Palladium-catalyzed coupling reactions towards the synthesis of well-defined thiophene-oligomers

Article abstract of DOI:10.1016/S0022-328X(03)00626-0

Heck- and Ullmann-type palladium-catalyzed reactions were used in order to perform the synthesis of 3′,4″-dioctyl-2,2′, 5′2″,5″,2′″-tetrathienyl. The desired oligothiophene was synthesized in five steps with a total yield of 38% by a Heck-type reaction of bromo-derivatives and a yield of 45% by an Ullmann-type reaction of iodo-precursors.

Full text of DOI:10.1016/S0022-328X(03)00626-0

Journal of Organometallic Chemistry 687 (2003) 280ꢀ283
/
www.elsevier.com/locate/jorganchem
Palladium-catalyzed coupling reactions towards the synthesis of well-
defined thiophene-oligomers
Jwanro Hassan a, Christel Gozzi a, Emmanuelle Schulz b, Marc Lemaire a,*
a Laboratoire de Catalyse et Synthe`se Organique, UMR 5622, UCBL, CPE, 43, Bd du 11 Novembre 1918, F-69622 Villeurbanne Cedex, France
b Laboratoire de Catalyse Mole´culaire, UMR 8075, ICMMO, Universite´ Paris-Sud, baˆtiment 420, 91405 Orsay Cedex, France
Received 31 March 2003; accepted 24 June 2003
Dedicated to Professor J.P. Geneˆt on the occasion of his birthday.
Abstract
Heck- and Ullmann-type palladium-catalyzed reactions were used in order to perform the synthesis of 3?,4ƒ-dioctyl-
2,2?,5?2ƒ,5ƒ,2?ƒ-tetrathienyl. The desired oligothiophene was synthesized in five steps with a total yield of 38% by a Heck-type
reaction of bromo-derivatives and a yield of 45% by an Ullmann-type reaction of iodo-precursors.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Heck-type and Ullmann-type reactions; Regioregular oligothiophenes; Thiophene; Palladium acetate
1. Introduction
already reported. We also described the direct arylation
of thiophenes in position 2 or 5, using Heck-type
Thiophene oligomers are starting materials for the
preparation of organic conductors [1,2]. The electronic
properties of the obtained conjugated polymers are
determined by the thorough control of the structural
order. Therefore, syntheses leading to regioregular
polymers are of utmost importance. Methods involving
organometallic compounds for the coupling of arylder-
ivatives [3] have thus been used in the synthesis of
poly(alkylthiophenes) and afford high molecular
weights and regioregular head-to-tail poly(alkylthio-
reactions [10ꢀ12] (Scheme 1).
/
Then, we successfully applied this method to the
polymerization of 2-iodo- and 2-bromo-3-alkylthio-
phenes in the presence of Pd(OAc)2 as a catalyst
[13,14]. This coupling procedure presents several ad-
vantages compared with reported methods such as the
use of a catalytic amount of palladium and the easy
availability of the functionalized monomers, for exam-
ple. We also described the efficiency of Pd(OAc)2 as a
catalyst for the synthesis of symmetrical and unsymme-
trical biaryls [15,16] in a catalytic version of the
Ullmann coupling reaction.
phenes) [4ꢀ6]. The main drawbacks of these procedures
/
are the difficult access to the monomer in its highly
purified form and the requirement of a stoichiometric
amount of the organometallic intermediate. The simple
access to well-defined oligomers is also important to
mimic, and then predict, the behavior of longer poly-
mers for their various applications. Thus, stepwise
syntheses based on the repetitive use of the Stille [7],
Suzuki [8] and Kumada [9] coupling reactions were
We report here the stepwise synthesis of a tetramer
based on the aforementioned Heck- and Ullmann-type
reactions.
2. Synthesis
2-Iodo-3-octylthiophene 2 was first regiospecifically
synthesized according to a procedure described by
Miller and co-workers [17]. This method requires the
use of mercuric oxide and iodine in benzene as solvent.
A selectivity higher than 95% was obtained for mono-
* Corresponding author. Tel.: ꢁ
431408.
E-mail address: marc.lemaire@univ-lyon1.fr (M. Lemaire).
/
33-4-72-431407; fax: ꢁ33-4-72-
/
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-328X(03)00626-0

