6-(Arylvinylene)-3-pyridinylboronic esters. Part 2: Versatile building blocks for push-pull nonlinear optical chromophores

Article abstract of DOI:10.1016/S0040-4039(03)01427-8

This paper describes a general approach for the synthesis of push-pull 6,6′-disubstituted-3,3′-bipyridine chromophores. As examples, 6-(4-ethanol-2-thienylvinylene)-5-methyl-3-bromopyridine, 6-(4-hydroxy-phenylvinylene)-5-methyl-3-bromopyridine, and the corresponding 3-pyridinylboronic esters have been prepared as building blocks end-capped with electron donor groups (D). 6-(4-Cyano-phenylvinylene)-5-methyl-3-bromopyridine, and 6-(4-cyano-phenylvinylene)-3-bromopyridine have been synthesized as building blocks end-capped with electron acceptor groups (A). {A x D} type cross-couplings via Suzuki reaction gave the push-pull chromophores (I) and (II) in high yields and multigram scales.

Full text of DOI:10.1016/S0040-4039(03)01427-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5883–5887
6-(Arylvinylene)-3-pyridinylboronic esters. Part 2: Versatile
building blocks for push–pull nonlinear optical chromophores
Nicolas Leclerc, Laurent Galmiche 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 2 June 2003; revised 3 June 2003; accepted 3 June 2003
Abstract—This paper describes a general approach for the synthesis of push–pull 6,6%-disubstituted-3,3%-bipyridine chromophores.
As examples, 6-(4-ethanol-2-thienylvinylene)-5-methyl-3-bromopyridine, 6-(4-hydroxy-phenylvinylene)-5-methyl-3-bromopyridine,
and the corresponding 3-pyridinylboronic esters have been prepared as building blocks end-capped with electron donor groups
(D). 6-(4-Cyano-phenylvinylene)-5-methyl-3-bromopyridine, and 6-(4-cyano-phenylvinylene)-3-bromopyridine have been synthe-
sized as building blocks end-capped with electron acceptor groups (A). {A x D} type cross-couplings via Suzuki reaction gave the
push–pull chromophores (I) and (II) in high yields and multigram scales.
© 2003 Elsevier Ltd. All rights reserved.
Organic second-order nonlinear optical (NLO) poly-
meric materials have been intensively studied for many
years.1,2 In these systems NLO noncentrosymmetric
chromophores are either covalently attached to the
backbone as side-groups, or are made part of the
polymer backbone itself. A typical NLO chromophore
consists of an electron-accepting group and an electron-
donating group connected by a p-conjugated bridge
(push–pull structure). The structure–property relation-
ships of the molecular NLO property (i) of these
one-dimensional dipolar chromophores have been theo-
retically and experimentally established.3–5
with corresponding aromatic aldehydes: thienyl ring as
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,6,7 electrochemical,6,7 photo-
luminescent,6,7 and second- as well as third-order NLO
properties of the chromophores.7–9 However, despite
the above-mentioned attractive features, the previous
two-step synthetic route, in the case of the nonsymmet-
ric chromophores, restricts the yield because of separa-
tion and purification difficulties. Consequently, it was
difficult to access many combinations of donor/accep-
tor pairs. This is the reason why it was necessary to
define a new more efficient synthetic route to obtain
such unsymmetrical conjugated chromophores. More-
over, we were interested in synthesizing chromophores
with reactive functionalities (e.g. hydroxyl groups) at
one end to covalently couple the chromophores to a
polymer backbone.
In previous papers,6–9 we have described a novel class
of conjugated molecules.
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%-bipyridines by a Ni(0)-coupling of 3-
halopyridines,10 only, to our knowledge, the synthesis
of 3-heteroarylpyridines,11 and unsubstituted symmetric
3,3%-bipyridines,12 by Pd(0)-catalyzed cross-coupling of
3-stannylpyridines or 3-pyridylboranes with heteroaryl
halides or 3-bromopyridine respectively, have been
reported in the literature.
These compounds are either symmetric molecules (a) or
asymmetric 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
* 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)01427-8

