Suzuki coupling reactions in pure water catalyzed by supported palladium -relevance of the surface polarity of the support

Article abstract of DOI:10.1002/adsc.201000891

Heterogeneous (supported) palladium catalysts like palladium on carbon and a variety of metal oxides have been shown to be highly active for Suzuki coupling reactions in neat water under mild reaction conditions (T=65°C). It has been demonstrated for the first time that hydrophobic effects of the catalyst surface play an important role for the catalyst activity in water. Catalysts possessing hydrophobic surfaces (e.g., palladium on carbon) show higher activity for Suzuki coupling reactions in water than their hydrophilic counterparts (palladium on metal oxides). Tuning of the surface polarity of metal oxide supports (by silylation) results in higher activity under these conditions. Stronger alkaline conditions (three-fold excess of base) compensate the effect of hydrophobic supports and result in high activity of the catalysts also with hydrophilic supports. The addition of tetrabutylammonium bromide to generate, activate and stabilize the catalytic species (dissolved palladium complexes) is necessary for the conversion of more demanding substrates. The reaction is considered to be homogeneous taking place near the catalyst surface inside a droplet or layer of the reactant. Copyright

Full text of DOI:10.1002/adsc.201000891

FULL PAPERS
DOI: 10.1002/adsc.201000891
Suzuki Coupling Reactions in Pure Water Catalyzed by Supported
Palladium – Relevance of the Surface Polarity of the Support
Saeeda S. Soomro,a Christoph Rçhlich,b and Klaus Kçhlerb,*
a
CAT Catalytic Center, Institut fꢀr Technische und Makromolekulare Chemie, RWTH Aachen, Worringerweg 1, 52074
Aachen, Germany
b
Technische Universitꢁt Mꢀnchen, Department Chemie, Lichtenbergstraße 4, 85747 Garching, Germany
Fax : (+49)-89-289-13183; e-mail: klaus.koehler@ch.tum.de
Received: November 26, 2010; Revised: February 10, 2011; Published online: March 16, 2011
Abstract: Heterogeneous (supported) palladium cat- conditions (three-fold excess of base) compensate
alysts like palladium on carbon and a variety of the effect of hydrophobic supports and result in high
metal oxides have been shown to be highly active for activity of the catalysts also with hydrophilic sup-
Suzuki coupling reactions in neat water under mild ports. The addition of tetrabutylammonium bromide
reaction conditions (T=658C). It has been demon- to generate, activate and stabilize the catalytic spe-
strated for the first time that hydrophobic effects of cies (dissolved palladium complexes) is necessary for
the catalyst surface play an important role for the the conversion of more demanding substrates. The
catalyst activity in water. Catalysts possessing hydro- reaction is considered to be homogeneous taking
phobic surfaces (e.g., palladium on carbon) show place near the catalyst surface inside a droplet or
higher activity for Suzuki coupling reactions in water layer of the reactant.
than their hydrophilic counterparts (palladium on
metal oxides). Tuning of the surface polarity of
metal oxide supports (by silylation) results in higher Keywords: palladium; supported catalysts; Suzuki–
activity under these conditions. Stronger alkaline Miyaura reaction; water
Introduction
For reactions involving lipophilic substrates in
water, hydrophobic effects may play a pivotal role in
The Suzuki cross-coupling reaction (Scheme 1) is a the reaction mechanism. The hydrophobic effect is
simple synthetic route to the fabrication of biaryls the tendency of non-polar molecules and molecular
from aryl halides and arylboronic acids.[1,2] The reac- segments in water to avoid contact with water, either
tion is typically catalyzed by palladium in organic or by escaping to a separate phase or by clustering so as
water/organic (co-)solvents and, as an intriguingly to diminish the amount of non-polar surface that is
flexible reaction, it offers considerable potential in exposed to water. So, besides the usual problems as-
the synthesis of natural products, herbicides, pharma- sociated with homogeneous catalysis (catalyst separa-
ceuticals, and conducting polymers.[3]
tion, product contamination, etc.), the conversion of
In the past few years, a number of attempts have the hydrophobic substrates is still a critical dilemma
been used to get commercially viable and highly for water-soluble catalysts. In order to circumvent
active “green” catalysts for these reactions. Several these problems, a number of polymeric materials[10–17]
strategies have been adopted which approach towards has been developed and utilized as supports to carry
increasing the potentials of water as an inexpensive, out Suzuki coupling reactions in water. Several efforts
non-toxic and safe reaction medium.[4] One approach have been devoted to convert hydrophobic substrates
is to utilize water-soluble (hydrophilic) Pd cata- through this approach.
