Heck and Suzuki coupling reactions in water using poly(2-oxazoline)s functionalized with palladium carbene complexes as soluble, amphiphilic polymer supports

Article abstract of DOI:10.1016/j.jorganchem.2005.07.053

This paper describes the application of a novel class of amphiphilic, water-soluble diblock copolymers based on 2-oxazoline derivatives with pendant N-heterocyclic carbene/palladium catalysts in the hydrophobic block for Heck and Suzuki coupling in neat water. Heck coupling reaction of iodobenzene with styrene proceeded rapidly after optimization of various reaction parameters such as the base, the reaction temperature and the catalyst amount. High activities with turn over frequencies (TOF) of up to 2700 h^-1 were observed at 110 °C. Furthermore, the Suzuki coupling reaction of phenylboronic acid was studied in detail with different haloarenes (iodobenzene and various bromoarenes). The observed catalytic activity is even higher and TOF numbers of up to 5200 h^-1 were achieved at 80 °C. Therefore, the presented micellar catalytic system reveals turn over frequencies which are the highest ever reported for such transformations in neat water without the addition of an organic cosolvent.

Full text of DOI:10.1016/j.jorganchem.2005.07.053

Journal of Organometallic Chemistry 690 (2005) 4648–4655
www.elsevier.com/locate/jorganchem
Heck and Suzuki coupling reactions in water using
poly(2-oxazoline)s functionalized with palladium carbene
complexes as soluble, amphiphilic polymer supports
Daniel Sch o¨ nfelder, Oskar Nuyken, Ralf Weberskirch *
TU M u¨ nchen, Department Chemie, Lehrstuhl f u¨ r Makromolekulare Stoffe, Lichtenbergstr. 4, D-85747 Garching, Germany
Received 27 April 2005; received in revised form 7 June 2005; accepted 11 July 2005
Available online 2 September 2005
Abstract
This paper describes the application of a novel class of amphiphilic, water-soluble diblock copolymers based on 2-oxazoline
derivatives with pendant N-heterocyclic carbene/palladium catalysts in the hydrophobic block for Heck and Suzuki coupling in neat
water. Heck coupling reaction of iodobenzene with styrene proceeded rapidly after optimization of various reaction parameters such
À1
as the base, the reaction temperature and the catalyst amount. High activities with turn over frequencies (TOF) of up to 2700 h
were observed at 110 °C. Furthermore, the Suzuki coupling reaction of phenylboronic acid was studied in detail with different haloa-
À1
renes (iodobenzene and various bromoarenes). The observed catalytic activity is even higher and TOF numbers of up to 5200 h
were achieved at 80 °C. Therefore, the presented micellar catalytic system reveals turn over frequencies which are the highest ever
reported for such transformations in neat water without the addition of an organic cosolvent.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: Green chemistry; Heck coupling; Suzuki coupling; Polymer support
1
. Introduction
Well known materials for catalysts heterogenization
are Pd/C [7–11], zeolites/silica [12–15], metal oxides
[16–18] and polymer resins [19–23] that show remark-
able activities in Heck and Suzuki reactions under rather
mild reaction conditions.
The palladium catalyzed C–C coupling reactions be-
long to the most powerful processes for carbon–carbon
bond formation [1]. As most important representatives
of this class of reactions Heck and Suzuki coupling have
to be noted. In this context the Heck reaction is the
transformation between an aryl halide and an olefin to
form cinnamic acid and stilbene derivatives, respectively
With the increasing interest in Green Chemistry Pro-
cessing the replacement of expensive, toxic and flamma-
ble organic solvents by water as the preferred solvent is
highly desirable due to economically and safety related
process engineering reasons [24–26]. Whereas most of
the heterogenized catalysts mentioned above have been
applied in organic solvents an increasing number of re-
search groups have recently focused on the development
of new polymeric support materials for catalysis in
water based on polyethylene glycol [27,28] poly(acrylic
acid)s [29] or poly(N-isopropylacrylamide) copolymers
[30,31]. However, the transformation of hydrophobic
substrates in pure aqueous media without the usage of
[
2,3]. The corresponding reaction between an aryl halide
and an arylboronic acid yields in a biphenyl derivative
and is called Suzuki coupling [4–6]. Although homoge-
neous catalysts have many advantages, catalyst immobi-
lization is a well known methodology to allow efficient
catalyst separation and to obtain metal-free products.
*
Corresponding author.
E-mail address: ralf.weberskirch@ch.tum.de (R. Weberskirch).
0
022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.07.053

D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
4649
any organic cosolvent remains still a challenging task
due to their limited water solubility. The most promising
approach to increase the solubility of hydrophobic sub-
strates in aqueous media is based on the use of amphi-
philic polymer supports. Of particular interest is the
work of Uozumi et al., who utilized commercially avail-
able poly(ethylene glycole) (PEG) modified poly(sty-
rene) (PS) resins for catalyst immobilization in various
transition-metal catalyzed reactions in neat water [32].
