Enhanced catalytic properties of copper in O- and N-arylation and vinylation reactions, using phosphorus dendrimers as ligands

Article abstract of DOI:10.1021/ja066505s

Imino pyridine-capped phosphorus dendrimers were found to strongly enhance the catalytic activity of copper in arylations and vinylations of O- and N-nucleophiles. These reactions could indeed be performed under very mild conditions, often the mildest to

Full text of DOI:10.1021/ja066505s

Published on Web 11/21/2006
Enhanced Catalytic Properties of Copper in O- and N-Arylation and Vinylation
Reactions, Using Phosphorus Dendrimers as Ligands
Armelle Ouali,† Re´gis Laurent,‡ Anne-Marie Caminade,‡ Jean-Pierre Majoral,*,‡ and Marc Taillefer*,†
AM2N, UMR CNRS 5076, ENSCM, 8 rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France, and Laboratoire
de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France
Received September 13, 2006; E-mail: marc.taillefer@enscm.fr; majoral@lcc-toulouse.fr
The chemistry of dendrimers is a blossoming area of research
with many applications ranging from biology to materials science.1
The use of these nano-objects in catalysis is also well documented.2
Metallodendrimerssin which early or late transition metals are
incorporated at the focal point, within the cascade structure, or
grafted on the surfaceshave been found to be good catalysts in a
number of reactions. However, among several hundred publications
presenting catalytic behavior of metallodendrimers, only a few
report a strong positive catalytic effect of dendrimers compared to
that of monomeric species.3
The use of dendrimers as ligands for the copper catalyzed
arylation or vinylation of nucleophiles with respectively aryl or vinyl
halides has apparently not been reported. These are, however, key
The coupling of PhI with 3,5-dimethylphenol was performed
using our standard conditions for this reaction (acetonitrile with
K3PO4 as base).5b The catalytic system combines CuI (10 mol %)
and a monomeric or a dendritic ligand involving imino-pyridine
N,N-chelates. The loading of the latter has been chosen so that the
ratio N,N-chelate-to-copper is equal to 1 in all cases (Table 1).
We observed an optimum catalytic activity when using 2-G3 as
the ligand, while monomer M, 2-G1, and 2-G2 were found to
promote the reaction with comparable efficiency. The dendritic
effect is significant since the yield of diarylether could be improved
reactions for carbon-heteroatom or carbon-carbon bond formation
in organic synthesis,4 leading to a wide range of intermediates and
targets for the life science and polymer industries.
Recently, some of us discovered that multidentate donor ligands
(with nitrogen-, oxygen-, or mixed N, O- binding sites), in
association with copper precursors, are able to efficiently catalyze
C-N, C-O, and C-C bond formation under some of the mildest
conditions ever reported.5
Among them, the bidentate N-[(1E)-pyridin-2-ylmethylene]-
aniline A involving one imino-pyridine chelating ligand, is easily
by about 40% by using third-generation dendrimer (2-G3). It must
obtained by straightforward condensation of aniline and 2-pyridi-
be emphasized that no catalytic activity is observed using copper
necarboxaldehyde. However, this ligand is less versatile than our
and dendrimers not decorated with chelating end-groups (1-Gn for
instance).
best polydentate ligands (such as B), which require the use of more
expensive starting materials.5 It thus appeared challenging to take
We next tried to take advantage of this dendritic effect to perform
advantage of a potential positive catalytic effect of dendrimers in
the reaction at lower temperatures (Table 1, entries 6, 7) Interest-
the hope of improving the activity conferred to copper by the
ingly, diarylether could be obtained in good yield (72%) from
bidentate chelator A. Hence, phosphorus dendrimers of generation
1 to 3 incorporating the linkage A on their outer shell were prepared.
Table 1. Coupling of 3,5-Dimethylphenol with PhI in the Presence
of Monomer M or Dendritic Ligands 2-G1 to 2-G3a
Herein we report the outcomes of copper-dendrimer catalyzed
arylations and vinylations of oxygen and nitrogen nucleophiles and
observe a strong positive dendritic effect for some of these reactions.
monomer or dendrimer
no. of
yield
(%)b,c
% mol
N,N-chelate
T (
°
C)
t (h)
1
2
3
4
5
6
7
M
10
1
12
24
48
48
1
80
80
80
80
80
55
55
20
20
20
20
30
70
70
61
65
69
85
98
24
72d
New dendrimers 2-Gn (n ) 1, 2, 3) were prepared from
dendrimers 1-Gn bearing respectively 6, 12, or 24 P(S)Cl2 end
groups6 and the phenol 3 in the presence of cesium carbonate (see
Supporting Information).
The catalytic activity conferred by dendritic ligands to copper
was first evaluated in O-arylation reactions and compared to that
of the model monomeric ligand M, in which the phenolic linker in
3 is capped (Table 1).
2-G1
2-G2
2-G3
