A convenient method of producing thiophene linked bipyridine oligomers

Article abstract of DOI:10.1016/j.tetlet.2004.08.062

New ligands bearing thiophene, alkyne and bipyridine subunits have been synthesized. A series of soluble polybipyridine ligands comprising one to five bipyridine modules sandwiched between rigid carbon-carbon triple bonds substituted by 3,4-dibutylthiophene repeating units was synthesized. Two different protocols have been explored with the idea to use a divergent/convergent approach starting from bisymmetrically and symmetrically substituted bipyridine modules. At each stage of the iteration two bipy/thiophene modules are connected. The use of triethylsilylacetylene and 2-methylbut-3-yn-2-ol insures an easy entry to pivotal building blocks, which could be selectively deprotected from the TES or 2-hydroxyprop-2-yl sites. All cross-coupling reactions are promoted with palladium(0) tetrakistriphenylphosphine under mild conditions.

Full text of DOI:10.1016/j.tetlet.2004.08.062

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7963–7967
A convenient method of producing thiophene
linked bipyridine oligomers
*
´
Antoinette De Nicola, Sebastien Goeb and Raymond Ziessel
´ ` ´
Laboratoire de Chimie Moleculaire, Ecole de Chimie, Polymeres, Materiaux (ECPM), Universite Louis Pasteur (ULP),
25 rue Becquerel, 67087 Strasbourg Cedex 02, France
´
Received 28 July 2004; accepted 10 August 2004
Available online 11 September 2004
Abstract—A series of soluble polybipyridine ligands comprising one to five bipyridine modules sandwiched between rigid carbon–
carbon triple bonds substituted by 3,4-dibutylthiophene repeating units was synthesized. Two different protocols have been explored
with the idea to use a divergent/convergent approach starting from bisymmetrically and symmetrically substituted bipyridine mod-
ules. At each stage of the iteration two bipy/thiophene modules are connected. The use of triethylsilylacetylene and 2-methylbut-3-
yn-2-ol insures an easy entry to pivotal building blocks, which could be selectively deprotected from the TES or 2-hydroxyprop-2-yl
sites. All cross-coupling reactions are promoted with palladium(0) tetrakistriphenylphosphine under mild conditions.
Ó 2004 Elsevier Ltd. All rights reserved.
The design and tailoring of new molecules with special
electrochemical and/or optical properties for application
in the fields of supramolecular chemistry,1 molecular
materials2 and nanoelectronic architectures,3 has re-
ceived considerable attention over the past several years.
Such systems may play crucial roles in the areas of light
emitting materials for displays,4 sensors in environmen-
tal chemistry,5 photocatalysis6 and energy supply sys-
tems.7 Following a lot of successful examples of
luminescent transition metals complexes8 it is still highly
challenging to achieve the preparation of segmented
multitopic ligands in which each compartment is con-
nected to its neighbour via an unsaturated linker. To
achieve such a conjugation our particular interest has
been directed at the development of alkyne and alkene
connectors.9,10 We have recently reported that hetero-
topic ligands constructed from a large variety of oligo-
pyridines are easily produced in good yields. Whereas
this approach seems promising for efficient CC cou-
plings, the prospects seem less hopeful for the selective
complexation sequence.10 This is due to the high reactiv-
ity of the metal precursors and the lack of selectivity of
the incoming bi- or tridentate ligand fragment. There-
fore, we decided to start a programme for the construc-
tion of homotopic ligands in which each bipyridine
module is connected to a 3,4-dibutyl-2,5-diethynylthio-
phene fragment and end-capped by a 3,4-dibutyl-2-ethy-
nylthiophene fragment. Such features will insure that
each unit lies in the same electronic and topological
environment. These sophisticated molecular structures
should allow to shed more light on multinuclear transi-
tion metal systems with the aim of studying light har-
vesting and energy conversion systems. In these
respects, we examined different synthetic strategies for
the step-by-step construction of homopolypyridine
architectures. The representative targets are sketched
in Chart 1.
The choice of thiophene is motivated by the prominent
role it plays in plastic electronics11 whereas the ethynyl
and butyl functions will, respectively, insure a good
N
S
N
N
S
N
S
n
n = 0 to 4
Keywords: Segmented ligands; Thiophene; Bipyridine; Triple bonds;
Palladium.
*
Corresponding author. Tel./fax: +33 (0)390242689; e-mail: ziessel@
chimie.u-strasbg.fr
Chart 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.062