More recently, Yamada et al. described the preparation
of a heterogeneous palladium catalyst by supramolecu-
lar self-assembling of (NH ) PdCl and poly[(N-isopro-
H3C
N
N
N
N
O
O
O
CH3
(CH2)n
(CH2)n
H
x
N
N
z
N
N
I
I
Pd
y
stat.
4
2
4
pylacrylamide)-co-(4-diphenylstyrylphosphine)] [33,34].
However, typical limitations of cross-linked polymer
materials, such as lowered reactivity and extended reac-
tion times remain unsolved. In addition, fine tuning of
the structure and composition of the polymer support
to allow a better correlation with catalyst activity as
an important feature of any support material is difficult
to achieve with heterogeneous catalyst supports.
.
-1
P1: n = 4 (But) x = 28.4 y = 1.5 z = 2.9 M = 3920 g mol
n
.
-1
-1
P2: n = 6 (Hex) x = 29.9 y = 1.8 z = 3.2 M = 4400 g mol
n
.
P3: n = 8 (Oct) x = 30.4 y = 1.9 z = 3.4 M = 4730 g mol
n
Fig. 1. Structure and composition of the amphiphilic poly(2-oxazo-
line) block copolymers P1–P3 functionalized with NHC/Pd catalyst
complexes in the hydrophobic block [44].
In the past years, metal complexes of N-heterocyclic
carbenes (NHC) have been reported as a class of mois-
ture, temperature and air-stable catalysts with remark-
able activity in various C–C coupling reactions [35–
of three 2-oxazoline monomers M1–M3 functionalized
with a heteroleptic NHC/Pd complex and (ii) the copo-
lymerization of one of these monomers with 2-methyl-2-
oxazoline and 2-alkyl-2-oxazoline monomers for build-
ing up the corresponding amphiphiles P1–P3 [44]. The
general formula of these polymers is depicted in Fig. 1.
4
0]. Recently, we have introduced a new class of soluble,
amphiphilic polymer supports based on poly(2-oxazo-
line)s which indicated remarkable activities in various
transition-metal catalyzed reactions such as asymmetric
hydrogenation, ATRP, and alkine polymerization [41–
2.2. Heck reaction
4
3]. Based on these design criteria we have prepared a
soluble, amphiphilic block copolymer with pendent N-
heterocyclic carbene (NHC)/palladium complexes in
the hydrophobic block [44]. First results of these poly-
mer bound catalysts in a micellar catalytic variant of
Heck reaction of iodobenzene with styrene in water re-
The Heck reaction of sp2-halides with alkenes is pro-
moted by palladium catalysts and meanwhile one of the
most important methods for C–C coupling in organic
synthesis [45] in the synthesis of intermediates for phar-
maceuticals [46] and also for the preparation of conduct-
ing polymers [47].
À1
vealed turnover frequencies (TOF) up to 570 h which
are the highest ever reported for this reaction in neat
water without addition of any organic cosolvent. The
scope of this contribution is a detailed investigation of
these polymers in Heck reaction and Suzuki coupling
by varying several reaction parameters such as tempera-
ture, catalyst amount and amphiphilic structure as well
as the substrate.
2.2.1. Heck reaction in aqueous media
In the last years only a few reports have been pre-
sented that deal with Heck coupling in neat water with-
out usage of any organic cosolvents. Jeffery for example
studied intensively the transformation of iodobenzene
with methyl acrylate in the presence of Pd(OAc) /PPh
2
3
in pure aqueous solution and explored in particular
the beneficial effect of various tetrabutylammonia ha-
lides [48]. Another typical test reaction is the coupling
of styrene with iodobenzene to give trans-stilbene. The
transformation of these substrates in neat water is con-
siderably more complicated due to the higher hydropho-
bicity and the accordingly lower water solubility of
styrene (water solubility: 280 ppm) comparing to methyl
acrylate (water solubility: 52000 ppm) [49]. The first ap-
proach to react iodobenzene derivatives and various ole-
fins under Heck coupling conditions in pure water was
presented by Uozumi et al. [50]. They have used a palla-
dium catalyst which is supported on a PS-PEG resin and
2
. Results and discussion
2.1. Poly(2-oxazoline)s functionalized by a palladium
carbene complex
Recently, we have reported on the synthesis of a new
class of amphiphilic, water-soluble diblock copolymers
based on 2-oxazoline derivatives with pendant NHC/
Pd catalysts in the hydrophobic block [44]. The synthesis
of these polymers is divided into two stages and already
described in detail in our recent paper (i) the preparation

4650
D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
obtained a yield of 92% of trans-stilbene after 14 h reac-
tion time in case of styrene and iodobenzene as sub-
strates. But unfortunately high catalyst amounts of
In our first publication we have already studied the
effect of spacer length on catalytic activity (see Table
1, exp. (10), (11), (01)) and have also demonstrated cat-
alyst recycling and reusage in three consecutive cycles
[44]. Herein we aimed to further optimize the reaction
conditions and evaluated the dependence of the catalytic
activity on characteristic system parameters, such as (i)
the base, (ii) the reaction temperature and (iii) the catalyst
amount. All Heck coupling reactions are summarized in
Table 1. In Sections 2.2.2.1, 2.2.2.2, 2.2.2.3 these cata-
lytic results are arranged according to the respective
parameter.
