Heck reaction using palladium complexed to dendrimers on silica

Article abstract of DOI:10.1139/v00-018

Polyamidoamine dendrimers, constructed on the surface of silica, were phosphonated using diphenylphosphinomethanol (prepared in situ) and complexed to form a palladium-dimethyl TMEDA complex. This catalyst was found to be effective in the Hack reaction of aryl bromides with both butyl acrylate and styrene, affording coupling products in moderate to good yields. The heterogeneous palladium catalyst can also be recycled and reused with only moderate reduction in activity.

Full text of DOI:10.1139/v00-018

920
Heck reaction using palladium complexed to
dendrimers on silica
Howard Alper, Prabhat Arya, S. Christine Bourque, Gary. R. Jefferson,
and Leo E. Manzer
Abstract: Polyamidoamine dendrimers, constructed on the surface of silica, were phosphonated using
diphenylphosphinomethanol (prepared in situ) and complexed to form a palladium–dimethyl TMEDA complex. This
catalyst was found to be effective in the Heck reaction of aryl bromides with both butyl acrylate and styrene, affording
coupling products in moderate to good yields. The heterogeneous palladium catalyst can also be recycled and reused
with only moderate reduction in activity.
Key words: dendrimer, Heck, palladium, silica.
Résumé : Utilisant du diphénylphosphinométhanol (préparé in situ), on a réalisé la phosphonation de dendrimères de
polyamidoamines synthétisés sur une surface de silice et en a fait un complexe de palladium–« TMEDA » de
diméthyle. On a trouvé que ce catalyseur est efficace dans la réaction de Heck des bromures d’aryles avec aussi bien
l’acrylate de butyle que le styrène et que ces réactions fournissent des produits de couplage avec des rendements allant
de modérés à bons. On peut aussi régénérer le catalyseur hétérogène et le réutiliser avec une perte mineure d’activité.
Mots clés : dendrimère, Heck, palladium, silce.
[Traduit par la Rédaction] Alper et al. 924
Introduction
the practical ease of reaction and the reliably good yields,
the Heck reaction has not developed past a laboratory
method, bar a few examples (2).
The demand for cleaner, environmentally friendly chemis-
try is coming from many quarters. Legislative, public, and
corporate pressure has led to the rapid development of new
innovations in green technology. While the majority of new
chemical processes developed in the last 50 years are cata-
lytic, there are still problems associated with catalyst recov-
ery, both in terms of reusing the catalyst or at least recovery
of the precious metals often used, with the added advantage
of easier purification of products.
Over the past 20 years the Heck reaction, used in the cou-
pling of aryl halides with vinylic substrates, has been shown
to be a versatile tool which allows easy access to often com-
plex products from relatively simple substrates (1). Despite
The lack of transfer to an industrial scale is primarily due
to the expense of the palladium catalyst, as high loadings of
palladium (e.g., 10 mol%) (3) and, as with homogeneously
catalyzed systems, costly removal of the catalyst residues
are required. Only when the reaction products are of high
commercial value (e.g., pharmaceutical products) can this
catalytic system be used viably because the cost of the cata-
lyst is appreciably a smaller percentage of the final product
than in the bulk chemical case. Hence in the large scale syn-
thesis of bulk chemicals, the Heck reaction has made little
impact.
Over approximately the last 10 years, in an attempt to ex-
tend the Heck reaction to the bulk chemical sector, several
groups have worked on developing heterogeneous catalytic
systems (4). Such systems could, in principle, reduce the
cost and technical problems associated with removal of the
catalyst and also increase the lifetime of the palladium cata-
lyst. The use of lower concentrations of palladium might
also be a consequence of heterogenizing the catalyst. Many
groups have attacked this problem and have made consider-
able headway in some cases. Of particular note is the work
of Ying et al. (5), who have developed a palladium [0] com-
plex on silica which shows very high turnover rates espe-
cially for activated bromoarene systems. However it should
be noted that the catalyst preparation requires specialized
techniques.
Received July 7, 1999. Published on the NRC Research Press
website on June 14, 2000.
Dedicated to Steve Hanessian – a trailblazer in research; a
first class supervisor of some of our leaders of tomorrow; a
genuine friend.
H. Alper,1 S.C. Bourque, and G.R. Jefferson. Department
of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa,
ON K1N 6N5, Canada.
P. Arya. Steacie Institute for Molecular Sciences, National
Research Council Canada, 100 Sussex Dr. Ottawa, ON K1A
0R6, Canada.
L.E. Manzer. DuPont Central Research & Development,
Experimental Station, Wilmington, DE 19880–0262, U.S.A.
1Author to whom correspondence may be addressed.
Telephone: (613) 562-5189. Fax: (613) 562-5871.
e-mail: halper@science.uottawa.ca
Most of the other examples in the literature utilize
iodoarenes (6), the most reactive of the haloarene family in
the Heck reaction, but unfortunately the most expensive and
Can. J. Chem. 78: 920–924 (2000)
© 2000 NRC Canada