lysts.[5–9]
Pd on activated carbon as a typical hydrophobic
support represents a simple and commercially avail-
able catalyst. Its activity in Suzuki coupling in water
using water-soluble substrates, or under microwave
heating, has been reported.[18,19] Dissolved Pd, gener-
ated from Pd nanoparticles mainly via the oxidative
addition of aryl halides, was demonstrated to be the
true active species.[19–25] High activity of Pd/C in
Scheme 1. Suzuki coupling of aryl halides and phenylboronic
acid.
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Suzuki coupling reactions with hydrophobic substrates ultra-traces (residues) of Pd, and therefore are sus-
was also demonstrated and reported by Lysen ceptible to errors.[25]
et al.[26,27] A large variety of substrates including acti-
The reactions were carried out at low temperature
vated or deactivated aryl chlorides were efficiently (658C) for a number of related advantages. In gener-
coupled with arylboronic acids in pure water at 100– al, heterogeneous palladium catalysts show high activ-
1408C.
ity at higher reaction temperatures (>1008C). Re-
Though rarely, Pd on modified or unmodified metal garding practical use of heterogeneous Suzuki cou-
oxides has also been applied for such reactions.[28] pling reactions, it is highly desirable to develop a cata-
Overall, although high catalytic activities are ob- lytic protocol that could work at low temperatures.
served for Suzuki couplings in pure water, the influ- Moreover, investigations of the reaction at mild tem-
ence of the hydrophobic effect, and the related influ- peratures are expected to show reactivity differences
ence of surface properties (hydrophobic or hydrophil- and parameter influences more clearly. The present
ic surface) of supported Pd catalysts, has not been a investigations aim at understanding the role of the
matter of focus in these reports. Principally, catalysts support, and mechanistic features that are distinctive
having greater affinity towards water (hydrophilic) for Suzuki coupling reactions in water. The optimiza-
are considered to have reduced contacts with lipophil- tion of the reaction conditions and the related support
ic substrates, and vice versa. The surface hydrophobic- effects are described in the following sections.
ity plays a pivotal role to decide the phase resided by
supported catalysts. The concept has been highlighted
in an earlier report which showed that surface-modi- Activity of Pd/C vs. Pd/MOx Catalysts in Suzuki
fied catalysts were located only in one of two immisci- Coupling Reactions at 658C in Water
ble liquid phases, considerably affecting the yields in
ꢀ
C C coupling reactions and hydrogenation reac- The chosen commercially available Pd/activated
tions.[29]
carbon (Pd/C) catalyst shows high activity and selec-
ꢀ
In order to extend the concept towards C C cou- tivity in the Suzuki reaction of phenylboronic acid
pling reactions catalyzed by supported Pd catalysts in with various aryl bromides. As expected, 4’-bromo-
water, and to establish a clear structure-property rela-
ACHTUNGTRENaNGNU cetophenone led to high yields (Table 1, entry 1), but
tionship for such reactions, we performed Suzuki cou- so did substrates with lipophilic substituents (Table 1,
pling reactions in water under mild reaction condi- entries 2 and 3), normally considered hard to convert
tions and investigated the influence of several param- for reactions conducted in water. Also, 4’-chloroaceto-
eters, most prominently the hydrophilicity of the cata- phenone could quantitatively be coupled with phenyl-
lyst support. Surface modification (hydrophobization) boronic acid (entry 4) within 4 h using low Pd equiva-
of Pd/MOx catalysts results in higher activity for these
reactions. On the other hand, hydrophilic Pd/MOx
catalysts are effective for such reactions under rela-
tively strong alkaline conditions. The outcome of the
present investigations should support synthetic and in-
dustrial organic chemists in choosing the appropriate
solid catalysts and reaction conditions for Suzuki cou-
pling reactions in water.