1
0 mol% were needed to achieve this result. The corre-
sponding turnover frequency (TOF) as a measure of cat-
À1
alyst activity is less than 1 h . Thus, the presented
system shows excellent recyclability but poor activities.
2
.2.2. Heck reaction in aqueous media using micellar
catalysis
To solve this problem of low activities when trans-
forming hydrophobic substrates in neat water, we have
studied our amphiphilic polymers P1–P3 in a micellar
catalytic variant of the Heck coupling reaction of iodo-
benzene and styrene (Scheme 1). The course of the reac-
tion was monitored by periodically taking samples and
analyzing them by means of gas chromatography. The
activity of the catalyst was determined from the point of
inflection of substrate conversion. The primary product
of this conversion is trans-stilbene 1. Furthermore, the
formation of the by-products cis-stilbene and 1,1-diphe-
nylethene could be observed. In all coupling experiments
the ratio of the three products trans-stilbene:1,1-diphenyl-
ethene:cis-stilbene was approximately 95:4:0.5.
2.2.2.1. Dependence on the base (B). In the first set of
experiments the influence of the base on catalytic activ-
ity and induction time was studied. The transformations
were conducted at 90 °C using the amphiphile P3 with a
palladium content of 0.67 mol%. Fig. 2 shows the kinet-
ics of iodobenzene conversion as a function of different
base used. We have used inorganic [K CO (01/02),
2
3
KOAc (03)] and organic bases [NEt (04), NBu (05)]
3
3
as well. As can be seen from the kinetics the investigated
systems differ strongly in the duration of the induction
period and formation of Pd(0) formation which is well
[
Pd-polymer], B, H O
2
I
+
-
HB+I-
1
Scheme 1. Aqueous Heck coupling reaction of iodobenzene and styrene using the catalyst functionalized amphiphilic polymer P1–P3 [Pd-polymer]
and a base B (see Table 1, entries 1–11).
Table 1
Aqueous Heck coupling reactions
a
b
c
d
À1
TOF (h )
exp.
P
nPd/nPhI (mol%)
T (°C)
Base B
t (h)
x (%)
Yield 1 (%)
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
a
P3
P3
P3
P3
P3
P3
P3
P3
P3
P1
P2
P3
P3
P3
P3
0.67
0.67
0.67
0.67
0.67
0.67
0.67
0.10
0.01
0.67
0.67
0.67
0.67
0.10
0.10
90
90
90
90
90
70
110
90
90
90
90
90
110
110
110
K
K
KOAc
NEt
NBu
K
K
K
K
K
K
K
K
K
K
2
CO
CO
3
1.5
1.5
3.0
3.0
5.0
7.0
0.5
6.0
72.0
2.0
1.5
3.0
3.0
3.0
3.0
97
97
93
95
93
53
96
94
81
96
97
97
95
97
97
>93
>93
27
52
5
46
>93
>93
72
>93
>93
2
530
200
110
84
88
36
2700
540
620
150
570
n.d.
n.d.
n.d.
n.d.
e
2
3
3
3
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
3
3
3
3
3
3
3
3
3
3
f
f
4
3
5
f
f
Number of the experiment.
b
P
P = polymer; the concentration of the polymeric amphiphile in water was c = 0.57 mM for all experiments, if not otherwise noted (see
footnotef).
c
Conversion of iodobenzene or various bromoarenes (see Scheme 2, exp. 12–15).
Yield of trans-stilbene (1).
d
e
f
Additional 1.0 equiv. of tetrabutylammonia bromide NBu
The concentration of the polymeric amphiphile in water was c
4
Br was added.
= 0.17 mM.
P

D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
4651
Fig. 2. Kinetic of the aqueous Heck coupling reaction of iodobenzene
PhI) and styrene in the presence of different bases (01–05; PhI:sty-
rene:base = 1.0:1.25:1.5, T = 90 °C, P3 = 0.57 mM,
.67 mol%).
Fig. 3. Kinetic of the aqueous Heck coupling reaction of iodobenzene
(PhI) and styrene in dependence on the temperature T (06, 01, 07;
(
c
nPd/nPhI
=
PhI:styrene:K CO = 1.0:1.25:1.5,
cP3 = 0.57 mM,
nPd/nPhI =
2
3
0
0.67 mol%).
known to be the active species in heck reaction and also
in their catalytic efficiency.
