Efficient synthesis of 3,4-ethylenedioxythiophene (EDOT)-based functional π-conjugated molecules through direct C-H bond arylations

Article abstract of DOI:10.1021/ol201571u

A variety of 3,4-ethylenedioxythiophene (EDOT)-based π-conjugated molecules were efficiently synthesized in good yields through Pd-catalyzed direct C-H bond arylations, wherein a detailed synthetic investigation, including the screening of various kinds o

Full text of DOI:10.1021/ol201571u

ORGANIC
LETTERS
2011
Vol. 13, No. 15
4068–4071
Efficient Synthesis of
3,4-Ethylenedioxythiophene (EDOT)-Based
Functional π-Conjugated Molecules
through Direct CꢀH Bond Arylations
Ching-Yuan Liu, Haichao Zhao, and Hsiao-hua Yu*
Yu Initiative Research Unit, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako,
Saitama 351-0198, Japan
bruceyu@riken.jp
Received June 11, 2011
ABSTRACT
A variety of 3,4-ethylenedioxythiophene (EDOT)-based π-conjugated molecules were efficiently synthesized in good yields through Pd-catalyzed
direct CꢀH bond arylations, wherein a detailed synthetic investigation, including the screening of various kinds of palladium catalysts, ligands,
additives, and solvents, was carried out. In addition, the spectroscopic and electrochemical properties of these EDOT-containing molecules were
also investigated.
Syntheses and applications of thiophene-based organic
electronic materials have been widely investigated in recent
years, and their importance cannot be overemphasized.1
Very recently, much attention has been drawn to the efficient
synthesis of thiophene-containing organic materials due to
the importance of atom-economics and green chemistry.2
As a result, the direct CꢀH arylation of various (hetero)arenes
including thiophenes has become a viable and popular
alternative method to conventional cross-coupling reac-
tions.3 Among all thiophene derivatives, 3,4-ethylene-
dioxythiophene (EDOT)-based π-conjugated materials have
been extensively investigated for the past decade because the
incorporation of the EDOT moiety resulted in a smaller
intrinsic band gap in polymers,4 enhanced π-donor ability in
tetrathiafulvalene analogues,5 and improved electrochromic
properties.6 However, in-depth synthetic studies concerning
the conjugation extension of EDOT building blocks through
atom-economical approaches are quite limited.7
(1) Perepichka, I. F.; Perepichka, D. F. Handbook of Thiophene-
Based Materials; John Wiley & Sons: Chichester, U.K., 2009.
(2) (a) Schipper, D. J.; Fagnou, K. Chem. Mater. 2011, 23, 1594 and
ꢀ
references cited therein. (b) Liegault, B.; Lapointe, D.; Caron, L.;
Vlassova, A.; Fagnou, K. J. Org. Chem. 2009, 74, 1826. (c) Borghese,
A.; Geldhof, G.; Antoine, L. Tetrahedron Lett. 2006, 47, 9249. (d) Masui,
K.; Mori, A.; Okano, K.; Takamura, K.; Kinoshita, M.; Ikeda, T. Org.
Lett. 2004, 6, 2011. (e) Masui, K.; Ikegami, H.; Mori, A. J. Am. Chem.
Soc. 2004, 126, 5074.
(3) (a) Ueda, K.; Yanagisawa, S.; Yamaguchi, J.; Itami, K. Angew.
Chem., Int. Ed. 2010, 49, 8946. (b) Yanagisawa, S.; Ueda, K.; Sekizawa,
H.; Itami, K. J. Am. Chem. Soc. 2009, 131, 14622. (c) Join, B.;
Yamamoto, T.; Itami, K. Angew. Chem., Int. Ed. 2009, 48, 3644. (d)
Yanagisawa, S.; Sudo, T.; Noyori, R.; Itami, K. Tetrahedron 2008, 64,
6073. (e) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int.
Ed. 2009, 48, 9792. (f) Yanagisawa, S.; Sudo, T.; Noyori, R.; Itami, K. J.
