6-(Arylvinylene)-3-pyridinylboronic esters. Part 1: Versatile building blocks for conjugated chromophores via Suzuki cross-coupling

Article abstract of DOI:10.1016/S0040-4039(03)01393-5

This paper describes a general approach for the synthesis of conjugated 6,6′-disubstituted-3,3′-bipyridine chromophores. As preliminary results, 6-(4-hexyl-2-thienylvinylene)-5-methyl-3-bromopyridine, 6-(4-ethanol-2-thienylvinylene)-5-methyl-3-bromopyridine, and the corresponding 3-pyridinylboronic esters have been prepared. Coupled by Suzuki reaction, they gave the conjugated chromophores (I) and (II) in high yields and multigram scales.

Full text of DOI:10.1016/S0040-4039(03)01393-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5879–5882
6-(Arylvinylene)-3-pyridinylboronic esters. Part 1: Versatile
building blocks for conjugated chromophores via Suzuki
cross-coupling
Nicolas Leclerc, Isabelle Serieys and Andre´-Jean Attias*
Laboratoire de Chimie des Polyme`res (CNRS, UMR 7610), Universite´ P. et M. Curie, 4 place Jussieu, F-75252 Paris Cedex 05,
France
Received 17 April 2003; revised 2 June 2003; accepted 3 June 2003
Abstract—This paper describes a general approach for the synthesis of conjugated 6,6%-disubstituted-3,3%-bipyridine chromophores.
As preliminary results, 6-(4-hexyl-2-thienylvinylene)-5-methyl-3-bromopyridine, 6-(4-ethanol-2-thienylvinylene)-5-methyl-3-bro-
mopyridine, and the corresponding 3-pyridinylboronic esters have been prepared. Coupled by Suzuki reaction, they gave the
conjugated chromophores (I) and (II) in high yields and multigram scales.
© 2003 Elsevier Ltd. All rights reserved.
p-Conjugated organic compounds have emerged as a
promising class of materials for use in electronics and
optoelectronics. Besides semi-conducting (conjugated)
main-chain polymers used in light emitting devices
(LEDs),1 third-order nonlinear optics (NLO),2,3 and
photovoltaic cells,4 are the side-chain polymers (SCPs)
which have been investigated as active layers in LEDs,5
and mainly as second-order NLO materials.2,6 In these
SCPs, active conjugated chromophores are covalently
bound on a saturated polymer backbone as pendant
groups.
donor group, or benzene ring para-substituted with
electron-donor (D) or electron-acceptor (A) groups. By
lateral substitutions of the p-conjugated bridge and by
varying the nature of the acceptor/donor pair, we were
able to tune the mesogenic,7,8 electrochemical,7,8 photo-
luminescent,7,8 and second-order NLO properties of the
push–pull chromophores ((b) series).8 We have also
shown that symmetrical p-conjugated bridge on the one
hand, and reduction of the ground-state aromatic char-
acter by incorporating thienyl ring as electron-rich moi-
ety in the p-conjugated system on the other hand,
enhanced the third-order NLO properties ((a) series).9
In previous papers,7–9 we have described a novel class
of conjugated chromophores.
Considering all the above molecules as model com-
pounds, the use of aldehydes bearing reactive function-
alities (e.g., hydroxyl groups) at one end should offer
the opportunity to synthesize reactive chromophores
able to be grafted on a macromolecular chain, in order
to obtain side-chain polymers exhibiting NLO and/or
emitting properties. It should be noted that whatever
the structure of parents (symmetric chromophores (a)
or push–pull (b)), all the expected functionalized
molecules are unsymmetrical. However, despite the
above-mentioned attractive features, the previous two
steps synthetic route, in the case of the non-symmetric
chromophores, restricts the yield because of separation
and purification difficulties, and consequently the
potential combinations of donor/acceptor pairs. This is
the reason why it was necessary to define a new more
efficient synthetic route to obtain such unsymmetrical
conjugated chromophores.
These compounds are either symmetric molecules (a) or
non-symmetric push–pull molecules (b). They were pre-
pared by a one-step ((a) series) or a two-steps ((b)
series) Knoevenagel type condensation, under acidic
conditions, of 6,6%-dimethyl-3,3%-bipyridine derivatives
with corresponding aromatic aldehydes: thienyl ring as
* Corresponding author. Tel.: +33-1-44-27-53-02; fax: +33-1-44-27-
70-89; e-mail: attias@ccr.jussieu.fr
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01393-5