Fig. 3 shows also the influence of the temperature on the
duration of the induction period. Within the investigated
temperature range the induction period decreases from
about 2 h (70 °C, 06) down to 15 min (90 °C, 01) reach-
ing finally a duration of less than 3 min at 110 °C (07).
Altogether a reaction temperature of about 110 °C can
be considered as an optimal value with respect to a high
reaction rate and a very short induction period.
The highest activity was obtained by using potassium
À1
carbonate (01, TOF = 530 h ) with an induction period
of 15 min. The addition of tetrabutylammonia bromide
does not cause an increase of the reaction rate (02).
Rather, we have observed a decrease of the turnover fre-
À1
quency down to 200 h . However, in this case the induc-
tion period was depleted down to 3 min. This can be
ascribed to the fact, that tetrabutylammonia bromide is
able to reduce Pd(II) to Pd(0), which is already described
in the literature for the analogous catalyst complex with
low molecular weight [51]. By using the bases potassium
2.2.2.3. Dependence on the catalyst amount (nPd/
nPhI). Beside the possibility to recycle a catalytic sys-
tem the use of small catalyst amounts is another impor-
tant aim in catalyst design. Both factors will reduce the
economical costs of a catalytically synthesized product.
Due to this fact in the next three experiments the cata-
À1
acetate (03, TOF = 110 h ), triethylamine (04, TOF =
À1
À1
8
4 h ) and tributylamine (05, TOF = 88 h ) the cata-
lytic activity decreased also. Moreover, the yield of
trans-stilbene was far smaller, although the starting com-
pounds were converted completely within a few hours.
This fact was especially pronounced by using tributyl-
amine as base. In this case mainly the dehalogenation
of iodobenzene was observed and the yield of the cou-
pling product was 5% only. The influence of the base
on the catalytic activity of the system is very high and
potassium carbonate exhibits the best results among those
that have been investigated.
lyst amount n /n
to 0.10 mol% (08) and finally down to 0.01 mol% (09).
Thus, in relation to the starting compound iodobenzene
only a small amount of 10 molar equivalents of the
catalyst was used in experiment 09. The obtained three
kinetic plots are summarized in Fig. 4.
As can be seen from Fig. 4, the kinetic rate of the
Heck reaction decreased when a smaller catalyst amount
was used. Accordingly reaction time increased in the
same way and the turnover frequencies of all three trans-
was varied from 0.67 mol% (01)
Pd PhI
À4
À1
formations are approximately the same (530–620 h ).
2
.2.2.2. Dependence on the temperature (T). The tem-
Nevertheless, we have to emphasize that the Heck cou-
pling reaction takes place in a unrestricted manner even
at a catalyst amount of only 0.01 mol%, albeit the reac-
tion time rises up to 72 h to reach a yield of 72% of
trans-stilbene. Moreover, despite the longer reaction
time no deactivation of the catalyst and no precipitation
of palladium black was observed during this experiment
just as in all other conducted coupling experiments using
our micellar catalytic system.
perature of a reaction is an important influencing factor
especially for conversions with high activation energy,
like Heck coupling. Due to this the reaction temperature
was varied in the next set of experiments from 70 °C (06)
to 90 °C (01) and finally up to 110 °C (07). The corre-
sponding kinetic plots are represented in Fig. 3.
À1
The turnover frequency reaches a value of 2700 h at
1
10 °C (07) indicating excellent thermal stability and cat-
alytic activity of the catalyst system. Beside the strong
dependence of the catalytic reaction on the temperature,
However when studying bromoarenes as substrate
with the optimized reaction conditions very low activities

4652
D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
bromobenzene as substrate gave quantitative yield of
the desried biphenyl compound with various phenyl
boronic acid derivatives under the given reaction condi-
tions (T = 50 °C, t = 12 h, 2 mol% Pd) [53]. Recently,
Lee et al. have presented an NHC based palladium com-
plex, which is supported by a PS resin, for the Suzuki
coupling of iodobenzene and phenylboronic acid in
water [53]. Beside the catalyst complexes some cationic
imidazolium groups were attached to the outer sphere
of the resin to reach an enhanced water solubility of
the polymeric support. This system is outstandingly sui-
ted for the comparison with the system described in this
contribution due to the general similarity. Using
1
.2 mol% of the heterogenized catalyst the authors ob-
tained a yield of 48% of biphenyl after 12 h reaction time
Fig. 4. Kinetic of the aqueous Heck coupling reaction of iodobenzene
PhI) and styrene in dependence on the catalyst amount nPd/nPhI. The
diagram at the right bottom corner represents the kinetic plot of
at 50 °C. The corresponding turnover frequency is in the
(
À1
range of 10 h . This disadvantage could only be elimi-
experiment 09 (0.01 mol%) over the whole reaction period of 72 h
nated by adding an organic cosolvent, like toxic N,N-
dimethylformamide. Moreover, for the transformation
of less active substrates, such as aryl bromides, the addi-
tion of an organic cosolvent is even coercively required.
