Self-assembled poly(imidazole-palladium): Highly active, reusable catalyst at parts per million to parts per billion levels

Article abstract of DOI:10.1021/ja210772v

Metalloenzymes are essential proteins with vital activity that promote high-efficiency enzymatic reactions. To ensure catalytic activity, stability, and reusability for safe, nontoxic, sustainable chemistry, and green organic synthesis, it is important to develop metalloenzyme-inspired polymer-supported metal catalysts. Here, we present a highly active, reusable, self-assembled catalyst of poly(imidazole-acrylamide) and palladium species inspired by metalloenzymes and apply our convolution methodology to the preparation of polymeric metal catalysts. Thus, a metalloenzyme-inspired polymeric imidazole Pd catalyst (MEPI-Pd) was readily prepared by the coordinative convolution of (NH₄)₂PdCl₄ and poly[(N-vinylimidazole)-co-(N- isopropylacrylamide)₅] in a methanol-water solution at 80 °C for 30 min. SEM observation revealed that MEPI-Pd has a globular-aggregated, self-assembled structure. TEM observation and XPS and EDX analyses indicated that PdCl₂ and Pd(0) nanoparticles were uniformly dispersed in MEPI-Pd. MEPI-Pd was utilized for the allylic arylation/alkenylation/vinylation of allylic esters and carbonates with aryl/alkenylboronic acids, vinylboronic acid esters, and tetraaryl borates. Even 0.8-40 mol ppm Pd of MEPI-Pd efficiently promoted allylic arylation/alkenylation/vinylation in alcohol and/or water with a catalytic turnover number (TON) of 20 000-1 250 000. Furthermore, MEPI-Pd efficiently promoted the Suzuki-Miyaura reaction of a variety of inactivated aryl chlorides as well as aryl bromides and iodides in water with a TON of up to 3 570 000. MEPI-Pd was reused for the allylic arylation and Suzuki-Miyaura reaction of an aryl chloride without loss of catalytic activity.

Full text of DOI:10.1021/ja210772v

Article
pubs.acs.org/JACS
Self-Assembled Poly(imidazole-palladium): Highly Active, Reusable
Catalyst at Parts per Million to Parts per Billion Levels
Yoichi M. A. Yamada,*,† Shaheen M. Sarkar,† and Yasuhiro Uozumi*,†,‡
†RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan
‡Institute for Molecular Science and the Graduate School for Advanced Studies, Okazaki, Aichi 444-8787, Japan
S
* Supporting Information
ABSTRACT: Metalloenzymes are essential proteins with vital
activity that promote high-efficiency enzymatic reactions. To
ensure catalytic activity, stability, and reusability for safe,
nontoxic, sustainable chemistry, and green organic synthesis, it
is important to develop metalloenzyme-inspired polymer-
supported metal catalysts. Here, we present a highly active,
reusable, self-assembled catalyst of poly(imidazole-acrylamide)
and palladium species inspired by metalloenzymes and apply
our convolution methodology to the preparation of polymeric
metal catalysts. Thus, a metalloenzyme-inspired polymeric
imidazole Pd catalyst (MEPI-Pd) was readily prepared by the coordinative convolution of (NH4)2PdCl4 and poly[(N-
vinylimidazole)-co-(N-isopropylacrylamide)5] in a methanol−water solution at 80 °C for 30 min. SEM observation revealed that
MEPI-Pd has a globular-aggregated, self-assembled structure. TEM observation and XPS and EDX analyses indicated that PdCl2
and Pd(0) nanoparticles were uniformly dispersed in MEPI-Pd. MEPI-Pd was utilized for the allylic arylation/alkenylation/
vinylation of allylic esters and carbonates with aryl/alkenylboronic acids, vinylboronic acid esters, and tetraaryl borates. Even
0.8−40 mol ppm Pd of MEPI-Pd efficiently promoted allylic arylation/alkenylation/vinylation in alcohol and/or water with a
catalytic turnover number (TON) of 20 000−1 250 000. Furthermore, MEPI-Pd efficiently promoted the Suzuki−Miyaura
reaction of a variety of inactivated aryl chlorides as well as aryl bromides and iodides in water with a TON of up to 3 570 000.
