Investigating PdEnCat catalysis

Article abstract of DOI:10.1021/jo0517904

The catalytic behavior of three commercially available PdEnCat catalysts was explored. When the three-phase test was used, it was demonstrated that these microencapsulated palladium catalysts act as heterogeneous sources, or reservoirs, for soluble, catalytically active species. In addition, kinetic data coupled with transmission electron microscopy and solvent-dependent investigations were used to support this conclusion.

Full text of DOI:10.1021/jo0517904

and the use of inorganic2,3,25-27 and polymeric supports.1,4,28
Our research is focused on designing immobilized catalysts
capable of performing multistep one-pot reactions. The benefits
of performing multiple reactions simultaneously include lower
input and labor costs and decreased waste production. We are
interested in a transition metal immobilization approach where
the metal is site-isolated within the support throughout the entire
reaction. Palladium catalyzes a broad range of carbon-carbon,
carbon-oxygen, and carbon-nitrogen bond-forming reactions
and is an attractive choice for use in tandem catalysis.29,30
Palladium, however, may not be compatible with other catalytic
materials; therefore, the catalyst must remain site-isolated within
the support.
Investigating PdEnCat Catalysis
Steven J. Broadwater and D. Tyler McQuade*
Department of Chemistry and Chemical Biology,
Baker Laboratory, Cornell UniVersity,
Ithaca, New York 14853-1301
dtm25@cornell.edu
ReceiVed August 25, 2005
One of the most promising methods of catalyst immobilization
is microencapsulation. Ley and co-workers have used microen-
capsulation techniques to encapsulate Pd(OAc)2 within a poly-
urea matrix that can include phosphine ligands.22,31-35 These
commercially available PdEnCat catalysts can be used to
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The catalytic behavior of three commercially available
PdEnCat catalysts was explored. When the three-phase test
was used, it was demonstrated that these microencapsulated
palladium catalysts act as heterogeneous sources, or reser-
voirs, for soluble, catalytically active species. In addition,
kinetic data coupled with transmission electron microscopy
and solvent-dependent investigations were used to support
this conclusion.
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10.1021/jo0517904 CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/28/2006
J. Org. Chem. 2006, 71, 2131-2134
2131

catalyze a wide variety of reactions, including cross-couplings,
carbonylations, and hydrogenations.
PdEnCats are attractive for tandem catalysis because of their
wide substrate scope, high activity, low leaching, and strong
recycling capability. Active catalyst escape from PdEnCats,
however, has not been critically examined. Many reports indicate
that heterogeneous catalysts often serve as reservoirs for soluble,
catalytically active species.36-43 Prior to using these catalysts
in a multistep, one-pot synthesis, we investigated if an active
palladium catalyst leaches from the PdEnCat core under standard
reaction conditions.
FIGURE 1. Representation of the three-phase test. A: The palladium
catalyst remains site-isolated, allowing only solution-phase reagents
to participate in the reaction; the resin-bound reagent does not react.
B: The palladium catalyst leaches out of the heterogeneous support,
allowing both the solution-phase and the resin-bound reagents to react.
TABLE 1. Three-Phase Test Results of Heck Couplinga,b
Site isolation is our major requirement for an immobilized
catalyst; therefore, we determined that the three-phase test is
the most definitive indicator of active catalyst escape, Figure
1.37,44-48 In the three-phase test, an immobilized catalyst is
exposed to soluble reagents and reagents bound to a solid
support. As depicted in Figure 1, if an active catalyst leaches
from the immobilized media, it will result in conversion of the
resin-bound reagent.
Following the general method of Davies and co-workers,37
the base-stable Tenta-Gel Macrobead-supported aryl iodide (1)
was prepared. The three-phase test was performed using three
commercially available PdEnCats: 30, TPP30, and TOTP30.
PdEnCat 30 consists of palladium(II) ligated by the urea
encapsulation matrix, whereas PdEnCat TPP30 contains tri-
phenylphosphine and PdEnCat TOTP30 contains tri-o-tolylphos-
phine as catalyst modifiers. Heck and Suzuki reactions were
run to assess whether leaching was reaction dependent. When
performing the three-phase test on a palladium catalyst, it is
necessary to run the homogeneous reaction and the solid phase
reaction simultaneously in the same vessel.49-51 This is because
a Reagents and conditions: resin-bound Ar-I, PdEnCat (2.5 mol %),
4-bromoacetophenone (1.0 equiv), n-butyl acrylate (1.5 equiv), n-Bu4NOAc
(3.0 equiv), isopropyl alcohol, 90 °C, 24 h. b Yields determined by GC.
the leaching species is hypothesized to be a Pd(II) intermediate
formed after oxidative addition occurs.37,52
The three-phase test was used to examine the Heck coupling
of 4-bromoacetophenone and n-butyl acrylate, performed under
the optimized conditions of Ley et al., Table 1. We observed
high conversion of 1 to the corresponding cinnamate derivative
for all three PdEnCat catalysts after 24 h at 90 °C, indicating
that an active palladium catalyst leached out of the polyurea
matrix during the reaction. The homogeneous reaction also ran
to completion within the same period, indicating that the same
species may catalyze the reaction on and off the solid support.
We also used the three-phase test to study the Suzuki coupling
of 4-bromoacetophenone and phenylboronic acid. We found that
all three PdEnCat catalysts converted the resin-bound aryl iodide
to the biphenyl derivative in high yield, Table 2. In addition,
control experiments demonstrated that 1 was not functionalized
under Heck or Suzuki reaction conditions when the palladium
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in solution, see refs 49-51. All three of these examples report catalysts
that pass the three-phase test.
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2132 J. Org. Chem., Vol. 71, No. 5, 2006

