Oxime Carbapalladacycle Covalently Anchored to High Surface Area Inorganic Supports or Polymers as Heterogeneous Green Catalysts for the Suzuki Reaction in Water

Article abstract of DOI:10.1021/jo030302u

An oxime carbapalladacycle known as an extremely active homogeneous catalyst for the Suzuki coupling in water has been conveniently modified and anchored on high surface area SiO₂, MCM-41, and polystyrene-divinylbenzene and ethylenglycol dimethylacrylate polymers. The resulting solids were characterized by analytical and spectroscopic (UV-vis and IR) techniques and tested as catalysts for the reaction of 4-chloroacetophenone with phenylboronic acid in water, dioxane, and a mixture of both. Differences in activity depending on the support were remarkable, the palladium complex being more active for the reactions in water when supported on SiO₂ or MCM-41. The catalysts were truly heterogeneous (no leached palladium) and when anchored on SiO₂ were reused seven times without loosing activity. Palladium complex anchored in SiO₂ was also tested as Suzuki catalyst for a wide range of bromo-, chloro-, and even fluoroaromatics.

Full text of DOI:10.1021/jo030302u

Oxim e Ca r ba p a lla d a cycle Cova len tly An ch or ed to High Su r fa ce
Ar ea In or ga n ic Su p p or ts or P olym er s a s Heter ogen eou s Gr een
Ca ta lysts for th e Su zu k i Rea ction in Wa ter
Carlos Baleiza˜o,†,‡ Avelino Corma,*,† Hermenegildo Garc´ıa,*,† and Antonio Leyva†
Instituto de Tecnologı´a Quı´mica CSIC-UPV, Avda. de Los Naranjos s/ n, 46022 Valencia, Spain, and
INETI-DTIQ, Estrada do Pac¸o do Lumiar, 22, 1649-038 Lisboa, Portugal
hgarcia@quim.upv.es
Received September 23, 2003
An oxime carbapalladacycle known as an extremely active homogeneous catalyst for the Suzuki
coupling in water has been conveniently modified and anchored on high surface area SiO2, MCM-
41, and polystyrene-divinylbenzene and ethylenglycol dimethylacrylate polymers. The resulting
solids were characterized by analytical and spectroscopic (UV-vis and IR) techniques and tested
as catalysts for the reaction of 4-chloroacetophenone with phenylboronic acid in water, dioxane,
and a mixture of both. Differences in activity depending on the support were remarkable, the
palladium complex being more active for the reactions in water when supported on SiO2 or MCM-
41. The catalysts were truly heterogeneous (no leached palladium) and when anchored on SiO2
were reused seven times without loosing activity. Palladium complex anchored in SiO2 was also
tested as Suzuki catalyst for a wide range of bromo-, chloro-, and even fluoroaromatics.
In tr od u ction
that they can be prepared with larger surface areas, have
periodic structured porosity, and can resist thermal
regeneration. In contrast, polymers present a high hy-
drophobicity that makes them more suitable for reactions
in organic solvents.
In a preliminary communication we reported the
anchoring of a 10-undecenyl derivative of carbapallada-
cycle complex 5 on silica and found that the resulting
Pd on silica is an active catalyst for the reaction of boronic
acid for 4-bromo- or 4-chloroacetophenone.10 Herein we
have expanded the initial results to the preparation of a
related catalyst using MCM-41 as support and another
series in which PdL has been anchored to a polymeric
backbone. The results obtained confirm the high activity
of the supported carbapalladacycle on inorganic oxides
that can be used for a wide range of substrates, reaching
high conversion and selectivity.
In a series of papers Na´jera and co-workers have
reported a highly active water-soluble Pd-oxime carba-
palladacycle catalyst that is able to effect the Suzuki
reaction of arylboronic acids and aryl chlorides in wa-
ter.1,2 The problem with homogeneous catalysis is the
difficulty to separate the catalyst from the reaction
mixture and the impossibility to reuse it in consecutive
reactions. In contrast, solid catalysts can be easily
separated from the reaction mixture by simple filtration
and reused in successive reactions provided that the
active sites have not become deactivated. Heterogeneous
catalysis also helps to minimize wastes derived from
reaction workup, contributing to the development of
green chemical processes.3,4
One general methodology to transform a successful
homogeneous transition metal complex catalyst into a
heterogeneous catalyst consists of the anchoring the
conveniently modified complex onto an insoluble support.
Two types of insoluble solids are among the most useful
supports to anchor complex catalysts, inorganic oxides5-7
and polymers.8,9 Inorganic oxides have the advantage
Resu lts a n d Discu ssion
The route followed to prepare the solid catalysts is
depicted in Schemes 1 and 2. The preparation is based
on the synthesis of an oxime carbapalladacycle having a
terminal CdC double bond group in a long alkyl chain
that will enable the anchoring of the complex. This
undecenyl derivative of the Pd complex was prepared
from the corresponding oxime starting from 4-hydroxy-
acetophenone (Scheme 1). Other alternatives in which
Pd complexation was not accomplished in the last step
† Instituto de Tecnolog´ıa Qu´ımica CSIC-UPV.
