Synthesis of valuable terpyridine building blocks to generate a variety of metallodendrons by the convergent approach

Article abstract of DOI:10.1016/j.tetlet.2007.03.160

Efficient strategies for the synthesis of three building-blocks 4′-(functionalized)-2,2′:6′,2″-terpyridine have been developed for the convergent synthesis of metallodendrons; these strategies provide a practical approach for the rational design of highly

Full text of DOI:10.1016/j.tetlet.2007.03.160

Tetrahedron Letters 48 (2007) 4143–4146
Synthesis of valuable terpyridine building blocks to generate
a variety of metallodendrons by the convergent approach
*
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´
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´
Frederic Dumur, Cedric R. Mayer, Eddy Dumas, Jerome Marrot and Francis Secheresse
Institut Lavoisier de Versailles, UMR 8180 CNRS, Universite´ de Versailles, 45 Avenue des Etats-Unis, 78000 Versailles, France
Received 16 March 2007; accepted 28 March 2007
Available online 3 April 2007
Abstract—Efficient strategies for the synthesis of three building-blocks 40-(functionalized)-2,20:60,200-terpyridine have been developed
for the convergent synthesis of metallodendrons; these strategies provide a practical approach for the rational design of highly con-
jugated metallodendrimers.
Ó 2007 Elsevier Ltd. All rights reserved.
In the early 1990s, Balzani’s and Newkome’s research
groups extended the already active field of dendrimer
chemistry by incorporation of metallic centres in highly
branched macromolecules.1 These metallodendrimers
are of great interest because of their novel physico-
chemical properties (catalysis, optics, electrochemistry,
photochemistry, etc.).2 Newkome et al. distinguished
four main classes of metallodendrimers depending on
the position and the role played by the metallic centre
M.2 In the first one, metal cores bear organic dendritic
branches.2,3 In the second one, metals are located at
the periphery of an organic dendritic core leading to sur-
face functionalized metallodendrimers.2,4 In the third
class, metals act as branching centres. The [M(di-
imine)3]2+ unit has been often employed for this type
of metallodendrimers as a consequence of its D3 symme-
try, favourable for the synthesis of dentritic structures,
and also as a consequence of the facile functionalization
of the bipyridine or the phenanthroline units.2,5,6 In the
last main class distinguished by Newkome et al., metals
act as building-block connectors. The great majority of
metallodendrimers of this family is built up from the
[M(40-(functionalized)-2,20:60,200-terpyridine)2]2+ frag-
ment due to the high binding affinity of terpyridine with
transition metals and also due to the facile functionali-
zation of the 40-position of terpyridine.7 In all these sys-
tems, another distinction must be made according to the
nature of the organic component. The organic part of
the dendrimer either contains saturated carbon chains
of variable length, bearing, for example, ether func-
tions,8 or is constituted by a fully conjugated system.5,6
Such conjugated metallodendrimers are indeed tailored
to potentially enhance electronic transfers between the
metallic centres.
A large variety of approaches have been employed to
synthesize metallodendrimers such as the so-called ‘com-
plexes as metals/complexes as ligands’ strategy in which
metal complexes are used as building blocks,9 by pyr-
azine connection,10 imidazole junction11 or Suzuki cou-
pling.6 The Sonogashira cross-coupling reaction has
already been used successfully to synthesize binuclear
complexes12 or star-shaped p-conjugated ligands provid-
ing a platform to generate new metallodendrimers.13
The Sonogashira coupling,14 which can be used to intro-
duce the ethynyl group as a spacer between two aryl
groups, has been commonly carried out using aryl
bromides. However, it is now well established that the
aryl halide reactivity follows the expected trend
iodide > bromide ꢀ chloride.15
In this Letter, we report the synthesis of three 40-func-
tionalized terpyridine derivatives, 40-(4-iodophenyl)-
2,20:60,200-terpyridine (1),16 40-(3,5-diiodophenyl)-2,20:
60,200-terpyridine (2) and 40-(3,5-bis(ethynyl)phenyl)-
2,20:60,200-terpyridine (3), bearing one iodide, two iodides
or two ethynyl pendant groups, respectively. The three
derivatives were used to generate a ruthenium metallo-
dendron of first generation. The efficient strategy
reported here, in which the terpyridine iodide derivatives
were submitted to the Sonogashira coupling reactions,
can be easily tuned to synthesize a variety of symmetric
and asymmetric metallodendrimers.
Keywords: Terpyridine; Ruthenium(II); Sonogashira coupling.
*
Corresponding author. Tel.: +33 1 39 25 43 97; fax: +33 1 339 25 43
81; e-mail: cmayer@chimie.uvsq.fr
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.03.160