Alper et al.
921
Scheme 1.
also generally less readily available than its bromo and
chloro counterparts. One of the main goals of the Heck reac-
tion in both a heterogeneous and homogenous sense is to uti-
lize the cheaper bromo- and chloroarenes.
Polymer supported metal complexes have attracted con-
siderable interest over the last few years. Terasawa et al. (7)
have studied the Heck reaction of styrene with iodobenzene
comparing a variety of heterogeneous catalysts. A phosphinated
polystyrene complex was compared to palladium with the
analogous free palladium complex, palladium salts, Pd/C in
terms of catalytic activity and selectivity, and it was found
that the polymer supported palladium complex is highly ac-
tive but noticeable deactivation was observed during repeated
use. Zhang et al. reported a polymer supported phenan-
throline palladium catalyzed arylation of acrylamide (8);
however, when tributylamine was used the catalyst activity
declined significantly on recycling, and preparation of the
catalyst is complicated. Although there have been several
advances in the Heck reaction in terms of increased turn-
overs and catalyst stability for both heterogeneous and ho-
mogenous systems, the catalyst lifetimes and turnovers still
preclude industrial use.
Table 1. Palladium content of the various PPh2–PAMAM–SiO2
dendrimers.
Percentage
mµ mol Pd/25 mg
SiO2
Generation
palladium (%)a
g Pd/g Si
G-0
G-1
G-2
2.93
1.34
1.13
0.0293
0.0134
0.0113
6.91
3.16
2.66
aDetermined by ICP analysis
acrylate. Amidation of the ester units with ethylenediamine
completes the generation, with repetition of the two steps af-
fording the desired generation of the dendrimer.
We recently developed a dendritic silica supported
bidentate phosphine ligand (9). It was postulated that this
ligand could be utilized in the Heck reaction with a suitable
palladium catalyst. The dendritic support is thought to work
with many facets, one of which is to give the reaction a de-
gree of homogenous character, as the dendritic support
would be highly solvated in a suitable solvent system. It is
also speculated that the ligand increases the stability of the
catalytic system.
In recent years, major efforts have been directed toward
the development of new catalytic systems that effectively
combine the advantages of both heterogeneous and homoge-
neous catalysis (10). Such a catalyst would ideally be easily
recoverable and potentially recyclable while maintaining
high catalytic efficiency. Dendrimer–metal complexes are
particularly attractive in this regard.
Dendrimers are highly branched macromolecules, which
are capable of having multiple sites for metal coordination
(11). In 1994, van Koten and coworkers demonstrated that
soluble polycarbosilane dendrimer complexes of nickel (II)
catalyze the addition of polyhaloalkenes to double bonds
(12). Three years later, Reetz and coworkers synthesized a
polyaminodiphosphine dendrimer to coordinate to rhodium
and palladium catalysts (13). Our research has led to the de-
velopment of heterogeneous polyaminoamidodiphosphonated
dendrimers built on a silica gel core support (PPh2–
PAMAM–SiO2). This article describes the use of these
dendrimers, when complexed to palladium, as effective cata-
lysts for the Heck reaction.
Coordination of the dendrimers to palladium was effected
first by phosphonation. Diphenylphosphinomethanol, pre-
pared in situ from paraformaldehyde and diphenylphosphine,
was excellent for the double phosphinomethylation of each
terminal amine group.
The complex 2 is easily synthesized starting from palla-
dium chloride, in situ formation of the bis(acetonitrile)palla-
dium dichloride (15), followed by displacement of the
acetonitrile ligands with TMEDA forming complex 1. Reac-
tion of complex 1 with methyl lithium gives complex 2 in
65% overall yield (Scheme 1).
The palladium complex is coordinated to the dendrimer
on silica by simply stirring the dendrimer in degassed ben-
zene with one equivalent of palladium complex 2, relative to
the theoretical number of end phosphine groups for the re-
spective dendrimer. The dendrimer complexes are easily iso-
lated by microporous membrane filtration. The resulting
complexed dendrimers (see Fig. 1) were characterized by 31
P
solid state NMR (complexed δ = 6 ppm, uncomplexed δ =
–27 ppm) (13a).
The palladium complexed PPh2–PAMAM–SiO2 dendrimers
were digested with hydrofluoric acid or aqua regia
(nitrohydrochloric acid) by microwave heating and analyzed
for Pd content by ICP analysis. The palladium content of the
various generations is summarized in Table 1. The degree of
complexation decreases significantly with dendrimer genera-
tion from G-0 to G-2, and was so low for G-3 and G-4 as to
preclude further studies with the latter generations of
dendrimers. This is believed to be due to incomplete
phosphonation reactions arising from steric crowding and ul-
timately resulting in the threshold of dendrimer growth be-
ing reached.
Results and discussion
(a) Preparation of PAMAM–SiO2 dendrimers
Commercial aminopropyl silica gel was used to prepare
generation 0–4 polyaminoamido (PAMAM) dendrimers (9).
Propagation of the dendrimers was achieved by standard
dendrimer building methods pioneered by Tomalia and co-
workers (14). Amino propionate esters were obtained by Mi-
chael type addition of the preexisting amino group to methyl
(b) Catalytic heck reaction of aryl bromides using
palladium complexed silica supported dendrimers
As a model reaction for assessing the utility of these Heck
catalysts, the reaction of bromobenzene with styrene in
DMF at 120°C was investigated in the presence of sodium
acetate as base, primarily because these were the conditions
© 2000 NRC Canada