‡ INETI-DTIQ.
(1) Botella, L.; Najera, C. J . Organomet. Chem. 2002, 663, 46-57.
(2) Botella, L.; Najera, C. Angew. Chem., Int. Ed. 2002, 41, 179-
181.
(3) Poliakoff, M.; Fitzpatrick, J . M.; Farren, T. R.; Anastas, P. T.
Science 2002, 297, 807-810.
(4) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686-
694.
(5) Corma, A. Chem. Rev. 1995, 95, 559-614.
(6) Van Rhinj, W. M.; De-Vos, D.; J acobs, P. A. Fine Chemicals
through Heterogeneous Catalysis; Wiley-VCH: Weinheim, 2001; Vol.
106.
(8) Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102, 3217-3274.
(9) McNamara, C. A.; Dixon, M. J .; Bradley, M. Chem. Rev. 2002,
102, 3275-3300.
(10) Baleizao, C.; Corma, A.; Garcia, H.; Leyva, A. Chem. Commun.
2003, 606-607.
(7) Corma, A.; Garcia, H. Chem. Rev. 2002, 102, 3837-3892.
10.1021/jo030302u CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/20/2003
J . Org. Chem. 2004, 69, 439-446
439

Baleiza˜o et al.
SCHEME 1 a
a
(i) NH2OH, NaOAc, H2O, reflux, 1 h; (ii) CH2dCH(CH2)9Br, K2CO3; (iii) Li2PdCl4, NaOAc, MeOH, rt, 72 h.
SCHEME 2. An ch or in g P r oced u r e of Oxim e
but in an earlier stage of the synthesis led to poor
complex yields. The reaction intermediates and the final
oxime carbapalladacycle 5 were fully characterized by
analytical and spectroscopic means. Particularly infor-
mative were the data corresponding to the Pd complex.
The FAB-MS spectrum exhibits the characteristic mo-
lecular cluster11 due to the different palladium isotopes
from 404 to 410 amu corresponding to the mass of the
monomeric carbapalladacycle after losing a Cl- anion.
This indicates that, in our case, the complex 5 is in a
monomeric form rather than a dimer as previously
reported for the 4-hydroxy derivative of complex 3.10 The
monomeric nature of complex 5 suggests that the termi-
nal CdC double bond is somehow interacting with the
Pd, disfavoring the dimer formation, but a definitive
confirmatory structure determination based on a single-
crystal XRD has not yet being possible. Also important
Ca r ba p a lla d a cycle 5 on to
Mer ca p top r op yl-Mod ified High Su r fa ce Silica
Su p p or ts
1
is the information obtained by H and 13C NMR. In 1H
NMR the characteristic pattern for the aromatic protons
was observed for the ligand, and they shift toward lower
δ values, indicating that the Pd is bonded to the aryl ring.
Also in support of the CdC double bond interaction with
the Pd some variations in the chemical shift of these
hydrogens were observed. The 13C NMR was also in good
agreement with the data previously reported for the
4-hydroxy derivative 3,1 but some additional studies are
still necessary to address the bonding of Pd with the
terminal CdC double bond. Complex 5 having the
terminal CdC double bond can be easily anchored
through a radical chain mechanism onto 3-mercaptopro-
pyl-modified silicas, which are easily obtained by reacting
3-mercaptopropyl trimethoxysilane with silicas silanol
groups (Scheme 2). Both reactions, mercaptopropyl sily-
lation and radical-chain anchoring of mercapto groups
on terminal CdC double bonds, have been widely used
in precedents in which organic molecules and complexes
have been successfully bound to inorganic surfaces.12 This
procedure was applied to amorphous silica (PdL@SiO2)
and to an MCM-41 silicate having a large surface (720
m2) and a pore diameter of 38 Å (PdL@MCM-41). The
TABLE 1. An a lytica l a n d Sp ectr oscop ic Da ta of Solid
Ca ta lysts Used
BET surface combustion analysis Pd content
catalyst
(m2 g-1
)
(mmol g-1
)
(mmol g-1
)
PdL@SiO2
PdL@MCM-41
PdL@PS
380
720
C 5.97; N 0.29; S 0.8
C 8.14; N 0.41; S 0.77
C 74 H 81 N 0.16
0.27
0.41
0.15
0.35
PdL@PEA
C 48 H 70 N 0.37
two solids were characterized by chemical analysis (Pd,
C, N, S) and optical and IR spectroscopy.