MEPI-Pd was reused for the allylic arylation and Suzuki−Miyaura reaction of an aryl chloride without loss of catalytic activity.
sites and stabilization of polypeptides.6 Therefore, we
considered that some insoluble self-assembled catalysts of
polymeric imidazole amphiphiles and platinum group metal
INTRODUCTION
Metalloenzymes are supramolecular metal−organic hybrids of
polypeptides and metal ions, which are essential proteins with
■
vital activity to promote high-efficiency enzymatic reactions.1,2
species should offer high catalytic activity as metalloenzymes,
but with much higher reusability; that is, metalloenzyme-
The high catalytic activity of metalloenzymes is attributable to
(1) regulation of the molecular orientation between substrates,
reactants, and the metalloenzyme; (2) cooperative catalysis of
inspired polymeric metal catalysts.
We have reported convoluted polymeric metal catalysts for
organic transformation reactions, in which a soluble linear
functional groups in the metalloenzyme; and (3) regulation of
polymer having multiple ligand groups is noncovalently cross-
the reaction field in the metalloenzyme. To go even further and
linked with transition metals via coordinative or ionic
also ensure catalytic activity, stability, and reusability for safe,
complexation.7 We envisaged how the application of our
nontoxic, sustainable chemistry, and green organic synthesis,
concept to the preparation of metalloenzyme-inspired poly-
the development of polymer-supported metal catalysts is of
particular interest.3,4
Metalloenzymes show the importance of amphipathic
meric imidazole platinum group metal catalysts could overcome
the issues, providing highly active, reusable, heterogeneous, self-
assembled catalysts. Here, we report the full details of the
imidazole units in themselves. Imidazole units in histidine
development of a novel polymeric imidazole-acrylamide
coordinate to metal species to provide their catalytic site, the
palladium catalyst.8 The catalyst was utilized for the allylic
supramolecular tertiary structure of proteins, and their Lewis
arylation/alkenylation/vinylation of allylic esters and carbo-
basicity. Imidazole units themselves also play a role in building
nates with aryl/alkenylboronic acids, vinylboronic acid esters,
the quaternary structure of proteins through ionic interaction
and tetraaryl borates. Even 0.8−40 mol ppm Pd of the catalyst
efficiently promoted the allylic arylation/alkenylation/vinyl-
ation in alcohol and/or water with a catalytic turnover number
and hydrogen-bond formation; thus, polymeric imidazole
ligands are widely used as the building blocks of artificial
metal−organic self-assembled supramolecules for functional
materials including catalysts.5 We focused on one metal-
loprotein, urease, where the bond formation between
imidazoles and nickel species is important for creating catalytic
Received: November 15, 2011
Published: January 16, 2012
© 2012 American Chemical Society
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(TON) of 20 000−1 250 000. This time, we found that the
catalyst efficiently drove the Suzuki−Miyaura reaction of a
variety of inactivated aryl chlorides as well as aryl bromides and
iodides in water with a TON of up to 3 570 000. The catalyst
was reused for the allylic arylation and Suzuki−Miyaura
reaction of an aryl chloride without loss of catalytic activity.
We found that our molecular convolution methodology
provided the globular-aggregated, self-assembled structure of
the catalyst.
observation revealed the formation of palladium nanoparticles
having a diameter of 4.9
2.5 nm. Palladium nanoparticles
could be prepared by reduction using MeOH as a reducing
agent. These results indicate that MEPI-Pd 3 is a metal−
organic composite of the polymeric imidazole 1, PdCl2, and
Pd(0) species including palladium nanoparticles, in which
palladium species are well-dispersed in the composite. The
palladium complexes should act as cross-linkers between the
polymeric imidazoles 1 through Pd−imidazole coordination,
and the imidazole units in 1 could stabilize the Pd nanoparticles
as Lewis bases. Elemental analysis and ICP-AES analysis of the
palladium supported the structure shown in Scheme 1.