5884
N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5883–5887
(Scheme 2) by utilizing, for the first time to our knowl-
edge, a nonsymmetric Suzuki-type palladium-catalyzed
cross-coupling of a conjugated 6-substituted-3-pyridyl-
borane based building block with a conjugated 6-substi-
tuted-3-bromopyridine based building block. To
illustrate the versatility of this pathway, the cross-cou-
pling of Br(3) with B(1), and of Br(3) with B(2) have
been tested, giving (I) and (II) as {Br(3) x B(1)} and
{Br(3) x B(2)} type chromophores respectively. More-
over, as shown in Schemes 1 and 2, the lateral substitu-
tion of the pyridinic ring was also a parameter of the
cross-coupling.
We have recently described a new general route to
access to 6,6%-(disubstituted)-3,3%-bipyridine based con-
jugated chromophores.13 This new large-scale strategy
was based on (i) the synthesis of a library of p-conju-
gated 6-substituted-3-bromopyridine 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. As an example, we have reported on the
synthesis of novel conjugated 6-substituted-3-bromopy-
ridine and 6-substituted-3-pyridylboronic diester build-
ing blocks incorporating the electron-rich thienyl ring
(Br(1) and B(1) respectively as reported in Schemes 1
and 2), and successfully demonstrated that such blocks
can be homo- and cross-coupled in high yields and
multigram scales, leading to {Br(1) x B(1)} type
chromophores.
The key materials, 2,3-dimethyl-5-bromopyridine (1a)
and 2-methyl-5-bromopyridine (1b), were prepared as
described previously.6 The hydroxyl group of (5) was
protected with TBDMS, which is chosen because it can
tolerate later lithiation. The hydroxy functionalized
derivative (3) was obtained by formylation, with n-
butyllithium (n-BuLi) and DMF, of the protected 2-(2-
thienyl)ethanol, as shown in Scheme 1. The detailed
procedure has been reported previously.13
The goal of the present paper is to extend this strategy
to push–pull chromophores, highlighting the main
advantage of the synthetic pathway, that is the flexibil-
ity to combine ‘tailor-made’ building blocks depending
on the expected mesogenic, electrochemical or optical
properties of the chromophore. This second contribu-
tion describes (i) the synthesis of p-conjugated 6-substi-
tuted-3-bromopyridine building blocks incorporating or
an electron donor group (Br(2)) either an electron
attractor group (Br(3)) (Scheme 1), (ii) borylation of
some of them by using a boronic diester (B(2)), and (iii)
the modular preparation of different unsymmetrically
Two different routes were used for the synthesis of the
conjugated 6-substituted-3-bromopyridine building
blocks, depending on the electron-donor or electron-
attractor character of the substituent. We have previ-
ously defined a two-step procedure to access the
building block with electron-rich ring (Br(1)). This
route has been adapted for the synthesis of the building
block bearing the protected p-hydroxybenzaldehyde as
6,6%-disubstituted-3,3%-bipyridine
chromophores
Scheme 1. Obtention of bromo building blocks Br(1), Br(2) and Br(3).

N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5883–5887
5885
Scheme 2. Obtention of boronic esters building blocks B(1)–B(2), and chromophores I–II.
of boronic diesters. As examples, TBDMS-protected
hydroxy functionalized building block Br(1) and Br(2)
has been converted to boronated building blocks B(1)
and B(2) upon reaction with n-BuLi and 2-isopropoxy-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane in anhydrous
THF. The new compound B(2) was isolated, after
purification, in a 90% yield, and a multigram scale. As
B(1), this compound is stable. However, it should be
noted that this route is not available for building blocks
bearing the electron-withdrawing cyano-group, because
of the sensitivity of this one towards n-BuLi.
donor group. In this general procedure, reaction of (1a)
with lithium diisopropylamide (LDA) generated the
red-colored lithio-anion, which reacted with the appro-
priate aldehyde to give the corresponding alcohol
(Scheme 1a). Subsequent treatment with p-toluenesul-
fonic acid produced the respective p-conjugated 6-sub-
stituted-3-bromopyridine building blocks in 80–85%
yield on the 10–20 g scale: Br(1), previously described,13
and the new molecule Br(2). On the other hand,
because the presence of the cyano electron acceptor
group precludes the use of this general procedure in the
case of the aldehyde (8), an alternative route has been
used,14 as reported in Scheme 1b. Thus, the building
blocks end-capped with the cyano substituent (Br(3a)
and Br(3b)) have been obtained in reasonable yield
(31%) on the multigram scale from the one-step Knoev-
enagel type condensation reaction, in acidic medium, of
1a and 1b respectively, with the para-cyanobenzalde-
hyde (8). The three novel compounds Br(2), Br(3a) and
Br(3b) have been characterized by NMR spectroscopy.
Whatever the synthetic sequence, the presence exclu-
sively of the trans-vinylene unit was clearly evidenced
by the three bonds coupling constant (3JH,H:16 Hz) in
1H NMR spectra.
As our main aim was to use the palladium-catalyzed
Suzuki cross-coupling for the preparation of various
push–pull chromophores, two representative chro-
mophores (I–II) have been synthesized.15 As sketched in
Scheme 2, the brominated building block Br(3) was
coupled with the pyridylborane based building blocks
(B1 and B2), giving, after deprotection, chromophores I
and II respectively in 75% yield and on the gram scale.
Chromophores I and II bearing a hydroxyl group could
be grafted as side-groups, onto a polymer backbone.
All these compounds had spectral data consistent with
the assigned structure.16
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). We
have previously reported on a one-pot procedure for
the incorporation of the coupling functionality (boronic
acid diester function).13 It involves (i) the regiospecific
lithiation at position 3 of appropriate 3-bromopyridine
based building block followed by (ii) the introduction
Because linear optical properties of II have been
reported elsewhere, only the absorption and emission
characteristics of I in solution have been measured. As
illustrated in Figure 1, II exhibits an intense absorption
band in the UV-blue range (uabs=383 nm), whatever
the solvent, which indicates that no noticeable solva-
tochromic shift is observed. This is a feature of this
series of chromophores, in contrast to typical NLO
ones. The value of uabs lies near the one of I (373 nm).
On the other hand, an evolution of the position of the

