crystal analyses revealed that
they have planar skeletons. Their fundamental character-
istics were clarified by UV and CV analyses, and the results
suggested that their HOMOꢀLUMO levels are tuned by
the functional group on the N-atoms. Further studies on
NBTTs are underway in our laboratory.
2a
0.08
0.04
ꢀ5.18
ꢀ5.14
ꢀ5.15
ꢀ5.12
ꢀ5.11
ꢀ5.05
ꢀ5.03
ꢀ5.25
357
341
356
340
358
342
354
338
354
339
355
339
354
339
309
298
4.34
4.31
4.54
4.59
4.44
4.48
4.58
4.58
4.54
4.54
4.51
4.51
4.62
4.62
4.23
4.28
379
381
383
375
380
388
375
324
ꢀ1.91
ꢀ1.89
ꢀ1.91
ꢀ1.81
ꢀ1.85
ꢀ1.85
ꢀ1.72
ꢀ1.42
2b
2c
0.05
2d
2e
0.02
0.01
2f
ꢀ0.05
ꢀ0.07
0.15
2g
DTPb
a Eonset values were detemined by the onset of CV in CH2Cl2. V vs Fc/
Fcþ in 0.1 M TBABF4. EHOMO values were determined in reference to
ferrocene (5.1 eV vs vacuum).10 ELUMO = EHOMO þ λonset
.
b n-Butyl-
DTP.
Acknowledgment. This work was supported in part by
MEXT, JSPS, and Kuraray Co. Ltd. The authors are
grateful to Prof. Yoshihiro Kubozono, and Ms. Noriko
Komura at Okayama University for valuable discussions.
We also thank the SC-NMR Laboratory of Okayama
University for the NMR measurement.
from N-functionalization and mainly influenced by the
NBTT skeleton. Similar results were reported on DTP.1a
Cyclic voltammetry (CV) of 2aꢀg was carried out next.9
As shown in Figure 3, the first peak potential for oxidation
of 2a was observed clearly at 0.25 V (vs Fc/Fcþ), and the
second and third oxidation peaks were observed at around
1.0ꢀ1.2 V (vs Fc/Fcþ). The oxidation potential was more
negative than that of n-butyl-DTP (0.58 V vs Fc/Fcþ), due
to the π-expansion of the structure. The oxidative poten-
tials of NBTTs were highly influenced by the substituents
Supporting Information Available. Experimental de-
tails, spectral data for all new compounds, results of CV
analysis, theoretical calculations, and the crystallo-
graphic information file (CIF) of 2aꢀc and 2eꢀg. These
materials are available free of charge via the Internet at
http://pubs.acs.org.
(10) Cardona, C. M.; Li, W.; Kaifer, A. E.; Stockdale, D.; Bazan,
G. C. Adv. Mater. 2011, 23, 2367–2371.
(11) Evenson, S. J.; Pappenfus, T. M.; Delgado, M. C. R.; Radke-
Wohlers, K. R.; Navarrete, J. T. L.; Rasmussen, S. C. Phys. Chem.
Chem. Phys. 2012, 14, 6101–6111.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 11, 2012
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