Allylic Arylation/Alkenylation/Vinylation of Allylic
Acetates and Carbonates with Tetraarylborates, Aryl/
Alkenylboronic Acid, and Vinylboronic Acid Esters. Since
an insoluble metal−polymer composite MEPI-Pd 3 was readily
prepared and characterized, its catalytic activity and reusability
were examined for allylic arylation/alkenylation/vinylation of
allylic esters with tetraarylborates, aryl/alkenylboronic acid, and
vinylboronic acid esters. While there are numerous reports on
aryl−aryl coupling with aryl boron reagents (Suzuki−Miyaura
reaction), little attention has been paid to the more challenging
allyl−aryl coupling (allylic arylation), which often requires
relatively high reaction temperature with a large amount (1−10
mol %) of catalyst.10−12 We previously reported the allylic
arylation of allylic esters and tetraaryl borates using a
microchannel reactor with a PA-TAP-Pd catalytic membrane.13
However, both the reactivity and substrate generality were
insufficient. The results suggested that the newly developed
catalysts should be applied to the allylic arylation to provide
high catalytic activity and reusability as well as high substrate
tolerance.
RESULTS AND DISCUSSION
■
Preparation of Metalloenzyme-Inspired Polymeric
Imidazole Pd Catalyst (MEPI-Pd). A novel metalloenzyme-
inspired polymeric imidazole Pd catalyst (MEPI-Pd) was
readily prepared from an amphiphilic acrylamide-imidazole
polymer and Pd(II) species. Thus, when the coordinative
convolution of poly[(N-vinylimidazole)-co-(N-isopropylacryla-
mide)5]9 (1; 2 mol equiv imidazole) and (NH4)2PdCl4 (2; 1
mol equiv Pd) was performed in a methanol/water solution at
80 °C for 30 min, MEPI-Pd 3 was precipitated out as a brown
powder at a yield of 92% (Scheme 1). While polymer 1 was
Scheme 1. Preparation of Metalloenzyme-Inspired
Polymeric Imidazole Pd Catalyst (MEPI-Pd) 3 and Photo
Images of 1 (left) and MEPI-Pd 3 (right)
The allylic arylation of cinnamyl acetate (4a) and sodium
tetraphenylborate (5a) using 40 mol ppm Pd (0.004 mol % Pd)
of MEPI-Pd 3 was selected for the examination of catalytic
activity and reusability (Scheme 2). Thus, when the reaction of
4a and 5a was carried out in i-PrOH−H2O with 40 mol ppm
Pd (0.004 mol % Pd) of MEPI-Pd 3 at 50 °C, the reaction
proceeded smoothly to quantitatively give 1,3-diphenylpropene
(6a) in 4 h. The turnover number and frequency were 25 000
and 6250 h−1, respectively, which are the highest numbers for
allylic arylation. In contrast, the reaction without catalysts or
with the polymer 1 did not proceed. Moreover, MEPI-Pd 3 was
reused five times without any loss of catalytic activity to
quantitatively give 6a. The coupling reaction with the reused
(fifth) catalyst provided no leaching of Pd species in the
reaction mixture (ICP-AES analysis; detection limit 5 ppb Pd;
>99.5% of Pd was retained in 3). SEM, TEM, and HR-TEM
observation and XPS analysis of fresh MEPI-Pd 3 and reused
MEPI-Pd indicated that the catalyst was undamaged and
unchanged under the reaction conditions (Figure 2). XPS
analysis of the Pd3d5/2 showed a major peak at 336 eV and a
minor peak at 334 eV, which were assigned as Pd(II) as a major
species and Pd(0) as a minor species, respectively. The
proportion is similar to that of the fresh MEPI-Pd (Figure 2,
bottom vs top). HR-TEM showed that the mean diameter of
the palladium nanoparticles in the fresh and reused (fifth)
catalyst was 4.9 2.5 and 4.8 2.4 nm, respectively. Pd(0)
species were intact and did not aggregate during the recycling
reactions.
soluble in water, methanol, DMF, THF, CH2Cl2, MEPI-Pd 3
was hardly soluble in water, methanol, DMF, EtOAc, CH2Cl2,
and hexane.