5886
N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5883–5887
5. Alheim, M.; Barzoukas, M.; Bedworth, P. V.; Blanchard-
Desce, M.; Fort, A.; Hu, Z. Y.; Marder, S. R.; Perry, J.
W.; Runser, C.; Staehelin, M.; Zysset, B. Science 1996,
271, 335–337.
6. (a) Attias, A.-J.; Cavalli, C.; Bloch, B.; Guillou, N.; Noe¨l,
C. Chem. Mater. 1999, 11, 2057–2068; (b) Attias, A.-J.;
Hapiot, P.; Wintgens, V.; Valat, P. Chem. Mater. 2000,
12, 461–471.
7. Lemaˆıtre, N.; Attias, A.-J.; Ledoux, I.; Zyss, J. Chem.
Mater. 2001, 13, 1420–1427.
8. Che´rioux, F.; Attias, A.-J.; Maillotte, H. Adv. Funct.
Mater. 2002, 12, 203–208.
9. Chen, Q.; Sargent, E. H.; Leclerc, N.; Attias, A.-J. Appl.
Phys. Lett. 2003, 82, 4420–4422.
Figure 1. Normalized absorption and fluorescence emission
spectra of I in dioxane, CH2Cl2 and DMF.
10. Constable, E. C.; Morris, D.; Carr, S. New J. Chem.
1998, 22, 287–291 and references cited therein.
11. (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis
1984, 936–938; (b) Gronowitz, S.; Bjo¨rk, P.; Malm, J.;
Ho¨rnfeld, A.-B. J. Org. Chem. 1993, 460, 127–129; (c)
Bouillon, A.; Lancelot, J. C.; Collot, V.; Bovy, P. R.;
Rault, S. Tetrahedron 2002, 58, 3323–3328.
12. (a) Lopez, S.; Kahraman, M.; Harmata, M.; Keller, S. W.
Inorg. Chem. 1997, 36, 6138–6140; (b) Radig, R. S.; Lam,
R.; Zavalij, O. Y.; Katala Ngala, J.; LaDuca, R. L.;
Greedam, J. E.; Zubieta, J. Inorg. Chem. 2002, 41, 2124–
2133.
emission maximum is observed according to the solvent
polarity. A large shift (2600 cm−1) is observed when
dioxane is replaced with DMF. This large solva-
tochromic behavior observed for the new molecule I is
attributed to an intramolecular charge transfer (ICT)
state involving charge separation within the whole
molecule, inducing consequently a large dipole moment
for the excited state, and NLO properties as observed
for the other push–pull chromophores of this series.7
Because the thienyl group is a weak donor group, the
NLO properties should be relatively low, similar to the
ones measured previously for II (viꢀ20×10−48 esu). It
should be noted that the goal of this work was not to
synthesize chromophores with large molecular nonlin-
earities, but to test a synthetic strategy.
13. Leclerc, N.; Serieys, I.; Attias, A.-J. Tetrahedron Lett.
2003, 44, 5879–5882.
14. 2,3-Dimethyl-5-bromopyridine (1b) (4.255 g, 22.9 mmol),
4-cyanobenzaldehyde (2) (3 g, 22.9 mmol) and p-toluene-
sulfonic acid (0.805 g, 4.58 mmol) were blended. The
mixture was then stirred at 160°C. After 36 h, the mixture
was cooled to room temperature and washed with brine.
The aqueous layer was extracted with dichloromethane.
The resulting organic layer was washed with distilled
water and dried over Na2SO4. The solvent was removed
under reduced pressure. The crude product was purified
by three washings with acetone. 2.14 g (7.16 mmol) of
clear powder was obtained (Yield: 31%). 1H NMR
In summary, we have defined a combinatorial strategy
to synthesized symmetric,13 and nonsymmetric 6,6%-(di-
substituted)-3,3%-bipyridine based conjugated chro-
mophores. First we have described the synthesis of
novel conjugated 6-substituted-3-bromopyridine and 6-
substituted-3-pyridylboronic 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 conditions. This versatile approach opens
up the way to develop this family of reactive chro-
mophores for optoelectronics, and more particularly to
obtain new chromophores with enhanced NLO perfor-
mances by using stronger electron-donor and -acceptor
groups.
3
(CDCl3) l [ppm]: 2.45 (s, 3H), 7.35 (d, 1H, JH,H=15.7
3
Hz), 7.65 (m, 5H), 7.79 (d, 1H, JH,H=15.7 Hz), and 8.52
4
(d, 1H, JH,H=2.3 Hz). 13C NMR (CDCl3) l [ppm]: 17.8,
110.7, 118.1, 118.7, 125.7, 126.7, 126.9, 127.1, 131.6,
132.1, 139.6, 140.0, 140.5, 147.3, 147.7 and 150.4.
15. Typical procedure: Dioxaborolane derivative B(1) (1.518
g, 3.2 mmol), bromide derivative Br(3a) (0.90 g, 3.2
mmol) and (PPh3)4Pd(0) (0.5–2.0 mol%) were dissolved in
a mixture of THF ([B(1)]=[Br(3a)]=0.4 M) and aqueous
2 M K2CO3 (1:1.5 THF). The solution was first put under
argon atmosphere and was heated at 80°C with vigorous
stirring for 48 h. After extraction, the aqueous layer was
extracted with dichloromethane and the combined
dichloromethane layers were washed with distilled water
and dried over Na2SO4. The solvent was removed under
reduced pressure. The crude product was crystallized
twice from hexane and acetonitrile, yielding compound I,
protected (1.39 g, 2.62 mmol, 82%). Dimethyl-tert-
butylsilyl ethers are cleaved rapidly to alcohols by treat-
ment with fluoride acid (10 equiv.) in tetrahydrofuran at
room temperature for 5 h. Then the mixture was poured
into ammoniac solution. The two phases were separated.
The aqueous phase was extracted with dichloromethane
and the combinated organic phases were washed with
References
1. Nalwa, H. S.; Miyata, S. Nonlinear Optics of Organic
Molecules and Polymers; CRC Press: Boca Raton, FL,
1997.
2. Dalton, L. Adv. Polym. Sci. 2001, 158, 1–121.
3. Kanis, D. R.; Ratner, M. A.; Marks, T. J. Chem. Rev.
1994, 94, 195–242.
4. Robinson, B. H.; Dalton, L. R.; Harper, A. W.; Ren, A.;
Wang, F.; Zhang, C.; Todorova, G.; Lee, M.; Anisfeld,
R.; Garner, S.; Chen, A.; Steier, W. H.; Houbrecht, S.;
Persoons, A.; Ledoux, I.; Zyss, J.; Jen, A. K. Y. Chem.
Phys. 1999, 245, 35–50.

