Dendrimers functionalized with palladium complexes of n-, n,n-, and n,n,n-ligands

Article abstract of DOI:10.3390/molecules26082333

Pyridine, pyridine imine, and bipyridine imine ligands functionalized by a phenol have been synthesized and characterized, in many cases by X-ray diffraction. Several of these N-, N,N-, and N,N,N,-ligands have been grafted onto the surface of phosphorhydr

Full text of DOI:10.3390/molecules26082333

molecules
Article
Dendrimers Functionalized with Palladium Complexes of N-,
N,N-, and N,N,N-Ligands
Quentin Vanbellingen 1,2,3, Paul Servin 1,2, Anaïs Coinaud 1,2, Sonia Mallet-Ladeira 1,2, Régis Laurent 1,2
and Anne-Marie Caminade 1,2,
*
1
Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099,
CEDEX 4, 31077 Toulouse, France; quentin.vanbellingen@servier.com (Q.V.);
paul.servin@xeroscleaning.com (P.S.); amors.anais@gmail.com (A.C.); sonia.ladeira@lcc-toulouse.fr (S.M.-L.);
regis.laurent@lcc-toulouse.fr (R.L.)
LCC-CNRS, Université de Toulouse, CNRS, CEDEX 4, 31077 Toulouse, France
Technologie Servier—Center of Excellence in Drug Safety and Pharmacokinetics 25/27 rue Eugène Vignat,
CS 11749, CEDEX 1, 45007 Orléans, France
2
3
*
Correspondence: anne-marie.caminade@lcc-toulouse.fr
Abstract: Pyridine, pyridine imine, and bipyridine imine ligands functionalized by a phenol have
been synthesized and characterized, in many cases by X-ray diffraction. Several of these N-, N,N-,
and N,N,N,-ligands have been grafted onto the surface of phosphorhydrazone dendrimers, from
generation 1 to generation 3. The complexation ability of these monomers and dendrimers towards
palladium(II) has been assayed. The corresponding complexes have been either isolated or prepared
in situ. In both cases, the monomeric and dendritic complexes have been tested as catalysts in Heck
couplings and in Sonogashira couplings. In some cases, a positive dendritic effect has been observed,
that is, an increase of the catalytic efficiency proportional to the dendrimer generation.
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Citation: Vanbellingen, Q.; Servin, P.;
Coinaud, A.; Mallet-Ladeira, S.;
Laurent, R.; Caminade, A.-M.
Dendrimers Functionalized with
Palladium Complexes of N-, N,N-,
and N,N,N-Ligands. Molecules 2021,
26, 2333. https://doi.org/10.3390/
molecules26082333
Keywords: dendrimer; ligands; imine; palladium; complexes; phenol; X-ray diffraction; catalysis
1. Introduction
Dendrimers are hyperbranched nanomolecules, also called molecular trees, which
pertain to the “nanoworld” by virtue of their size, but which differ fundamentally from
“hard” nanoparticles constituted of metals. Dendrimers are most generally synthesized by a
divergent process, starting from a multifunctional core to which are attached progressively
several layers of branching units. Each sequence of reactions increases the number of
terminal functions and provides a new “generation” of the dendrimers. Different types
of dendrimers are known, which differ by the nature of their core and of their branches.
Academic Editor: Michal Szostak
Received: 26 March 2021
Accepted: 12 April 2021
Published: 17 April 2021
Among all types of dendrimers [
units have often exceptional properties [
purely organic dendrimers [ ]. Two principal types of dendrimers comprising main group
elements in their structure are known: carbosilane dendrimers [ ], and phosphorhydrazone
dendrimers [ ]. One of the main advantages of the latter is their easy characterization by
31P NMR. Indeed, this technique allows monitoring each step of the synthetic process [
1
], those possessing main group elements as branching
2], which in some cases are not attainable with
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iations.
3
4
5
6]
and is powerful to ascertain the completion of the reactions that occur on the surface of
the dendrimers [7].
Phosphorhydrazone dendrimers have outstanding properties in many different fields,
Copyright:
© 2021 by the authors.
related to catalysis, nanomaterials, and also biology/nanomedicine [
used successfully as soluble supports of catalytic entities, allowing for instance the use of
less expensive metals such as copper [ ]. Dendrimer complexes have been recovered and
8]. They have been
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Attribution (CC BY) license (https://
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4.0/).
9
reused many times [10], and even the possibility to switch ON/OFF the catalytic efficiency
has been proven [11].
In this paper, we report the synthesis and characterization (often by X-ray crystal
structure diffraction) of ligands incorporating one, two, or three nitrogen atoms in their
Molecules 2021, 26, 2333. https://doi.org/10.3390/molecules26082333
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 2333
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structure. These ligands are functionalized in all cases by a phenol to enable their grafting to
the P(S)Cl2 terminal functions of phosphorhydrazone dendrimers (see the first generation
of these dendrimers,
G1, in Figure 1). We report also in this paper that the palladium
complexes of these dendrimers are useful catalysts in C-C cross-coupling reactions, in
particular of Heck [12] and Sonogashira [13,14] types.
Figure 1. Full structure of the first generation of phosphorhydrazone dendrimer.
2. Results
2.1. Synthesis and Characterization of Functionalized Ligands
With the exception of 4-hydroxypyridine 1, which is commercially available, all the
other ligands were synthesized by condensation reactions. Some of them (compounds 2 and 3)
have been previously used for the functionalization of phosphorhydrazone dendrimers
in a biological context as anti-cancer agents [15], but their synthesis and characterization
were not described. Figure 2 displays all the potential ligands that have been synthesized
(2–6) for this new study about catalysis.
Figure 2. N-, N,N- and N,N,N-ligands functionalized by a phenol.

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Compounds
2
and
3
are synthesized by condensation reactions between tyramine
and either 2-pyridinecarboxaldehyde (for
2) or di(2-pyridyl)ketone (for 3). Analogous
derivatives with a methoxy group (compounds 2a and 3a) instead of the hydroxyl group
have been also synthesized, starting from 4-methoxyphenethylamine (family a) (Scheme 1).
Scheme 1. Synthesis of compounds 2, 2a, 3 and 3a.
2-pyridinecarboxaldehyde and di(2-pyridyl)ketone have been also condensed with
other phenol-amine derivatives, such as 4-aminophenol to afford compound , and 4-
. These reactions are shown in
4
hydroxybenzhydrazide to afford compounds
Scheme 2.
5 and 6
Scheme 2. Synthesis of phenols 4, 5, and 6.
All these compounds have been characterized by 1H NMR, including COSY (corre-
lation spectroscopy) and NOESY (nuclear Overhauser effect spectroscopy) experiments
when necessary, and 13C NMR, including JMOD (J-modulated spin-echo) and HMQC
(heteronuclear multiple-quantum correlation) experiments when necessary, to ascertain
in particular the disappearance of the HCO or CO group. For compounds having two
pyridine groups in their structure, such as compounds 3, 4, and 6, each pyridine group is
different, as illustrated by two different sets of signals both in 1H and 13C NMR spectra.
Several of these ligands have been characterized by X-ray diffraction studies. In all
cases, the ellipsoids are represented with 50% probability. Figure 3 displays the crystal
structure of the phenol derivative
2
. The formation of the C=N bond is demonstrated by
◦
the short N1-C9 distance (1.2671(17) Å). The dihedral angle N1-C9-C10-N2 (163.16(13) ), as
well as the N1 . . . N2 distance (3.534(2) Å) indicate that, in the crystal, the nitrogen atoms
are in the anti-conformation.