Low-resolution SEM observation (×1800) showed a lump of
3 with a width of 50 μm. As shown in Figures 1 and 2, SEM
images revealed that the precipitates formed a globular-
aggregated, self-assembled structure similar to the quaternary
structure of proteins. The globules ranged from 100 to 1000
nm in diameter and aggregated to construct a mesoporous
suprastructure. EDX/SEM mapping images and an EDS/SEM
image showed that both Pd (green dots) and Cl (red dots)
species were uniformly dispersed in the polymeric material
(Figure 1). C−N stretching absorption of 1 and 3 in IR was
observed at 1548 and 1530 cm−1, respectively. These results
suggest that polymeric imidazole units coordinate to palladium
species. XPS analysis of the Pd3d5/2 showed a major peak at
336 eV and a minor peak at 334 eV, which were assigned as
Pd(II) as a major species and Pd(0) as a minor species,
respectively (Figure 2). TEM and high-resolution TEM
Since the catalytic activity and reusability were satisfactory, a
variety of allylic acetates with tetraarylborates were utilized for
the allylic arylation with 40 mol ppm Pd of MEPI-Pd 3 (Table
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Figure 1. SEM and EDX/SEM images of MEPI-Pd 3: (top left) low-resolution SEM image (bar scale 10 μm), (top center) SEM image (bar scale 1
μm), (top right) EDX image, (bottom left) SEM image for elemental mapping, (bottom center) mapping image of Pd (green dots), and (bottom
right) mapping image of Cl (red dots) (bar scale 10 μm).
Figure 2. HR-SEM, XPS, TEM (90 kV), and HR-TEM (200 kV) images (from left to right) of MEPI-Pd 3 before use (top) and after the fifth reuse
(bottom).
1). Thus, the reaction of 4a and 5a in i-PrOH−H2O or in water
without using any organic solvents proceeded smoothly to give
6a at a yield of 99% and 98%, respectively (entries 1 and 2).
The reaction of phenyl vinyl carbinol ester 4b gave 6a at a yield
of 96% (entry 3). Electron donating and withdrawing group
substituted cinnamyl esters 4c−g with substituted tetraaryl
borates 5a−d were efficiently converted to the corresponding
products 6b−i at a yield of 93−98% (entries 4−11).
substituted tetraaryl borates 5a−d to quantitatively yield the
corresponding coupling products 6j−p (entries 12−19). The
reaction of alkyl vinyl carbinol esters must proceed via the
corresponding π-allylpalladium intermediate bearing the β-sp3-
hydride, which often suffers from β-hydride elimination under
palladium-catalyzed conditions to give undesirable 1,3-dienes.11
However, no trace of 1,3-dienes was observed in the reactions.
This palladium-catalyzed (40 mol ppm Pd of the catalyst)
reaction of 4i was also performed in water without using any
organic solvents to quantitatively give 6k (entry 14).
It is interesting to note that the methyl-, ethyl-, and
hexylvinyl carbinol esters 4h−k underwent palladium-catalyzed
(40 mol ppm Pd of the catalyst) allyl−aryl coupling with
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Scheme 2. Recycling of MEPI-Pd for Allylic Arylation of 4a
with 5a
Table 1. Allylic Arylation of Allylic Acetates with
Tetraarylborates
a
Furthermore, the coupling of aliphatic 2-alkenyl acetates is
more challenging than that of cinnamyl acetates in terms of
reactivity. However, geranyl acetate (4l), neryl acetate (4m),
prenyl acetate (4n), and 2-hexenyl acetate (4o) efficiently led
to the corresponding phenylated compounds 6q−t at a yield of
96−98% (entries 20−24). Isomerization was not observed in
the reactions, and water was used as a reaction solvent (entry
24). Alicyclic acetates 4p and 4q were readily converted to the
corresponding products 6u and 6v at a yield of 96% (entries 25
and 26); the reaction of cis-4q proceeded via net inversion to
give trans-5-methoxycarbonyl-3-phenyl-1-cyclohexene (6v) as a
single diastereomer (entry 26).
Since MEPI-Pd readily drove the allylic arylation of allylic
acetates, here we decided to apply the MEPI-Pd-catalyzed
system to the allylic arylation of allylic carbonates (Table 2).
Thus, the reaction of methyl cinnamyl carbonate (7a) and 5a
was performed with 40 mol ppm Pd (0.004 mol % Pd) of
MEPI-Pd 3 in aqueous i-PrOH at 50 °C for 4 h to afford 6a at a
yield of 97% (entry 1), where the turnover number and
frequency of 3 were also 24 250 and 6060 h−1, respectively. The
reaction rate of the cinnamyl acetate 4a and carbonate 7a was
similar (Table 1, entry 1 vs Table 2, entry 1). The reaction of
phenyl vinyl carbinol carbonate 7b gave 6a at a yield of 97%
(entry 2). It is also noteworthy that the allylic arylation of
methyl-, ethyl-, and hexylvinyl carbinol carbonates 7c−f also
proceeded smoothly to quantitatively give the corresponding
coupling products 6j−m (entries 3−6). In these reactions as
well, no trace of 1,3-dienes was observed. A 2-alkenyl
carbonate, methyl neryl carbonate (7g), was readily converted
to the phenylated product 6r at a yield of 98%. These results
indicated that a variety of allylic carbonates undergo the allylic
arylation with 40 mol ppm Pd of MEPI-Pd under mild
conditions.
