Number of terminal groups versus generation of the dendrimer, which criteria influence the catalytic properties?

Article abstract of DOI:10.1016/j.tetlet.2012.05.070

We report the synthesis of a dense dendrimer ended by the PTA ligand (1,3,5-triaza-7-phosphaadamantane), and the use of the corresponding Rh and Ru complexes for catalysis. The catalytic properties of these dendrimers are compared with those of two other dendrimers: a dendrimer of the same generation but having half the number of ligands, and a dendrimer of the next generation, but having the same number of ligands. The positive influence of the density of catalytic sites on the surface of these dendrimers for alcohol isomerization in water has been evidenced.

Full text of DOI:10.1016/j.tetlet.2012.05.070

Tetrahedron Letters 53 (2012) 3876–3879
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Number of terminal groups versus generation of the dendrimer, which
criteria influence the catalytic properties?
Paul Servin a,b, Régis Laurent a,b, Hanna Dib a,b, Luca Gonsalvi c, Maurizio Peruzzini c, Jean-Pierre
Majoral a,b, Anne-Marie Caminade a,b,
⇑
a CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France
b Université de Toulouse, UPS, INPT, F-31077 Toulouse Cedex 4, France
c Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti Organometallici (ICCOM CNR), Via Madonna del Piano 10, Polo Scientifico di Sesto Fiorentino,
50019 Sesto Fiorentino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
We report the synthesis of a dense dendrimer ended by the PTA ligand (1,3,5-triaza-7-phosphaadaman-
tane), and the use of the corresponding Rh and Ru complexes for catalysis. The catalytic properties of
these dendrimers are compared with those of two other dendrimers: a dendrimer of the same generation
but having half the number of ligands, and a dendrimer of the next generation, but having the same num-
ber of ligands. The positive influence of the density of catalytic sites on the surface of these dendrimers
for alcohol isomerization in water has been evidenced.
Received 26 April 2012
Accepted 11 May 2012
Available online 19 May 2012
Dedicated to Professor Henri-Jean CRISTAU
on the occasion of his 70th birthday
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Dendrimer
Catalysis
PTA (1,3,5-triaza-7-phosphaadamantane)
Introduction
of dendrimers,4 but also in the study of the catalytic properties
of the phosphorus dendrimers that we synthesize.5 In this commu-
Dendrimers1 are at the forefront of polymer researches since
two decades, because of their exceptional characteristics compared
to conventional polymers, such as a precisely defined and mono-
disperse structure, due to their step-by-step repetitive synthesis,
and a large number of terminal groups, the nature of which gov-
erns the interactions of the dendrimer with its environment.
Among many different uses, catalysis with dendrimers occupies
an important place since the first example in 1994.2 Several re-
views have covered this topic,3 but a lot of questions remain un-
solved, in particular the reasons of the so-called dendritic effect,
positive or negative, that is to say a difference in the efficiency
when catalytic entities are linked to the terminations of dendri-
mers. One of the parameters that may influence the catalytic prop-
erties is the density of the terminal groups. However, in the case of
dendrimers, the influence of this parameter is difficult to assess
since the modifications of density are correlated (not linearly) with
the modification of size (generation) in homogeneous families of
dendrimers.
nication, we report our attempts to determine if the density of ter-
minal groups may have some influence on the catalytic properties
of a dendrimer.
Results and discussion
Among the numerous types of ligands that could be used for
testing the influence of the density of terminal groups of dendri-
mers, we chose PTA (1,3,5-triaza-7-phosphaadamantane),6 which
is easy to graft to dendrimers (Fig. 1) thanks to its specific alkyl-
ation on one nitrogen atom, affording in addition a certain solubil-
ity in neat water or in aqueous media, due to the presence of
charges.7
Synthesis of dendrimers
We have already reported the synthesis of dendrimers 1-G1 and
8
1-G2 from dendrimers ended by aldehydes. For the synthesis of
We have been interested since a long time in studying the
influence of an increase of the internal density on the properties
the dense dendrimer, we have elaborated another synthetic route.
The starting compound is dendrimer 2-G1,9 which possesses 12 Cl
terminal groups. This dendrimer is reacted with twelve equivalents
of 5-hydroxy-dimethylisophthalate in the presence of 24 equiv of
cesium carbonate in THF at room temperature (Scheme 1). This
⇑
Corresponding author. Tel.: +33 561 333 100; fax: +33 561 553 003.
E-mail address: caminade@lcc-toulouse.fr (A.-M. Caminade).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.070