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N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5879–5882
(un)symmetrically 6,6%-disubtituted-3,3%-bipyridine chro-
mophores by utilizing, for the first time at our knowl-
edge, an non-symmetric Suzuki-type palladium-
catalyzed cross-coupling of a conjugated 6-substituted-
3-pyridylborane based building block with a conjugated
6-substituted-3-bromopyridine based building block
(Scheme 2).
While synthetic approaches to 2,2%-bipyridines and its
derivatives are well-established in the literature,10a–c
there are few strategies leading to unsymmetrical disub-
stituted 2,2%-bipyridines.10d,e They are mainly based on
palladium-catalyzed (Stille or Suzuki) cross-coupling
reactions of pyridine rings. Concerning substituted 3,3%-
bipyridines, few general routes have been described
whatever the symmetry of the molecule: besides the
synthesis of symmetrical 6,6%-disubstituted-3,3%-bipyridi-
nes by a Ni(0)-coupling of 3-halopyridines,11 only, to
our knowledge, the synthesis of 3-heteroarylpyridines,12
and unsubstituted symmetric 3,3%-bipyridines,13 by
Pd(0)-catalyzed cross-coupling of 3-stannylpyridines or
3-pyridylboranes with heteroaryl halides or 3-bromopy-
ridine respectively, have been reported in the litera-
ture.14 In this context, it was a challenge to define a
new, versatile and more efficient synthetic route, which
allows the preparation of unsymmetrical functionalized
p-conjugated 6,6%-disubstituted-3,3%-bipyridine deriva-
tives.
The starting materials, 2,3-dimethyl-5-bromopyridine
(1), was prepared as described previously.7 As reported
in Scheme 1, the hydroxy functionalized derivative (3)
was obtained by formylation, with n-butyllithium (n-
BuLi) and DMF, of the protected 2-(2-thienyl)ethanol,
whereas the 5-hexyl-2-thiophenecarboxaldehyde (6) was
obtained by formylation (Vilsmeier–Haack reaction) of
2-hexylthiophene.
Since the Knoevenagel type condensation, under acidic
conditions,7 afforded building blocks with electron-rich
ring (Br(1), Br(2)) in poor yield, an alternative pathway,
adapted from a procedure reported in the literature15
for symmetrical 4,4%-disubstituted-2,2%-bipyridines, has
been defined. Reaction of (1) with lithium diisopropyl-
amide (LDA) generated the red-colored lithio-anion,
which reacted with the appropriate aldehyde to give the
corresponding alcohol (Scheme 1). Subsequent treat-
ment with p-toluenesulfonic acid produced the respec-
This new large-scale strategy is based on (i) the synthe-
sis of a library of p-conjugated 6-substituted-3-bro-
mopyridine building blocks (functionalized or not), (ii)
their transformation to 6-substituted-3-pyridylboronic
ester building blocks, and (iii) the cross-coupling by the
metal-catalyzed Suzuki reaction. The main advantage
of this synthetic pathway is the flexibility to combine
‘tailor-made’ building blocks depending on the expected
mesogenic, electrochemical or optical properties of the
chromophore. It should be noted that this route allows
also the synthesis of symmetrical compounds.
tive
p-conjugated
6-substituted-3-bromopyridine
building blocks Br(1) and Br(2) in 80–85% yield on the
10–20 g scale. The presence exclusively of the trans-
vinylene unit is clearly evidenced by the three bonds
coupling constant (3JH,H:16 Hz) in H NMR spectra.
1
Because our synthetic approach is based on the non-
symmetric Suzuki-type transition metal-catalyzed cross-
coupling, previous building blocks needed to be
functionalized (borylation) in a way that they can be
used as building blocks in this reaction (Scheme 2). The
incorporation of the coupling functionality (boronic
This first contribution describes (i) the synthesis of
p-conjugated 6-substituted-3-bromopyridine building
blocks incorporating the electron-rich thienyl ring
(Scheme 1), (ii) borylation of them by using a boronic
diester, and (iii) the modular preparation of different
Scheme 1. Obtention of bromo building blocks Br(1) and Br(2).

N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5879–5882
5881
Scheme 2. Obtention of boronic esters building blocks B(1)–B(2), and chromophores I–II.
pounds had spectral data consistent with the assigned
structure.18
acid diester function) involves (i) the regiospecific lithia-
tion at position 3 of appropriate 3-bromopyridine
based building block followed by (ii) the introduction
of boronic diesters. Recently, a two-steps synthesis of
3-pyridinylboronic esters has been reported,12c based on
the preparation of the 3-pyridinylboronic acid, followed
by the in situ transesterification with pinacol. By adapt-
ing standard procedures described for borylation of
aryl halides, we have performed the obtention of the
pyridinylboronic ester in a one-pot procedure.16 As an
example, TBDMS-protected hydroxy functionalized
building block Br(1) has been converted to boronated
building blocks B(1) upon reaction with n-BuLi and
2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
in anhydrous THF. B(1) was isolated, after purification,
as yellowish oil, in a 90% yield, and a 10 g scale. This
compound is stable.
Preliminary linear optical measurements (i.e. absorp-
tion and emission spectra) have been performed in
dichloromethane. I and II exhibited a strong and
intense (m=78000 L mol−1 cm−1) low-lying absorption
band (395 nm), which indicates a highly p-conjugated
system, and intense fluorescence at 490 nm.
In summary, we have defined a strategy to synthesized
symmetric and non-symmetric 6,6%-(disubstituted)-3,3%-
bipyridine based conjugated chromophores. First we
have described the synthesis of novel conjugated 6-sub-
stituted-3-bromopyridine and 6-substituted-3-pyridyl-
boronic diester building blocks. Second, we have
successfully demonstrated, for the first time, that such
blocks can be homo- and cross-coupled in high yields
and multigram scales under standard Suzuki-type con-
ditions. Further experiments concerning the synthesis of
push–pull chromophores by using this approach are
currently under investigation. These results as well as
more information about the photophysical properties
will be published elsewhere.
As our main aim was to use the palladium-catalyzed
Suzuki cross-coupling for the preparation of various
p-conjugated 6,6%-disubstituted-3,3%-bipyridine deriva-
tives, two representative chromophores (I–II) have been
synthesized.17 As sketched in Scheme 2, the brominated
building block Br(1) was coupled with various pyridyl-
borane based building blocks (BrD1 and BrD2), giving,
after deprotection, chromophores I and II respectively
in 70–76% yield and multigram scale. After deprotec-
tion, chromophores I bearing a hydroxyl group could
be graft as side-group, onto a polymer backbone,
whereas II could be used as difunctional monomer and
introduced in a main-chain polymer. All these com-
Acknowledgements
The authors thank Dr. Eric Rose, Dr. Bruno Andrio-
letti and Guillaume Loire (Laboratoire de Synthe`se
Organique et Organome´tallique, Universite´ de Paris 6)
for many helpful discussions.

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N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5879–5882
Sandon, N.; Toupet, L.; Le Bozec, H. New J. Chem.
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