J. Hassan et al. / Journal of Organometallic Chemistry 687 (2003) 280ꢀ
/283
281
of an organic base, i.e. N,N-diisopropylethylamine
instead of potassium carbonate. We previously synthe-
sized a series of symmetrical functionalized bithiophenes
in good to excellent yields [15] under these Ullmann-type
coupling conditions.
Scheme 1. Arylation of 2-cyanothiophene by 4-iodomethoxybenzene.
The undesirable use of highly toxic products such as
mercuric oxide during the iodination step justified the
test of analogous brominated derivatives. 2-Bromo-3-
octylthiophene 6 was thus regioselectively synthesized
starting from 3-octylthiophene by using N-bromosucci-
nimide in a mixture of acetic acid and chloroform [8,18].
The addition reaction between 2-bromo-3-octylthio-
phene 6 and 2-chlorothiophene was carried out under
Heck-type coupling conditions leading to bithiophene 3
with a yield of 86%. Similarly as observed for iodinated
derivatives, 2-chlorothiophene was introduced in excess
to avoid the homopolymerization reaction of 2-bromo-
3-octylthiophene 6. This coupling was performed in 4 h
iodination with regards to diiodination. The addition of
this iodothiophene on 2-chlorothiophene under Heck-
type coupling conditions led to the dimer 3 with a good
yield. It is important to note that the Heck-type
coupling of the chlorinated derivatives does not take
place under our conditions. Furthermore, to avoid
polymerization of 2-iodo-3-octylthiophene under these
conditions, 2-chlorothiophene was added in a ten-fold
excess. The coupling of the thiophene rings was per-
formed in DMF using 2.5 M equivalents of base, 1 M
equivalent of tetra-n-butylammonium bromide and
palladium acetate (5 mol%) as a catalyst. The palladium
atom is selectively inserted into the Cꢀ/I bond, and the
chloride plays the role of a protecting group, preventing
a coupling reaction in position 2. Excess of 2-chlor-
othiophene is efficiently removed by vacuum evapora-
tion. Subsequent iodination is then regioselectively
performed in position 5 of dimer 3 giving product 4.
An excess of mercuric oxide ensures a complete reaction,
avoiding a purification stage, since 3-octyl-5?-chloro-
2,2?-bithiophene 3 and product 4 are not easily separ-
able. The tetrathiophene 5 was finally obtained with a
yield of 61% by another Heck-type coupling reaction
involving dimer 3 (Scheme 2).
Scheme 4. Synthesis of 3?,4ƒ-dioctyl-5,5?ƒ-dichloro-2,2?:5?,2ƒ:5ƒ,2?ƒ-tet-
rathienyl by Heck type reactions of brominated derivatives.
Alternatively, an Ullmann-type coupling of 5-iodo-3-
octyl-5?-chloro-2,2?-bithiophene 4 also afforded the
tetramer 5 with 83% yield (Scheme 3) by using
Pd(OAc)2ꢀn-Bu4NBr as catalytic system in the presence
/
Scheme 2. Synthesis of 3?,4ƒ-dioctyl-5,5?ƒ-dichloro-2,2?:5?,2ƒ:5ƒ,2?ƒ-tet-
rathienyl by Heck-type reactions of iodinated derivatives.
Scheme
5. Dehalogenation
of
3?,4ƒ-dioctyl-5,5?ƒ-dichloro-
2,2?:5?,2ƒ:5ƒ,2?ƒ-tetrathienyl.
Scheme 3. Synthesis of 3?,4ƒ-dioctyl-5,5?ƒ-dichloro-2,2?:5?,2ƒ:5ƒ,2?ƒ-tetrathienyl by an Ullmann-type reaction.