2-G3
M
0.84
0.42
0.21
0.21
10
2-G3
0.21
48
a PhI (0.5 mmol), 3,5-dimethylphenol (0.7 mmol), K3PO4 (0.7 mmol),
CuI (0.05 mmol), ligand, CH3CN (300 µL), 20 h. b GC yields determined
with 1,3-dimethoxybenzene as internal standard. c Selectivity (yield/conver-
sion of PhI) g 98%; only byproduct is benzene. d Under the same conditions,
diarylether is formed in only 30% yield with ligand B.
† AM2N, UMR CNRS 5076.
‡ Laboratoire de Chimie de Coordination du CNRS.
9
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J. AM. CHEM. SOC. 2006, 128, 15990-15991
10.1021/ja066505s CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Coupling of E-â-Bromostyrene with N- and
O-Nucleophiles in the Presence of Monomeric and Dendritic
Ligands.a
monomer or
yield
(%)b
nucleophile
dendrimer (mol %)
1
2
3
4
pyrazole
pyrazole
3,5-dimethylphenol
3,5-dimethylphenol
M (10)
2-G3 (0.21)
M (10)
70
100
35
2-G3 (0.21)
91
a E-â-bromostyrene (0.5 mmol), NuH (0.7 mmol), Cs2CO3 (0.7 mmol),
CuI (0.05 mmol), ligand, CH3CN (300 µL), 96 h. b GC yields determined
with internal standard, selectivity: 100%.
Figure 1. Coupling of pyrazole with PhI and PhBr in the presence of
monomer M or dendritic ligands 2-G1 to 2-G3.
complexes is favored, thus explaining the observed enhancement
of reactivity.
iodobenzene at 55 °C using the dendritic ligand 2-G3 (entry 7),
whereas the coupling was found to be much less efficient in the
presence of the monomeric ligand (entry 6) or with ligand B (Table
1, note d). To the best of our knowledge, these are among the
mildest temperature conditions to date to perform copper-catalyzed
arylation of phenols from iodobenzene.5b
Hence, these promising preliminary results encouraged us to
check if a dendritic enhancement was also observed using other
nucleophiles such as nitrogen heterocycles.
First of all, it is worth noting that copper-catalyzed arylation of
pyrazole with aryl halides can be efficiently performed by means
of different chelates such as oxime derivatives or polydentate Schiff
bases.5e,f However, in the presence of monomeric ligand M (one
N,N-chelate per copper atom), no coupling reaction occurred, neither
from iodobenzene, nor from bromobenzene (Figure 1). Thus this
reaction posed a particular challenge for the dendritic ligand. Indeed,
upon replacement of M by dendrimers 2, a very strong enhancement
of the reaction was observed regardless of the nature of the arylating
agent.
In the case of iodobenzene, 2-G1, 2-G2, and 2-G3 enabled
quantitative conversion of substrate into product within 20 h at 80
°C. When starting from less expensive bromobenzene, the better
catalytic activity was once more obtained in the presence of the
third generation dendritic ligand 2-G3, phenylpyrazole being
obtained in 80% yield after 20 h at 80 °C. As far we know, such
a strong dendritic effect has never been reported in the literature.
To expand the scope of the use of such copper-dendrimer
catalysts we also examined (under demanding low-temperature
conditions) the vinylation of 3,5-dimethylphenol and pyrazole with
E-â-bromostyrene.
N-vinylation of pyrazole quantitatively occurred at 25 °C within
4 days with 2-G3 whereas E-styrylpyrazole was obtained in only
70% yield under the same conditions with the monomer M (Table
2, entries 1,2). The related E-styrylarylether could be obtained in
91% yield after 4 days at room temperature when using 2-G3 as
the ligand, whereas in the presence of M, a poor conversion of
only 35% was observed (Table 2, entries 3,4).
Once more, these are the mildest conditions ever reported for
performing the coupling between vinyl bromides and nucleophiles
(azoles or phenols) using catalytic amounts of copper.5a
The general dendritic effect reported here for various coupling
reactions is remarkable although it is difficult to explain. For sure,
high local concentration of chelating imino-pyridine ligands on the
surface of dendrimers is crucial to obtain the best results. Under
these conditions, it is reasonable to think that the formation of
catalytically active species involving copper(I)/imino-pyridine ligand
In conclusion we have demonstrated specific advantages for
copper(I) catalysis of the very important O- and N-arylation and
vinylation of phenol and pyrazole using dendrimer-bound imino-
pyridine ligands. The highest yields under the mildest conditions
have been obtained for these conversions. Such dendritic enhance-
ment is very rare in the field of organometallic chemistry.
Work is underway to examine the scope of this new catalytic
system in arylation and to better understand the phenomena
underlying the observed dendritic enhancement.
Supporting Information Available: Synthesis and characterization
for dendrimers; procedures for catalysis. This material is available free
of charge via the Internet at http://pubs.acs.org.
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