Table 1. Pd/C-catalyzed Suzuki couplings of aryl halides
with phenylboronic acid.[a]
Entry Aryl halide
1
Conversion [%][b] Yield [%][c]
100
99
100
98
2
3
Results and Discussion
As has been demonstrated earlier,[26,27] palladium on
activated carbon in the presence of TBAB serves as a
highly active catalytic system for Suzuki coupling re-
actions in water. We first applied the same catalyst to
Suzuki reactions under milder reaction conditions
(air, 658C, 0.1 mol% of palladium). We have focused
on the conversion of rather demanding substrates
such as aryl chlorides and deactivated aryl bromides,
because their use decreases the possibility of misinter-
pretation of the experimental results. This is in con-
trast to the common approach of studying mechanistic
details with demandless substrates (aryl iodides),
which can be converted with many Pd catalysts and
94
94
4
95
95
[a]
Reaction conditions: aryl halide (2.9 mmol, 1 equiv.), phe-
nylboronic acid (3.2 mmol, 1.1 equiv.), NaOH (4.4 mmol,
1.5 equiv.), TBAB (1 mmol), water (4 mL), 0.1 mol% of
5% Pd/C (E 105 CA/W), 658C, 4 h (not optimized).
Conversion of aryl halide.
[b]
[c]
GC yield of cross coupled product using diethylene
glycol dibutyl ether as internal standard.
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Suzuki Coupling Reactions in Pure Water Catalyzed by Supported Palladium
strate with the supported Pd is the main factor for the
generation of the active species [oxidative addition
and dissolution of the generated Pd(II) species],[19–25]
this naturally results in higher conversions. This indi-
cates that the reaction takes place near the catalyst
surface, inside a droplet or layer of the substrate
around the catalyst, and is highly dependent on the
Scheme 2. Suzuki coupling reaction of 4’-chloroacetophe- substrate-support surface interactions. The assump-
none catalyzed by Pd/C or Pd/Al2O3 in water.
tion prompts us to investigate the role and signifi-
cance of water as solvent.
The effect of water as solvent was verified by carry-
lents (0.1 mol%). A selectivity of 100% for the ing out the Suzuki coupling reaction of 4’-chloroace-
Suzuki cross-coupled product is found nearly without tophenone in varying amounts of water (Figure 1). No
exception.
yield of cross-coupled product was obtained in the ab-
In comparison, when the coupling reaction of 4’- sence of water. The yield increased smoothly with in-
chloroacetophenone was tried using Pd/Al2O3 cata- creasing the volume of water in the reaction mixture
lysts (Scheme 2), only low conversion to the desired and reached a maximum (95%) in the presence of
coupling product was obtained under the same reac- 4 mL of water. Our explanation is that water as reac-
tion conditions as in Table 1.
tion medium is important and apparently serves as a
The low activity of Pd/Al2O3 in contrast to Pd/C medium to (i) dissolve the base, thereby to produce
can firstly be explained by the exceedingly higher sur- the boronate from boronic acid and keep it dissolved
face area of the active carbon support compared to (i.e., active), and (ii) dissolve the by-products (salts),
Al2O3, but also the surface properties of the two cata- thereby pushing the reaction equilibrium in the for-
lyst supports can be taken into account. Pd/Al2O3 is ward direction.
better dispersed in water due to the hydrophilicity of
As discussed, a hydrophobic surface of the support
surface hydroxy groups; hence it is poorly available to facilitates the reaction in water, and the performance
organic substrates. In contrast, the surface of Pd/C is of hydrophilic catalysts for such reactions could, thus,
highly hydrophobic and allows better catalyst disper- be improved by modifying the surface polarity of the
sion in the phase containing organic substrates, and/or support in such a way that the heterogeneous catalyst
causes enrichment of the substrate at the catalyst sur- will be located closer to the organic substrates. The
face. Keeping in mind that the contact of the sub- concept has been successfully applied to hydrogena-
tion and Heck reactions in biphasic media.[29] In order
to verify this perception, the surface of alumina was
modified using n-octylACTHNUTRGNEU(GN dimethyl)chlorosilane under
carefully controlled conditions (Scheme 3). Although
the modification of a silica surface with a layer of mo-
lecular functionalities (polyethylene glycol) has earli-
er been reported for Suzuki coupling reactions in
water,[30,31] the high relevance for overcoming funda-
mental problems associated with hydrophilic supports
was not the focus of the corresponding reports. In ad-
dition to the hydrophobically modified alumina used
in the present investigations, commercially available
hydrophobic titania (T805) and an amphiphilic mate-
rial (T2000) were also used to immobilize Pd. The
source and properties of the surface materials used in
this study are summarized in Table 2.
