Rational synthesis of regioregular oligothiophenes via palladium catalyzed coupling reactions

Article abstract of DOI:10.1016/S0040-4039(02)01464-8

The synthesis of bis-, ter-, quater- and sexithiophenes using Stille methodology allows a controlled thiophene chain elongation.

Full text of DOI:10.1016/S0040-4039(02)01464-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6541–6544
Rational synthesis of regioregular oligothiophenes via palladium
catalyzed coupling reactions
Guillaume Loire,a,c Damien Prim,b Bruno Andrioletti,a Eric Rose,a,* Andre´ Persoons,c,*
Sonja Sionckec and Jacqueline Vaissermannd
aLaboratoire de Synthe`se Organique et Organome´tallique UMR 7611, Universite´ P. et M. Curie, Tour 44–45, case 181,
4, Place Jussieu, 75252 Paris cedex 05, France
bLaboratoire SIRCOB UPRESA 8086, Universite´ de Versailles, 45, Avenue des Etats-Unis, 78035 Versailles cedex, France
cLaboratory for Chemical and Biological Dynamics, University of Leuven, Celestijnenlaan 200D, B-3001 Heverlee, Belgium
dLCIM2 UA 7071 Universite´ P. et M. Curie, Batiment F, case 42, 4, Place Jussieu, 75252 Paris cedex 05, France
Received 28 June 2002; accepted 16 July 2002
Abstract—The synthesis of bis-, ter-, quater- and sexithiophenes using Stille methodology allows a controlled thiophene chain
elongation. © 2002 Elsevier Science Ltd. All rights reserved.
During the last two decades, chemistry of oligothio-
phenes has received considerable attention. For instance,
in June 2002, a SciFinder® Scholar 2001 data search on
‘oligothiophenes’ revealed 814 hits containing this termi-
nology. Undoubtedly, these ongoing efforts are related
to the moderate resonance energy of thiophene that
allows a good p-electron delocalization, and explains
why polythiophenes are among the best candidates for
second-order NLO applications. Recently, we and others
have shown that increasing the number of thiophene
units in a linker results in a concomitant increase of the
i-values of donor–acceptor systems.1–4 In order to
systematically study the influence of oligomerization on
the optical properties, we therefore initiated a palladium-
based, rational synthetic approach toward well-defined,
regioregular oligothiophenes. The synthetic scheme we
adopted expands and improves the scope of Barbarella’s
preliminary approach to bisthiophenes.5 It consists in
employing the key synthon 4 that presents a univocal and
suitable functionality for Stille-type palladium couplings.
structure of quaterthiophene 7 (Scheme 4) reveals an
uncommon symmetry where the thiophene units adopt
a syn–anti–syn arrangement rather than the more classi-
cal all-anti (all-trans) geometry.6
Preparation of thiophene 4 involves O-benzylation of
commercially available 3-thienylethanol7 followed by
quantitative and selective bromination of the O-pro-
tected thiophene 2 (Scheme 2).
Scheme 1.
Herein, we wish to report a new, convenient synthesis of
regio-controlled poly[n]thiophenes (25n56, Scheme 1).
In particular, we will show how the fine tuning of the
experimental conditions allows the selective preparation
of bis-, ter-, quater- and sexithiophenes. X-Ray crystal
* Corresponding authors. Tel.: 33(0)1 4427 6235; fax: 33(0)1 4427
5504 (E.R.); tel.: 0 321 632 7445; fax: 0 321 632 7982 (A.P.); e-mail:
rose@ccr.jussieu.fr; andre.persoons@fys.kuleuven.ac.be
Scheme 2.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01464-8

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G. Loire et al. / Tetrahedron Letters 43 (2002) 6541–6544
Lithium–halogen exchange at −90°C followed by addi-
tion of Me3SnCl afforded the trimethylstannylthio-
phene 4 in 90% overall yield (three steps). As already
reported by others,8 trialkylstannylthiophenes exhibit
low stability upon silica gel chromatography purifica-
tion. Attempts to purify the raw material only led to
destannylation. Fortunately, compound 4 was pure
enough to be used in the following step without any
additional purification.
Validation of the coupling method was first carried out
using 2-bromothiophene and stannylated thiophene 4.
Combination of Pd2dba3 as a catalyst precursor and
AsPh3 as ligand was used to generate the catalytic
species for the Stille reaction.9 As shown in Scheme 3,
compound 4 smoothly reacted with 2-bromothiophene
at 60°C in DMF under the above mentioned catalytic
conditions, cleanly affording the monosubstituted
bisthiophene 5 in 75% yield. Optimizing the coupling
conditions led to the use of low catalyst loading.