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Figure 3. Crystal structure of compound 2.
Figure 4 displays the crystal structure of compound
3. The N1-C9 bond length (1.271(2)
Å) corresponds well to a double bond. The two dihedral angles N-C-C-N are very different.
◦
The N1-C9-C10-N2 angle is 75.3(2) , with an N1 . . . N2 distance of 3.100(3) Å, indicating a
tendency to a syn-conformation for this part of the molecule, which should be favorable for
the complexation. The dihedral angle N1-C9-C15-N3 is
−
178.23(19)◦, with N1 . . . N3 of
3.539(3) Å, indicating a tendency to an anti-conformation of this part of the molecule. The
N2 . . . N3 distance is 3.503(3) Å. These data corroborate the presence of two very different
sets of pyridine signals observed in the 1H and 13C NMR spectra of 3.
Figure 4. Crystal structure of compound 3.
The crystal structure of compound 3a is shown in Figure 5. The only difference with
compound 3 is the replacement of the HO group by an MeO group, thus only small changes
are expected in the structure. The length of the imine bond N1-C10 (1.2714(17) Å) is very
similar, and there are also two different pyridine groups. The dihedral angle N1-C10-
C11-N2 is
−
94.06(16)◦, and the N1 . . . N2 distance is 3.261(2) Å; these values indicate a
tendency to a syn-conformation. The dihedral angle N1-C10-C16-N3 is
the N1 . . . N3 distance is 3.550(2) Å, corresponding to an anti-conformation. The N2 . . .
N3 distance in compound 3a (3.323(2) Å) is shorter than for 3 (3.503(3) Å).
−
175.73(12)◦, and
Figure 5. Crystal structure of compound 3a.

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Figure 6 displays the crystal structure of compound
4. The difference with compound
3 is that the imine bond is directly attached to the phenol group, instead to an ethyl chain
used as linker. However, this difference has only a marginal influence on the imine bond
length (N1-C7 = 1.2796(16) Å). The pyridine groups are different, but not as different as
for the other compounds. The dihedral angle N1-C7-C8-N2 is
. . . N2 distance of 3.522(2) Å; the dihedral angle N1-C7-C13-N3 is
N1 . . . N3 distance of 3.419(2) Å. Both pyridine groups are in anti-positions relative to the
imine bond. The consequence is that the N2 . . . N3 distance (between the nitrogen atoms
of the pyridine groups) is the shortest of the series (3.180(2) Å).
−
155.47(12)◦, with an N1
116.67(13)◦, with an
−
Figure 6. Crystal structure of compound 4.
The crystal structure of compound
pound is that the CH2-CH2 linkage is replaced by a CO-NH linkage. Despite these
changes, the imine bond length is very similar (N2-C8 = 1.2763(16) Å), as well as the di-
hedral angle N2-C8-C9-N3 (
165.54(13)◦) and the N2 . . . N3 distance (3.530(2) Å). As
5 is shown in Figure 7. The difference with com-
2
−
expected when considering the packing of compound 5 in the crystal, the OH group is in-
volved in H bonding with the nitrogen atom of another molecule (d H1A . . . N3 = 1.73(3) Å).
In addition, the CO-NH linkage is also involved in hydrogen bonding. The hydrogen
atom linked to N1 (H1B) interacts both with N2 and O2 of another molecule (d H1B
. . . O2 = 2.146(18) Å, H1B . . . N2 = 2.535(18) Å). Both molecules are oriented head to tail
(Figure 7B).
Figure 7.
(A) Crystal structure of compound 5. (B) Packing in the crystal showing the arrangement of three molecules of
compound 5, and the hydrogen bonds.
2.2. Grafting of The Functionalized Ligands to The Surface of Dendrimers
The grafting of the ligands as terminal groups of the phosphorhydrazone dendrimers
is carried out in all cases in the presence of a base, either potassium carbonate or cesium
carbonate. Six equivalents of 4-hydroxypyridine
1 have been grafted to generation 0 of

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the dendrimers (N3P3Cl6). The reaction is monitored by 31P NMR, which displays the
replacement of the singlet at
the course of the reaction, followed by the appearance of a single singlet at
corresponding to the full substitution, that is, to compound 1-G0. The same reaction
was carried out using 12 equivalents of compound to react with the first generation
of the dendrimer 1, which structure is shown in Figure 1 to afford dendrimer 1-G1
Scheme 3). The reaction is also monitored by 31P NMR, which first displays the decrease
of the signal corresponding to the P(S)Cl2 terminal functions ( = 65.8 ppm) on behalf of
the appearance of another singlet at = 71.7 ppm, corresponding to the monosubstitution
δ
= 20.8 ppm (N3P3Cl6) by a complex series of signals during
δ
= 10.2 ppm,
1
G
(
δ
δ
on each terminal phosphorus atom (P(S)Cl(OC5H4N)). The full substitution affords another
singlet at δ = 62.4 ppm. Figure 8 displays the 31P NMR spectra of the terminal groups of
compounds for the reaction from
G1 to 1-G1. Of course, in all cases the signal corresponding
to the N3P3 core is also detected, at δ = 11.2 ppm in the case of dendrimer 1-G1.
Scheme 3. Synthesis of phosphorus dendrimers 1-G0 and 1-G1, functionalized by the N-ligand 1.
Figure 8. Changes in the 31P {1H} NMR spectra during the synthesis of dendrimer 1-G1 from G1
.
Only the part of the spectra corresponding to the terminal groups is shown.

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The reaction of ligand
2
has been carried out with phosphorhydrazone dendrimers of
generations 1 to 3, that is, dendrimers G1
as a base, using 12, 24, and 48 equivalents of ligand
resulting dendrimers 2-G1 2-G2, and 2-G3 was carried out as previously reported [15],
thus only their linear representation is shown in Figure 9. The same experiments, in
the same conditions, were carried out with ligand and generations 1, 2, and 3 of the
phosphorhydrazone dendrimers, to afford dendrimers 3-G1 3-G2, and 3-G3, possessing
12, 24, and 48 ligands as terminal functions, respectively (Figure 9).
,
G
2, and
G
3, in the presence of cesium carbonate
2, respectively. The synthesis of the
,
3
,
Figure 9. Phosphorhydrazone dendrimers from generations 1 to 3, functionalized with ligands
2 and 3, affording dendrimers
2-Gn and 3-Gn respectively. Structure of the palladium complexes the 3-Gn family, namely 3-Gn-Pdx (n = 1–3, x = 12, 24, 48).
Ligand
aromatic in
4
is relatively similar to ligand
3
, but the nitrogen atom is directly linked to the
. Despite an increased temperature
4
, instead of an ethyl linker in the case of 3
and a longer reaction time, no reaction was observed when attempting to react ligand
with dendrimer
1, as shown by 31P NMR. Other attempts were made with compounds
and , to be grafted to dendrimer 1. In these cases, the reaction begun easily, but the
4
G
5
6
G
dendrimer precipitated before the completion of the reaction. Changing the solvent to
DMF improved the advancement of the reaction. However, no fully substituted dendrimer
could be isolated in these improved conditions.