Table 3 presents the results of Suzuki coupling reac-
tions using the catalysts prepared in this work. A posi-
tive influence of the surface modification was ob-
served in the case of the Pd/Al2O3-catalyzed Suzuki
Figure 1. Effect of water on Pd/C catalyzed Suzuki coupling
reaction of 4’-chloroacetophenone (“0 mL of water” means
reaction in the pure substrate). Reaction parameters: See
Table 1, footnote[a]
.
Scheme 3. Surface modification of Al2O3 to produce hydrophobic alumina (Al2O3-C8).
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Table 2. Metal oxides used as supports for palladium in this study.
Support
Surface Characteristics
Mean Particle
Size
Al2O3
Al2O3-C8
100 m2 gꢀ1: hydrophilic, hydroxy groups on the surface
100 m2 gꢀ1: hydrophobic, modified using n-octyl-dimethylchlorosilane before using it
for catalyst preparation
13 nm
13 nm
TiO2 (P-25)
T805
T2000
50 m2 g,ꢀ1, hydrophilic, hydroxy groups on the surface
45 m2 gꢀ1: hydrophobic, octyl silane coating on the surface
~30 nm
15–20 nm
10–15 nm
100 m2 gꢀ1: amphiphilic, titania (80%) surface is coated with Al2O3 (~8%) and Simethicone
(a mixture of silica gel (~3%) and polydimethylsiloxane), primary particles aggregate to give
roughly 100 nm sized needles
Table 3. Heterogenous Suzuki coupling of 4’-chloroaceto- transport of the substrates to the aqueous phase (as
phenone and phenylboronic acid by different Pd/MOx cata-
depicted in Figure 2, a). The presence of a phase-
transfer agent (PTA) can bring some activity in this
case. On the other hand, the catalyst possessing a hy-
drophobically modified surface would have an in-
creased contact with lipophilic substrates (S), result-
ing in an ultimate increase in catalyst activity
(Figure 2, b). An appropriate amount of water is re-
quired to provide the phenylboronate, and to simulta-
neously extract the salts generated during the catalyt-
ic reaction.
Thus, the polarity of the support is an important pa-
rameter for reactions carried out in neat water, and
should not be neglected when using supported cata-
lysts in water. Nevertheless, the activity of Pd/C
(Table 1) is clearly higher as compared with that of
Pd/MOx catalysts (Table 3). A complete hydrophobic
surface and much higher surface area (~1100 m2 gꢀ1)
of Pd/C as compared to metal oxides (50–100 m2 gꢀ1)
is responsible for its increased contact with the organ-
lysts.[a]
Entry
Catalyst
ACHTUNGTRENNUNG[mol%]
Surface
Conv.
[%][b]
Yield
[%][c]
1
2
3
4
5
Pd/Al2O3 (0.1)
Pd/Al2O3-C8 (0.1)
Pd/TiO2 (0.1)
Pd/T805 (0.1)
Pd/T2000 (0.1)
hydrophilic
hydrophobic
hydrophilic
hydrophobic
amphiphilic
13
22
23
45
41
13
22
22
45
40
[a]
Reaction conditions: 4’-chloroacetophenone (2.9 mmol,
1 equiv.), phenylboronic acid (3.2 mmol, 1.1 equiv.),
NaOH (4.4 mmol, 1.5 equiv.), TBAB (1 mmol), water
(4 mL), 658C, air, 4 h.
Conversion of 4’-chloroacetophenone.
GC yield of cross-coupled product using diethylene
glycol dibutyl ether as internal standard.
[b]
[c]
cross-coupling reaction of 4’-chloroacetophenone with ic substrates, thus showing remarkable activity in
phenylboronic acid (compare entries 1 and 2). The Suzuki coupling reactions. In fact, the metal oxides
effect was even more obvious in entries 3–5 where hy- retain a more or less hydrophilic character depending
drophobic catalysts (Pd/T805 and Pd/T2000) show on the degree of modification [silylation grade; s(Si)
higher activity than their hydrophilic counterpart (Pd/ for Al2O3-C8 =16] and the reaction conditions have to
TiO2). As stated earlier, the influence of the support be optimized to bring the activity to a desirable level.
can be explained on the basis of the dispersion of the
catalysts in the reaction mixture and enrichment of
the organic substrate near the catalyst surface.