The most relevant analytical data of the solid catalysts
are summarized in Table 1. Comparison of the palladium
and nitrogen content of the solids gives a similar ratio
as in the precursor 5, suggesting that the Pd complex
has survived the anchoring procedure. The complex
loading of the silica samples is around 0.3 mmol g-1. On
the other hand, comparison of the sulfur to nitrogen
atomic ratio establishes that less than 50% of the
mercaptopropyl groups of the modified silica or MCM-
41 have reacted and must contain the Pd oxime complex.
About 50% of unreacted mercaptopropyl groups remain
free. Oversilylation with mercaptopropylsilyl groups
serves to mask free silanol groups that could introduce
some weak Bro¨nsted acidity in the solids. A test reaction
using the mercaptopropyl-modified silica lacking an-
(11) McLafferty, F. W. Interpretation of Mass Spectra, 3rd ed.;
University Science Books: Mill Valley, 1980.
(12) Baleizao, C.; Gigante, B.; Garcia, H.; Corma, A. J . Catal. 2003,
215, 199-207.
440 J . Org. Chem., Vol. 69, No. 2, 2004

Green Catalysts for Suzuki Reaction in Water
SCHEME 3. F or m a tion of P d L@P S by in Situ Ra d ica l Cop olym er iza tion
SCHEME 4. F or m a tion of P d L@P EA by in Situ Ra d ica l Cop olym er iza tion
chored PdL as catalyst was performed without reactant
conversion. Diffuse reflectance UV-vis spectra of
PdL@SiO2 and PdL@MCM-41 exhibit a peak at λmax 380
nm characteristic of the carbapalladacycle complex in
solution. This absorption band is absent in the mer-
captopropyl modified solids. The IR spectra of the
PdL@MCM-41 coincides with that previously reported by
us10 for PdL@SiO2 where, in addition to strong vibration
bands at 2950 and 2900 cm-1 corresponding to the CH2
groups of the spacer connecting the complex to the silica
walls, other absorption bands in the aromatic region
compatible with the structure of the carbapallacycle
complex are also recorded.
A different type of solid catalyst where the oxime
carbapalladacycle complex is anchored on two different
polymeric backbones was also prepared. One of these
polymeric catalysts termed as PdL@PS was obtained
starting from complex 5 having the terminal CdC double
bond upon copolymerization with styrene and p-divinyl-
benzene (Scheme 3). The latter monomer acts as cross-
linker of the polymeric backbone and increases the
insolubility of the polymer, allowing easier recovery of
the heterogeneous catalyst. Polymerization of the CdC
double bond was carried out through a radical chain
mechanism using azobisisobutyronitrile (AIBN) as radi-
cal initiator in the absence of oxygen, and a mixture of
toluene and 1-dodecanol as solvent. The presence of
1-dodecanol in the medium increases the porosity and
the surface area of the polystyrene.13
tion was also effected using AIBN as initiator and
toluene/ethanol as solvent (Scheme 4). The palladium
loading of the two polymeric solid catalysts based on the
ligand content is also contained in Table 1. Noteworthy
from these data is that the Pd loading is in the same
range for the four samples, thus allowing a straightfor-
ward comparison between the catalytic activity of the
PdL supported on silicates or polymers.
The two solid catalysts in which PdL was anchored on
the polymeric scaffold were also characterized by diffuse
reflectance UV-vis spectroscopy. The PdL@PS and
PdL@PEA samples exhibit the metal to ligand charge-
transfer band at about 350 nm (Figure 1), which is
somewhat shifted with respect to the λmax recorded for
the same complex supported on silicates (380 nm). This
variation in λmax may reflect differences in the po-
larity/hydrophobicity of the polymers compared to
that of silicates. The IR spectra of the solid catalysts
PdL@PS and PdL@PEA contain some bands character-
istic of complex 5 embedded within much more intense
vibrations corresponding to the polymeric backbone
(Figure 2).
To determine the catalytic activity of the samples the
Suzuki reaction of phenylboronic acid with 4-chloroaceto-
phenone was carried out in water as well as dioxane or
a 3:2 water/dioxane mixture. Figures 3 and 4 show the
time conversion plot for the formation of 4-phenylaceto-
phenone in water and dioxane, respectively. Table 2
summarizes the results obtained for each solid catalyst.
As expected in view of the reported influence of the
solvent polarity on the activity of oxime carbapalladacycle
complex, the reaction in water was much faster and led
to higher conversions than in dioxane.14 An intermediate
situation is observed for mixtures of water/dioxane. Since
The second polymer (PdL@PEA) was obtained starting
from ethylene glycol bis(methacrylate) (EA) as monomer
through copolymerization with lesser amounts of ω-ter-
minal CdC double bond complex 5. Radical polymeriza-
(13) Bevington, J . C. J . Polym. Mater. 1993, 10, 195-202.