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F. Dumur et al. / Tetrahedron Letters 48 (2007) 4143–4146
N
O
(a)
(b)
I
I
N
N
1
N
I
I
O
N
I
I
N
2
Scheme 1. Reagents and conditions: (a) 2-acetylpyridine, KOH,
MeOH/NH3 (30%); (b) (i) 2-acetylpyridine, KOtBu, THF; (ii)
NH4OAc, MeOH.
Terpyridine iodide derivatives 1 and 2 were synthesized
starting from 4-iodobenzaldehyde17 and 3,5-diiodobenz-
aldehyde,18 respectively. Two methods were used for the
synthesis of each molecule 1 and 2. The first method
(Scheme 1, synthesis of 1) was a one-pot procedure using
2-acetylpyridine and the appropriate benzaldehyde
derivative in alkaline methanolic solution.19a In the
second method (Scheme 1, synthesis of 2), the first step
afforded the 3-(functionalized)-1,5-di(pyridin-2-yl)-pent-
2-ene-1,5-dione while the second step was a cyclization
reaction generating the central pyridine by reaction
with ammonium acetate in methanol.19b Compound 1
was obtained with similar yields (ꢁ63%) using both
methods; nevertheless, using the first method, the pure
product was easily recovered by direct precipitation
from the reaction medium while the second method
required a purification by chromatography. The one-
pot method did not allow the synthesis of 2 due to rapid
precipitation of 3-(3,5-diiodophenyl)-1-(pyridin-2-yl)-
prop-2-en-1-one in the reaction medium. Compound
2 was isolated in 57% yield using the second method.
Recrystallization from DMSO afforded colourless
crystals suitable for single-crystal X-ray diffraction
analysis (Fig. 1).20
Figure 1. Structure of 40-(3,5-diiodophenyl)-2,20:60,200-terpyridine (2).
Ellipsoids are at the 30% probability level.
Me3Si
SiMe3
I
I
(a)
(b)
O
O
O
(c)
SiMe3
Me3Si
I
I
(a)
(d)
N
N
N
N
N
N
N
N
N
2
3
Scheme 2. Reagents and conditions: (a) Me3Si–C„CH, Pd(PPh3)2Cl2,
CuI, DMF/Et3N; (b) NaOH, THF; (c) (i) 2-acetylpyridine, KOtBu,
THF; (ii) NH4OAc, MeOH; (d) NaOH, THF/MeOH.
Terpyridine derivative 3, bearing two ethynyl pendant
groups, was synthesized using two different strategies
summarized in Scheme 2. In the first route, 3,5-bis-(ethyn-
yl)benzaldehyde was prepared according to previously
published procedures except that 3,5-diiodobenzalde-
hyde was used as the starting reagent instead of 3,5-
dibromobenzaldehyde.21 3,5-Bis-(ethynyl)benzaldehyde
was finally reacted with 2 equiv of 2-acetylpyridine and
KOtBu in THF to give 3 that was further purified by
flash chromathography (45% yield). In the second route,
the Sonogashira cross-coupling reaction of 2 and 2 equiv
of trimethylsilylacetylene, in the presence of catalytic
amounts of Pd(PPh3)2Cl2 and CuI, gave 40-(3,5-bis-
(trimethylsilyl-ethynyl)-phenyl)-2,20:60,200-terpyridine in
96% yield. The trimethylsilyl groups were removed in
the final step with sodium hydroxide in THF to obtain
3 in 90% yield.
ing from the core of the metallodendrimer while the con-
vergent approach starts from the periphery and
proceeds by iterative growth of the branches towards
the core of the metallodendrimer. The metallodendrons
and the method described thereafter, summarized in
Scheme 3, are perfectly adapted to generate ruthenium-
or mixed-metal-dendrimers using the convergent
approach. Ruthenium complex 4 was obtained by reac-
tion of 1 with an excess of RuCl3Æ3H2O in refluxing
ethanol. Compound 4 was then reacted with 40-(4-
tolyl)-2,20:60,200-terpyridine (denoted Tolyl Terpy) to give
[(Tolyl Terpy)Ru(1)]2+ (5) in 75% yield. The Sonogashira
coupling in DMF of 2 equiv of the hexafluorophosphate
salt of 5 with 1 equiv of 3 afforded the dinuclear complex
6. Compound 6 was purified by column chromatogra-
phy and its hexafluorophosphate salt isolated as a red
solid in 50% yield. Compound 6 is a key intermediate
complex bearing one pendant terpyridine group that
can potentially react with a variety of metal ions to
generate pentanuclear metallodendrimers of the general
The second part of this Letter is devoted to the synthesis
of metallodendrons by using the above-described
ligands. The so-called divergent and convergent
methods have been described in the literature to gener-
ate metallodendrimers.2 The divergent approach can
be described as the sequential growth of branches start-