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2.3. Complexation of Palladium by Monomers and Dendrimers
Having in hand several dendrimers functionalized with nitrogen ligands, their ability
to complex palladium derivatives has been assayed. Compound 2a was reacted with
PdCl2COD (COD = cyclooctadiene) to afford compound 2a-Pd, in which the complexa-
tion occurs between the nitrogen atoms of the imine function and of the pyridine group
(
Figure 10). In the case of the family of compounds 3, there is an ambiguity concerning
which nitrogen atoms are implied in the complexation. Indeed, the complexation may
occur either between the two pyridines, to form a 6-membered ring, or between the imine
and one pyridine, to form a 5-membered ring. The complexation was first carried out with
ligand
3
and PdCl2COD to afford 3-Pd. Characterization of 3-Pd by 1H NMR could not
ascertain the localization of palladium in this compound, either the form 30-Pd or 300-Pd
(Figure 10). Indeed, the chemical shifts of the hydrogen atoms on the carbon adjacent to
the nitrogen atom of both pyridine rings are shifted upon complexation, from 8.45 and
8.65 ppm for 3 to 8.88 and 9.18 ppm, respectively, for 3-Pd. This may correspond to form
3”-Pd, as both signals are modified (∆δ = +0.43 and +0.53 ppm, respectively). 13C NMR
affords additional information, when considering the carbon atom of the imine function,
and both carbon atoms attached to it. Indeed, the imine carbon atom gives a signal at
166.6 ppm for
imine carbon give signals at 155.3 and 156.8 ppm for
∆δ 6.6 ppm, and +0.5 ppm, respectively). These data suggest that palladium in 3-Pd
3, and 176.3 ppm for 3-Pd
(
∆δ = +9.7 ppm). Carbon atoms attached to the
3
, and 148.7 and 157.3 ppm for 3-Pd
(
=
−
should be complexed as shown in structure 30-Pd. In view of the contradictory results
afforded by 1H and 13C NMR, it appears necessary to use another method for finding the
real structure of compound 3-Pd.
Figure 10. Complexation of compound 2a, and the two possible forms of the Pd complex of 3.
In order to ascertain the location of the complexation with this type of multifunctional
ligands, attempts were made to crystallize a palladium complex. Attempts were successful
with 3a-Pd, and the structure of this complex could be obtained by X-ray diffraction
(Figure 11). This structure shows unambiguously that the complexation of palladium
occurs between the imine and one pyridine group, thus corresponding to the form 30-Pd
in Figure 10. A few other examples of bipyridine imine palladium complexes are known.
The complexation between both pyridine groups was proposed in several cases [16
but each time a crystal structure was obtained, the complexation was observed between
the imine and one pyridine [18 21]. In the case of compound 3a-Pd, the imine bond
,17],
–
(
N2-C6 = 1.290(2) Å) is slightly longer than for the same (free) ligand 3a (1.2796(16) Å◦).
Obviously, the pyridine rings are very different. The dihedral angle N2-C6-C5-N1 is -2.9(2)
(almost flat), with the shortest N2 . . . N1 distance of the series (2.◦613(2) Å). The dihedral
angle N2-C6-C7-N3 of the non-complexed pyridine ring is
−
69.1(2) , with a relatively short
N2 . . . N3 distance of 3.082(2) Å. On the contrary, the distance between the nitrogen atoms
of both pyridine rings is the largest of the series, with N1 N3 = 4.623(2) Å. Of course, in
solution, the free rotation around the C6-C7 bond can lead the N3 atom closer to palladium.

Molecules 2021, 26, 2333
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Figure 11. Crystal structure of the palladium complex 3a-Pd.
The same type of complexation was carried out with dendrimers 3-G1, 3-G2, and 3-G3,
using 12, 24, and 48 equivalents of PdCl2COD, respectively. The corresponding complexes
3-G1-Pd12, 3-G2-Pd24 and 3-G3-Pd48 are less soluble than the non-complexed dendrimers.
In consequence, the quality of the spectra is lower. However, 31P NMR data confirmed that
there is no cleavage of the structure upon complexation. Furthermore, comparison of 1H
NMR data between free and complexed dendrimers are coherent with the data obtained
with the monomer
3
and 3-Pd. Moreover, 13C NMR is very informative of the formation of
the complexes, in particular with the presence of a signal at ca 176.4 ppm for the carbon of
the imine bond, instead ca 167.0 for the non-complexed dendrimer (Figure 12). Thus, the
complexation of the dendrimers 3-Gn-Pd12n should be analogous to that of the monomer
3a-Pd, between the imine and one pyridine group, as shown in Figure 9.
Figure 12. 1H NMR data for the hydrogen atoms on the carbon adjacent to the nitrogen atom of both pyridine rings (C12-H
and C17-H), and 13C NMR data of the carbon of the imine bond (C7), for monomer and dendrimers, free and complexed in
both cases.
2.4. Catalytic Attempts
Most of the nitrogen ligands shown in this paper contain Schiff bases in their structure.
The importance of Schiff base complexes used as catalysts in a wide range of reactions such
as polymerizations, oxidations, or additions, has been reviewed previously [22]. Being
interested since a long time in catalyzed C–C cross-couplings [23], essentially with dendritic
phosphine complexes [24], it appeared tempting to perform such types of reactions with
nitrogen complexes. Schiff bases palladium complexes have been used as catalysts in

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Heck couplings, but in most cases, the phenol function pertaining to the ligand act also
as ligand for the palladium [25,26]. The complexes can be either isolated or generated in
situ. Thus, first attempts were carried out with the aim of determining if it was needed
to isolate the complexes, or if mixing the dendrimers with palladium (II) was sufficient.
The catalyzed coupling of iodobenzene with styrene was chosen as a test reaction. It was
carried out essentially with the family of compounds 3, monomers and dendrimers, either
pre-complexed with PdCl2, or complexed in situ with Pd(OAc)2. The results are gathered
in Table 1. In all cases 1 mol% of palladium was used. It means that the quantity of
palladium is identical in all experiments. For instance, if one equivalent of generation
1 dendrimer is used, it will be compared with 12 equivalents of monomer, because the
first generation dendrimer has 12 Pd complexes on its surface. At 40◦ C, only the in situ
prepared complexes (entries 2 and 4) display a weak activity. At 70◦ C, all the complexes
are efficient, but the preformed complexes seem slightly more efficient than the in situ
prepared complexes (compare entry 5 to 6, or entry 7 to 8). Besides, the first generation of
the dendrimer 3-G1-Pd12 (entry 7) is more efficient than the larger generations (entries 9
and 10). An attempt has been made with the N ligand 1-G1, treated with 12 equivalents of
Pd(OAc)2, but a poor efficiency was observed (entry 11 in Table 1). One may presume that
a simple pyridine group is not sufficient to ensure a stable complexation of palladium.
Table 1. Catalysis of Heck couplings between iodobenzene and styrene.
◦
Entry
T C
Catalyst Pd
Conversion %
1
2
3
4
5
6
7
8
9
40
40
40
40
70
70
70
70
70
70
70
3-Pd
3 + Pd(OAc)2
3-G1-Pd12
0
12
0
3-G1 + 12 Pd(OAc)2
3-Pd
3 + Pd(OAc)2
3-G1-Pd12
3-G1 + 12 Pd(OAc)2
3-G2-Pd24
5
98
91
90
80
60
66
16
10
11
3-G3-Pd48
1-G1 + 12 Pd(OAc)2
Another series of experiments was carried out using again iodobenzene but with
a more reactive alkene,◦namely butyl acrylate. In that case, all the experiments have
been carried out at 70 C with the in situ formed complexes (Table 2), as the in situ
complexation is easier to carry out. Furthermore, the results obtained for the previous Heck
couplings indicated that there is not a large difference in the catalytic efficiency between
the pre-formed and in situ formed complexes. For the reaction of butyl acrylate, 1 mol%
of palladium was used at the beginning (entries 1 to 4). In view of the excellent results
obtained, the quantity of palladium was decreased to 0.1 mol%, remarkably with the same
efficiency (entries 5 to 8 in Table 2).