Am. Chem. Soc. 2006, 128, 11748. (g) Derridj, F.; Roger, J.; Djebbar, S.;
ꢀ
Doucet, H. Org. Lett. 2010, 12, 4320. (h) Roy, D.; Mom, S.; Beauperin,
M.; Doucet, H.; Hierso, J. C. Angew. Chem., Int. Ed. 2010, 49, 6650. (i)
Lapointe, D.; Markiewicz, T.; Whipp, C. J.; Toderian, A.; Fagnou, K. J.
Org. Chem. 2011, 76, 749. (j) Tamba, S.; Okubo, Y.; Tanaka, S.;
Monguchi, D.; Mori, A. J. Org. Chem. 2010, 75, 6998. (k) Chen, X.;
Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
5094. (l) Li, H.; Sun, C.-L.; Yu, M.; Yu, D.-G.; Li, B.-J.; Shi, Z.-J.
Chem.;Eur. J. 2011, 16, 3593. (m) Sun, C.-L.; Li, H.; Yu, D.-G.; Yu,
M.; Zhou, X.; Lu, X.-Y.; Huang, K.; Zheng, S.-F.; Li, B.-J.; Shi, Z.-J.
Nat. Chem. 2010, 2, 1044. (n) Liu, W.; Cao, H.; Zhang, H.; Zhang, H.;
Chung, K. H.; He, C.; Wang, H.; Kwong, F. Y.; Lei, A. J. Am. Chem.
Therefore, we report herein a comprehensive synthetic
investigation of Pd-catalyzed direct CꢀH bond arylations
(4) (a) Apperloo, J. J.; Groenendaal, L. B.; Verheyen, H.; Jayakannan,
ꢀ
M.; Janssen, R. A. J.; Dkhissi, A.; Beljonne, D.; Lazzaroni, R.; Bredas, J. L.
Chem.;Eur. J. 2002, 8, 2384. (b) Akoudad, S.; Roncali, J. Chem. Commun.
€
1998, 2081. (c) Huchet, L.; Akoudad, S.; Levillain, E.; Emge, A.; Bauerle,
P.; Roncali, J. J. Phys. Chem. 1998, 102, 7776.
€
ꢁ
(5) Akoudad, S.; Frere, P.; Mercier, N.; Roncali, J. J. Org. Chem.
1999, 64, 4267.
Soc. 2010, 132, 16737. (o) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius,
F. Chem. Soc. Rev. 2011, advanced article.
r
10.1021/ol201571u
Published on Web 07/06/2011
2011 American Chemical Society

of EDOT through the screening of various palladium
catalysts, ligands, bases, and solvents. We envisaged that
the reaction of EDOT 1 with aryl bromides 2 under well-
optimized reaction conditions would lead to the formation
ofdiarylatedEDOT3 in comparableyields4a and thedirect
CꢀH arylation of EDOT would become a viable alter-
native, thus providing a more efficient and atom-econom-
ical synthetic approach than the traditional cross-coupling
reactions (Scheme 1).
Table 1. Optimization of the Direct CꢀH Arylation of EDOTa
Pd
yield
entry catalystsb
ligands
additives solvents (%)c
1
2
3
4
5
PdCl2
bipyridyl
Ag2CO3 xylene
Ag2CO3 xylene
Ag2CO3 xylene
Cs2CO3 toluene
Cs2CO3 toluene
5
27
30
5
PdCl2(PPh3) bipyridyl
Scheme 1. Synthesis of EDOT-Based Functional π-Conjugated
Molecules
Pd(dba)2
Pd(dba)2
Pd(OAc)2
bipyridyl
PPh3
PPh3
88
6
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
dppe
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
Cs2CO3 toluene
68
92
73
62
98
91
54
97
48
47
39
20
33
0
7
dppb
8
dppf
9
P(o-Tol)3
P(m-Tol)3
P(p-Tol)3
P(furyl)3
P(Cy)3HBF4
P(t-Bu)3
XPhos
10
11
12
13
14
15
16
17
18
19
bipyridyl
phenanthroline Cs2CO3 toluene
We aimed to develop a general and efficient synthetic
method for the Pd-catalyzed direct CꢀH diarylation of
EDOT and EDOT dimer 4. We selected EDOT 1 as the
core and bromobenzene 2a as the coupling partner for
the initial screening of reaction conditions (Table 1). First,
the direct diarylation of EDOT 1 was carried out in the
presence of PdCl2 (5 mol %) following an early report’s
reaction condition,3b resulting in the diphenyl EDOT 3a in
only 5% yield (entry 1, Table 1).