Effect of Excess Base on the Activity of Pd/MOx
According to this concept, heterogeneous Suzuki Catalysts for Suzuki Coupling Reactions in Water
coupling reactions carried out in water can be viewed
as a 3-phase system: a solid catalyst, a lipophilic As shown in Table 4, the addition of an increased
phase comprising organic substrates, and an aqueous amount of base (3 instead of 1.5 equivalents) led to
phase of water. It has been shown (for Pd/C and Pd 100% conversion of 4’-chloroacetophenone with high
on metal oxides)[19,21] that the contact of supported Pd selectivity towards the desired cross-coupled product.
with the aryl halide substrate leads to the generation The reaction is completed within five hours using
of the true active species, that is, dissolved Pd gener- only 0.2 mol% Pd (entry 3) at 658C. An inert atmos-
ated by oxidative addition (Pd leaching). Thus, since phere accelerated the reaction. Interestingly, the opti-
the hydrophilic catalysts (like Pd/Al2O3) would more mized reaction conditions resulted in a high conver-
likely be confined in the aqueous phase with mini- sion to the desired coupling product with all selected
mum possible contact with the organic substrates, the Pd/MOx catalysts irrespective of the hydrophilic or
catalytic activity will be low, strictly depending on the hydrophobic nature of the surface (Table 4, entries 5–
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Suzuki Coupling Reactions in Pure Water Catalyzed by Supported Palladium
Table 4. Reaction of 4’-chloroacetophenone with phenylbor-
onic acid catalyzed by Pd/MOx applying different parame-
ters.[a]
Entry Catalyst
Atmosphere Time [h] Yield [%][b]
1
2
3
4
5
6
7
8
Pd/T2000
Pd/T2000
Pd/T2000
Pd/T805
Pd/T805
Pd/TiO2
air
4
4
5
4
5
5
5
5
53
88
100
65
95
100
86
80
argon
argon
air
argon
argon
argon
Pd/Al2O3
Pd/Al2O3-C8 argon
[a]
Reaction conditions: 4’-chloroacetophenone (2.9 mmol,
1 equiv.), phenylboronic acid (3.2 mmol, 1.1 equiv.),
TBAB (1 mmol), NaOH (8.7 mmol, 3 equiv.) water
(4 mL), 0.2 mol% [Pd], 658C.
GC yield using diethylene glycol dibutyl ether as internal
standard.
[b]
equivalent of base is required to convert the boric
acid, produced from the coupling reaction, into
sodium borate. This keeps the reaction medium more
basic. It must also be taken into account that the sur-
face of the supports is negatively polarized and may
be partially destroyed under strongly alkaline condi-
tions, thereby overriding any effects of hydrophobici-
ty, and possibly enhancing the dissolution of active
anionic Pd complexes from the support.
A variety of aryl bromides (activated or deactivat-
ed) were tested under different reaction conditions
(Table 5). High reaction yields were achieved only
under conditions that were primarily optimized for 4’-
chloroacetophenone (argon atmosphere, excess of
base). Thus, a range of aryl bromides could efficiently
be coupled using modified or un-modified Pd/MOx
catalysts under optimized reaction conditions. Similar
results have earlier been reported by Lysen et al.
where comparable activities of Pd/C and Pd/NaY cat-
alysts were observed for the Suzuki coupling reaction
Figure 2. Visualization of the dynamics of the Suzuki cou-
pling in water. (a, top): Hydrophilic catalysts are dispersed
in the water phase, contact with the substrate (S) is minimal.
(b, bottom): Hydrophobic catalysts are enclosed with the
substrate, active Pd species are dissolved, and conversion to
the product (P) can occur easily. PTA=phase-transfer agent
(TBAB in the present case).