The insoluble self-assembled catalyst MEPI-Pd 3 efficiently
promoted allylic substitution with aryl/alkenylboronic acids,
which are versatile and readily available boron reagents (Table
3). Thus, the allylic phenylation of 4a with phenylboronic acid
(8a) with methanolic or aqueous KF solution at 70 °C
proceeded smoothly to quantitatively yield 6a (entries 1 and 2).
Substituted arylboronic acids 8b−d readily underwent allylic
arylation under similar conditions to give 6h,w,x at a yield of
98% (entries 3−5). The alkyl vinyl carbinol esters 4i,k, neryl
acetate (4m), and cyclohexenyl acetate (4p) were converted to
the corresponding alkenes 6k,m,r,u at 97−99% yield (entries
6−9). Allylic alkenylation, the allyl−alkenyl coupling reaction,
of allylic acetates with alkenylboronic acids is more challenging
in terms of reactivity as well as isomerization of olefins
compared to allylic arylation.14 However, the reaction of 4a
with (E)-1-pentenylboronic acid (8e) proceeded smoothly with
40 mol ppm Pd of MEPI-Pd under similar conditions to give
(1E,4E)-1-phenyloctadiene (9a) at a yield of 98%, where no
a
Conditions: 4 (0.5 mmol), 5 (1 mmol), MEPI-Pd 3 (20 nmol), i-
b
PrOH−H2O (0.75 mL each) or H2O (1.5 mL), 50 °C, 4 h. The
reaction was carried out in water for 8 h. The reaction was carried out
in water for 24 h.
c
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a
Table 2. Allylic Arylation of Allylic Carbonates with 5a
Table 3. Allylic Arylation/Alkenylation of Allylic Acetates or
Allylic Carbonates with Arylboronic/Alkenylboronic Acid
Derivatives
a
a
Conditions: 7 (0.5 mmol), 5a (1 mmol), MEPI-Pd 3 (20 nmol), i-
PrOH−H2O (0.75 mL each), 50 °C, 4 h.
isomerization was observed (entry 10). Neryl acetate (4m) was
also cross-coupled with the alkenylboronic acid 8e to afford the
triene 9b at a yield of 98% (entry 11). Furthermore, the allylic
vinylation proceeded smoothly under similar conditions. Thus,
the allylic vinylation of 4a,h,i with dibutyl vinylboronate (8f)
and vinylboronic acid pinacol ester (8g) yielded the
corresponding exo-dienes 9c−e at 95%, 95%, and 92% yield
without the formation of isomers (entries 12−14). The
catalytic system was also applied to the reaction of allylic
carbonates. Cinnamyl carbonate (7a), phenyl vinyl carbinol
carbonate (7b), and neryl carbonate (7g) underwent arylation
under similar conditions to afford the corresponding
phenylated products 6a and 6r at a yield of 98% (entries
15−17). In the reaction of 7g with 5a, a hot filtration test was
conducted to prove that the insoluble catalyst promotes the
reaction under heterogeneous conditions (Figure 3).15 The
reaction of 7g with 5a was performed under identical
conditions as that in Table 3, entry 17. After 2 h, MEPI-Pd 3
was subjected to membrane filtration (ϕ = 0.45 μm) at 70 °C,
and the resulting filtrate was stirred at 70 °C for an additional 2
h. As shown in Figure 3, GC analysis showed the yield of 6r
after the filtration. The results indicate that the reaction
proceeded under heterogeneous conditions. Moreover, as
shown in Figure 2, ICP-AES analysis proved that there was
no leaching of Pd in the reaction mixture (detection limit 5 ppb
Pd; >99.5% of Pd was retained in 3). Ultimately, MEPI-Pd
promoted the reaction under heterogeneous conditions without
leaching of Pd species.
a
Conditions: 4 or 7 (0.5 mmol), 8 (0.6 mmol), 3 (20 nmol), MeOH
b
(1.5 mL), 70 °C, 3 h. The reaction was carried out in water for 60 h.