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J. Hassan et al. / Journal of Organometallic Chemistry 687 (2003) 280ꢀ283
/
with iodinated derivatives and 5 mol% of catalyst, but it
lasted 40 h and required 10 mol% of Pd(OAc)2 to allow
a total conversion of the brominated derivative 6.
Bithiophene 3 was then selectively brominated in posi-
tion 5. Using another Heck-type coupling reaction
between 3 and 7, the tetrathiophene 5 was obtained
with 65% yield (Scheme 4).
solvent was evaporated under vacuum. The crude
product was then purified by column chromatography,
using silicagel 60 and heptane as the eluent to give a
yellow solid product.
3.3. Analyses
Finally, free-ends tetramer (8) was obtained by two
dehalogenative procedures. The use of an over-stoichio-
metric amount of tributyltin hydride in the presence of
azobisisobutyronitrile (AIBN), gave the free-ends oligo-
mer with a yield of 83% after 9 h of reaction.
Dehalogenation was also alternatively performed by
using H2 over Pd/C in ethylacetate and in the presence
of triethylamine, giving 8 in 52% yield in 48 h [8]
(Scheme 5).
In summary, we have developed new methodologies
for the synthesis of regioregular oligothiophenes with
good yields. The reported methods for the synthesis of
tetramers were thus improved by using methodologies
based on a succession of Heck- and Ullmann-type
reactions. These methodologies are economically com-
petitive since they do not require a stoichiometric
organometallic intermediate, and the functionalized
monomers are easily obtained in their highly purified
form.
3.3.1. 2-Iodo-3-octylthiophene 2
Prepared according to reference [17]; yield: 80%; b.p.
136ꢀ
CDCl3) d (ppm): 7.37 (d, 1H, Jꢄ
Jꢄ5.4 Hz); 2.56 (t, 2H, Jꢄ7.4 Hz); 1.58ꢀ
12H); 0.90 (t, 3H, Jꢄ
6.4 Hz); 13C-NMR (50 MHz,
/
141 8C (4ꢂ
/
10ꢃ4 bar); 1H-NMR (200 MHz,
/5.4 Hz); 6.77 (d, 1H,
/
/
/
1.30 (m,
/
CDCl3) d (ppm): 147.2; 130.3; 128.0; 74.0; 32.3; 32.0;
30.1; 29.5; 29.3; 22.7; 18.1; 14.2; MS, m/z (%): 322 (65)
[Mꢁ]; 323 (10) [Mꢁ
1]; 225 (12); 224 (30); 223 (100); 196
(15); 195 (70); 139 (15); 137 (20); 123 (20).
/
3.3.2. 2-Bromo-3-octylthiophene 6
Prepared according to references [8,18]; yield: 85%;
b.p. 91 8C (3ꢂ
d (ppm): 7.36 (d, 1H, Jꢄ
Hz); 2.53 (t, 2H, Jꢄ4.0 Hz); 1.40ꢀ
(t, 3H, Jꢄ
6.4 Hz); 13C (50 MHz, CDCl3) d (ppm):
141.0; 130.9; 128.7, 109.3; 32.5; 32.4; 30.3; 30.0; 29.9;
/
10ꢃ2 bar); 1H-NMR (200 MHz, CDCl3)
/
5.5 Hz); 6.73 (d, 1H, Jꢄ
/5.5
/
/1.20 (m, 12H); 0.87
/
23.2; 23.1; 14.0; MS, m/z (%): 276 (35) [Mꢁ2]; 274 (20)
/
[Mꢁ]; 238 (22); 236 (85); 234 (100); 202 (8); 201 (45); 199
(75); 178 (18); 177 (80); 175 (75); 164 (45); 155 (75).
3. Experimental
3.3.3. 3-Octyl-5?-chloro-2,2?-bithiophene 3
Following the general procedure for Heck-type reac-
tions; yield: 86%; 1H-NMR (200 MHz, CDCl3) d (ppm):
3.1. General procedure for Heck-type reactions
A mixture of potassium carbonate (20 mmol), palla-
dium acetate (0.4 mmol), tetra-n-butylammonium bro-
mide (8 mmol) and 2-chlorothiophene (80 mmol) or 2-
chlorobithiophene (80 mmol) in DMF (18 ml) was
stirred under nitrogen atmosphere with a mixture of
thiophene iodide (2 or 4) or thiophene bromide (6 or 7)
(8 mmol) in DMF (3 ml). The mixture was maintained
at 80 8C for the period of time indicated in the text.
After cooling to room temperature, water and ether
were added. The organic phase was washed with water
and dried over MgSO4. The solvent was evaporated
under vacuum. The crude product was then purified by
column chromatography, using silicagel 60 and heptane
as the eluent.
7.2 (d, 1H, Jꢄ
2H); 2.7 (t, 2H, Jꢄ
0.9 (t, 3H, Jꢄ
6.4 Hz); 13C (50 MHz, CDCl3) d (ppm):
/
5.2 Hz); 6.9 (d, 1H, Jꢄ
/
5.2 Hz); 6.8 (s,
/4.0 Hz); 1.6 (m, 2H); 1.3 (m, 10H);
/
140.2; 135.3; 133.6; 130.0; 129.6; 126.6; 125.2; 124.3;
32.2; 31.0; 30.2; 29.8; 29.4; 23.1; 22.8; 14.5; MS, m/z (%):
314 (30) [Mꢁ
2]; 312 (80) [Mꢁ]; 215 (60); 213 (95); 180
(15); 179 (25); 178 (100); 147 (8); 134 (35).
/
3.3.4. 5-Iodo-3-octyl-5?-chloro-2,2?-bithiophene 4
Prepared according to reference [17]; yield: 95%; H-
NMR (200 MHz, CDCl3) d (ppm): 7.10 (s, 1H); 6.87 (d,
1
1H, Jꢄ
/
3.9 Hz); 6.81 (d, 1H, Jꢄ3.9 Hz); 2.60 (t, 2H,
/
Jꢄ
/
4 Hz); 1.50 (m, 2H); 1.30 (m, 10H); 0.90 (t, 3H, Jꢄ
/
6.4 Hz); 13C (50 MHz, CDCl3) d (ppm): 152.7; 142.1;
139.7; 135.6; 133.5; 130.2; 126.6; 73.0; 32.0; 31.5; 30.8;
3.2. General procedure for Ullmann-type reactions
29.5; 29.3; 23.5; 22.8; 14.3; MS, m/z (%): 440 (35) [Mꢁ
/
2]; 438 (100) [Mꢁ]; 341 (15); 339 (45); 304 (70); 213 (20);
178 (20).
A mixture of diisopropylethylamine (8 mmol), palla-
dium acetate (0.4 mmol), tetra-n-butylammonium bro-
mide (4 mmol) and 5-iodo-3-octyl-5?-chloro-2,2?-
bithiophene (8 mmol) in DMF (30 ml) was stirred for
6 h under nitrogen atmosphere at 110 8C. After cooling
to r.t., water and ether were added. The organic phase
was washed with water and dried over MgSO4. The
3.3.5. 5-Bromo-3-octyl-5?-chloro-2,2?-bithiophene 7
Prepared according to references [8,18]; yield: 96%;
1H-NMR (200 MHz, CDCl3) d (ppm): 6.90 (s, 1H); 6.85
(d, 1H, Jꢄ
/
3.9 Hz); 6.81 (d, 1H, Jꢄ/3.9 Hz); 2.60 (t, 2H,
Jꢄ7.4 Hz); 1.20ꢀ
/
/
1.40 (m, 12H); 0.88 (t, 3H, Jꢄ
/7.0