8). It should be pointed out here that the beneficial of 4’-chloroacetophenone in water under harsh condi-
effect of an excess or high concentration of base is tions (Tꢁ1008C, 3 equivalents of NaOH).[26,27] The re-
not related to the formation of phenylboronate. From sults represent a broad scope of supported catalysts
the pKa of phenylboronic acid (8.86),[32] one can calcu- for applications to catalysis in water. It can be con-
late that in the experiments with 1.5 equivalents of cluded that the effects of hydrophobic supports oper-
NaOH, >97% of phenylboronic acid are present as ate under rather mild conditions and are no longer
(the water-soluble salt) sodium phenylboronate determining under strong basic conditions. The
Na[B(Ph)(OH)3].[33]
knowledge about these effects is relevant for the
ꢀ
The results, that is, the positive effect of an excess design of heterogeneous catalysts to be used in C C
of base, can be explained when we consider the reac- coupling reactions in water.
tion equation Eq. (1) which shows that one additional
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Table 5. Suzuki coupling of of aryl bromides using palladium supported on metal oxides.[a]
Entry
Catalyst (mol%)
Base (equiv.)
TBAB [mmol]
Aryl bromide
Time [h][b]
Yield [%]
100
1
Pd/Al2O3 (0.1)
Na2CO3 (1.1)
–
4
4
4
5
5
5
5
5
5
2
Pd/Al2O3 (0.1)
Pd/Al2O3 (0.1)
Pd/Al2O3 (0.2)
Pd/TiO2 (0.2)
Pd/T805 (0.2)
Pd/T2000 (0.2)
Pd/T2000 (0.2)
Pd/Al2O3 (0.2)
Pd/TiO2 (0.2)
Pd/T805 (0.2)
Pd/T2000 (0.2)
Pd/T2000 (0.2)
Na2CO3 (1.1)
Na2CO3 (1.1)
Na2CO3 (3)
Na2CO3 (3)
Na2CO3 (3)
Na2CO3 (3)
NaOH (3)
NaOH (3)
NaOH (3)
NaOH (3)
NaOH (3)
NaOH (3)
–
–
–
–
–
–
1
1
1
1
1
1
27
5
3
4
8
5
10
n.d.[d]
11
76
91
91
76
88
100
6
7
8[c]
9[c]
10[c]
11[c]
12[c]
5
5
5
4
13[b,c]
[a]
Reaction conditions: aryl bromide (2.9 mmol, 1 equiv.), phenylboronic acid (3.2 mmol, 1.1 equiv.), 658C, water (4 mL).
Reaction time is not optimized.
Performed under argon.
[b]
[c]
[d]
Solids clump, difficulties with extraction.
Effect of Additives – the Role of
Tetraalkylammonium Halides
(Table 2) catalysts under the same reaction conditions
(as given in Table 1) but no additive (TBAB) was
used in this case. Whereas no conversion of 4’-chloro-
The reaction protocol was verified by performing two
ACHTUNGTRENaNUNG cetophenone was observed with any of the selected
parallel sets of reactions involving aryl chloride (4’- catalysts under these conditions, a full conversion to
chloroacetophenone) on one hand and 4’-bromoace- the desired cross coupled product was achieved for 4’-
tophenone on the other hand. The reactions were car- bromoacetophenone with all of these catalysts
ried out with Pd/C and aforementioned Pd/MOx (Scheme 4). In contrast, deactivated aryl bromides
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Suzuki Coupling Reactions in Pure Water Catalyzed by Supported Palladium
is, however, not perspicuous why a phase-transfer cat-
alyst would be needed for reactions with aryl chlor-
ides, while aryl bromides could be effectively convert-
ed in biphasic mixtures without additive, as demon-
strated in this work. Also, some examples of TBAB-
free Suzuki reactions of aryl chlorides in water have
been reported before.[9,12]
In spite of the potential phase-transfer catalytic
nature of any of the following additives, the activity
as well as selectivity towards cross-coupled product
was lost when TBAB was replaced with TBAC (tetra-
Scheme 4. Suzuki coupling reaction of 4’-chloro- and 4’-bro-
moacetophenone catalyzed by various palladium catalysts
without any additive.