(
08, 01, 09; PhI:styrene:K
2 3
CO = 1.0:1.25:1.5, T = 90 °C, cP3(01) =
0.57 mM, cP3(08/09) = 0.17 mM).
were observed even at 110°C. Although bromobenzene
12, 13, Table 1), 4-bromobenzaldehyde (14, Table 1)
(
2.3.2. Suzuki reaction in aqueous media using micellar
catalysis
and 4-bromoacetophenone (15, Table 1) are still con-
verted very fast, only about 2–5% of the trans-stilbene
Heck products were formed. The major part of bromoea-
renes dehalogenated under the reaction conditions indi-
cating clearly that the catalyst is most likely not active
enough for the less active haloarenes.
Although the results are already very promising con-
sidering the pure aqueous reaction conditions they are still
far away from results obtained with other supports. . .
In analogy to the Heck coupling experiments we have
tested our amphiphiles P1–P3 also in a micellar catalytic
variant of Suzuki reaction. Therefore, the conversions of
iodobenzene and substituted bromobenzenes with phen-
ylboronic acid to the corresponding biphenyl derivative
2 were explored (Scheme 2).
In the beginning, we have carried out a set of exper-
iments to evaluate the dependence of the catalytic activ-
ity on characteristic parameters. Furthermore, different
starting compounds were applied. All Suzuki experi-
ments are summarized in Table 2 and discussed in Sec-
tions 2.3.2.1, 2.3.2.2, 2.3.2.3 with respect to the
diversified parameters.
2
.3. Suzuki reaction
The Suzuki coupling of aryl halides with arylboronic
acids is also promoted by palladium catalysts and now-
adays a very important tool for building up biphenyl
derivatives, which are required for a lot of pharmaceuti-
cal intermediates and fine chemicals.
2.3.2.1. Dependence on the temperature (T). As visual-
ized in Fig. 5 the catalyst shows also high activity in Su-
zuki coupling reaction and a pronounced dependency
between reaction temperature and catalytic activity.
Even at 50 °C the starting compounds were converted
completely to the product biphenyl within 5 h (1). By
increasing the reaction temperature up to 80 °C this
2
.3.1. Suzuki reaction in aqueous media
Uozumi and co-worker reported for the first time on
the successful use of amphiphilic PEG-PS resin sup-
ported triphenyl phosphine palladium complexes in Su-
zuki coupling reactions in aqueous media under mild
reaction conditions (T = 25 °C, t = 24 h) [52]. Also
yield can be reached already within 30 min (2). The cor-
À1
responding turn over frequency is more than 1000 h
.
[
Pd-polymer], KOH, H O
2
R1
X
(HO) B
R1
+
2
+
-
-
HB X
2
Scheme 2. Aqueous Suzuki coupling reaction of different halobenzenes with phenylboronic acid using the catalyst functionalized amphiphilic
polymer P1–P3 [Pd-polymer] and potassium hydroxide as base (see Table 2).

D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
4653
Table 2
Aqueous Suzuki coupling reactions
a
b
1
c
d
À1
exp.
P
nPd/nPhI (mol%)
T (°C)
R
X
t (min)
x (%)
Yield 2 (%)
TOF (h
)
0
0
0
0
0
0
0
0
0
1
1
2
3
4
5
6
7
8
9
0
a
P3
P3
P1
P2
P1
P2
P3
P2
P2
P3
1.00
1.00
1.00
1.00
0.10
0.10
0.10
0.67
0.10
0.10
50
80
80
80
80
80
80
110
110
110
H
H
H
H
H
H
H
H
CH
I
I
I
I
I
I
I
Br
Br
Br
240
20
20
98
95
99
96
92
98
98
97
97
98
91
91
94
92
87
>95
>95
30
84
90
110
1200
1200
2600
1100
3800
5200
520
20
300
180
180
90
300
300
e
3
CO
560
2900
CHO
Number of the experiment.
b
P
P = polymer; the concentration of the polymeric amphiphile in water was c = 0.17 mM for all experiments, if not otherwise noted (see
footnotee).
c
Conversion of haloarene.
Yield of biphenyl derivative (2).
The concentration of the polymeric amphiphile in water was c = 0.57 mM.
P
d
e
Fig. 5. Kinetic of the aqueous Suzuki coupling reaction of iodoben-
zene (PhI) and phenylboronic acid and biphenyl formation as a
function of reaction temperature T. The diagram at the right bottom
corner represents an enlargement of the kinetic plot of experiment 2
Fig. 6. Kinetic of the aqueous Suzuki coupling reaction of iodoben-
zene (PhI) and phenylboronic acid in dependence on the amphiphilic
structure P1–P3 at a catalyst amount of nPd/nPhI = 0.1 mol% (5–7;
PhI:PhB(OH)
2
P
: KOH = 1.0:1.5:2.0, T = 80 °C, c = 0.17 mM).