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Table 2. Catalysis of Heck couplings between iodobenzene and butyl acrylate.
Entry
Mol % Pd
Catalyst Pd
Conversion %
1
2
3
4
5
6
7
8
1
1
1
3 + Pd(OAc)2
100
100
100
100
100
100
100
100
3-G1 + 12 Pd(OAc)2
3-G2 + 24 Pd(OAc)2
3-G3 + 48 Pd(OAc)2
3 + Pd(OAc)2
3-G1 + 12 Pd(OAc)2
3-G2 + 24 Pd(OAc)2
3-G3 + 48 Pd(OAc)2
1
0.1
0.1
0.1
0.1
In view of these interesting results with Heck couplings, other catalytic tests were
carried out for another type of cross-coupling reactions, that is, Sonogashira couplings,
using both the 2 and 3 families of ligands for the in situ complexation of Pd(OAc)2. The first
example of Sonogashira coupling concerns 4-iodotoluene and phenylacetylene (Table 3).
Experiments were carried out at 40 and 70 ◦C, with the monomer 2a and the dendrimers
2-Gn (generations 1, 2, and 3), in the presence of Pd(OAc)2 (one Pd per pyridine imine
group in all cases). A positive dendritic effect [27] is observed at 40 ◦C, with an increase
in the percentage of conversion, from the first generation (55%) to the second (69%) and
the third (71%) generation. The second and the third generations perform better than
the monomer. Of course, the quantity of pyridine imine groups and of palladium is kept
constant in all experiments. Surprisingly, the results are worse when the temperature is
increased to 70 ◦C.
Table 3. Catalysis of Sonogashira couplings between iodotoluene and phenylacetylene.
◦
Entry
T C
Catalyst Pd
Conversion %
1
2
3
4
5
6
7
8
40
40
40
40
70
70
70
70
2a + Pd(OAc)2
2-G1 + 12 Pd(OAc)2
2-G2 + 24 Pd(OAc)2
2-G3 + 48 Pd(OAc)2
2a + Pd(OAc)2
2-G1 + 12 Pd(OAc)2
2-G2 + 24 Pd(OAc)2
2-G3 + 48 Pd(OAc)2
64
55
69
71
68
53
61
59
A second example of Sonogashira couplings was attempted using iodo- or bromo-
benzene and phenylacetylene, catalyzed by the in situ prepared Pd complexes of 1-G1
and of the family of compounds
of the results shown above. 100% conversion is observed with iodobenzene and 1 mol%
of catalyst with all the compounds of the family (monomer and dendrimers) (Table 4
3 (3
and 3-Gn, n = 1–3), in all cases at 40◦ C, in view
3
,
entries 2 to 5). In contrast, the dendrimer 1-G1 affords only 66% conversion (entry 1), and
thus it was not used in other experiments. In view of the good results obtained with the
3
family, experiments were carried out using a lower quantity of catalysts (0.1 instead
of 1 mol%). In these conditions, the conversion was still good: 73% with compound
(entry 6) and 81% with dendrimer 3-G1 (entry 7). Experiments were also carried out with
3

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the more challenging bromobenzene, using 1 mol% of catalyst. Both
diphenylacetylene in 37% conversion (entries 8 and 9).
3
and 3-G1 afforded
Table 4. Catalysis of Sonogashira couplings between iodo- or bromo-benzene and phenylacetylene,
◦
at 40 C.
Entry
X
Mol % Pd
Catalyst Pd
Conversion %
1
2
3
4
5
6
7
8
9
I
I
I
I
I
I
I
Br
Br
1
1
1
1
1
0.1
0.1
1
1-G1 + 12 Pd(OAc)2
3 + Pd(OAc)2
3-G1 + 12 Pd(OAc)2
3-G2 + 24 Pd(OAc)2
3-G3 + 48 Pd(OAc)2
3 + Pd(OAc)2
3-G1 + 12 Pd(OAc)2
3 + Pd(OAc)2
3-G1 + 12 Pd(OAc)2
66
100
100
100
100
73
81
37.5
37
1
3. Discussion
Among the six phenol amino ligands shown in Figure 2, only compounds
successfully grafted on the surface of the dendrimers. No reaction was observed with
compound . This absence of reactivity is possibly due to a large delocalization of the
phenate form (impossible for instance in compound ), which should largely decrease
its reactivity. The problem is different with compounds and , which reacted, but the
1-3 were
4
3
5
6
dendrimer precipitated before completion of the reaction. The problem is presumably due
to the hydrazide linkage which may induce multiple hydrogen bonding. We have already
demonstrated that other types of hydrazide derivatives (namely P and T Girard’s reagents)
linked to phosphorhydrazone dendrimers or dendrons induced the spontaneous formation
of hydrogels in water [28
Furthermore, the packing in the crystal structure of compound
–
31], characteristic of a decreased solubility of the dendrimer.
(Figure 7B) has pointed
5
out the presence of such interactions, in a head to tail arrangement, which will favor the
interactions between dendrimers, thus decreasing largely the solubility.
The first catalytic attempts were carried out with the aim of determining if it was
needed to isolate the complexes, or if creating it in situ was suitable. As there was no
large difference in the catalytic efficiency between both methods, in situ formation of the
complex was chosen in most cases. On the contrary, there are large differences in the
catalytic efficiency depending on the type of ligands. It can be shown from the comparison
between Tables 3 and 4 that the family of compounds
pyridine groups, affords more efficient catalysts than the family of compounds
also possesses one imine, but only one pyridine group. The difference might be related to
the presence of a pyridine group in the second coordination sphere in the series but which
does not exist in the series . Indeed, the second pyridine group possibly acts as a ligand of
3, which possesses one imine and two
2, which
3
2
the second coordination sphere, which is well known to play a key role in catalysis [32],
including for Heck couplings [33].
Our catalytic attempts compare well with recently published results, using nitrogen
complexes of palladium. As an example, 2,20-(bisdiamino)azobenzene ligands (H2L) com-
plexing Pd ([(HL)Pd(PPh3)]ClO4) was used as a catalyst (1 mol%) in refluxing THF for
Heck coupling of iodobenzene with styrene. trans-stilbene was isolated in 94% yield [34].
This result compares well with 90–98% conversion obtained in our case (Table 1). The
coupling of iodobenzene and butyl acrylate is generally easier than the coupling with
styrene. The monomer and the three generations of the
3 family are particularly efficient as
the yield is 100% even when using only 0.1 mol% of catalyst. This result is better than a