Since MEPI-Pd 3 promoted efficient allylic arylation and
alkenylation without leaching of Pd under heterogeneous
conditions, 0.8 mol ppm Pd of MEPI-Pd was used for the
reaction of 4a and 5a (Scheme 3). We found that the desired
coupling product 6a was quantitatively obtained in 12 h at 50
°C, in which the TON and the turnover frequency (TOF) were
more than 1 million (1 250 000) and 104 000 h−1, respectively.
To the best of our knowledge, this is the highest TON and
TOF for allylic arylation.
Figure 3. Hot filtration test of allylic arylation of 7g with 5a (vs Table
3, entry 17).
Plausible Catalytic Pathway. The plausible reaction
pathway is as follows (Figure 4).12 The oxidative addition of
an allylic acetate (carbonate) to Pd(0) species A proceeds to
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ditions.18,19 Although polymer-supported alkyl phosphine
ligands have been used, they generally are readily decomposed
(oxidized) under atmospheric conditions. The progress of
heterogeneous catalysts for this purpose is still in the
development stage in terms of both high catalytic activity and
reusability. Since MEPI-Pd 3 demonstrated its high catalytic
activity and reusability for the allylic arylation, the big challenge
for us was its application to the Suzuki−Miyaura reaction of
aryl chlorides as well as aryl bromides and iodides in water (on
water) under aerobic conditions with high catalytic activity and
reusability.
Scheme 3. Allylic Arylation of 4a with 5a Catalyzed by 0.8
mol ppm Pd of MEPI-Pd 3
As shown in Scheme 4, when the Suzuki−Miyaura reaction
of a less reactive and more electron-rich aryl chloride, 4-
Scheme 4. Suzuki−Miyaura Reaction of an Electron-Rich
Aryl Chloride 10a with 8a in Water
chloroanisole (10a), with phenylboronic acid (8a) was carried
out with 0.1 mol % Pd of MEPI-Pd 3 at 100 °C for 20 h under
aerobic and aqueous conditions, the reaction proceeded
smoothly to afford 4-methoxybiphenyl (11a) at a yield of
98%. The insoluble catalyst was readily recovered by filtration
and reused four times to give 11a at a yield of 99% (second
use), 97% (third use), 96% (fourth use), and 97% (fifth use).
The reaction proceeded under air, which generally oxidizes
alkylphosphine ligands and deactivates alkylphosphine Pd
catalysts. ICP-AES analysis of the reaction mixture in the fifth
reaction showed no detection of Pd species (detection limit 5
ppb Pd; >99.95% of Pd were retained in 3).
Figure 4. Plausible catalytic cycle of allylic arylation of 4q with 5a.
give the π-allylpalladium intermediate B, which undergoes
transmetalation to afford the π-allyl(aryl)palladium intermedi-
ate C. Reductive elimination provides the corresponding
product and the regeneration of A. In the reaction of cis-4q
with 5a, trans-6v was yielded as a single diastereomer. This
result suggests that the oxidative addition proceeds via
inversion to give trans-B and the transmetalation proceeds via
retention to afford trans-6v.
Since catalytic activity and reusability were also satisfactory,
the Suzuki−Miyaura reaction of a variety of aryl chlorides was
investigated (Table 4). Thus, the reaction of 10a with 8a
afforded 11a at a yield of 98% (entry 1). The coupling of the
electron-rich 4-chlorotoluene (10b) also proceeded smoothly
under similar conditions to give 4-methylbiphenyl (11b) in
93% yield (entry 2). The electron-poor 4-chloroacetophenone
(10c) and 4-chlorobenzonitrile (10d) were readily converted to
the corresponding biaryl products 11c and 11d in 90% and
95% yield, respectively (entries 3 and 4). Phenol and aniline
moieties did not disturb the coupling; the reaction of 4-
chlorophenol (10e) and 4-chloroaniline (10f) gave the desired
biaryls 11e and 11f in 94% and 95% yield, respectively (entries
5 and 6). The cross-coupling of aryl chlorides 10a−f with 4-
tolylboronic acid (8h) was carried out under similar conditions
to afford the corresponding 4-methylbiaryl products 11g−l in
89−94% yield (entries 7−12). The electron-rich boronic acid
8c was coupled with aryl chlorides 10b−f to give the
corresponding 4-methoxybiaryl compounds and 11g,m−p in
88−94% yield (entries 13−17). An electron-sufficient 3,4-
dimethoxyphenylboronic acid (8d), an o-substituted 2-
tolylboronic acid (8i), and a bulky 2-naphthylboronic acid
(8j) were also reacted with aryl chlorides 10c,e,b to give the
corresponding couplings 11q−s in 89−92% yield (entries 18−
20).