922
Can. J. Chem. Vol. 78, 2000
Fig. 1. Dendrimer generations (CH3)2Pd-PPh2–PAMAM–SiO2.
employed by Reetz and co-workers for their dendritic Heck
system. The catalytic activity of the palladium complexed
PPh2–PAMAM–SiO2 dendrimers was investigated with re-
Table 2. Conversions in the Heck reaction of styrene and
bromobenzene using the Pd–PPh2–PAMAM–SiO2 catalysts.a
Time
G-0
G-1
G-2
6 h
24 h
48 h
67%b
76%
79%
10%
37%
47%
17%
49%
59%
a6.0 mmol each of styrene and bromobenzene, 6.6 mmol of NaOAc,
and 50 mL of DMF.
gards to the Heck reaction (Reaction [1]) and the results are
summarized in Table 2. Treatment of styrene and
bromobenzene in dimethylformamide, with Pd complexed
PPh2–PAMAM–SiO2 dendrimer, and sodium acetate affords
trans stilbene in good yield and regioselectivity for genera-
tions 0, 1, and 2. The yields of stilbene was significantly less
when generation 3 and 4 dendrimer complexes are used as
catalysts.
bYields determined by GC and NMR analysis.
Table 3. Turnovers for generations 0, 1, and 2 of the
Pd–PPh2–PAMAM–SiO2 dendrimers.a
Dendrimer
generation
Turnovers (h
after 6 h)
Turnovers (h
after 24 h)
The best turnovers in terms of molecules of trans-stilbene
formed per mol of palladium was achieved with the genera-
tion 2 catalyst, as may be expected as this catalyst would
have the greatest homogenousity factor (Table 3).
The effect of temperature on the Heck reaction was stud-
ied with the generation 2 catalyst and it was found that the
best yields were obtained when the temperature was in the
110 to 140°C range (Table 4). At lower temperatures the
yields were low due to either poor conversion of the catalyst
precursor to the catalyst via reductive elimination of the
methyls, or just a factor of low turnovers at low tempera-
tures. At temperatures above 140°C the yield was reduced
by catalyst deactivation with noticeable palladium black for-
mation.
0
1
2
72
31
81
21
30
58
a6.0 mmol each of styrene and bromobenzene, 6.6 mmol of NaOAc, 50
mL of DMF.
used as well as the organic base, triethylamine. Potassium
carbonate and sodium acetate gave the best yields, and low
product yield was found using triethylamine (13a). This
triethylamine effect was also observed by Reetz and co-
workers using their dendritic Heck catalyst system.
As some loss in activity of the catalyst was noticed we ex-
amined the possibility of leaching of the catalyst into the re-
action mixture. The reaction was carried out with styrene
and bromobenzene using the G-2 catalyst, and after 16 h, the
reaction was filtered under nitrogen. A further 2 mmol of
The effect of the base on the reaction was studied in terms
of yield and recoverability of the catalyst (Table 5). The in-
organic bases; potassium carbonate and sodium acetate were
© 2000 NRC Canada