(
n
2
T = 80 °C). (1, 2; PhI:PhB(OH) :KOH = 1.0 : 1.5:2.0, cP3 = 0.17 mM,
Pd/nPhI = 1.0 mol%).
amphiphiles P2 and P3 again. More precisely, the turn
over frequency in experiment 5 (P1) is by a factor of
3.5 and 4.7 lower than the corresponding value of reac-
tion 6 (P2) and 7 (P3) respectively. We attribute this
smaller activity of amphiphile P1 to the effect of spacer
length mentioned before [44].
2
.3.2.2. Dependence on the catalyst amount (n /nPhI)
Pd
and the amphiphilic structure (P1–P3). In the next set
of experiments (02–04, Table 2) the amphiphiles P1–P3
were used at a constant catalyst amount of 1.0 mol%.
All reactions were characterized by a quantitative con-
version of iodobenzene and a yield of biphenyl of more
than 91% after less than 30 min. Unfortunately, the ki-
netic rates were too fast to identify reliably potential dif-
ferences in the catalytic activities of the respective
polymers. As a consequence, we have repeated the exper-
iments using a smaller catalyst amount of 0.1 mol% (5–
In addition, it should be stressed here that the activity
of our micellar catalytic system is in case of Suzuki
coupling even higher than in Heck reaction and the
À1
achieved turn over frequencies are up to 5200 h (7)
thus being a multiple higher than the activity of the also
Pd/NHC based system of Lee and co-worker [31].
7
). By this means the reaction time decreased as expected
2.3.2.3. Using different halobenzenes as starting com-
pounds. In the last set of experiments we have used dif-
ferent halobenzenes as starting compounds. In detail we
have tested 4-bromoacetophenone (9) and 4-bromo-
benzaldehyde (10) as activated bromobenzenes and
by a factor of 10 so that even small differences of polymer
activities could be detected (Fig. 6). In accordance to the
Heck coupling experiments the catalytic activity of poly-
mer P1 is smaller than the activity of the both other

4654
D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
Fig. 8). But unfortunately, even at a quantitative degree
of conversion of bromobenzene the yield of biphenyl as
coupling product was comparatively small at T = 90 °C
with 6% yield of the biphenyl product. Only when we in-
creased the reaction temperature to 110 °C biphenyl
yield could be increased to 30% and the remaining por-
tion of bromobenzene was dehalogenated to benzene
(
8). We assume, that the limited activity of the catalyst
is the reason for this since also under homogenous con-
ditions high temperature with T = 140 °C are required
for this substrate. New NHC /Pd catalysts with bulky
substituents however seem to be more promising to en-
hance the catalytic activity of our micellar catalytic sys-
tem [55]. The preparation of these amphiphiles should
be feasible in an analogous manner as the described one.
Fig. 7. Kinetic of the aqueous Suzuki coupling reaction of 4-
bromobenzophenone (9) and 4-bromobenzaldehyde (10) with phen-
2
ylboronic acid (9, 10; RPhBr:PhB(OH) :KOH = 1.0:1.5:2.0, T =
1
10 °C, c = 0.17 mM, nPd/nRPhBr = 0.1 mol%).
P
3
. Conclusion
In this contribution we have demonstrated the appli-
bromobenzene (8) as a non-activated one. The catalytic
activity of our system for the transformation of acti-
vated bromobenzenes is with turn over frequencies of
cability of polymeric amphiphiles with pendant carbene/
palladium complexes in Heck and Suzuki coupling reac-
tions in water as solvent and investigated the effect of
several reaction parameters such as temperature, cata-
lyst amount, amphiphile structure and starting com-
pounds on catalytic activity. The polymer supported
catalyst indicated excellent activities in the Heck reac-
tion of iodobenzene with styrene with TOF numbers
À1
À1
5
60 h (9) and 2900 h (10) just a little bit lower than
the activities for the conversions of iodobenzene (see
Fig. 7).
An interesting difference between these both transfor-
mations is the lack of an induction period in case of
4
-bromobenzaldehyde and the resulting extensive
À1
up to 2700 h at 110 °C. In the Suzuki reaction of iod-
advantage in the conversion-time dependence of the cor-
responding reaction. This fact can be attributed to the
reducing character of the formyl group and is already
described for the analogous palladium complexes with
low molecular weight [54].
obenzene with phenylboronic acid the polymer catalyst
showed highest activities with TOF numbers up to
À1
5
4
200 h . In addition also 4-bromobenzophenone and
-bromobenzaldehyde could be successfully converted
with phenylboronic acid. In summary, the successful
catalyst immobilization on defined amphiphilic block
copolymers in combination with easy catalyst handling
and high activity makes these polymer supports very
attractive for the preparation of various biaryl and stil-
bene derivatives under environmental benign reaction
condition in the future.