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A. De Nicola et al. / Tetrahedron Letters 45 (2004) 7963–7967
electronic connectivity and solubility of the oligomers.
From a general point of view bipyridine and thiophene
have been associated in molecular12 or polymeric struc-
tures.13 Firstly, we examined the simplest route for the
synthesis of the dimer and trimer using, as shown in
Scheme 1, a common building block 3.
deprotection of the TMS is straightforward and effective
under mild conditions.14 Reaction of 5,50-diethynyl-2,20-
bipyridine with 3,4-dibutyl-2-iodothiophene15 gives the
dithienyl compounds, which is readily metallated with
LDA at low temperature. Subsequent reaction with io-
dine afforded compound 2 in fair yield. With these two
starting materials in hands it was easy to produce the di-
mer and trimer by cross-coupling half an equivalent of
3,4-dibutyl-2,5-diiodothiophene15 or compound 2 with
2equiv of compound 3 in the presence of low valent pal-
ladium(0) complexes (Scheme 1).16 The dimer17 and tri-
mer18 were produced in, respectively, 70% and 86%
isolated yields. The monomer19 was synthesized in 71%
yield according to a three-steprpotocol sketched in
Scheme 2.
The first trial is to prepare the starting material 3
(Scheme 2). As foreseen, the mono-substitution of 5,50-
dibromo-2,20-bipyridine using a single acetylene source
in sub-stoichiometric conditions failed due to the very
difficult separation step induced by the close polarity
of the resulting products. After some experimentation
we were pleased to find that access to derivative 3 first
requires the dissymmetrization of the bipyridine frame-
work by a palladium promoted reaction with two differ-
ent acetylene sources displaying different polarities. We
succeeded to produce the pivotal intermediate (TES or
TMS/2-hydroxyprop-2-yl alcohol) in 33% isolated yield
by the mean of a facile chromatographic separation
from the less-polar bis-TES or TMS derivatives and
the most polar bis-2-hydroxyprop-2-yl derivative
(Scheme 2). These side products could be used in the
production of symmetrically substituted bipyridine
synthons.
Unfortunately, both dimer and trimer remain unreactive
towards metallation and iodation sequence of reactions
and consequently this drastically limits the engineering
of the higher oligomers by implementation with building
block 3. However, these ligands are themselves interest-
ing scaffolds for the complexation of luminescent transi-
tion metals.
One elegant way to circumvent this lack of reactivity is
to suggest a protocol where the pivotal building block
carries an iodothiophene group on one side and a kinet-
ically stable and protected acetylene function on the
As previously reported subjecting 5,50-dibromo-2,20-
bipyridine to 2equiv of TMS–acetylene followed by
I
N
S
I
I
S
N
S
I
1
2
S
N
H
2
N
S
N
3
N
S
S
N
N
N
S
5
N
N
N
S
S
4
N
N
S
Scheme 1.