The ability of the imidazole ligand to coordinate with the
palladium species is categorized as “moderate” in the HSAB
theory16 and is lower than that of phosphine ligands. One of
the imidazole ligands should readily dissociate from the
palladium species in the catalytic route from A to B to
efficiently promote the catalytic reaction. Since the catalyst 3
was prepared as the most thermodynamically stable form and
the imidazole ligands were connected by the main-chain
polymer backbone, the imidazole ligand readily associated with
the palladium species in the catalytic route from C to A to
stabilize the catalyst. We believe that the efficient dissociation−
transformation−association process in the catalytic reaction
overcomes the issues of low catalytic activity and reusability to
provide a highly active and reusable heterogeneous catalytic
system.
The Suzuki−Miyaura Reaction of Aryl Chlorides,
Bromides, and Iodides. The Suzuki−Miyaura cross-coupling
is among the most important reactions for synthetic organic
chemistry and process chemistry which is applied to the
preparation of pharmaceutical compounds, solar cells, organic
conductors, and a variety of functional materials.17 One
contemporary topic is the development of highly active and
reusable solid-phase catalysts for the Suzuki−Miyaura reaction
of aryl chlorides, versatile and readily available substrates, but
inactivated in water (on water) under atmospheric con-
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a
Table 4. Suzuki−Miyaura Reaction of Aryl Chlorides
entry
R1 10
R2 8
time (h)
11
yield (%)
1
4-OCH3 10a
4-CH3 10b
4-COCH3 10c
4-CN 10d
H 8a
8a
20
10
9
11a
11b
11c
11d
11e
11f
98
93
90
95
94
95
92
91
89
93
94
94
91
88
94
93
92
92
90
89
2
3
8a
4
8a
9
5
4-OH 10e
8a
9
6
4-NH2 10f
4-OCH3 10a
4-CH3 10b
4-COCH3 10c
4-CN 10d
8a
9
7
4-CH3 8h
12
12
12
8
11g
11h
11i
8
8h
9
8h
10
11
12
13
14
15
16
17
18
19
20
8h
11j
4-OH 10e
8h
8
11k
11l
4-NH2 10f
4-CH3 10b
4-COCH3 10c
4-CN 10d
8h
8
4-CH3O 8c
8
11g
11m
11n
11o
11p
11q
11r
11s
8c
8
8c
8
4-OH 10e
8c
8
4-NH2 10f
4-COCH3 10c
4-OH 10e
8c
8
3,4-(CH3O)2 8d
2-CH3 8i
12
12
12
4-CH3 10b
2-naphB(OH)2 (8j)
a
Conditions: 10 (0.5 mmol), 8 (0.6 mmol), 3 (500 nmol), TBAF (1.0 mmol), K2CO3 (1.0 mmol), H2O (1.5 mL), 100 °C.
a
Table 5. Suzuki−Miyaura Reaction of Aryl Bromides
entry
R1 12
time (h)
11
yield (%)
1
2
3
4
5
4-OCH3 12a
4-CH3 12b
4-CN 12c
3
11a
11b
11d
11t
97
98
98
97
98
2.5
2
3-NH2 12d
4-C4H9 12e
2
2.5
11u
a
Conditions: 12 (0.5 mmol), 8a (0.6 mmol), 3 (20 nmol), TBAF (1.0 mmol), K2CO3 (1.0 mmol), H2O (1.5 mL), 100 °C.