TABLE 2. Three-Phase Test Results of Suzuki Couplinga,b
FIGURE 3. (A) TEM image of Heck reaction supernatant catalyzed
by PdEnCat 30 in isopropyl alcohol. (B) TEM image of the same sample
using energy filtration specific for Pd.
a Reagents and conditions: resin-bound Ar-I, PdEnCat (5.0 mol %),
4-bromoacetophenone (1.0 equiv), phenylboronic acid (1.5 equiv), n-Bu4NOAc
(3.0 equiv), isopropyl alcohol, 90 °C, 24 h. b Yields determined by GC.
TABLE 3. ICP Analysis of Heck Reaction Filtrates
% Pd
catalyst
solvent
toluene
isopropyl alcohol
DMF
toluene
isopropyl alcohol
DMF
leached
PdEnCat 30
PdEnCat 30
PdEnCat 30
PdEnCat TOTP30
PdEnCat TOTP30
PdEnCat TOTP30
37
0.5
46
42
9
52
which indicate palladium leaching and subsequent formation
of nanoparticles.55 Reactions performed in these solvents are
sluggish when aryl bromides are used as substrates, suggesting
that the formed palladium species are not very active. Induc-
tively coupled plasma (ICP) analysis of the reaction filtrates
indicated that both of these solvents caused substantially higher
levels of palladium leaching compared to that of isopropyl
alcohol, Table 3. It is plausible to conclude that increased
palladium leaching favors deactivation pathways (e.g., pal-
ladium-black formation), resulting in lower activity.56,57 Also,
it is worth mentioning that PdEnCat TOTP30 leached signifi-
cantly more in isopropyl alcohol than PdEnCat 30, suggesting
that the co-encapsulated phosphine ligand promotes palladium
escape.
It has been demonstrated that the powerful and versatile
PdEnCat systems behave as heterogeneous sources for soluble,
catalytically active species during the course of Heck and Suzuki
couplings. This is not to say that catalysis is occurring only in
solution, but there is a solution-phase contribution that one must
be aware of when using these materials. This conclusion is
supported by kinetic behavior displayed by these catalysts, the
observation of nanoparticles by TEM, and the solvent depen-
dence of reactivity and leaching. Although these catalysts are
highly useful, caution must be exercised when considering these
materials, as well as other heterogeneous catalysts, for use in
systems where site isolation is required.
FIGURE 2. Plot of yield vs reaction time for the Heck reaction of
4-bromoacetophenone with n-butyl acrylate at 90 °C in isopropyl
alcohol; base, n-Bu4NOAc; catalyst, (A) PdEnCat 30, (B) PdEnCat
TOTP30, and (C) PdEnCat TPP30.
source was excluded. The observation that both the Heck and
Suzuki reactions fail the three-phase test is strong evidence that
the PdEnCat serves as a reservoir or precatalyst.53 We chose to
examine reaction kinetics coupled with transmission electron
microscopy (TEM) and catalyst decomposition as further means
to support this hypothesis.
Monitoring product formation via GC yielded sigmoidal
kinetic profiles for TPP30 and TOTP30, which is consistent
with previous findings, Figure 2.51 The observation of a
sigmoidal conversion plot is indicative of in situ maturation of
a precatalyst into an active catalyst.54 The induction period may
be related to the additional phosphine ligands retarding the rate
of oxidative addition of the aryl halide.
To further characterize the nature of the catalytic species that
caused the failure of the three-phase test, TEM was used to
analyze the supernatant from the Heck reaction catalyzed by
PdEnCat 30. The reaction mixture was sampled at 85%
conversion, hot filtered, and deposited on a TEM grid. Palladium
nanoparticles in the size range of 5-10 nm were observed, and
the identity of the metal was confirmed using X-ray analysis
and energy filtration imaging, Figure 3.
Experimental Section
General Method for Carrying out the Three-Phase Test:
Heck Reaction. Following the method of Ley et al.,22 4-bromo-
acetophenone (0.050 g, 0.25 mmol), n-Bu4NOAc (0.23 g, 0.75
To determine if leaching is a solvent-dependent process, we
ran the same Heck reaction using either toluene or DMF as
solvent. These reactions yielded dark red solutions upon heating,
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Henderickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285-3288.
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H. M.; de Vries, J. G. AdV. Synth. Catal. 2004, 346, 1812-1817.
(53) Functionalization of resin-bound reagents occurred at roughly the
same rate as with soluble reagents.
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317-341.
J. Org. Chem, Vol. 71, No. 5, 2006 2133