Molecules 2021, 26, 2333
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recent example using 0.8 mol% of dendrimers complexing palladium and linked to silica,
used as catalysts in the same reaction [35].
In a third example, N,N-bidentate ligands bearing N=PV-C-C-NH backbones were lig-
ands complexing PdCl2, which was used as catalyst (1 mol%) in the Sonogashira coupling
of 4-iodotoluene with phenylacetylene in hard conditions (110◦ C in DMF). 1-methyl-4-(2-
phenylethynyl)-benzene was obtained in 97% yield◦(measured by GC) [36]. Our experi-
◦
ments were carried out in really milder conditions (40 C instead of 110 C) and in the pres-
ence of water (CH3CN/water (6:1)) and afforded 1-methyl-4-(2-phenylethynyl)-benzene in
reasonable yields (71% with the generation 3 dendrimer) as shown in Table 3. In a fourth
example, glycine was the ligand of PdCl2, affording complex [PdCl2(NH2CH2COOH)2],
which was used as catalyst (1 mol%) in the Sonogashira coupling of iodobenzene with
phenylacetylene at 60◦ C. Diphenyl acetylene was isolate in 30% to 93% yield, depending
on the solvent used, the best result being obtained in water/acetone (3/3mL) [37]. Our
◦
results in CH3CN/water (6:1) are carried out in milder conditions (40 C) (Table 4), and the
conversion was quantitative with 1 mol% of dendritic catalysts. The experiments carried
out with 0.1 mol% dendritic catalysts, which afforded 81% conversion, are better than those
obtained previously.
4. Materials and Methods
The NMR data were obtained with Bruker AV 300, DPX 300 or AV 400. Chemical
shifts are reported in ppm, relative to SiMe4 for 1H and 13C NMR, and to 85% H3PO4 for
31P NMR. Catalytic experiments have been carried out with a Radley system (Carousel12
Reaction Station).
Crystallography data were collected on a Bruker Kappa Apex II diffractometer
equipped with a 30 W air-cooled microfocus source (3a-Pd), on a Rigaku Oxford Gemini
EOS dual source diffractometer (
2
,
3a
,
4
λ
and
5
), or on a STOE Imaging Plate diffractome-
= 1.54184 Å).
ter System ( ), with MoKα radiation (
3
= 0.71073 Å) or CuKα radiation (λ
Cooler devices were used to collect the data at low temperature (180(2) K or 100(2) K
for 3a-Pd). Phi- and omega- scans were performed for data collection and an empirical
absorption correction was applied. The structures were solved by intrinsic phasing method
(SHELXT) [38] or by direct methods with SIR92 [39] and refined by means of least-squares
procedures on F2 with SHELXL [40] and on F with CRYSTALS [41]. All non-hydrogen
atoms were refined anisotropically. Hydrogen atoms were located in a difference map but
those attached to carbon atoms were repositioned geometrically and then refined using a
riding model. For 5, the solvent molecules were highly disordered and difficult to model
correctly. Therefore, the SQUEEZE function of PLATON [42] was used to eliminate the
contribution of the electron density in the solvent region from the intensity data, and
the solvent-free model was employed for the final refinement. CCDC 1991349, 1991350,
1991351, 1991352, 1991353 and 1991354 contain the supplementary crystallographic data
for compounds 2, 3, 3a, 3a-Pd, 4 and 5, respectively. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (accessed on 1 April 2021),
or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or email: deposit@ccdc.cam.ac.uk.
All reactions were carried out under argon, generally using Schlenk tubes. Solvents
were dried before use. Dendrimers 2-Gn (n = 1–3) and 3-Gn (n = 1–3) have been synthesized
according to published procedures [15], as well as compound 1-G0 [43]. The numbering
used for NMR assignment of the ligands and dendrimers is shown in Figure 13. Dendrimers
are able to entrap solvent molecules, which are very difficult to eliminate, thus perturbing
elemental analyses. Mass analyses cannot be performed for dendrimers due to cleavages
and rearrangement at the level of the hydrazone linkages [44].

Molecules 2021, 26, 2333
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Figure 13. Numbering used for NMR assignment. The atoms in grey color are not present in
some compounds.
Compound 2. In a Schlenk tube, a mixture of 1g (7.25 mmol) of tyramine, 1 equivalent
of pyridine-2-carboxaldehyde (0.775 g), 20 mL of THF, and molecular sieves were heated
at 60◦ C for 6h. The mixture was filtered, and the solution was centrifuged to eliminate
traces of molecular sieves. The solution was evaporated to dryness, then compound
2 was
recrystallized in absolute ethanol, to afford compound as a white powder in 84% yield.
2
Crystals of
2
suitable for X-ray diffraction were obtained by a further recrystallization
3
in absolute ethanol. 1H NMR (300 MHz, CDCl3):
δ
= 3.00 (t, JHH = 9 Hz, 2H, C5H),
3.91 (t, 3JHH = 9 Hz, 2H, C6H), 5.15 (s, 1H, OH), 6.77 (d, 3JHH = 8.4 Hz, 2H, C2H), 7.09 (d,
3JHH = 8.4 Hz, 2H, C3H), 7.34 (dd, 3JHH = 8 Hz, 1H, C11H), 7.9 (dd, 3JHH = 8 Hz, 1H, C10H),
8.00 (d, 3JHH = 8 Hz, 1H, C9H), 8.30 (s, 1H, C7H), 8.65 (d, 3JHH = 4 Hz, 1H, C12H). 13C {1H}
NMR (75 MHz, CDCl3):
δ = 36.2 (C5), 62.9 (C6), 115.5 (C2), 121.5 (C9), 125.0 (C11), 129.9 (C3),
130.9 (C4), 137.1 (C10), 149.1 (C12), 154.1 (C8), 154.8 (C1), 162.2 (C7).
Compound 2a. In a Schlenk tube, a mixture of 1g (6.61 mmol) of 4-methoxyphenethylamine,
1.1 equivalent of pyridine-2-carboxaldehyde (0.779 g), 15 mL of THF, and molecular sieves
◦
were heated at 60 C for 6h. The mixture was filtered, then evaporated to dryness, to afford
an oil, which was evaporated to dryness overnight. Compound 2a was obtained as an
1
orange oil in 51% yield. H NMR (400 MHz, DMSO-d6):
δ
= 2.89 (t, 3JHH = 8 Hz, 2H, C5H),
3.69 (s, 3H, CH3), 3.84 (t, 3JHH = 8 Hz, 2H, C6H), 6.83 (d, 3JHH = 8 Hz, 2H, C2H), 7.16 (d,
3JHH = 8 Hz, 2H, C3H), 7.38 (dd, 3JHH = 8 Hz, 1H, C11H), 7.81 (dd, 3JHH = 8 Hz, 1H, C10H),
7.98 (d, 3JHH = 8 Hz, 1H, C9H), 8.29 (s, 1H, C7H), 8.62 (d, 3JHH = 4 Hz, 1H, C12H). 13C {1H}
NMR (100 MHz, DMSO-d6):
δ = 36.28 (C5), 55.30 (CH3), 62.57 (C6), 114.07 (C2), 120.80 (C9),
125.36 (C11), 130.21 (C3), 131.99 (C4), 137.09 (C10), 149.71 (C12), 154.71 (C8), 158.08 (C1),
162.43 (C7).
Compound 3. Into a small round bottom flask were added 1.3 g (7.1 mmol) of di(2-
pyridyl)ketone, 0.97 g (7.1 mmol) of tyramine and three small spoons of MgSO4. To the flask
was added 7.5 mL of chloroform giving a slurry. After five hours of reaction (supervised
by TLC THF/Hexane (1:1)) a filtration and evaporation were made. The product 3 was a
white powder, obtained in 79% yield. Recrystallization in DCM gave colorless crystals of
suitable for analysis by X-ray diffraction. H NMR (300 MHz, CDCl3/THF-d8): δ = 2.92
3
,
1
3
3
3
(t, JHH = 7.5 Hz, 2H, C5H), 3.61 (t, JHH = 7.5 Hz, 2H, C6H), 6.61 (d, JHH = 8.4 Hz, 2H,
C2H), 6.91 (d, 3JHH = 8.4 Hz, 2H, C3H), 6.95 (d, 3JHH = 7.8 Hz, 1H, C9H), 7.23 (m, 2H, C11H,
C16H), 7.69 (m, 2H, C10H, C15H), 8.10 (d, 3JHH = 8.1 Hz, 1H, C14H), 8.45 (d, 3JHH = 4.2 Hz,
1H, C17H), 8.65 (d, 3JHH = 4.8 Hz, 1H, C12H). 13C {1H} NMR (75 MHz, CDCl3/THF-d8):
δ = 36.45 (C5), 55.85 (C6), 115.07 (C2), 122.19 (C14), 122.91 (C11), 123.56 (C9), 123.96 (C16),
129.71 (C3), 130.83 (C4), 135.84 (C10), 136.21 (C15), 148.64 (C17), 149.40 (C12), 155.33 (C8),
155.42 (C1), 156.85 (C13), 166.63 (C7).
Compound 3a. Into a small round bottom flask were added 1.0 g (5.5 mmol) of di(2-
pyridyl) ketone, 0.83 g (5.5 mmol) of methoxyphenethylamine and three small spoons of
MgSO4 in 20mL of THF. After five hours of reaction (supervised by TLC THF/Hexane
(1:1)) a filtration and evaporation were made. The resulting powder was washed with
dichloromethane/pentane. The product 3a was a white powder, obtained in 80% yield.