Furthermore, we succeeded to convert the non-acti-
vated bromobenzene in a fast reaction too (8, TOF =
À1
5
20 h ) using our micellar catalytic system (see
4
. Experimental
4
.1. Measurements
Gas chromatographic analyses were performed on a
Varian CP-3380, capillary column CP-Sil 8 CB, length:
5 m, with helium in combination with a flame ioniza-
tion detector FID/1177.
2
4
.2. Materials
Fig. 8. Kinetic of the aqueous Suzuki coupling reaction of bromo-
benzene with phenylboronic acid and biphenyl formation (8;
All chemicals and solvents were purchased from Al-
drich Chemical Co. and Fluka. The solvents were dis-
tilled under argon and additional degassed twice
PhBr:PhB(OH)
2
P
:KOH = 1.0:1.5:2.0, T = 110 °C, c = 0.57 mM, nPd/
nPhBr = 0.67 mol%).

D. Sch o¨ nfelder et al. / Journal of Organometallic Chemistry 690 (2005) 4648–4655
4655
before use. Furthermore, they were stored under argon
atmosphere.
[18] S.S. Prockl, W. Kleist, M.A. Gruber, K. Kohler, Angew. Chem.
Int. Ed. 43 (2004) 1881.
[
[
[
19] M.R. Buchmeiser, K. Wurst, J. Am. Chem. Soc 121 (1999) 11101.
20] C.A. Lin, F.T. Luo, Tetrahedron Lett. 44 (2003) 7565.
21] M.M. DellÕAnna, P. Mastrorilli, F. Muscio, C.F. Nobile, G.P.
Suranna, Eur. J. Inorg. Chem. 5 (2002) 1094.
4
.3. Poymeric macroligands P1–P3
Synthesis and characterization of the amphiphilic,
[22] M.M. DellÕAnna, P. Mastrorilli, F. Muscio, C.F. Nobile, G.P.
Scranna, Eur. J. Inorg. Chem. 5 (2002) 1094.
water-soluble block copolymers P1–P3 with pendant
NHC/palladium catalysts in the side chain has been
reported in a recent publication [44].
[
[
23] A. Datta, K. Ebert, H. Plenio, Organometallics 22 (2003) 4685.
24] P.T. Anastas, J.C. Warner, Green Chemistry: Theory and
Practice, Oxford University Press, Oxford, 1998.
[
[
25] P. Tundo, P. Anastas, D.S. Black, J. Breen, T. Collins, S. Memoli,
J. Miyamoto, M. Polyakoff, W. Tumas, Pure Appl. Chem. 72
4
.4. Micellar catalysis
(
2000) 1207.
26] B. Cornils, W.A. Herrmann, Aqueous Phase Organometallic
Catalysis – Concept and Application, Wiley–VCH, Weinheim,
Catalysis experiments: All catalysis experiments were
carried out under argon in 50 mL reaction tubes. In
0 mL of degassed water a portion of the polymer
P1–P3) was dissolved so that the concentration of the
polymer is about 0.1–0.6 mM. The first starting com-
pound, a base and tetradecane as internal standard were
added in the respective ratio (Heck:haloarene:styrene:
1
998.
1
(
[27] F. Sieber, P. Wentworth, K.D. Janda, J. Combinat. Chem. 1
(1999) 540.
28] P. Wentworth, K.D. Janda, Chem. Commun. 19 (1999) 1917.
29] T. Malmstr o¨ m, C. Andersson, Chem. Commun. 10 (1996) 1135.
30] D.E. Bergbreiter, B.L. Case, Y.S. Liu, J.W. Caraway, Macro-
molecules 31 (1998) 6053.
[
[
[
base = 1.0:1.25:1.5,
Suzuki:haloarene:phenylboronic
[31] P.L. Osburn, D.E. Bergbreiter, Prog. Polym. Sci. 26 (2001) 2015.
[32] For a recent review see: Y. Uozumi, Top. Curr. Chem. 242 (2004)
acid:base = 1.0:1.5:2.0). The mixture was stirred and
heated to the reaction temperature. Then the catalysis
was started by adding the second starting compound.
The course of the reaction was monitored by periodi-
cally taking samples and analyzing them by means of
gas chromatographic analysis.
7
7, and references therein.
33] Y.M.A. Yamada, H. Takahashi, S. Ikegami, Tetrahedron Lett. 44
2003) 2379.
34] Y.M.A. Yamada, K. Takeda, H. Takahashi, S. Ikegami, Tetra-
hedron 60 (2004) 4097.
[
[
(
[35] C.W.K. Gstottmayr, V.P.W. Bohm, E. Herdtweck, M. Grosche,
W.A. Herrmann, Angew. Chem. Int. Ed. 41 (2002) 1363.
[36] H.M. Lee, C.Y. Lu, C.Y. Chen, W.L. Chen, H.C. Lin, P.L. Chiu,
P.Y. Chen, Tetrahedron 60 (2004) 5807.