A. De Nicola et al. / Tetrahedron Letters 45 (2004) 7963–7967
7965
X = TMS or TES
S
S
N
X
Br
N
N
N
(i)
1) (ii)
2) (iii)
(iv)
N
N
N
N
Br
OH
H
OH
1) (v)
2) (vi)
3
3) (vii)
I
N
(viii)
N
S
S
S
S
N
N
I
monomer19
2
Scheme 2. Reagents and conditions: (i) [PdCl2(PPh3)2], CuI, THF, i-Pr2NH, rt, HC„CX, then HC„CMe2OH, for X = TMS: 33%, for X = TES:
31%; (ii) For X = TMS: KF, MeOH, THF, 96%; (iii) 3,4-dibutyl-2-iodothiophene, [Pd(PPh3)4], n-PrNH2, 60°C, 98%; (iv) NaOH, toluene, 130°C,
97%; (v) [PdCl2(PPh3)2], CuI, THF, i-Pr2NH, rt, acetylene TMS, 77%; (vi) KF, MeOH, THF, 97%; (vii) 3,4-dibutyl-2-iodothiophene, [Pd(PPh3)4],
benzene, Et3N, 60°C, 95%; (viii) LDA, I2, THF, ꢀ78°C, 83%.
N
TES
N
OH
1) (i)
2) (ii)
3) (iii)
N
N
TES
H
H
S
N
I
N
6
(iv)
N
X
S
N
N
N
N
S
N
X
7a X = TES
7b X = H
(v)
(ii)
S
5
X =
Scheme 3. Reagents and conditions: (i) NaOH, anhydrous toluene, 130°C, 97%; (ii) 3,4-dibutyl-2-iodothiophene, [Pd(PPh3)4], benzene, Et3N, 60°C,
compound 6: 86%, compound 5: 86%; (iii) LDA, NIS, THF, ꢀ78°C, 80%; (iv) [Pd(PPh3)4], benzene, Et3N, 60°C, 93%; (v) K2CO3, MeOH, THF,
90%.
other side. This approach would lead to oligomers with
TES acetylene end groups, which might be easily depro-
tected and able to react smoothly with 3,4-dibutyl-2-
iodothiophene. Indeed, the key derivative 6 is prepared
as sketched in Scheme 3 from the dissymmetrically sub-
stituted TES/2-hydroxyprop-2-yl bipyridine moiety by a
sequence of reactions including: (i) a selective deprotec-
tion of the 2-hydroxyprop-2-yl with NaOH in refluxing
anhydrous toluene,20 (ii) a cross-coupling reaction with
3,4-dibutyl-2-iodothiophene and finally (iii) a metalla-
tion with LDA at ꢀ78°C followed by a reaction with
iodine. A double cross-coupling reaction with 5,50-die-
thynyl-2,20-bipyridine provides the TES protected trimer
7a, readily deprotected to 7b. Finally, trimer 5 is likely
synthesized by double cross-coupling of compound 7b
with 3,4-dibutyl-2-iodothiophene.

7966
A. De Nicola et al. / Tetrahedron Letters 45 (2004) 7963–7967
We next turned our attention to the dimer 4, which
could be conveniently produced in a similar fashion by
a double cross-coupling of the 3,4-dibutyl-2,5-diiodo-
thiophene with a dissymmetrically substituted TES/
2-hydroxyprop-2-yl bipyridine synthon, followed by
deprotection and end-capping with 3,4-dibutyl-2-iodo-
thiophene (Scheme 4). In the latter synthetic scheme
the choice of a TES versus TMS protecting group is
motivated by its good chemical stability.
The 1H NMR allows us to properly characterize the five
ligands. We can notice that the size of the ligands has no
influence on the chemical shift values of any protons of
the molecules. For each of them, we found three signals
at 8.78, 8.43 and 7.90ppm for the bipyridine protons,
one singlet at 6.92ppm for thiophene protons and two
signals for the CH2, in a-position of the thiophenes at
2.75 and 2.53ppm. This second signal is a triplet, inte-
grating for four protons corresponding to the a-CH2
of the two external chains on the two ÔendÕ thiophene
rings. These observations confirm that each unit (bipyri-
dine/C„C triple bond/3,4-dibutylthiophene/C„C triple
bond) lies in the same electronic and topological
environment.
Interestingly, derivatives 7b and 8b are useful platforms
for the preparation of the larger oligomers. For in-
stance, reaction of intermediates 7b and 8b with com-
pound 6 affords the opportunity to increase the
molecular size by adding two supplementary bipy/thio-
phene modules. The pentamer and tetramer precursors
9a and 10a could be end-capped by subsequent depro-
tection and reaction with 3,4-dibutyl-2-iodothiophene
leading to the target ligand 9c21 and 10c22 (Scheme 5).
In summary, we have outlined linear multistepprotocols
for the synthesis of symmetrically and unsymmetrically
substituted bipyridine synthons from readily availa-
ble precursors. These molecules were used to prepare
TES
X
X
N
N
N
S
N
N
(i)
I
I
+
2
S
8a X = TES
8b X = H
(v)
(ii)
N
1
S
4
X =
H
Scheme 4. Reagents and conditions: (i) [Pd(PPh3)4], benzene, Et3N, 60°C, 53%; (ii) K2CO3, MeOH, THF, 96%; (iii) 3,4-dibutyl-2-iodothiophene,
[Pd(PPh3)4], benzene, Et3N, 60°C, 70%.
H
N
N
N
S
H
S
N
N
N
N
N
7b
8b
N
H
H
S
N
N
TES
(i)
S
N
I
X
6
N
N
(i)
TES
N
S
N
X
I
N
6
S
S
N
N
N
N
N
N
S
S
N
X
S
N
N
N
N
9a X = TES
9b X = H
N
(ii)
(iii)
10a X = TES
10b X = H
S
S
(iv)
(iii)
N
S
9c X =
N
S
N
10c X =
X
Scheme 5. Reagents and conditions: (i) [Pd(PPh3)4], benzene, Et3N, 60°C, compound 9a: 86%, compound 10a: 87%; (ii) KF, THF, MeOH, 80%;
(iii) 3,4-dibutyl-2-iodothiophene, [Pd(PPh3)4], benzene, Et3N, 60°C, compound 9c: 38%, compound 10c: 33%; (iv) K2CO3, THF, MeOH, 81%.