Indeed, it has been determined that only 1.5% of palla-
dium source and 3% of ligand are sufficient to ensure
completion of the coupling reaction. Using the latter
conditions, bisthiophene 5 is isolated in 73% yield.
Scheme 5.
rather than 2,5-dibromothiophene. Surprisingly, traces
of a biproduct—namely sexithiophene 8—were also
isolated from the reaction mixture in ca. 3% yield by
washings with Et2O, and characterized by usual meth-
ods. The presence of the latter can be explained either
by homocoupling of two 5,5%-dibromo-2,2%-bisthiophene
units leading to dibromoquaterthiophene prior to bis
Stille reactions or a mono Stille reaction affording
brominated terthiophene subunit and further
dimerization.
The strategy presented in this paper allows the selective
access to oligothiophenes by iterative increase of the
thiophene chain. Thus, sexithiophene 9 was selectively
prepared in two steps starting from quaterthiophene 7
(Scheme 5).
We next examined the formation of ter- and quaterthio-
phene using the strategy described above.
Coupling 2,5-dibromothiophene with stannane 4 under
palladium catalysis readily afforded terthiophene 6 in
60% yield after 24 h under reflux in DMF (Scheme 4).
When the same strategy was applied to 5,5%-dibromo-
2,2%-bisthiophene and trimethylstannylthiophene 4,
quaterthiophene 7 was isolated in 50% yield.10 Interest-
ingly, it is worth noting that reaction of 5,5%-dibromo-
2,2%-bisthiophene with 4 readily proceeds at room
temperature. This enhanced reactivity illustrates the
fact that 5,5%-dibromo-2,2%-bisthiophene more likely
behaves like two independent 2-bromothiophene units
Compound 7 was quantitatively brominated in the two
unsubstituted a-positions affording the corresponding
dibromoquaterthiophene. The latter was then coupled
with stannane 4 affording sexithiophene 9 in 60% yield.
Once again, the catalyst loading could be lowered to
1.5% of palladium precatalyst and 3% of ligand without
visible decrease of the catalytic activity.
A UV–vis study of compounds 1, 5–9 revealed interest-
ing features (Fig. 1). Indeed, in our series, it appears
that the absorption coefficient of the oligothiophenes
generally linearly varies with the number of thiophene
units of the molecule.
Scheme 3.
Scheme 4.
Figure 1.

G. Loire et al. / Tetrahedron Letters 43 (2002) 6541–6544
6543
Acknowledgements
The only exception concerns sexithiophene 9. The
absorption coefficient m being closely related to elec-
tronic delocalization, it appears that 9 is not as conju-
gated as sexithiophene 8. This can be explained by the
increased steric bulk of 9 that possesses four chains
The authors would like to thank the CNRS and the
EU Training and Mobility of Researchers Program:
‘Organometallic Dipole with NLO Properties’ contract
c ERBFMRXCT-CT98-0166 and COST D14 for
financial support. E.R. and B.A. would like to thank
Drs. C. Rolando and G. Ricart (UST Lille, France)
for HRMS analyses.
grafted on four thiophenic b-positions. Thus,
9
probably adopts a twisted conformation that accom-
modates the steric hindrance at the expense of the
conjugation.
Single crystals of 7 suitable for X-ray analyses were
obtained by slow diffusion of pentane into a chloro-
form solution containing the quaterthiophene.11 The
study revealed a C2 symmetrical arrangement (Fig. 2)
where the thiophene units adopted a syn–anti–syn con-
formation rather than the expected all-antiplanar
symmetry.
References
1. Rao, V. P.; Jen, A. K.-Y.; Wong, K. Y.; Drost, K. J.
Tetrahedron Lett. 1993, 34, 1747–1750.
2. Kim, O.-K.; Fort, A.; Barzoukas, M.; Blanchard-Desce,
M.; Lehn, J.-M. J. Mater. Chem. 1999, 9, 2227–2232.
3. Garcia, M. H.; Royer, S.; Robalo, M. P.; Roma˜o Dias,
A.; Tranchier, J.-P.; Chavignon, R.; Prim, D.; Auffrant,
A.; Rose-Munch, F.; Rose, E.; Persoons, A.; Asselberghs,
I. Eur. J. Inorg. Chem., submitted for publication.
4. Nalwa, H. S.; Watanabe, T.; Miyata, S. In Nonlinear
Optics of Organic Molecules and Polymers; Nalwa, H. S.;
Miyata, S., Eds.; CRC Press: New York, 1997.