Molecules 2021, 26, 2333
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Recrystallized in DCM gave colorless crystals of 3a, suitable for analysis by X-ray diffraction.
1H NMR (400 MHz, CDCl3):
δ
= 3.02 (t, 3JHH = 8 Hz, 2H, C5H), 3.68 (t, 3JHH = 6 Hz, 2H,
C6H), 3.79 (s, 3H, CH3), 6.82 (d, 3JHH = 8.4 Hz, 2H, C2H), 7.03 (d, 3JHH = 7.8 Hz, 1H, C9H),
7.07 (d, 3JHH = 8.4 Hz, 2H, C3H), 7.30 (m, 2H, C11H, C16H), 7.75 (m, 2H, C10H, C15H), 8.14 (d,
3JHH = 8 Hz, 1H, C14H), 8.53 (br d, 3JHH = 4.2 Hz, 1H, C17H), 8.73 (br d, 3JHH = 4.8 Hz, 1H,
C12H). 13C {1H} NMR (100 MHz, CDCl3):
δ = 36.49 (C5), 55.24 (CH3), 55.78 (C6), 113.71 (C2),
122.23 (C14), 123.04 (C11), 123.51 (C9), 124.10 (C16), 129.83 (C3), 132.26 (C4), 135.96 (C10),
136.37 (C15), 148.88 (C17), 149.66 (C12), 155.34 (C8), 156.88 (C1), 157.96 (C13), 166.85 (C7).
Compound 4. In a Schlenk tube were mixed 4-amino phenol (296 mg, 2.71 mmol), di(2-
pyridyl) ketone (500 mg, 2.71 mmol) and THF (10 mL) in the presence of activated molecular
sieves. The mixture was stirred at 50◦ C for 12 h. Progress of the reaction was monitored
by thin layer chromatography (TLC) with THF/pentane as eluent (v:v 1/1). The mixture
was filtered, evaporated to dryness, and then recrystallized in dichloromethane. Yellow
crystals of
studies. H NMR (400 MHz, DMSO-d6):
4 were obtained in 58% yield. One of them was chosen for X-ray diffraction
1
δ
= 6.56 (s, 4H, C2, C3), 7.15 (d, 3JHH = 8 Hz, 1H,
C9), 7.30 (dd, 3JHH = 4 Hz, 1H, C11), 7.46 (dd, 3JHH = 4 Hz, 1H, C16), 7.71 (dd, 3JHH = 8 Hz,
1H, C10), 7.95 (dd, 3JHH = 8 Hz, 1H, C15), 8.23 (d, 3JHH = 8 Hz, 1H, C14), 8.49 (d, 3JHH = 4 Hz,
1H, C17), 8.54 (d, 3JHH = 4 Hz, 1H, C12), 9.26 (s, 1H, OH). 13C {1H} NMR (100 MHz, DMSO-
d6):
δ = 115.5 (C3), 122.7 (C14), 123.1 (C2), 123.5 (C11), 124.8 (C9), 125.2 (C16), 136.3 (C10),
137.3 (C15), 141.7 (C4), 148.9 (C17), 149.4 (C12), 154.8 (C1), 156.0 (C8), 157.2 (C13), 165.5 (C7).
Compound 5. In a Schlenk tube were mixed 4-hydroxybenzhydrazide (500 mg,
3.28 mmol), pyridine-2-carboxaldehyde (352 mg, 3.28 mmol) and DMF (30 mL) in the
presence of activated molecular sieves. The mixture was stirred at 70◦ C for 24 h, then
10 mL of DMF were added. The mixture was filtered, evaporated to dryness, by co-
evaporation with toluene. The compound was then recrystallized in absolute ethanol.
Compound
in absolute ethanol afforded crystals of
5
was obtained as a white powder in 45% yield. A further recrystallization
1
5
suitable for X-ray diffraction studies. H NMR
(400 MHz, DMSO-d6):
δ
= 6.88 (d, 3JHH = 8 Hz, 2H, C2), 7.40 (dd, 3JHH = 4 Hz, 1H, C11),
7.81 (d, 3JHH = 8 Hz, 2H, C3), 7.87 (d, 3JHH = 8 Hz, 1H, C9), 7.95 (m, 1H, C10), 8.45 (s, 1H,
C7), 8.61 (d, JHH = 4 Hz, 1H, C12), 10.11 (s, 1H, OH), 11.83 (s, 1H, NH). 13C {1H} NMR
3
(75 MHz, DMSO-d6):
δ = 115.5 (C2), 120.2 (C10), 124.1 (C11), 124.7 (C4), 130.3 (C3), 137.3 (C9),
147.5 (C7), 149.9 (C12), 153.9 (C8), 161.3 (C1), 163.5 (C5).
Compound 6. In a Schlenk tube were mixed 4-hydroxybenzhydrazide (410 mg,
2.7 mmol), di(2-pyridyl) ketone (500 mg, 2.7 mmol) and THF (15 mL). The mixture was
stirred at 60◦ C for 15 h. Progress of the reaction was monitored by TLC. The mixture
was evaporated to dryness and was washed 2 times with THF/pentane (1:2), to afford
1
compound
6
as a yellow powder in 92% yield. H NMR (300 MHz, DMSO-d6):
δ
= 6.95
3
(d, JHH = 8.4 Hz, 2H, C2H), 7.49 (m, 2H, C9H and C16H), 7.61 (m, 1H, C11H), 7.80 (d,
3JHH = 8.4 Hz, 2H, C3H), 7.92 (d, 3JHH = 8.1 Hz, 1H, C14H), 8.02 (m, 2H, C10H, and C15H),
8.62 (d, 3JHH = 4.5 Hz, 1H, C17H), 8.98 (d, 3JHH = 4.5 Hz, 1H, C12H). 13C {1H} NMR (75 MHz,
DMSO-d6):
δ = 116.1 (C2), 123.8 (C14), 124.3 (C11), 125.2 (C9), 127.5 (C16), 130.0 (br s, C3
and C4), 137.7 (C10), 138.3 (C15), 145.6 (C7), 148.6 (C17), 148.9 (C12), 152.0 (C8), 156.2 (C1),
161.7 (C13), 163.1 (br s, C5).
Dendrimer 1-G1. In a round bottom flask, we added 0.512 g (0.28 mmol) of first
generation dendrimer
G1, 0.351 g (3.7 mmol) of p-hydroxypyridine 1 and 1.02 g (7.4 mmol)
of K2CO3. To these solids were added 50 mL of acetone and the reaction was left stirring
overnight. The solvent was evaporated, and the resulting powder was solubilized with
CHCl3, then filtrated over Celite, washed with CHCl3 and evaporated to dryness. This
process was repeated one time to afford dendrimer 1-G1 as a pale yellow powder in 57%
1
yield. 31P {1H} NMR (81 MHz, CDCl3):
δ
6
= 11.20 (N3P3), 62.39 (P1). H NMR (200 MHz,
CDCl3), 3.34 (d, 3JHP = 10.7 Hz, 18H, C0 H), 7.02 (d, 3JHH = 8.5 Hz, 12H, C05H), 7.13 (d,
2
3JHH = 4.8 Hz, 24H, C2H), 7.51 (d, 3JHH = 8.5 Hz, 12H, C0 H), 7.58 (s, 6H, C0 H), 8.51 (d,
3
3JHH = 4.8 Hz, 24H, C3H). 13C {1H} NMR (50 MHz, CDCl3):
δ
= 32.68 (d, 2JCP = 13.0 Hz, C06),