J. Hassan et al. / Journal of Organometallic Chemistry 687 (2003) 280ꢀ
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283
Hz); 13C (50 MHz, CDCl3) d (ppm): 143.0; 140.9; 135.1;
133.9; 129.4; 124.0; 121.3; 113.8; 33.3; 32.5; 30.3; 30.0;
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/
(55) [Mꢁ]; 294 (20); 292 (90); 291 (55); 213 (40); 178
(25); 177 (100).
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3.3.6. 3?,4ƒ-Dioctyl-5,5?ƒ-dichloro-2,2?:5?,2ƒ:5ƒ,2?ƒ-
tetrathienyl 5
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Following the general procedure for Heck- and
Ullmann-type reactions; yield: 83%; 1H-NMR (200
MHz, CDCl3) d (ppm): 7.0 (s, 2H); 6.9 (d, 4H); 2.7 (t,
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¨ ¨
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4H); 1.6 (m, 4H); 1.3 (m, 20H); 1.0 (t, 6H, Jꢄ6.4 Hz);
/
13C (50 MHz, CDCl3) d (ppm): 143.4; 142.8; 138.0;
134.4; 129.0; 126.3; 124.0; 121.3; 33.4; 32.5; 30.3; 30.0;
29.9; 24.7; 23.1; 14.0; HRMS Calc. for C32H40Cl2S4
622.1390, Found 623, 1468.
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3.3.7. 3?,4ƒ-Dioctyl-2,2?:5?,2ƒ:5ƒ,2?ƒ-tetrathienyl 8
Prepared according to reference [8]; yield: 83%; H-
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1
NMR (200 MHz, CDCl3) d (ppm): 7.35 (d, 2H, Jꢄ
Hz); 7.32 (d, 2H, Jꢄ5.0 Hz); 7.15 (dd, 2H, Jꢄ5.0 Hz,
Jꢄ3.5 Hz); 7.10 (s, 2H); 2.80 (t, 4H, Jꢄ4.0 Hz); 1.70ꢀ
1.20 (m, 24H); 0.90 (t, 6H, Jꢄ
6.4 Hz); 13C (50 MHz,
CDCl3) d (ppm): 140.4; 136.1; 135.0; 129.6; 127.5; 126.4;
125.8; 125.3; 33.4; 32.5; 30.3; 30.6; 29.8; 29.6; 23.1; 14.0.
/
5.0
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/
/
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(2001) 7845.
/
/
/
/
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