P. Servin et al. / Tetrahedron Letters 53 (2012) 3876–3879
3877
Figure 1. Chemical structure of dendrimers 1-G1, 1-G2, and 6-G2, allowing the comparison between their size and their number of terminal groups.
reaction doubles the number of terminal functions, thus affording
the second generation of the dendrimer, 3-G2 which possesses 24
ester terminal groups. The completion of the reaction is easily
monitored by 31P NMR, which displays the disappearance of the
signal at 65.85 ppm for compound 2-G1 first on behalf of an inter-
mediate signal at ca. 72 ppm, which disappears whereas a signal at
66.22 ppm, appears, corresponding to 3-G2.10
The next step is the reduction of the ester functions of 3-G2,
which is carried out with LiAlH4 at low temperature for 2 h
(the mixture is cooled with acetone/liquid N2). Longer reaction
times lead to a partial destruction of the dendrimer (detected
by 31P NMR). The completion of the reaction affording dendri-
11
mer 4-G2
is monitored by 1H NMR, which displays the
disappearance of the signal corresponding to the methoxy
group of the ester at 3.83 ppm and the appearance of the signal
for CH2–OH at 4.51 ppm. The reaction also modifies the 13C
NMR spectra, with the disappearance of the signal for the
methoxy groups at 52.58 ppm as well as for the carboxyl at
165.06 ppm and the appearance of the signal for the CH2–OH
groups at 63.12 ppm.

3878
P. Servin et al. / Tetrahedron Letters 53 (2012) 3876–3879
Figure 2. Alcohol isomerization in water using Rh complexes of the dendrimers
shown in Figure 1 as catalysts.
PTA 1-Gn (n = 1–3) in mixtures H2O/heptane, for which we have
observed a positive dendritic effect, that is an increase of the cata-
lytic efficiency when the generation of the dendrimer increases.8
However, ruthenium is not the sole metal that could be used,
and rhodium has also given interesting results for allylic alcohol
isomerization.16 Thus we decided to test the rhodium dimer
[Rh(COD)Cl]2 for complexing the PTA terminal groups of our den-
drimers. The complexation is carried out in situ in water: the den-
drimers and the rhodium complex (Rh/PTA 1:1.1) are left reacting
for 15 minutes before the substrate was added and the heating was
started. The reactions are left stirring vigorously for one hour, then
the results are monitored by gas chromatography (GC). The reac-
tion seems to have favoured the smallest dendrimer since the 1st
generation dendrimer 1-G1 with only 12 PTA complexes shows
the best results, and when considering 24 PTA complexes, the
smaller compound 6-G2 is slightly better than 1-G2. However, none
of these results are good enough, presumably because of the poor
solubility in water of the complexes, the one of 1-G2 being the least
soluble ( Fig. 2). Thus we moved to study another reaction, the
hydration of alkynes.
The hydration of alkynes is formally the addition of water to a
triple bond, providing an important route to carbonyl com-
pounds.17 In general, addition of water to terminal alkynes follows
the Markovnikov’s rule, leading mainly to ketones. In a previous at-
tempt, we have used Ru(p-cymene)Cl2 complexes of dendrimers 1-
G1 and 1-G2 for catalyzing such reaction in mixtures H2O/iPrOH at