References
[37] A.R. Kovacevic, B.M. Zeglis, J.W. Faller, R.H. Crabtree,
Organometallics 23 (2004) 2461.
[
1] R.A. Sheldon, H. van Bekkum, Fine Chemicals through Heter-
ogeneous Catalysis, Wiley–VCH, Weinheim, 2001.
[38] M.T. Zarka, M. Bortenschlager, K. Wurst, O. Nuyken, R.
Weberskirch, Organometallics 23 (2004) 4817.
[39] N. Hadej, E.A.B. Kantchey, C.J. OÕBrien, M.G. Organ, Org.
Lett. 10 (2005) 1991.
[40] M. Shi, H.X. Qian, Tetrahedron 61 (2005) 4949.
[41] J.O. Krause, M.T. Zarka, U. Anders, R. Weberskirch, O.
Nuyken, M.R. Buchmeiser, Angew. Chem. Int. Ed. 42 (2003)
5965.
[
[
[
[
2] R.F. Heck, J.P. Nolley Jr., J. Org. Chem. 37 (1972) 2320.
3] R.F. Heck, Acc. Chem. Res. 12 (1979) 146.
4] N. Miyaura, A. Suzuki, Chem. Commun. (1979) 866.
5] N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 11 (1982)
513.
[
[
6] N. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457.
7] F.Y. Zhao, M. Shirai, Y. Ikushima, M. Arai, J. Mol. Catal. A 180
[42] T. Kotre, O. Nuyken, R. Weberskirch, Macromol. Rapid.
Commun. 23 (2002) 871.
(2002) 211.
[
[
8] M. Gruber, S. Chouzier, K. Koehler, L. Djakovitch, Appl. Catal.
A 265 (2004) 161.
9] K. Koehler, R.G. Heidenreich, J.G.E. Krauter, M. Pietsch, Chem.
Eur. J. 8 (2002) 622.
[43] M.T. Zarka, O. Nuyken, R. Weberskirch, Chem. Eur J. 9 (2003)
3228.
[44] D. Sch o¨ nfelder, O. Nuyken, R. Weberskirch, Macromolecules 38
(2005) 254.
[
10] D.A. Conlon, B. Pipik, S. Ferdinand, C.R. LeBlond, J.R. Sowa,
B. Izzo, P. Collins, J.M. Williams, Y.J. Shi, Y.K. Sun, Adv.
Synth. Catal. 345 (2003) 931.
[45] I.P. Beletskaya, A.V. Cheprakov, Chem. Rev. 100 (2000) 3009.
[46] J. Li, L.M. Zheng, I. King, T.W. Doyle, S.H. Chen, Curr. Med.
Chem. 8 (2001) 121.
[
[
[
[
11] C.R. LeBlond, A.T. Andrews, Y.K. Sun, J.R. Sowa, Org. Lett. 3
[47] A.D. Schl u¨ ter, G. Wegner, Acta Polym. 44 (1993) 59.
[48] T. Jeffery, Tetrahedron Lett. 35 (1994) 3051.
[49] H. Zhao, M.-Z. Cai, C.-Y. Peng, C.-S. Song, J. Chem. Res. (S)
(2002) 28.
[50] Y. Uozumi, T. Kimura, Synlett 12 (2002) 2045.
[51] W.A. Herrmann, M. Elison, J. Fischer, C. K o¨ cher, G.R.J. Artus,
Angew. Chem., Int. Ed. Engl. 34 (1995) 2371.
[52] Y. Uozumi, H. Danjo, T. Hayashi, J. Org. Chem. 64 (1999)
3384.
[53] Y. Uozumi, Y. Nakai, Org. Lett. 4 (2002) 2997.
[54] J.-W. Byun, Y.-S. Lee, Tetrahedron Lett. 45 (2004) 1837.
[55] C.W. Gst o¨ ttmayr, V.P.W. B o¨ hm, E. Herdtweck, M. Grosche,
W.A. Herrmann, Angew. Chem. Int. Ed. 41 (2002) 1363.
(
2001) 1555.
12] C. Baleizao, A. Corma, H. Garcia, A. Leyva, Chem. Commun. 5
2003) 606.
13] A. Corma, H. Garcia, A. Leyva, A. Primo, Appl. Catal. A 257
2004) 77.
(
(
14] M. Dams, L. Drijkoningen, B. Pauwels, G. vam Tendeloo, D.E.
De Vos, P.A. Jacobs, J. Catal. 209 (2002) 225.
15] L. Djakovitch, K. Koehler, J. Am. Chem. Soc. 123 (2001) 5990.
16] M. Wagner, K. Kohler, L. Djakovitch, S. Weinkauf, V. Hagne,
M. Muhler, Top. Catal. 13 (2000) 319.
[
[
[
17] B.M. Choudary, K. Jyothi, M. Roy, M.L. Kantam, B. Sreedhar,
Adv. Synth. Catal. 346 (2004) 1471.