Improved yields were observed by employing other
palladium catalysts such as PdCl2(PPh3)2 and Pd(dba)2
(27% and 30%, entries 2 and 3, respectively). In addition
to the selection of catalysts, we found that the reaction
yields of the diarylated adduct 3a were also significantly
altered due to the use of different ligands, additives, and
solvents (entries 1 and 5). These preliminary results en-
couraged us to search for the optimal reaction conditions
for the efficient preparation of these EDOT-based mole-
cules. We focused on Pd(OAc)2 as our catalyst because it
gave a promising yield (88%, entry 5). Moreover, Pd(OAc)2
is air stable and less expensive. Hence, a variety of different
ligands (10 mol %) were examined in the presence of
Pd(OAc)2 (5 mol %) and Cs2CO3 (2.4 equiv) in toluene
at 110 °C for 24 h (entries 5 to 18). The direct CꢀH
DavePhos
none
Cs2CO3 toluene
Cs2CO3 toluene
20
21
22
23
24
25
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
P(m-Tol)3
K2CO3
K2CO3
toluene
toluene
79
0
P(Cy)3HBF4
P(m-Tol)3
Na2CO3 toluene
Na2CO3 toluene
0
P(Cy)3HBF4
P(m-Tol)3
0
none
none
toluene
toluene
0
P(Cy)3HBF4
0
26
27
28
29
30
31
32
33
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
P(m-Tol)3
Cs2CO3 xylene
Cs2CO3 DMF
Cs2CO3 DMA
Cs2CO3 dioxane
Cs2CO3 xylene
Cs2CO3 DMF
Cs2CO3 DMA
Cs2CO3 dioxane
96
97
97
94
91
88
83
68
P(m-Tol)3
P(m-Tol)3
P(m-Tol)3
P(Cy)3HBF4
P(Cy)3HBF4
P(Cy)3HBF4
P(Cy)3HBF4
a Unless noted, the reaction was carried out with EDOT 1 (1 equiv)
and bromobenzene 2a (2.1 equiv) in the presence of Pd catalyst
(5 mol %), ligand (10 mol %), base (2.4 equiv) in toluene (5 mL) at
110 °C for 24 h. b No desired product was obtained when the palladium
catalyst was excluded from the direct arylation reaction. c Isolated yield.
(6) (a) Kumar, A.; Reynolds, J. R. Macromolecules 1996, 29, 7629. (b)
Sankaran, B.; Reynolds, J. R. Macromolecules 1997, 30, 2582. (c) Irvin,
D. J.; DuBois, C. J.; Reynolds, J. R. Chem. Commun. 1999, 2121. (d)
Gaupp, C. L.; Reynolds, J. R. Macromolecules 2003, 36, 6305. (e)
Thomas, C. A.; Zong, K.; Abboud, K. A.; Steel, P. J.; Reynolds, J. R.
J. Am. Chem. Soc. 2004, 126, 16440. (f) Nielsen, C. B.; Angerhofer, A.;
Abboud, K. A.; Reynolds, J. R. J. Am. Chem. Soc. 2008, 130, 9734.
(7) (a) Mohanakrishnan, A. K.; Amaladass, P.; Clement, J. A.