90 °C for 48 h (5% of catalyst); the percentage of conversion was
respectively 58% and 45%, with a selectivity to ketone of 95% and
98%.8 Here we have modified the experimental conditions by
decreasing the % of catalyst (1% instead of 5%), by decreasing the
time of reaction (17 h instead of 48 h), and by adding a co-catalyst
(10% of H2SO4). Under this case as previously, the complexes are
generated in situ. In these improved conditions, the catalysis pro-
ceeds more rapidly, as displayed in Figure 3, and the selectivity
in ketone is 100% with all dendrimers. A decrease of the efficiency
is observed when the generation of the dendrimer increases in the
homogeneous series 1-Gn (n = 1, 2), whereas the more dense
Scheme 1. Synthesis of the dense second generation dendrimer ended by 24 PTA
ligands.
Then SOCl2 is added to dendrimer 4-G2 until its total dissolution
(without solvent). The resulting solution is cooled with an ice bath
overnight under stirring to afford dendrimer 5-G2.12 A shift of the
benzyl group in 1H NMR is observed from 4.51 ppm (CH2–OH) to
4.44 ppm (CH2–Cl) for the chlorinated product. In the 13C NMR
spectra, the CH2 alcohol signal was at 63.12 ppm whereas CH2
chloride appears at 45.11 ppm.
In the last step, 24 equiv of PTA are reacted with dendrimer 5-
G2 in THF at room temperature. A shift of PTA phosphorus from
À99.0 ppm to À76.4 ppm for dendrimer 6-G2 is observed in 31P
13
NMR. This compound dissolved in water gives a 31P NMR spectrum
in D2O which displays the phosphorus atoms of the surface and of
the branches, but the core cannot be seen since that part of the
dendrimer is too hydrophobic for the water to enter. By addition
of acetonitrile the internal structure of dendrimer 6-G2 is better
dissolved, thus the signal of the core can be seen. We have already
observed such phenomenon for another type of water-soluble
phosphorus-containing dendrimer.14
Having in hand dendrimer 6-G2, the next step is the comparison
of its catalytic properties with that of dendrimer 1-G1 (same size,
8
but half the number of PTA ligands) and dendrimer 1-G2 (same
number of PTA ligands, but larger size) (Fig. 1).
Catalysis experiments
In order to allow a fair comparison between the properties of
various dendrimers, the number of catalytic sites (i.e. in general
the number of terminal functions) is always kept constant. For in-
stance, if one equivalent of dendrimer 6-G2 is used, it will be com-
pared with one equivalent of dendrimer 1-G2, but with two
equivalents of dendrimer 1-G1. We have tested the three dendri-
mers as ligands in two different types of catalytic experiments.
The isomerization of allylic alcohols is a reaction that proceeds
with atom economy, if it is catalyzed. Indeed, without a catalyst,
this reaction necessitates two steps (reduction of alkene and oxida-
tion of alcohol), whereas it is performed one-pot with a catalyst.
This reaction is of current interest, as emphasized by a recent the-
oretical and experimental investigation upon the use of ruthenium
catalysts for such purpose.15 We have previously reported the
isomerization of allylic alcohol with Ru complexes of dendrimeric
Figure 3. Hydration of alkyne using Ru complexes of the dendrimers shown in
Figure 1 as catalysts.