gave very low yields in the absence of TBAB. In fact, butylammonium chloride), TBAF·3H2O (tetrabutyl-
palladium black was observed in cases where such ammonium fluoride trihydrate), or TBA(PF6), keep-
substrates were used to couple with phenylboronic ing otherwise the same reaction conditions. While tet-
acid in the absence of TBAB as additive. raheptylammonium bromide (THpAB) led to compa-
A
ACHTUNGTRENNUNG
Furthermore, the influence of various tetraalkylam- rable reaction results, tetramethylammonium bromide
monium salts was investigated for the Pd/T2000 cata- (TMAB) was inefficient, as was simple potassium bro-
lyzed Suzuki coupling reaction of 4’-chloroacetophe- mide (also in conjunction with 18-crown-6). Interest-
none. The results in Figure 3 show that TBAB is the ingly, cetyltrimethylammonium bromide (CTAB) was
inefficient as well, although it is known as a typical
surfactant, indicating that the Suzuki reaction is pro-
moted by being performed in a system with two sepa-
rate phases. While showing lower performance, tetra-
butylammonium hydroxide revealed potential applica-
bility as both additive and base in this reaction.
As these results indicate, the positive effect of
TBAB is neither attributable to it solely being a
phase-transfer agent, nor to the ammonium or bro-
mide ions alone, but is rather synergistic.[36] Supposed-
ly, on the one hand, it serves as a bromide source to
generate highly active palladium complexes in solu-
tion.[20–25] The corresponding chloro- and fluoro-palla-
dium complexes are less stable, forcing precipitation
of palladium under these conditions. TBAB has also
been shown to cause substantial Pd leaching in the re-
action mixture,[21] whereas negligible leaching has
been observed when Pd/Al2O3 or Pd/C were stirred in
Figure 3. Comparison of the yields obtained for the Suzuki
coupling reaction between 4’-chloroacetophenone and phe-
water for one hour at 658C (<2%). This suggests a
homogeneous nature of the reaction whereby leached
active Pd species play a significant role.[19–25] In the
absence of TBAB the minimum amount of leached
Pd can cause the conversion of extremely active sub-
strates (as 4’-bromoacetophenone) only. On the other
hand, the tetrabutylammonium ion may serve as a
nylboronic acid with different additives (abbreviations are
explained in the text). Reaction conditions: 4’-chloroaceto-
phenone (2.9 mmol, 1 equiv.), phenylboronic acid (3.2 mmol,
1.1 equiv.), NaOH (8.7 mmol, 3 equiv.), additive (1 mmol),
0.2 mol% Pd/T2000, water (4 mL), 658C, argon, 5 h.
best choice as compared to other additives. Generally, phase-transfer agent for reactions of organic sub-
among the tetraalkylammonium salts, TBAB leads to strates in water, but even more importantly, provide
[34]
ꢀ
the best performances in C C coupling reactions,
activity-increasing counter-ions for anionic species
and is considered to electrosterically stabilize palladi- (palladates, boronates[38]) involved in the catalytic
um nanoparticles against agglomeration, thereby pre- process, and shield Pd nanoparticles from further ag-
venting premature formation of Pd black and, hence, glomeration, thereby delaying the catalyst deactiva-
deactivation.[20,25,34–36] TBAB has also been discussed tion.[20,25,34–36]
to enhance Pd leaching from dissolved and supported
nanoparticles, and to build stable and highly active
low-nuclear bromo complexes of Pd.[21–24] Especially, Conclusions
TBAB has also often been stated to be needed as a
phase-transfer catalyst in Suzuki reactions in pure Using a variety of supported palladium catalysts
water and similar biphasic reaction mixtures.[37,38b] It having different surface properties (hydrophilic, hy-
Adv. Synth. Catal. 2011, 353, 767 – 775
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
773

Saeeda S. Soomro et al.
FULL PAPERS
drophobic, amphiphilic) in Suzuki coupling reactions Preparation of Catalysts
in water, it has been verified that the surface proper-
Pd/Al2O3 and Pd/TiO2: The catalysts were obtained by wet
impregnation.[39] For the preparation of 1 g of catalyst with
1% palladium loading on hydrophilic surfaces (Al2O3 and
TiO2), 0.99 g of the support material was suspended in
30 mL of water. 2.0 g of a palladium chloride solution (0.5%
Pd in 5% HCl) were added dropwise under vigorous stirring
and the suspension was further stirred at room temperature
for one hour. This was followed by titration with 10%
NaOH until pH 10 was reached. At the end, the suspension
was filtered, washed with a few mL of water and the solid
catalyst was dried at room temperature for 24 h before its
use in Suzuki reactions.