A. De Nicola et al. / Tetrahedron Letters 45 (2004) 7963–7967
9. Ziessel, R. Synthesis 1999, 1839.
7967
new-segmented ligands bearing a controlled number of
chelating fragments in a convergent manner by a ra-
tional approach using palladium catalyzed CC bond
formation reactions. Notice that each bipyridine unit
is from an electronic point of view in the same environ-
ment and that such a protocol may serve as a useful han-
dle for further manipulation. Work is currently in
progress in order to further define the overall scope of
the sequence and to complex the free sites with lumines-
cent metals. The results of these findings will be reported
in the due course.
10. Ziessel, R.; Stroh, C. Tetrahedron Lett. 2004, 45,
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11. Fichou, D. In Handbook of Oligo- and Polythiophenes;
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Acknowledgements
15. Ringenbach, C.; De Nicola, A.; Ziessel, R. J. Org. Chem.
2003, 68, 4708.
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This work was supported by the Centre National de la
´
Recherche Scientifique, the Universite Louis Pasteur
and the Ministere de la Recherche Franc¸aise et des Nou-
`
´
velles Technologies. We warmly thank Aurelien Viterisi
17. Spectral data for dimer 4: 1H NMR (200MHz, CDCl3): d
8.78 (m, 4H), 8.43 (m, 4H), 7.89 (m, 4H), 6.92 (s, 2H), 2.75
(m, 8H), 2.53 (m, 4H), 1.53 (m, 24H), 0.98 (m, 18H);
FAB+ m/z (nature of the peak, relative intensity) 989.5
([M+H]+, 100).
and Marina Traore for their contribution in the devel-
opment of this research programme.
References and notes
18. Spectral data for trimer 5: 1H NMR (200MHz, CDCl3): d
8.78 (m, 6H), 8.43 (m, 6H), 7.89 (m, 6H), 6.92 (s, 2H), 2.72
(m, 12H), 2.53 (m, 4H), 1.52 (m, 32H), 0.98 (m, 24H);
FAB+ m/z (nature of the peak, relative intensity) 1385.6
([M+H]+, 100).
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19. Spectral data of monomer: H NMR (200MHz, DCl3): d
8.77 (d, 4J = 2.1Hz, 2H), 8.41 (d, 3J = 8.1Hz, 2H), 7.88
(dd, 3J = 8.1Hz, 4J = 2.1Hz, 2H), 6.92 (s, 2H), 2.75 (m,
4H), 2.53 (m, 4H), 1.50 (m, 32H), 0.98 (m, 6H), 0.96 (m,
6H); FAB+ m/z (nature of the peak, relative intensity)
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21. Spectral data for the pentamer 9c: 1H NMR (200MHz,
CDCl3): d 8.78 (m, 10H), 8.44 (m, 10H), 7.90 (m, 10H),
6.92 (s, 2H), 2.75 (m, 20H), 2.53 (m, 4H), 1.55 (m, 48H),
0.99 (m, 36H); FAB+ m/z (nature of the peak, relative
intensity) 2179.2 ([M+H]+, 100).
22. Spectral data for tetramer 10c: 1H NMR (200MHz,
CDCl3): d 8.78 (m, 8H), 8.43 (m, 8H), 7.90 (m, 8H), 6.92
(s, 2H), 2.75 (m, 16H), 2.53 (m, 4Hz), 1.53 (m, 40H), 0.99
(m, 30H); FAB+ m/z (nature of the peak, relative intensity)
1782.7 ([M+H]+, 100).