Tetrahedron Lett. 2007, 48, 539. (b) Amaladass, P.; Clement, J. A.;
Mohanakrishnan, A. K. Tetrahedron 2007, 63, 10363. (c) Borghese, A.;
Geldhof, G.; Antoine, L. Tetrahedron Lett. 2006, 47, 9249.
arylation of EDOT using the bidentate phosphine ligands
afforded the product in 68ꢀ92% isolated yields (entries 6
to 8). In comparison, moderate to excellent yields were
obtained when monodentate ligands (47ꢀ98%, entries 9
to 15) were used. Among these phosphine ligands, tri-m-
tolylphosphine (P(m-Tol)3) and tricyclohexylphosphine
Org. Lett., Vol. 13, No. 15, 2011
4069

(P(Cy)3•HBF4) yielded 3a in almost quantitative yields
(98% and 97%, entries 10 and 13, respectively). With
further screening, we found that P, N- or N, N-ligands
were less efficient in the direct arylation reactions and
the desired adduct 3a was produced in only 20ꢀ39%
yields (entries 16 to 18). In the absence of ligands, the
Pd-catalyzed direct diarylation of EDOT did not occur at
all (entry 19).
Table 2. Substrate Scope (Bromoarenes) of the Pd-Catalyzed
Direct CꢀH Arylation of EDOTa
We then focused on the screening of reaction conditions
using P(m-Tol)3 and P(Cy)3•HBF4 as ligands. In the
presence of P(m-Tol)3 and K2CO3 as base instead of
Cs2CO3, the reaction resulted in 79% of 3a (entry 20),
whereas the combination of P(Cy)3•HBF4 and K2CO3 did
not afford any desired product (entry 21). Other combina-
tions such as using Na2CO3 or additive-free conditions were
shown to be inefficient, and the arylated adducts were not
formed (entries 22 to 25). Finally, different kinds of solvents
were also evaluated with both ligands. In most cases, the
diphenyl EDOT 3a was readily obtained in good to excellent
yields in either nonpolar or polar solvent (68ꢀ97%, entries
26 to 33). After trying these reaction conditions, we con-
cluded that the reaction conditions of entry 10 are optimal,
and they were further employed to investigate the substrate
scope of the direct CꢀH arylation (Table 2).
The optimized reaction conditions found in Table 1
(5 mol % Pd(OAc)2, 10 mol % P(m-Tol)3, 2.4 equiv of
Cs2CO3 in 5 mL of toluene at 110 °C for 24 h) were
subsequently applied to the facile preparation of the
EDOT-based π-conjugatedmolecules3bꢀ3hstarting from
EDOT 1 and various bromoarenes 2bꢀ2h (Table 2).
Compounds 3b and 3c with trifluoromethyl electron-with-
drawing groups at the terminal positions could be
potentially useful as n-type organic field-effect transistors
(OFET).8 In general, these types of molecules were synthe-
sized using traditional Suzuki8a or Stille8b coupling reac-
tions; however, 3b and 3c were, for the first time, readily
obtained through the more straightforward and atom-
economical CꢀH arylations in good yields (77% and
83%, entries 1 and 2, respectively). A biphenyl-incorpo-
rated compound 3dbearing the aliphatic end groups (81%,
entry 3) are potentially useful to raise some interesting
optoelectronic properties9 and applied in the preparation
of liquid crystals10 or organic crystal transistors.11
a General reaction conditions: EDOT 1 (1 equiv), bromoarene 2
(2.1 equiv), Pd(OAc)2 (5 mol %), P(m-Tol)3 (10 mol %), Cs2CO3
(2.4 equiv) in toluene (5 mL) at 110 °C for 24 h. b Isolated yield.