P. Servin et al. / Tetrahedron Letters 53 (2012) 3876–3879
3879
6. (a) Bravo, J.; Bolano, S.; Gonsalvi, L.; Peruzzini, M. Coord. Chem. Rev. 2010, 254,
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Figure 4. Numbering scheme used for NMR assignment.
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Caminade, A. M. Dalton Trans. 2009, 4432–4434.
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10. Synthesis of dendrimer 3-G2. 0.500 g (274 lmol) of 2-G1, 0.747 g (3.56 mmol)
dendrimer 6-G2 gives the best results. An estimation of the density
of the terminal groups was obtained assuming a spherical shape
for the dendrimers. A correlation between the density and the cat-
alytic efficiency is observed; increasing the local density of cata-
lytic entities increases the catalytic efficiency (right part of Fig. 3).
In conclusion, by using three dendrimers related either by the
number of terminal groups or by the size, our experiments, and
more precisely the catalyzed hydration of alkynes, have demon-
strated for the first time the importance, and the positive influence
of the density of the catalytic entities on the efficiency of the catal-
ysis. We intend to expand the scope of this study to other dendri-
mers and other catalyzed reactions.
of 5-hydroxy-dimethylisophthalate, and 2.32 g (7.11 mmol) of Cs2CO3 were
dissolved in 50 mL distilled THF. The reaction mixture was left stirring
overnight and two filtrations over celite were made and an evaporation. 3-G2
was obtained as a white powder in 60% yield. 3-G2: 31P {1H} NMR (81 MHz,
CDCl3), 11.2 (s, P0), 66.2 (s, P1). 1H NMR (200 MHz, CDCl3), 3.31 (d,
3
3JHP = 10.7 Hz, 18 H, C06H), 3.83 (s, 72 H, CH3O), 7.09 (d, JHH = 8.4 Hz, 12 H,
C02H), 7.62 (d, 3JHH = 8.4 Hz, 12 H, C03H), 7.67 (s, 6 H, C05H), 8.02 (s, 24 H, C12H),
8.45 (s, 12 H, C14H). 13C {1H} NMR (50 MHz, CDCl3), 32.92 (d, JCP = 12.8 Hz,
2
3
C06H), 52.58 (s, CH3O), 121.12 (s, C02), 126.78 (d, JCP = 4.3 Hz, C12), 127.69 (s,
C14), 128.45 (s, C03), 131.65 (s, C04), 132.12 (s, C13), 139.98 (d, JCP = 14.3 Hz,
3
C05), 150.49 (d, 2JCP = 7.1 Hz, C11), 151.41 (d, 2JCP = 6.8 Hz, C01), 165.06 (s, C@O).
The numbering used for the assignment of NMR signals for this compound and
others is displayed in Figure 4.
Acknowledgments
11. Synthesis of dendrimer 4-G2. 3-G2 (1.04 g, 266 lmol) was dissolved in distilled
THF (100 mL). The solution was cooled by acetone/N2(liquid). A 1 M solution of
LiAlH4 in THF (5.3 mL, 5.3 mmol) was added to the cooled solution, and the
reaction was left stirring for 2 hours. The reaction was quenched by the
addition of a few drops of H2O and then aqueous HCl to correct the pH. A
filtration was made and the residual solid was freeze-dried. 4-G2 was obtained
as a white powder in 31% yield. 4-G2: 31P {1H} NMR (81 MHz, CD3OD), 12.4 (s,
P0), 65.6 (s, P1). 1H NMR (200 MHz, CD3OD), 3.29 (d, 3JHP = 10.5 Hz, 18 H, C06H),
Thanks are due to the European Community through the con-
tract MRTN-CT-2003-503864 (AQUACHEM) for financial support
(grant to P. Servin) and the COST program CM0802 (PhoSciNet).
This work was also supported by the CNRS and by the ANR DEND-
SWITCH (grant to H. Dib). M.P. and L.G. thank MIUR for partial sup-
port through PRIN 2009 program.
3
4.51 (s, 48 H, C25H), 6.94 (d, JHH = 8.6 Hz, 12 H, C02H), 7.13 (s, 36 H,
3
C12H + C14H), 7.60 (d, JHH = 8.6 Hz, 12 H, C03H), 7.70 (s, 6 H, C05H). 13C {1H}
NMR (63 MHz, CD3OD), 32.26 (d, 2JCP = 11.32 Hz, C06), 63.12 (s, C25), 117.91 (d,
3JCP = 4.4 Hz, C12), 120.99 (br s, C02), 121.50 (s, C14), 128.19 (s, C032), 132.56 (s,
References and notes
3
C04), 139.29 (d, JCP = 14.5 Hz, C05), 143.57 (s, C13), 151.06 (br d, JCP = 7.6 Hz,
C01 + C11). See Figure 4 for the numbering used.
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4-G2. The mixture was cooled by means of ice-bath and left stirring overnight.
To evaporate the excess SOCl2, toluene was used for co-evaporation. 5-G2 was
obtained as a white powder in 79% yield. 5-G2: 31P {1H} NMR (81 MHz, CDCl3),
11.4 (s, P0), 65.3 (s, P1). 1H NMR (200 MHz, CDCl3), 3.27 (d, 3JHP = 10.7 Hz, 18 H,
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3
C06H), 4.44 (s, 48 H, C25H), 7.03 (d, JHH = 8.5 Hz, 12 H, C02H), 7.18 (br s, 36 H,
3
C12H + C14H), 7.56 (br d, JHH = 8.5 Hz, 18 H, C05H + C03H). 13C {1H} NMR
2
(63 MHz, CDCl3), 33.01 (d, JCP = 12.5 Hz, C06), 45.11 (s, C25), 121.36 (s, C12),
121.43 (s, C02), 125.46 (s, C14), 128.34 (s, C03), 131.88 (s, C04), 139.22 (d,
2
3JCP = 14.2 Hz, C05), 139.62 (s, C13), 150.81 (d, JCP = 7.30 Hz, C11), 151.33 (br s,
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31P {1H} NMR (81 MHz, D2O/CD3CN), À76.4 (s, P2), 14.4 (s, P0), 70.6 (m, P1). 1
H
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H,
C25H + C26H + C27H + C28H + C29H),
6.43-8.15
(br
m,
66
H,
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