5. Barbarella, G.; Zambianchi, M. Tetrahedron 1994, 50,
11249–11256.
6. Siegrist, T.; Kloc, C.; Laudise, R. A.; Katz, H. E.;
Haddon, R. C. Adv. Mater. 1998, 10, 379–382.
7. Lemaire, M.; Garreau, R.; Delabouglise, D.; Roncali, J.;
Youssoufi, H. K.; Garnier, F. New J. Chem. 1990, 14,
359–364.
Although already reported in the literature,12–14 such
an arrangement remains unusual as the vast majority
of X-ray crystal structures reveal the more common
all-anti conformation in which the sulfur atoms all
point inward. A commonly admitted explanation for
this peculiar arrangement deals with the minimization
of steric energy involving S–S interactions and repul-
sions due to the presence of the b-substituents. As for
the spatial arrangement, the molecule possesses two
almost coplanar central thiophenes and two external
b-substituted thiophenes slightly twisted—the dihedral
angle is ca. 30°—from the main plane.
8. Miller, L. L.; Yu, Y. J. Org. Chem. 1995, 60, 6813–6819.
9. (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113,
9585–9595; (b) Farina, V.; Krishnan, B.; Marshall, D. R.;
Roth, G. P. J. Org. Chem. 1993, 58, 5434–5444; (c) Prim,
D.; Tranchier, J.-P.; Rose-Munch, F.; Rose, E.; Vaisser-
mann, J. Eur. J. Inorg. Chem. 2000, 5, 901–905.
10. Typical experimental procedure: To a solution of [3-(2-
In conclusion, we have described selective, rational
accesses to bis-, ter-, quater- and sexithiophenes.15
The latter were isolated in moderate to good yields
owing to palladium-based couplings between bro-
mothiophenes and stannylated derivatives. The X-ray
crystal structure of quaterthiophene 7 showed an
unusual syn–anti–syn arrangement of the thiophene
units.
benzyloxy-ethyl)-thiophen-2-yl]-trimethyl-stannane
DMF, was added a solution of 0.5 equiv. of 2,5-dibro-
mothiophene (resp. 5,5%-dibromo-2,2%-bisthiophene),
4 in
0.015 equiv. of Pd2dba3 and 0.03 equiv. of AsPh3 in
DMF. The mixture was stirred for 24 h at appropriate
temperature. The reaction mixture was then poured into
cold water, extracted three times with ether, washed with
water and dried over MgSO4 before being concentrated
under reduced pressure. The crude oil was then purified
on a silica gel column chromatography and eluted with
an increasing amount of dichloromethane in cyclohexane
affording the bis-coupled compounds in 50–73% yield as
orange solids.
11. Crystallographic data for 7: Orange yellow plate, mono-
clinic, space group P21/n, Z=2, a=5.653(1), b=7.780(2),
3
,
,
c=34.013(13) A, i=91.44(2)°, V=1495.4(8) A , zcalcd
=
1.33 g cm−3, F(000)=628, v=0.33 mm−1. A total of 4264
reflections were measured (range 1–28°), 3614 unique
(Rint=0.05), on an Enraf–Nonius MACH-3 diffractome-
ter using graphite monochromatized Mo Ka radiation
,
(u=0.71069 A) at room temperature. The structure was
refined on F to R=0.0553, Rw=0.0736 (2045 reflections
with I>3|(I)), and a goodness of fit=1.01 for 182 refined
parameters. The molecule lies on a crystallographic inver-
Figure 2.

6544
G. Loire et al. / Tetrahedron Letters 43 (2002) 6541–6544
sion center. CCDC-188181 contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic
Data Centre, 12, Union Road, Cambridge CB21EZ, UK;
fax: (+44)1223-336-033; or deposit@ccdc.cam.ac.uk).
Found 516.1246; UV–vis (CHCl3) nm: umax (m)=334
(17 000). Compound 7: H NMR (200 MHz, CDCl3): l
1
7.34 (m, 10H), 7.20 (d, J=5.2 Hz, 2H), 7.01 (d, J=5.2
Hz, 2H), 7.12 (d, J=3.9 Hz, 2H), 7.05 (d, J=3.9 Hz,
2H), 4.56 (s, 4H), 3.75 (t, J=6.9 Hz, 4H), 3.14 (t, J=6.9
Hz, 4H); 13C NMR (50 MHz, CDCl3): 138.5, 137.1,
135.9, 135.1, 131.7, 130.5, 128.6, 127.8, 127.1, 124.3,
124.2, 73.1, 70.2, 30; MALDI-TOF HRMS calcd for
C34H30O2S4: 598.1123. Found 598.1044; UV–vis (CHCl3)
12. Barbarella, G.; Zambianchi, M.; Del Fresno, I.; Mari-
mon, M.; Antolini, L.; Bongini, A. Adv. Mater. 1997, 9,
484–487.