The reaction of EDOT 1 with bromoarenes 2e or 2f
under our optimized reaction conditions led to the forma-
tionof the desiredproducts 3eor 3f in75% and 73% yields,
respectively (entries 4 and 5). These molecules represent
favorable structures for organic electroluminescent devices.12
In addition, compounds 3g and 3h were efficiently synthe-
sized and isolated in good yields (83% and 78%, entries 6
and 7); interestingly, 3g bearing the macrocyclic ether rings
as end caps would be able to act as metal ion sensors,13 and
molecule 3h is particularly of interest as a hole injection/
transport layer in organic electronic devices.14
(8) (a) Ando, S.; Nishida, J.; Tada, H.; Inoue, Y.; Tokito, S.;
Yamashita, Y. J. Am. Chem. Soc. 2005, 127, 5336. (b) Ie, Y.; Nitani,
M.; Uemura, T.; Tominari, Y.; Takeya, J.; Honsho, Y.; Saeki, A.; Seki,
S.; Aso, Y. J. Phys. Chem. C 2009, 113, 17189.
(9) Katagiri, T.; Ota, S.; Ohira, T.; Yamao, T.; Hotta, S. J. Hetero-
cycl. Chem. 2007, 44, 853.
The scope of the direct CꢀH arylation reaction was
extended to the use of the EDOT dimer 4 as the core
(10) Schubert, H.; Sagitdinov, I.; Svetkin, J. V. Z. Chem. 1975, 15,
222.
(11) Yamao, T.; Miki, T.; Akagami, H.; Nishimoto, Y.; Ota, S.;
Hotta, S. Chem. Mater. 2007, 19, 3748.
(13) Kadarkaraisamy, M.; Thammavongkeo, S.; Basa, P. N.; Caple,
G.; Sykes, A. G. Org. Lett. 2011, 13, 2364.
(12) (a) Takata, Y.; Iwata, T. Jpn. Kokai Tokkyo Koho 2009, 43. (b)
Kido, J.; Osachi, Y.; Yoshizaki, M.; Omae, Y.; Yasuda, H. Jpn. Kokai
Tokkyo Koho 2008, 102.
(14) (a) Lim, Y.; Park, Y.-S.; Kang, Y.; Jang, D. Y.; Kim, J. H.; Kim,
J.-J.; Sellinger, A.; Yoon, D. Y. J. Am. Chem. Soc. 2011, 133, 1375. (b)
Terao, K.; Shinohara, Y.; Shinohara, T. Jpn. Tokkyo Koho 2010, 36.
4070
Org. Lett., Vol. 13, No. 15, 2011

(Scheme 2). Reaction of 4 with different bromoarenes
(2b, 2h, and 2i) under the optimized reaction conditions
provided the desired products 5aꢀ5c in moderate yields
(53ꢀ66%). We noted that compound 5b has been used
as high-luminance organic electroluminescent devices.
However, its preparation, as previously described,15
required tedious chemical transformations by the tra-
ditional synthetic route with the generation of a large
number of metal-containing side products. Besides, we
speculated that the relatively lower yields of 5aꢀ5c
might be due to the partial loss of the products while
carrying out the reaction workup and purification be-
cause we observed that these molecules displayed poor
solubility in commonly used organic solvents.16
Table 3. Spectroscopic and Electrochemical Properties of the
EDOT (3aꢀh)- and Bis-EDOT (5aꢀc)-Based Molecules
λ
max (abs)a
[nm]
λ
max (em)b
[nm]
compd
E1/2 [V]c
3a
3b
3c
3d
3e
3f
345
380, 399
390, 409
469
0.72
0.97
353
428
ꢀ1.71, 1.08
0.54, 1.04
0.41
374
422, 447
460
372, 393
380
470
0.38, 0.63
0.30
3g
3h
5a
5b
5c
357
401, 422
449
399
0.13, 0.30, 1.06
0.35, 0.90
ꢀ0.03, 0.15, 0.89
0.34, 0.72
408, 431
430
454
482, 518
481, 514
427, 452
a abs = UVꢀvis absorption (measured in CH2Cl2 solution). b em =
fluorescence emission (measured in CH2Cl2 solution). c Potential/V vs
Fcþ/Fc.