J . Org. Chem, Vol. 69, No. 2, 2004 441

Baleiza˜o et al.
F IGURE 4. Time conversion plot for the Suzuki reaction of
p-chloroacetophenone (31 mg, 0.2 mmol), phenylboronic acid
(36 mg, 0.3 mmol) and K2CO3 (55 mg, 0.4 mmol) in dioxane (5
mL) at 100 °C using PdL@PEA (a), PdL@PS (b), and PdL@SiO2
(c) as catalysts.
tion. However, this cannot be the only factor since the
solvent polarity changes the relative activity of the
catalysts, the influence being considerably higher for PdL
anchored on silicates than anchored on polymers. In fact,
PdL@PEA is the most active solid catalyst in dioxane and
its activity is only 0.75 times lower in dioxane than in
water. In contrast, the activities for PdL@SiO2 and
PdL@MCM-41 are reduced at least 0.002 times going
from water to dioxane. Although the influence of solvent
polarity on the activity of the oxime carbapalladacycle
in solution has been previously reported,14 we believe that
solvent polarity only does not explain the dramatic effect
observed in the activity when PdL is anchored on silicates
compared to that on polymers. Leaching of palladium
species for PdL anchored on silicates was considered and
disregarded (vide infra). In other words, the support plays
a critical role on the activity of the complex depending
on the solvent. PdL anchored on polymers is relatively
insensitive to the polarity of the medium since the minor
decrease can be explained just by considering the lower
carbonate solubility.
F IGURE 1. Diffuse reflectance UV-vis spectra (plotted as
the Kubelka-Munk function of the reflectance, R) of
PdL@MCM-41 (a) and PdL@PEA (b).
In view of the above results, we propose that the
carbapalladacycle complex in the polymeric scaffold is
entangled and embedded within the hydrophobic polymer
chains, being protected from water. This would explain
the low activity of PdL in water when anchored on
polymer. On the other hand, the much higher hydrophi-
licity of silica and MCM-41 permits free access of this
solvent to all of the pores, effectively surrounding the PdL
complex. In other words, PdL will interact more freely
with water when anchored on silicates than in polymers.
The above findings constitute a remarkable example of
the influence of the nature of the support in heteroge-
neous catalysis, this effect arising from the intrinsic
dramatic change of the PdL activity as a function of the
solvent.
F IGURE 2. Infrared spectra of oxime carbapalladacycle 5 (a),
PdL@PS (b), and PdL@PEA (c).
F IGURE 3. Time conversion plot for the Suzuki reaction of
p-chloroacetophenone (31 mg, 0.2 mmol), phenylboronic acid
(36 mg, 0.3 mmol), and K2CO3 (55 mg, 0.4 mmol) in neat water
(5 mL) at 100 °C using PdL@SiO2 (a), PdL@MCM-41 (b),
PdL@PS (c), and PdL@PEA (d) as catalysts.
We have expanded the study to other substrates using
water as solvent and PdL@SiO2 and PdL@MCM-41 as
catalysts. To cover a wide range of substrates, bromi-
nated, chlorinated, and fluorinated aromatic compounds
were tested. The results are summarized in Table 3. In
some cases, particularly with low reactive chloro deriva-
tives and at long reaction times, significant amounts of
biphenyl arising from the homocoupling of phenylboronic
acid15 were observed accompanying the corresponding
potassium carbonate is not fully soluble in dioxane, one
obvious factor decreasing the reaction rate in this solvent
as compared to that in water is the lower base concentra-
(14) Alonso, D. A.; Najera, C.; Pacheco, M. C. J . Org. Chem. 2002,
67, 5588-5594.
(15) Kochi, J . K. J . Organomet. Chem. 2002, 653, 11-19.
442 J . Org. Chem., Vol. 69, No. 2, 2004

Green Catalysts for Suzuki Reaction in Water
TABLE 2. Resu lts for Su zu k i Rea ction of
p-Ch lor oa cetop h en on e (31 m g, 0.2 m m ol), P h en ylbor on ic
Acid (36.6 m g, 0.3 m m ol), a n d K2CO3 (55.3 m g, 0.4 m m ol)
in Nea t Wa ter (5 m L) a t 100 °C in th e P r esen ce of Solid
Ca ta lyst (30 m g)a
course of the reaction some active palladium species is
present in the solution, the anchored reagent will be
converted in some degree. To completely rule out the
occurrence of the leaching, we prepared a modified silica
functionalized with p-chlorobenzamide as well as p-iodo-
benzamide (Scheme 5). Control reactions in homogeneous
phase using p-iodo-N-butylbenzamide as model com-
pound established that the Suzuki reaction of this
substrate with phenylboronic acid is readily catalyzed by
the oxime carbapalladacycle and that the hydrolysis of
4-phenyl-N-butylbenzamide can be performed in basic
media (Scheme 6).
catalyst
time (h)
conversion (%)
PdL@SiO2
0.25
91
>99
43
94
38
2
0.25
2
PdL@MCM-41
PdL@PS
2
13
2
76
18
PdL@PEA
13
18
As a matter of fact, when the Suzuki reaction of
phenylboronic acid and 4-chloroacetophenone using
PdL@SiO2 as catalyst was performed in the presence of
silica-bound ClPhCONH, after workup the Suzuki prod-
uct was not detected. 4-Chlorobenzoic acid was the only
compound observed besides the 4-phenylacetophenone.