Pd/T2000: The catalyst on amphiphilic support (T2000)
was prepared using the same procedure as above, except
that the support material was suspended in a water:THF 1:4
mixture.
Pd/Al2O3-C8 and Pd/T805: For palladium on hydropho-
bic surfaces (T805 and Al2O3-C8), a solution of PdACHTNUGTRENUNG(OAc)2 in
ties of the support materials have a pronounced influ-
ence on the catalyst activity. Hydrophobic supports
(like Pd/C) are advantageous for the Suzuki coupling
reactions under mild reaction conditions in water. An
excess of base (NaOH, Na2CO3) is necessary to
obtain high conversions with the catalysts bearing
completely or partially hydrophilic surfaces. TBAB
facilitates the reaction of non-/deactivated aryl halides
by several synergistic mechanisms. Bromide ions en-
hance the dissolution of active Pd species, and stabi-
lize these species in solution. Tetrabutylammonium
ions provide activating counterions for the boronate
and palladate species, and work as a phase-transfer
agent. This implies that the reaction takes place in so-
lution phase (and not on the surface of noble metal).
The support represents a relevant parameter for the
design and development of catalysts for Suzuki cou-
pling reactions in pure water.
THF was used as catalyst precursor. After stirring the sus-
pension in THF for 24 h at room temperature, the catalyst
was filtered and washed with THF until the filtrate was
clear. The catalyst was dried at room temperature before
use. The final palladium content of the catalyst was mea-
sured through atomic absorption spectroscopy (AAS).
Experimental Section
Materials and Methods
Procedures for Catalytic Tests
All reactants were obtained from Aldrich, Fluka or Merck
in “for synthesis” quality or higher, and were used as re-
ceived without further purification or drying. Palladium on
activated carbon (Pd/C: E 105 CA/W 5%, water content:
50.5%) and oxidic supports (TiO2 P25, T805 and alumina-C)
were received from Degussa AG. T2000 was obtained from
Merck. All chemicals were used without special treatment.
The palladium content of the catalysts was determined by
flame atomic absorption spectroscopy (FAAS).
The qualitative and quantitative analysis of the reactants
and products was performed by gas-liquid-chromatography
(GLC) or GC-MS. Products were identified by comparison
with authentic samples. Conversion and selectivity are rep-
resented by product distribution (=relative area of GLC sig-
nals) and GLC yields (=relative area of GLC signals refer-
enced to an internal standard calibrated to the correspond-
ing pure compound, Drel <ꢂ5%).
In a typical Suzuki reaction, aryl halide (2.9 mmol, 1 equiv.),
phenylboronic acid (3.2 mmol, 1.1 equiv.), TBAB (1 mmol)
and sodium hydroxide (8.7 mmol, 3 equiv.) were weighed
into a pressure tube along with 0.2 mol% of the palladium
catalyst. Water (4 mL) was added and the reaction mixture
was brought to a preheated oil bath (658C) after purging
thoroughly with argon. After the reaction time (5 h), the re-
action mixture was allowed to cool down and then extracted
with 2ꢃ5 mL of dichloromethane. The organic layer was
dried over magnesium sulfate and analyzed through gas
liquid chromatography.
Acknowledgements
The authors thank the “Bayerische Forschungsstiftung” for fi-
nancial support. S.S.S. acknowledges the “Bayerische For-
schungsstiftung” for a grant.
Modification of Al2O3 Surface (Al2O3-C8
Preparation)[29]
Four grams of support were dried in a Schlenk tube under References
vacuum at 1408C for 24 h. Under an argon atmosphere,
15 mL of n-hexane were transferred into the Schlenk tube,
and the mixture was stirred for 10 min. n-Octyldimethyl-
chlorosilane (31 mmol) was added dropwise to the suspen-
sion within 1 min and the mixture was stirred for 24 h, fil-
tered off and washed six times with n-hexane. The silylated
product was dried under vacuum for 24 h before its use as
support for the preparation of the catalysts. The hydropho-
bicity of the material was estimated by calculating the silyla-
tion grade (s) which is a measure of silylated versus total
number of OH groups on the surface.
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775