Molecules 2021, 26, 2333
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116.28 (d, 3JCP = 4.5 Hz, C2), 121.27 (C02), 128.19 (C03), 131.57 (C04), 139.58 (d, 3JCP = 14.5 Hz,
5
1
C0 ), 150.79 (br s, C0 ), 151.60 (C3), 157.15 (d, 2JCP = 7.2 Hz, C1).
Compound 2a-Pd. In a Schlenk tube 0.18 g (0.631 mmoles) of PdCl2COD and 0.154 g
(0.631 mmoles) of ligand 2a were mixed in 10 mL of THF. The mixture was stirred at room
temperature for 22h. After filtration, the product was washed with THF/pentane (1/10),
then with THF/ether (1:10). Complex 2a-Pd was obtained as a yellow-orange powder in
1
75% yield. H NMR (400 MHz, DMSO-d6):
δ
= 3.04 (t, 3JHH = 8 Hz, 2H, C5H), 3.71 (s, 3H,
CH3), 3.89 (t, 3JHH = 8 Hz, 2H, C6H), 6.88 (d, 3JHH = 8 Hz, 2H, C2H), 7.21 (d, 3JHH = 8 Hz, 2H,
C3H), 7.88 (dd, 3JHH = 8 Hz, 1H, C11H), 8.04 (d, 3JHH = 8 Hz, 1H, C9H), 8.33 (dd, 3JHH = 8 Hz,
1H, C10H), 8.41 (s, 1H, C7H), 8.99 (d, 3JHH = 4 Hz, 1H, C12H). 13C {1H} NMR (100 MHz,
DMSO-d6):
δ = 35.77 (C5), 55.48 (Me), 61.11 (C6), 114.44 (C2), 128.57 (C11), 129.11 t(C9),
130.04 (C3), 130.46 (C4), 141.87 (C10), 150.69 (C12), 156.15 (C8), 158.45 (C1), 171.82 (C7).
Compound 3-Pd. In a Schlenk tube were mixed 0.19 g (0.66 mmoles) of PdCl2COD
and 0.2 g (0.66 mmoles) of ligand
3 in 10 mL of THF. The mixture was stirred at room
temperature for 15h. After filtration, the product was washed two times with THF/pentane
(1/10), and one time with THF/ether (1:10). Complex 3-Pd was obtained as a yellow
powder in 81% yield. 1H NMR (300 MHz, DMSO-d63):
δ = 3.00 (m, 2H, C5H), 3.65 (m,
3
2H, C6H), 6.60 (d, JHH = 8.4 Hz, 2H, C2H), 6.78 (d, JHH = 8.4 Hz, 2H, C3H), 7.21 (d,
3JHH = 7.8 Hz, 1H, C9H), 7.73 (m, 2H, C11H, C14H), 7.93 (m, 1H, C16H), 8.11 (m, 1H, C10H),
8.21 (m, 1H, C15H), 8.88 (d, 3JHH = 4.2 Hz, 1H, C17H), 9.18 (d, 3JHH = 4.8 Hz, 1H, C12H),
9.22 (s, 1H, HO). 13C {1H} NMR (75 MHz, THF-d8):
δ = 35.85 (C5), 57.2 (C6), 115.8 (C2),
124.9 (C14), 126.5 (C11), 129.5 (C9), 129.7 (C16), 130.0 (C3), 128.1 (C4), 138.4 (C10), 141.8 (C15),
148.7 (C8), 150.9 (C17), 151.05 (C12), 156.5 (C1), 157.3 (C13), 176.3 (C7).
Compound 3a-Pd. In a Schlenk tube were mixed 0.20 g (0.631 mmol) of ligand 3a
and 0.18 g (0.631 mmol) of PdCl2COD, in 10 mL of THF. The mixture was stirred at room
temperature for 20h, affording a yellow-orange mixture. After filtration, the product was
washed with THF/pentane (1/10), then with THF/ether. Single crystals were obtained by
1
slow evaporation at room temperature of solutions of 3a-Pd in dichloromethane. H NMR
(400 MHz, DMF-d6):
δ = 3.31 (br s, 2H, C5H), 3.94 (s, 3H, Me), 4.05 (br s, 2H, C6H), 7.00 (d,
3JHH = 8 Hz, 2H, C2H), 7.21 (d, 3JHH = 8 Hz, 2H, C3H), 7.58 (d, 3JHH = 7.8 Hz, 1H, C9H),
7.99 (m, H, C11H), 8.11 (d, 3JHH = 8 Hz, 1H, C14H), 8.21 (m, 1H, C16H), 8.40 (t, 3JHH = 8 Hz,
3
3
1H, C15H), 8.52 (t, JHH = 8 Hz, 1H, C10H), 9.14 (d, JHH = 4 Hz, 1H, C17H), 9.52 (d,
3JHH = 4 Hz, 1H, C12H). 13C {1H} NMR (100 MHz, DMF-d6):
= 35.95 (C5), 55.02 (Me),
δ
57.22 (C6), 114.19 (C2), 124.98 (C14), 126.33 (C11), 129.25 (C9), 129.60 (C16), 129.85 (C3),
130.14 (C4), 138.20 (C10), 141.54 (C15), 149.04 (C8), 150.90 (C17), 151.01 (C12), 157.53 (C1),
158.79 (C13), 176.41 (C7).
Dendrimer 3-G1-Pd. Into a Schlenk tube were added 400 mg (0.08 mmol) of den-
drimer 3-G1 and 273 mg (0.95 mmol) of PdCl2(COD) to10 mL of THF. The reaction was
left stirring at room temperature for 15 h. A solid had started to precipitate in the Schlenk.
The solvent was evaporated and the product was washed twice with THF/pentane (1:10),
and then with THF/ether. Dendrimer 3-G1-Pd was obtained as a pale yellow powder in
86% yield. 31P {1H} NMR (121 MHz, DMSO-d6):
(300 MHz, DMSO-d6):
δ
= 8.5 (N3P3), 62.6 (P1). 1H NMR
3
6
δ
= 2.97 (m, 24H, C5H), 3.17 (d, JCP = 10.2 Hz, 18H, C0 H),
2
3
3.60 (m, 24H, C6H), 6.93 (br m, 60H, C0 H, C2H, C3H), 7.16 (d, JHH = 7.8 Hz, 12H,
C9H), 7.54 (m, 12H, C11H), 7.57 (d+s, 3JHH = 8.4 Hz, 12H, C0 H and 6H, C0 H), 7.73 (d,
3
5
3JHH = 8.1 Hz, 1H, C14H), 7.85 (m, 12H, C16H), 8.02 (m, 12H, C10H), 8.18 (m, 12H, C15H),
3
3
8.78 (d, JHH = 4.5 Hz, 12H, C17H), 9.04 (d, JHH = 4.5 Hz, 12H, C12H). 13C {1H} NMR
(75 MHz, DMSO-d6):
δ
= 33.36 (d, 2JCP3 = 12 Hz, C06), 35.85 (C5), 56.91 (C6), 121.48 (C02, C2),
4
125.01 (C14), 126. 44 (C11), 128.66 (C0 ), 129.55 (C9), 129.82 (C16), 130.27 (C3), 132.47 (C0 ),
135.37 (C4), 138.24 (C10), 140.20 (br, C0 ), 141.77 (C15), 148.48 (C8), 149.11 (d, 2JCP = 7 Hz,
5
1
C1), 150.39 (C17), 150.85 (C0 ), 150.99 (C12), 157.25 (C13), 176.46 (C7).
Dendrimer 3-G2-Pd. Same experimental procedure as for 1-G1-Pd, but with 200 mg
(0.018 mmol) of dendrimer 3-G2 and 122 mg (0.43 mmol) of PdCl2(COD) in10 mL of THF.
The dendrimer 3-G2-Pd was obtained as a yellow powder in 76% yield. 31P {1H} NMR