However, in the case of IPhCONH@SiO2, together with
4-iodobenzoic and 4-hydroxybenzoic acid, the predomi-
nant product observed in the basic hydrolysis of the
solids was the corresponding Suzuki coupling product
4-phenylbenzoic acid.
The above results using the three-phase methodology
clearly indicates that although some palladium species
sufficiently active to promote the coupling with iodoaro-
matics has to be present in the solution, the Suzuki
product from 4-chloroacetophenone is a completely het-
erogeneous process. In other words, the leached species
is not sufficiently active to catalyze the Suzuki coupling
of chloroaromatics. It is well-documented20-22 that reac-
tion of chloroaromatics requires more active palladium
catalysts than those required for iodocompounds. The
above explanation is also compatible with the “conven-
tional” leaching experiment consisting of filtration of the
catalyst while hot and also with the lack of detectable
palladium depletion on the solid and with the reusability
of the catalyst (see below).
Reusability of the PdL@SiO2 catalyst was demon-
strated by performing a series of reactions using 4-chlo-
roacetophenone and phenylboronic acid as substrates in
which the catalyst PdL@SiO2 was filtered at the end of
the reaction; washed consecutively with aliquots of
distilled water, ethanol, and ethyl ether; dried over
reduced pressure, and reused for a new batch. Up to eight
consecutive reactions were carried out with the same
catalyst at the same substrate-to-catalyst ratio without
observing any decrease in the final conversion or selectiv-
ity of the process.
a
The only product observed was the corresponding 4-phenyl-
acetophenone. Selectivity >95%.
cross-coupling product. As expected,16,17 the bromo de-
rivatives react much faster to give high yields of the
Suzuki product in short reaction times. However, it is
worth remarking that moderate to high yields are also
obtained with chloro compounds, particularly those hav-
ing electron-withdrawing groups. The activity of the PdL
anchored on silicates is so high that even conveniently
substituted fluoroaromatics can undergo coupling with
phenylboronic (see Table 3, last entry).
Lea ch in g a n d Reu se Tests
With a heterogeneous catalyst, two issues need to be
addressed. The first is to demonstrate the heterogeneity
of the process and the absence of catalytically active
species in solution leached from the solid. This crucial
point was addressed in three different ways. In one of
the approaches the Suzuki coupling of phenylboronic acid
and 4-bromoacetophenone in water was performed in the
presence of the most active PdL@SiO2, and the solid was
filtered at 22% conversion while hot, observing that the
reaction completely stops when the resulting clear solu-
tion was heated for 24 h. In the second approach,
chemical analysis of a PdL@SiO2 catalyst reused in eight
consecutive runs (see below for reusability) showed
within the experimental error the same palladium con-
tent as the fresh catalyst.
In the third more elaborated strategy, the “boomerang”
leaching mechanism, proposed by Lipshutz as operating
on related catalysts of Pd metal supported on carbon, was
scrutinized and disregarded.18,19 According to the Lip-
shutz’s proposal, catalytically significant amounts of
supported Pd metal can be dissolved during the reaction
and would redeposit quickly on the solid during the
filtration as a result of unavoidable minor temperature
decreases during the filtration workup. To determine the
occurrence of the homogeneous catalysis, Lipshutz pro-
posed the so-called “three-phase test” consisting of an-
choring one of the reagents onto a solid in addition to
using the solid catalyst. In this way, if the process is
completely heterogeneous, no transformation should be
observed for the anchored reagent, whereas if during the
Con clu sion s
Covalent attachment of the oxime carbapalladacycle
catalyst to silicates renders solid catalysts that are
extremely active for the Suzuki cross-coupling and can
be reused for a series of consecutive runs without
(20) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: New York, 1985.
(21) Tsuji, J . Wiley: New York, 1995.
(22) Hassan, J .; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359-1469.
(23) Beck, J . S.; Vartuli, J . C.; Roth, W. J .; Leonowicz, M. E.; Kresge,
C. T.; Schmitt, K. D.; Chu, C. T. W.; Olson, D. H.; Sheppard, E. W.; et
al. J . Am. Chem. Soc. 1992, 114, 10834-10843.
(24) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J .; Vartuli, J . C.; Beck,
J . S. Nature 1992, 359, 710-712.