mmol), PdEnCat (15.7 mg, 0.00625 mmol), mesitylene (0.050 mL,
internal standard), Tenta-Gel MB-supported aryl iodide (1; 0.025
g, 0.010-0.015 mmol loading), and isopropyl alcohol (1.25 mL)
were added to a screw-cap vial equipped with a septum. n-Butyl
acrylate (0.054 mL, 0.375 mmol) was added, and the reaction
mixture was warmed to 90 °C. The solution-phase reaction was
monitored via GC. After 24 h, the reaction mixture was transferred
to a syringe equipped with a frit. The insoluble material was washed
thoroughly with H2O (3 × 2 mL), MeOH (3 × 2 mL), EtOAc (3
× 2 mL), THF (3 × 2 mL), and CH2Cl2 (3 × 2 mL). The resin-
bound material was liberated by treatment with 20% v/v TFA in
CH2Cl2 (2.5 mL) and agitated for 30 min. The cleavage solution
was removed, and the resin was washed with CH2Cl2 (3 × 2 mL),
EtOAc (3 × 2 mL), and THF (3 × 2 mL). The combined filtrates
were evaporated, redissolved in THF, and analyzed by GC.
Acknowledgment. We thank John Grazul for help with TEM
analysis, Christopher Simoneau for discussion, and the ARO
DAAD19-02-1-0275 Macromolecular Architecture for Perfor-
mance, the Cornell Center for Materials Research (CCMR,
DMR-0079992), Cornell University, the Dreyfus Foundation,
NSF (SENSORS), and NYSTAR for support.
Supporting Information Available: Representative reaction
conditions, experimental details for the three-phase test, ICP
analysis, and TEM characterization. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO0517904
2134 J. Org. Chem., Vol. 71, No. 5, 2006