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1
(121 MHz, DMSO-d6):
δ = 8.3 (N3P3), 62.5 (br s, P2, P1). H NMR (300 MHz, DMSO-d6):
6
6
δ
= 3.01 (m, 48H, C5H), 3.20 (m, 54H, C0 H, C1 H), 3.60 (m, 48H, C6H), 6.93 (br m, 108H,
2
2
3
6
C0 H, C2H, C3H), 7.13 (br m, 72H, C1 H, C9H, C11H), 7.62 (br m, 102H, C0 H, C0 H,
C13H, C16H, C14H, C16H), 8.00 (br m, 24H, C10H), 8.13 (br m, 24H, C15H), 8.77 (br m, 24H,
C17H), 9.07 (br m, 24H, C12H). 13C {1H} NMR (75 MHz, DMSO-d6):
δ
= 33.42 (m, C06, C16),
35.90 (C5), 56.78 (C6), 121.48 (C02, C12, C2), 124.94 (C14), 126. 48 (C11), 128.87 (C03, C13, C9),
4
4
5
5
129.72 (C16), 130.28 (C3), 132.50 (C0 , C1 ), 135.27 (C4), 138.24 (C10), 140.20 (br, C0 , C1 ),
141.72 (C15), 148.42 (C8), 149.12 (C1), 150.80 (br, C01, C11, C12, C17), 157.15 (C13), 176.39 (C7).
Dendrimer 3-G3-Pd. Same experimental procedure as for 1-G1-Pd, but with 200 mg
(0. 0085 mmol) of dendrimer 3-G3 and 117 mg (0.41 mmol) of PdCl2(COD) in10 mL of THF.
The dendrimer 3-G3-Pd was obtained as a yellow powder in 74% yield. 31P {1H} NMR
(121 MHz, DMSO-d6):
DMSO-d6):
δ
= 8.1 (br s, N3P3), 62.5 (br s, P3,
P
P ). 1H NMR (300 MHz,
2,
1
6
6
6
δ
= 3.00 (m C5H, 96H), 3.21 (m, 126H, C0 H, C1 H, C2 H), 3.60 (m, 96H, C6H),
6.93 (br m, 204H, C02H, C2H, C3H), 7.10 (br m, 168H, C12H, C22H, C9H, C11H), 7.62 (br m,
3
6
3
6
3
6
222H, C0 H, C0 H, C1 H, C1 H, C2 H, C2 H, C14H, C16H), 7.99 (br m, 48H, C10H), 8.11
(br m, 48H, C15H), 8.75 (m, 48H, C17H), 9.03 (m, 48H, C12H). 13C {1H} NMR (75 MHz,
6
6
6
2
2
2
DMSO-d6):
δ
= 33.48 (m, C0 , C1 , C2 ), 35.90 (C5), 56.73 (C6), 121.49 (C0 , C1 , C2 , C24),
3 3 3
124.78 (C14), 126. 50 (C11), 128.87 (C0 , C1 , C2 , C9), 129.56 (C16), 130.30 (C3), 132.50 (C0 ,
4
4
5
5
5
C1 , C2 ), 135.26 (C4), 138.22 (C10), 140.20 (br, C0 , C1 , C2 ), 141.69 (C15), 148.40 (C8),
149.30 (C1), 151.09 (br, C0 , C1 , C2 , C12, C17), 157.11 (C13), 176.37 (C7).
1
1
1
5. Conclusions
A series of N-, N,N- and N,N,N-ligands based on pyridine and pyridine-imine func-
tions, and further functionalized with a phenol (eventually protected by a methyl) has been
synthesized. Characterization of most of these compounds by X-ray diffraction studies
confirms their structure. The phenols have been tentatively grafted to phosphorhydra-
zone dendrimers, generally up to the third generation (48 ligands on the surface). Three
families of dendrimers have been synthesized, possessing either one pyridine group on
each terminal function (1-Gn, n = 0, 1), or one pyridine imine (
two pyridines and one imine ( 3a 3-Gn, n = 1–3). The PdCl2 complexes of the family
of compounds have been synthesized and isolated. The crystal structure of compound
2, 2a, 2-Gn, n = 1–3), or
3,
,
3
3a-Pd was recorded, to ascertain the location of Pd. The complexation was not between
the two pyridine groups (as often proposed in the literature), but between the imine and
one pyridine.
The isolated Pd complexes of the family
the complexation of Pd(OAc)2 with the , and
in several catalytic C-C cross-coupling reactions, of type Heck and Sonogashira. The family
(only pyridine terminal functions) was found poorly efficient in both cases. Family was
3, and also the complexes prepared in situ by
1
,
2
3
families of compounds have been tested
1
2
found relatively efficient for Sonogashira couplings, and displayed a positive dendritic
effect, the best results being obtained with the third generation 2-G3. However, this family
of compounds is less efficient than the family of compounds
3, which was thus applied in
more catalytic tests. With this family , 0.1 mol% of Pd was sufficient for catalyzing Heck
3
couplings between iodobenzene and butyl acrylate, and also for Sonogashira couplings
between iodobenzene and phenylacetylene. These results compare very well in terms of
quantity of metal and of temperature with the best results in the literature concerning
catalysis with Schiff bases palladium complexes, as emphasized in a recent review [27].
Supplementary Materials: The following are available online, NMR spectra (1H, 13C and 31P NMR)
of all new compounds (
2, 2a, 2a-Pd, 3, 3a, 3-Pd, 3a-Pd, 4, 5, 6, 1-G0, 1-G1, 3-G1-Pd12, 3-G2-Pd24,
3-G3-Pd48). CIF files for compounds 2, 3, 3a, 3a-Pd, 4 and 5.
Author Contributions: Conceptualization, A.-M.C.; methodology, R.L.; software, S.M.-L.; validation,
Q.V., P.S. and A.C.; formal analysis, S.M.-L., Q.V., P.S. and R.L.; data curation, A.-M.C.; writing—
original draft preparation, A.-M.C.; writing—review and editing, Q.V., P.S., R.L. and A.-M.C.; super-

Molecules 2021, 26, 2333
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vision, A.-M.C. and R.L.; project administration, A.-M.C.; All authors have read and agreed to the
published version of the manuscript.
Funding: This research received no external funding.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data is contained within the article or supplementary material.
Acknowledgments: The authors thank the CNRS (Centre National de la Recherche Scientifique) and
the GRD Phosphore for financial support. We also thank M Zhaoxiang Wang for his contribution.
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: No samples of compounds are available from the authors.
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