(16) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(17) Fu, G. C.; Littke, A. F. Angew. Chem., Int. Ed. 2002, 41, 4176-
4211.
(18) Davies, I. W.; Matty, L.; Hughes, D. L.; Reider, P. J . J . Am.
Chem. Soc. 2001, 123, 10139-10140.
(19) Lipshutz, B. H.; Tasler, S.; Chrisman, W.; Spliethoff, B.; Tesche,
B. J . Org. Chem. 2003, 68, 1177-1189.
J . Org. Chem, Vol. 69, No. 2, 2004 443

Baleiza˜o et al.
TABLE 3. Resu lts for Su zu k i Rea ction of Ar yl Ha lid es (0.2 m m ol), P h en ylbor on ic Acid (0.3 m m ol), a n d K2CO3
(0.4 m m ol) in Nea t Wa ter (5 m L) in th e P r esen ce of P d L@SiO2 (30 m g) or P d L@MCM-41 (24.4 m g) a s Ca ta lysts
a
Biphenyl comes from homocoupling reaction of phenylboronic excess, and the % value is referred to the initial amount.
b
4-Methylphenylboronic acid was used as reagent instead of phenylboronic acid and 4,4′-dimethylbiphenyl was resulting as by-product.
c Products coming from SNAr are also found. Carboxylic acids and diols together with aldehydes are present as final reaction products.
deactivation or leaching. Silica is a particular suitable
support that can effect the Suzuki reaction with chlori-
nated substrates. No advantages of using mesoporous
MCM-41 as support were apparent. In contrast to this,
anchoring of the palladium complex on polymeric back-
bones derived from styrene or methyl acrylate gives much
less active solid catalysts. The present results show the
importance of the support, solvent, and reaction condi-
tions on the catalytic activity. Based on PdL@SiO2,
“green” Suzuki reaction using water as solvent and a
reusable catalyst can be developed.
Exp er im en ta l Section
For reagents, general instrumentation, characterization,
recovery, and reuses of the catalysts and leaching tests see
Supporting Information.
Syn th esis of 2. To a solution of hydroxylamine hydrochlo-
ride (5.13 g, 0.074 mol) and sodium acetate (10.26 g, 0.125 mol)
444 J . Org. Chem., Vol. 69, No. 2, 2004

Green Catalysts for Suzuki Reaction in Water
precipitate as a white solid (3.97 g, 13 mmol, 80%). Mp: 67-
69 °C. IR (KBr, cm-1): 3449, 2929, 2841, 1640, 1606, 1505,
1471, 1316, 1248, 1174, 1012, 938, 904, 830, 635. 1H NMR
(ppm, 300 MHz, CDCl3): δ 8.8 (1H, brs), 7.56 (2H, d, J ) 7
Hz), 6.89 (2H, d, J ) 7 Hz) 5.82 (1H, m), 4.95 (2H, m) 3.97
(2H, t, J ) 6.5 Hz), 2.27 (3H, s), 2.05 (2H, m), 1.78 (2H, m),
1.43 (14H, m). 13C NMR (ppm, 300 MHz, CDCl3): δ 160.1,
155.6, 139.2, 128.8, 127.6, 127.3 (2C), 115.4, 114.4 (2C), 114.1,
68.1, 33.8, 29.5, 28.9, 26.0, 12.1. MS (FAB): m/z 304 (peaks
at 286 and 151). Anal. Calcd for C19H29NO2 (305.15): C, 74.72;
H, 9.50; N, 4.59. Found: C, 74.53; H, 9.78; N, 4.62.
SCHEME 5. An ch or in g P r oced u r e of p-Ch lor o- or
p-Iod o-N-bu tyl Ben za m id e on to th e
Am in op r op yl-Mod ified High Su r fa ce Silica
Syn th esis of 5. To a solution of Li2PdCl4 (1.048 g, 4 mmol)
in methanol (8 mL) was added a methanolic solution (4 mL)
of 4 (1.212 g, 4 mmol) and sodium acetate (0.328 g, 4 mmol).
The mixture was stirred at room temperature for 72 h. The
mixture was filtered, and after water (10 mL) was added, the
cyclopalladated complex (5) precipitated as a yellow solid.