Clearly, the Suzuki−Miyaura coupling of aryl bromides
methylbiphenyl (11b) at a yield of 96% (TON 15 000). The
reaction of 4-chloroacetophenole (10c) and 4-chlorobenzo-
phenone (10d) with 8a also proceeded with 66 mol ppm Pd of
MEPI-Pd to give the corresponding biaryls 11c and 11d in 98%
and 96% yield, respectively. Moreover, the coupling of 4-
iodotoluene (13) with 8a proceeded with 0.28 mol ppm Pd
(280 ppb, 0.000 028 mol %) of MEPI-Pd 3 to quantitatively
give the cross-coupling product 11b, whereas the same reaction
did not proceed without the catalysts. The TON and TOF in
this reaction were 3 570 000 and 119 000 h−1, respectively,
which are, as far as we know, the highest TON and TOF for the
heterogeneous catalyst-promoted Suzuki−Miyaura coupling.
Scheme 6 shows the effect of the imidazole unit and the
polymeric backbone in the allylic arylation and the Suzuki−
Miyaura coupling of an aryl chloride. Thus, MEPI-Pd (40 mol
ppm Pd) drove the allylic arylation of 4a with 8a to afford 6a
proceeded more efficiently (Table 5). Thus, the reaction of an
electron-sufficient 4-bromoanisole (12a) was carried out with
40 mol ppm Pd of MEPI-Pd 3 under aqueous and aerobic
conditions to quantitatively give 4-methoxybiphenyl (11a)
(entry 1). Methyl-, nitrile-, amino-, and n-butyl-substituted aryl
bromides were readily reacted with 8a under similar conditions
to quantitatively give the corresponding biaryl compounds, in
which TON and TOF were up to 25 000 and 12 500 h−1,
respectively (entries 2−5).
To exhibit the highest catalytic activity for the heterogeneous
catalyst-promoted Suzuki−Miyaura coupling, the reaction of
aryl chlorides and iodide was demonstrated (Scheme 5). We
found that the reaction of an inactivated, less reactive 4-
chlorotoluene (10b) with 8a was carried out with 66 mol ppm
Pd of MEPI-Pd 3 under otherwise similar conditions to give 4-
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Journal of the American Chemical Society
Article
backbone provide extremely high catalytic activity. It should be
emphasized that the concept for the preparation of metal-
loenzyme-inspired polymeric metal catalysts will be important
for designing highly active and reusable catalysts.
Scheme 5. Suzuki−Miyaura Reaction with High TON and
TOF in Water
CONCLUSIONS
■
We developed a highly active, reusable, self-assembled catalyst
of poly(imidazole-acrylamide) and palladium species inspired
by metalloenzymes and applied our convolution methodology
to the preparation of polymeric metal catalysts. The metal-
loenzyme-inspired polymeric imidazole Pd catalyst (MEPI-Pd)
was readily prepared by the coordinative convolution of
(NH4)2PdCl4 and poly[(N-vinylimidazole)-co-(N-isopropyla-
crylamide)5] in a methanol/water solution. MEPI-Pd (0.8−40
mol ppm Pd) promoted the allylic arylation/alkenylation of
allylic acetates and carbonates with tetraarylborates, arylboronic
acid, and alkenyl boron reagents in alcohol and/or water with a
catalytic TON of 20 000−1 250 000. Moreover, MEPI-Pd
efficiently drove the Suzuki−Miyaura reaction of a variety of
inactivated aryl chlorides as well as aryl bromides and iodides
with aryl boron reagents in water with a TON of up to 3 570
000. MEPI-Pd was reused for the allylic arylation and Suzuki−
Miyaura reaction of an aryl chloride without loss of catalytic
activity. We found that our molecular convolution methodology
provided the globular-aggregated, self-assembled structure of
MEPI-Pd.
ASSOCIATED CONTENT
* Supporting Information
Scheme 6. MEPI-Pd vs PA-TAP-Pd and [(NH4)2PdCl4 + N-
Me-imdazole]
■
S
Experimental details, compound data, and NMR charts. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
ymayamada@riken.jp; uo@ims.ac.jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the RIKEN ASI Advanced Technology Support
Division, the Chemical Analysis Team for elemental (Dr.
Yoshio Sakaguchi), TEM (Ms. Tomoka Kikitsu), XPS (Dr.
Aiko Nakao), and ICP (Dr. Yoshio Sakaguchi) analyses,
respectively, and Ms. Aya Ohno (our team) for measurement of
SEM and EDS. We gratefully acknowledge financial support
from JSPS (Grant-in-Aid for Scientific Research #20655035;
Grant-in-Aid for Scientific Research on Innovative Areas
#2105) and RIKEN ASI (Fund for Seeds of Collaborative
Research).
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