F. Dumur et al. / Tetrahedron Letters 48 (2007) 4143–4146
4145
2+
N
N
N
Cl
Ru Cl
Cl
N
N
N
RuCl3
EtOH
TolylTerpy
EtOH/H2O
I
I
N
I
N
N
Ru N
N
N
6+
1
4
5
N
4+
N
N
N
N
N
N
N
N
Ru
Ru
N
N
N
N
N
N
N
N
N
N
Ru
N
Ru
N
N
N
N
N
N
N
Cl
Ru Cl
Cl
N
N
I
N
N
N
N
Ru
N
N
N
N
N
4
3
N
5
Pd(PPh3)4, CuI
DMF/DIPA
DMF/EtOH/H2O
6
I
7
Scheme 3. Synthesis of the metallodendrons.
formula [M(6)2]n+ (M = Fe, Zn, Ru, Os, Ir, etc.). In our
study, 6 was reacted with 1 equiv of 4 to give the trinu-
clear metallodendron 7 in 69% yield. Compound 7 can
be described as a first generation metallodendron pos-
sessing a single functional aryl iodide unit that could
be further involved in a Sonogashira coupling reaction
to build metallodendrimers of higher generation.
References and notes
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In summary, we synthesized and characterized three ter-
pyridine derivative ligands bearing aryl iodide or ethynyl
functional pendant units. These ligands have been used
to prepare mono-, di- and tri-nuclear complexes of
ruthenium. The ligands and the ruthenium complexes
described in this Letter are very attractive building
blocks for several reasons. They possess functional pen-
dant groups that make them ideal candidates for the
Sonogashira coupling reaction; they are therefore valu-
able building blocks to generate a variety of metalloden-
drons and metallodendrimers using the convergent
method. The synthetic approach can also be easily tuned
in order to obtain mixed-metal dendrons and dendri-
mers. The methodology presented in this Letter also
allows the straightforward synthesis of fully conjugated
metallodendrimers that could facilitate potential elec-
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metallic complexes such as compound 6 that can be
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l(MoKa) = 3.350 mmꢂ1
, 10,054 reflections measured,
2447 independent (Rint = 0.0428), 229 parameters, R1 =
0.0825, wR2 = 0.1997 with I > 2r(I). The data were
collected on a Bruker X8-APEX2 CCD area-detector
diffractometer using MoKa radiation. Semiempirical
absorption correction was applied. Crystallographic data
(excluding structure factors) for the structure of 2 have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC 635519.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK, (fax: +44-(0)1223-336033 or e-mail: deposit@
ccdc.cam.ac.uk).
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20. Crystal data for 2: C21H13I2N3, M = 561.14, monoclinic,
´
space group P21/c, a = 18.794(2), b = 4.5829(6), c =
24.954(3) A, b = 118.851(4)°, V = 1882.6(4) A , Z = 4,
23. Mayer, C. R.; Dumas, E.; Michel, A.; Secheresse, F.
3
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Chem. Commun. 2006, 4183.