Mp: 135-137 °C. IR (KBr, cm-1): 3435, 2922, 2848, 1633,
1584, 1560, 1458, 1340, 1263, 1211, 1033, 960, 800, 636. 1H
NMR (ppm, 300 MHz, CDCl3): δ 8.4 (1H, s), 7.1 (1H, s), 6.85
(1H, d, J ) 8 Hz), 6.35 (1H, d, J ) 8 Hz), 5.35 (2H, s), 3.9 (2H,
t), 2.2 (2H,d), 1.9 (3H, s), 1.7 (2H, brs), 1.6 (2H, brs), 1.4 (10H,
m), 0.9 (2H, m). 13C NMR (300 MHz, CDCl3) δC (ppm): δ 165.0,
157.2, 154.1, 134.2, 131.6, 125.0, 117.4, 114.4, 111.1, 67.9, 34.7,
32.5, 29.6, 29.4, 29.3, 29.1, 26.0, 17.9, 14.0. MS (FAB) m/z (M
- Cl); typical isotopic distribution for Pd: 406(17%), 407(22%),
408(27%), 410 (24%), 412(6%). Anal. Calcd for C19H28NO2PdCl
(445.02): C, 51.12; H, 6.28; N, 3.14. Found: C, 52.10; H, 6.53;
N, 3.18.
SCHEME 6 a
Gen er a l P r oced u r e for An ch or in g th e Cyclop a lla -
d a ted Com p lex on th e Su r fa ce of th e Mod ified Solid s.
To a solution of 5 (178 mg) in degassed chloroform were added
the modified solid (1 g, see Supporting Information) and AIBN
(6.5 mg, 10%) in a nitrogen atmosphere. The suspension was
stirred magnetically at 80 °C under nitrogen for 20 h. The solid
was filtered and Soxhlet extracted with dichloromethane for
24 h. After drying of the solids (at 45 °C under 10-1 Torr for
2 h), the quantity of palladium was determined by quantitative
atomic absorption spectroscopy.
P r oced u r e for Syn th esis of th e P d L@P S P olym er . A
mixture of styrene (0.545 g, 5.23 mmol), Pd complex 5 (50 mg),
divinylbenzene (50 mg, 0.38 mmol), toluene (0.3 mL), and
1-dodecanol (1.5 mL) was placed in a vessel and purged with
nitrogen for 15 min. After that time, 2,2′-azobisisobutyronitrile
(75 mg) was added, and the vessel was closed and heated at
80 °C for 24 h. The polymer was removed by filtration and
Soxhlet extracted with dichloromethane for 24 h. The content
of complex was determined by chemical analysis.
a
(i) PhB(OH)2, 3, K2CO3, water, 100 °C; (ii) KOH, ethanol/water
(2:1), 90 °C
in water (26 mL) was added 4-hydroxy-acetophenone (3 g,
0.022 mol). The solution was stirred at reflux temperature for
1 h. After this time, the aqueous solution was extracted
exhaustively with diethyl ether. The organic phase was dried,
and the solvent was evaporated under vacuum. To the result-
ing crude was added hexane, and 1-(4-hydroxyphenyl)-etha-
none oxime (2) started to precipitate as a white solid (3.25 g,
0.0215 mol, 98%). Mp: 146-147 °C. IR (KBr, cm-1): 3324,
1642, 1603, 1514, 1444, 1316, 1240, 1176, 940, 825, 589. 1H
NMR (ppm, 300 MHz, CD3OD): δ 7.49 (2H, d, J ) 5 Hz), 6.77
(2H, d, J ) 5 Hz), 2.18 (3H, s). 13C NMR (ppm, 300 MHz,
CD3OD): δ 159.9, 156.7, 130.2, 128.9, 116.5, 12.55. MS
(FAB): m/z 151. Anal. Calcd for C8H9NO2 (151.15): C, 63.5;
H, 5.95; N, 9.26. Found: C, 63.19; H, 6.22; N, 9.35.
P r oced u r e for Syn th esis of th e P d L@P EA p olym er . Pd
complex 5 (50 mg) and ethylene glycol dimethacrylate (EGD-
MA) (1.5 mL) were dissolved in toluene (2.1 mL) and ethanol
(0.9 mL). The polymerization mixture was bubbled with
nitrogen for 30 min. 2,2′-Azobisisobutyronitrile (25 mg) was
added, and the mixture was heated at 80 °C for 24 h. The
polymer was removed by filtration and Soxhlet extracted with
dichloromethane for 24 h. The content of complex was deter-
mined by elemental analysis.
Typ ica l P r oced u r e for Su zu k i Cou p lin g of Ar yl Br o-
m id es, Ch lor id es, a n d F lu or id es. Suzuki reactions in water
were carried out by stirring magnetically the corresponding
aryl halide (0.2 mmol), boronic acid (0.3 mmol, 1.5 equiv), and
K2CO3 (0.4 mmol, 2 equiv) in water, water/dioxane, or dioxane
(5 mL) in the presence of the solid catalyst (5 mol % Pd) at
reflux temperature. In neat water and water/dioxane the
course of the reaction was followed periodically by extracting
aliquots (0.5 mL) of the aqueous phase with ethyl acetate and
analyzing the extract with GC using nitrobenzene as external
standard. When pure dioxane was the test reaction solvent,
the aliquots (0.1 mL) were analyzed as taken using nitroben-
zene as external standard.