N. Leclerc et al. / Tetrahedron Letters 44 (2003) 5883–5887
5887
distilled water and dried over Na2SO4. The crude product
was precipitated from dichloromethane solution into hex-
ane solution, yielding pure chromophore I (1.06 g, 2.37
mmol, 74%).
3JH,H=7.8 Hz), 7.67 (s, 4H), 7.68 (d, 1H), 7.71 (d, 1H,
3
4
3JH,H=14.2 Hz), 7.91 (dd, JH,H=8 Hz, JH,H=2.5 Hz),
3
4
7.93 (d, 1H, JH,H=15.9 Hz), 8.70 (d, 1H, JH,H=2.3 Hz)
and 8.89 (d, 1H, 4JH,H=2 Hz). 13C NMR (CDCl3) l [ppm]:
18.9, 40.7, 63.8, 111.4, 118.8, 121.5, 122.8, 124.7, 126.1,
127.5, 128.3, 130.5, 130.6, 130.7, 130.9, 131.9, 132.5, 134.4,
134.6, 135.6, 135.9, 137.9, 140.68, 141.0, 142.6, 144.3, 144.4,
145.1, 147.9, 148.0, 153.3, 153.7, 153.8 and 154.7.
16. Selected data for I: 1H NMR (CDCl3) l [ppm]: 2.49 (s, 3H),
2.91 (t, 2H), 3.62 (m, 2H), 4.85 (s, 1H), 6.77 (d, 1H,
3
3JH,H=3.5 Hz), 7.05 (d, 1H, JH,H=3.8 Hz), 7.06 (d, 1H,
3JH,H=15.2 Hz), 7.30 (d, 1H, 3JH,H=16.2 Hz), 7.49 (d, 1H,