Scheme 2. Synthesis of EDOT Dimer-Based π-Conjugated
Molecules
electrodes during the cyclic voltammetric measurements of
3h and 5b, indicating that these compounds may undergo
electropolymerization and deposit on the surface.17
In summary, we have demonstrated a general and atom-
economical approach for the syntheses of EDOT-based
π-conjugated molecules through Pd-catalyzed direct CꢀH
bond arylations. The optimized reaction conditions obtained
after the comprehensive synthetic investigations allow the
facile preparation of a variety of functional π-conjugated
EDOT- or EDOT-dimer-containing oligoarenes, which are
of pronounced importance in materials science. Ongoing
studies using this efficient synthetic strategy are focused
on the examinations of substrate scope and further appli-
cations in organic electronics.
Acknowledgment. This work was supported by the
RIKEN Advanced Science Institute and a Grant-in-Aid
for Young Scientists (Nos. 22681016 and 23700565)
from JSPS/MEXT, Japan. We thank Dr. Takashi Otani,
Dr. Liangchun Li, Dr. Tsukasa Matsuo, and Dr. Kohei
Tamao (RIKEN Advanced Science Institute) for their help
on the spectroscopic measurements. We also thank Prof.
Kenichiro Itami (Nagoya University) for useful discussions.
We also examined the spectroscopic and electrochemical
characteristics of the synthesized EDOT-based π-conjugated
molecules, and the results are summarized in Table 3. All
compounds displayed certain color with the absorption peak
in the visible range due to the extended conjugation from
diarylation, allowing delocalization of π-electrons. When the
core EDOT was replaced by the EDOT dimer (from 3b to 5a
and from 3h to 5b), the effect of the longer conjugation length
was clearly observed. The main absorption and fluorescence
peak in optical measurement shifted to a longer wavelength.
The half-wave potential (E1/2) was also reduced by 0.07ꢀ0.17
V. It was also noted that a film was formed onto the
Supporting Information Available. Experimental pro-
cedures and full characterization of all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(18) Typical Procedure: Preparation of Molecule 3h. To a solution of
Pd(OAc)2 (12 mg, 5 mol %), P(m-Typical Procedure: Preparation of
MoleculTol)3 (31 mg, 10 mol %), and Cs2CO3 (782 mg, 2.4 mmol) in
toluene (5 mL) in a flame-dried Schlenk tube (20 mL) were added EDOT
1 (142 mg, 1.0 mmol) and bromotriphenylamine 2h (680 mg, 2.1 mmol)
under N2. The reaction mixture was then heated at 110 °C under N2 for
24 h. After the reaction mixture had cooled to room temperature, water
(10 mL) was added. The mixture was extracted with ethyl acetate (2 ꢁ 30
mL), and the combined organic layers were washed with brine (50 mL),
dried (Na2SO4), and concentrated in vacuo. Purification by reprecipita-
tion from a mixture of dichloromethane and hexane gave the desired
product 3h (489 mg, 78%) as a yellow solid; mp: 279ꢀ281 °C.
(15) Synthesis and applications of molecule 5b have been previously
reported: Seki, M.; Agata, T.; Hirose, E.; Horiba, K.; Imai, A.; Ozaki,
T.; Nishino, Y.; Yoneyama, H.; Okuda, D.; Ishii, T.; Mashimo, K.; Sato,
K. Jpn. Kokai Tokkyo Koho 2008, 67.
(16) Compounds 5aꢀ5c are almost insoluble in ether, ethyl acetate,
chloroform, acetone, benzene, THF, and DMSO. Slightly better solu-
bility was observed in dichloromethane.
(17) (a) Chiang, C. C.; Chen, H. C.; Lee, C. S.; Leung, M. K.; Lin,
K. R.; Hsieh, K. H. Chem. Mater. 2008, 20, 540. (b) Chang, C. C.; Leung,
M. K Chem. Mater. 2008, 20, 5816.
Org. Lett., Vol. 13, No. 15, 2011
4071