Syn th esis of 3. To a solution of Li2PdCl4 (524.1 mg, 2 mmol)
in methanol (4 mL) was added a methanolic solution (2 mL)
of 2 (302 mg, 2 mmol) and sodium acetate (0.164 g, 2 mmol).
The mixture was stirred at room temperature for 72 h. The
mixture was filtered, and after water (5 mL) was added, the
cyclopalladated complex (3) started to precipitate as a yellow
solid (75%). IR (KBr, cm-1): 3429, 1627, 1584, 1472, 1430,
1375, 1326, 1260, 1211, 1037, 873, 799, 608. 1H NMR (ppm,
300 MHz, DMSO-d6): δ 10.38(1H, s), 9.88(1H, s), 9.77(1H, s)
9.63(1H, s), 7.3 (2H, s), 7.15 (2H, d, J ) 8 Hz), 6.5 (2H, d, J )
8 Hz), 2.23 (6H, s). 13C NMR (ppm, 300 MHz, DMSO-d6): δ
167.5, 157.3, 154.7, 133.1, 128.3, 122.1, 111.8, 11.6. MS
(FAB): m/z 584. Anal. Calcd for C16H16N2O4Pd2Cl2 (584.04):
C, 32.87; H, 2.74; N, 4.79. Found: C, 32.12; H, 2.87; N, 4.59.
Syn th esis of 4. A mixture of 2 (2.5 g, 16.55 mmol),
11-bromoundecene (3.695 g, 16.55 mmol), and K2CO3 (11.27
g, 82.78 mmol) in acetone (30 mL) was heated to reflux for 24
h. The suspension was filtered, and the solvent was evaporated
under vacuum. The crude was dissolved in AcOEt and ex-
tracted with water and brine. The organic phase was dried,
and the solvent evaporated under vacuum. To the resulting
crude was added hexane was added, and the mixture was
heated under reflux for 30 min. The solution was filtered, and
1-[4-(undec-10-enyloxy)-phenyl]-ethanone oxime (4) started to
P r oced u r e for Syn t h esis of ClP h CONH @SiO2 a n d
IP h CONH@SiO2. To anchor the p-chloro- or p-iodobenzamide,
J . Org. Chem, Vol. 69, No. 2, 2004 445

Baleiza˜o et al.
a solution of the corresponding acyl chloride (p-chloro, 0. 919
g, 5.25 mmol; p-iodo, 1.4 g, 5.25 mmol) in dry THF (10 mL)
was placed in a round-bottomed flask in the presence of
aminopropyl-modified solid (1 g, see Supporting Information)
and pyridine (404 µL, 5 mmol) under nitrogen atmosphere.
The suspension was stirred magnetically at 40 °C under
nitrogen atmosphere for 12 h. The solid was separated by
centrifugation and washed with 20 mL of HCl/H2O (5% v/v, 3
times), 20 mL of K2CO3/H2O (0.02 M, 2 times), neat water (2
times), and ethanol (2 times). Then the solid was Soxhlet
extracted with CH2Cl2 for 24 h. After drying the solids (at 45
°C under 10-1 Torr for 2 h), the anchored amount was
determined by combustion chemical analysis and confirmed
by thermogravimetric analysis. ClPhCONH@SiO2: 0.40 mmol/
g; IPhCONH@SiO2: 0.88 mmol/g.
(conversion >99%), and the solid was separated by filtration
under vacuum while hot, washed with ethanol, and Soxhlet
extracted with ethanol for 24 h. After that, the solid was
hydrolyzed in a 2 M solution of KOH (1.68 g) in ethanol/water
(10:5 mL) at 90 °C for 3 days. The solution was neutralized
with HCl 10% v/v (9.1 mL), extracted with CH2Cl2, concen-
trated and, analyzed by GC-MS.
Ack n ow led gm en t. Financial support by the Span-
ish D.G.E.S. (MAT2000-1768-C02-01) is gratefully as
acknowledged. A.L. thanks the Spanish Ministry of
Education for a post-graduated scholarship.
Su p p or tin g In for m a tion Ava ila ble: General procedure
for the preparation of mercaptopropyl- and aminopropyl-
functionalized solid supports as well as catalyst characteriza-
tion and reuse and leaching test data. This material is
available free of charge via the Internet at http://pubs.acs.org.
Th r ee-P h a se Tests. A solution of 4-chloroacetophenone
(0.2 mmol), phenylboronic acid (0.3 mmol, 1.5 equiv), and
K2CO3 (0.4 mmol, 2 equiv) in water (5 mL) ewas magnetic-
ally stirred in the presence of PdL@SiO2 (30 mg) and
ClPhCONH@SiO2 or IPhCONH@SiO2 (200 mg) at 100 °C for
2 h. At this time, the supernatant was analyzed by GC
J O030302U
446 J . Org. Chem., Vol. 69, No. 2, 2004