Alper et al.
923
Table 6. Catalytic activity of the G-2 complex catalyst for the
Table 4. Conversions in the Heck reaction of styrene and
bromobenzene using the Pd–PPh2–G2–PAMAM–SiO2 dendrimer
at different temperatures.a
reaction of a variety of haloarenes with styrene and butyl
acrylate.a
Temperature (°C)
Yieldb (%)
a2.0 mmol each of styrene and bromobenzene, 2.2 mmol of NaOAc,
and 50 mL of DMF.
bNR = No reaction, Yields were determined by NMR analysis.
25
NR
50
NR
80
5
110
69
140
44
170
NR
R group
X group Y = C(O)OnBu
Isolated yieldb (%) Isolated yieldb (%)
Y = Ph
H
H
H
I
—
85
—
76
75
61
45
68
69
0
Br
Cl
Br
Br
p-Me
p-OMe
p-C(O)OMe Br
81
85
59
31
Table 5. Conversions in the Heck reaction of styrene and
bromobenzene using the Pd–PPh2–G2–PAMAM–SiO2 dendrimer
with different bases.a
p-NO2
Br
Base
Cycle 1 (%)
Cycle 2 (%)
53b
5
43
—
Br
67
76
K2CO3
NEt3
NaOAc
39–69
20–45
a2.0 mmol each of styrene and haloarene, 2.2 mmol of NaOAc, 50 mL
a2.0 mmol each of styrene and bromobenzene, 2.2 mmol of NaOAc, 50
mL of DMF.
bYields were determined by NMR analysis.
of DMF.
bYields were determined by NMR analysis.
styrene and bromobenzene was added and sample was taken
for GC analysis. The reaction was run for a further 48 h and
no further reaction of the mixture took place.
General procedure for the complexation of PPh2–PAMAM–
SiO2 with palladium
The PPh2–PAMAM–SiO2 (1.0 mmol with respect to PPh2)
was added to a solution of Pd (Me2NCH2CH2NMe2)(Me)2
(0.5 mmol) in freshly distilled benzene (20 mL). The mix-
ture was stirred at room temperature overnight under nitro-
gen. The product was filtered through a 0.45 mm membrane
filter under a stream of nitrogen and washed with ether
(50 mL). Residual ether was removed in vacuo.
The generality of the catalytic system was investigated for
a variety of haloarenes, and the results are presented in Ta-
ble 6. Initially the nature of the halogen used was studied. It
was found that the reaction of bromo and iodobenzene gave
similar yields with no detectable product using chloroben-
zene. We then examined the effect of para substituents on
the haloarenes. It was surprising to find that electron with-
drawing substituents (nitro, ester) gave relatively low yields
and conversions, while electron donating groups (methoxy,
methyl) gave moderate to good yields of coupled products.
This observation suggests that the oxidative addition step of
the Heck reaction is relatively facile whereas the alkene in-
sertion or reductive elimination is the rate determining step.
This reactivity may be a function of the nitrogen in the
ligand donating into the metal center leading to facile oxida-
tive addition. The catalyst system was also found to be ac-
tive for thiophenes with no catalyst poisoning resulting from
the sulfur atom.
General procedure for the Heck reaction
The substrates, base, and solvent (dimethylformamide 20 mL)
were placed in a 50 mL round bottom-flask equipped with a
magnetic stirring bar and condenser connected to a vacuum
line. The solution was flushed five times with nitrogen using
a vacuum nitrogen cycle. The catalyst was then added. The
autoclave was placed in an oil bath and the desired tempera-
ture was reached by stirring on a hot plate. After the appro-
priate reaction time, the reaction was allowed to cool to
room temperature. The resulting solution was filtered to re-
move the catalyst. The filtrate was extracted with diethyl
ether (4 × 40 mL), and the ether extracts were washed with
brine and distilled water, followed by drying over magne-
Summary
1
sium sulfate. The product was analyzed by H NMR spec-
The dendrimer supported complexes, Pd–PPh2–PAMAM–
SiO2, are new and highly active catalysts for the Heck reac-
tion of a variety of bromoarenes with styrene and butyl
acrylate, affording para substituted stilbenes and cinnamate
esters in good yields. This dendritic system shows compara-
ble activity to the Reetz dendrimer system (13) and can be
easily recycled.
troscopy and (or) gas chromatography, and identified by
comparison of spectral results with literature data (6).
Acknowledgements
We are grateful to DuPont Canada and to the NSERC/
NRC Research Partnership Program for support of this re-
search.
Experimental
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