13. Mitzi, D. B.; Chondroudis, K.; Kagan, C. R. Inorg.
Chem. 1999, 38, 6246–6256.
1
nm: umax (m)=377 (28 000). Compound 8: H NMR (200
MHz, CDCl3): l 7.31 (m, 10H), 7.19 (d, J=5.1 Hz, 2H),
7.10 (d, J=3.9 Hz, 2H), 7.08 (s, 4H), 7.03 (d, J=3.9 Hz,
2H), 7.0 (d, J=5.1 Hz, 2H), 4.54 (s, 4H), 3.72 (t, J=6.9
Hz, 4H), 3.11 (t, J=6.9 Hz, 4H); 13C NMR (50 MHz
CDCl3): 139.0, 137.1, 136.6, 136.3, 136.2, 135.4, 131.7,
130.8, 128.6, 127.9, 127.8, 127.3, 124.8, 124.8, 124.5, 73.2,
70.4, 30.1; MALDI-TOF HRMS calcd for C42H34O2S6:
(M+H)+ 762.0883. Found 761.9950; UV–vis (CHCl3) nm:
umax (m)=428 (50174). Compound 9: 1H NMR (400
MHz, CDCl3): l 7.35 (m, 20H), 7.20 (d, J=5.1 Hz, 2H),
7.10 (d, J=3.6 Hz, 2H), 7.09 (d, J=3.6 Hz, 2H), 7.08 (s,
2H), 7.02 (d, J=5.1 Hz, 2H), 4.58 (s, 4H), 4.56 (s, 4H),
3.78 (t, J=7.1 Hz, 4H), 3.76 (t, J=7.1 Hz, 4H), 3.16 (t,
J=7.1 Hz, 8H); 13C NMR (100 MHz, CDCl3): 138.5,
138.4, 137.1, 136.3, 135.9, 134.7, 134.3, 131.7, 131.7,
130.4, 129.5, 128.5, 127.7, 126.9, 126.8, 124.2, 124.1, 73.1,
73.1, 70.2, 70.0, 30.1, 29.9, 29.8; MALDI-TOF HRMS
calcd for C60H54O4S6: 1030.2316. Found 1030.2341; UV–
vis (CHCl3) nm: umax (m)=411 (27 292).
14. Muguruma, H.; Kobiro, K.; Hotta, S. Chem. Mater.
1998, 10, 1459–1467.
15. Selected characterization. Compound 5: 1H NMR (400
MHz, CDCl3): l 7.32 (m, 5H), 7.3 (dd, J=5.2, 1.2 Hz,
1H), 7.19 (d, J=5.2 Hz, 1H), 7.12 (dd, J=3.6, 1.2 Hz,
1H), 7.05 (dd, J=5.2, 3.6 Hz, 1H), 7.0 (d, J=5.2 Hz,
1H), 4.53 (s, 2H), 3.71 (t, J=7.1 Hz, 2H), 3.1 (t, J=7.1
Hz, 2H); 13C NMR (100 MHz, CDCl3): 138.4, 135.8,
135.6, 131.8, 130.1, 128.4, 127.6, 127.5, 127.4, 126.3,
125.6, 124.0, 72.9, 70.1, 29.6; MALDI-TOF HRMS calcd
for C17H16OS2: (M+Na)+ 323.0549. Found 323.0535;
UV–vis (CHCl3) nm: umax (m)=293 (8614). Compound 6:
1H NMR (200 MHz, CDCl3): l 7.30 (m, 10H), 7.20 (d,
J=5.1 Hz, 2H), 7.05 (s, 2H), 7.00 (d, J=5.1 Hz, 2H),
4.53 (s, 4H), 3.72 (t, J=6.9 Hz, 4H), 3.11 (t, J=6.9 Hz,
4H); 13C NMR (100 MHz, CDCl3): 138.4, 136.0, 135.9,
131.6, 130.3, 128.4, 127.7, 126.7, 124.2, 73.0, 70.2, 29.8;
MALDI-TOF HRMS calcd for C30H28O2S3: 516.1423.