N-heterocyclic carbene coordinated heterogeneous Pd nanoparticles as catalysts for suzuki-miyaura coupling

Article abstract of DOI:10.1246/cl.160369

Palladium nanoparticle (Pd NP) catalysts immobilized in a polymer with an N-heterocyclic carbene (NHC) moiety (PICBNHC-Pd) have been developed, wherein the NHC moiety plays dual roles as a crosslinker and a ligand to activate the Pd NPs. The presence of both Pd NPs and NHC was confirmed by STEM/EDS and SR-MAS NMR analyses, respectively. This PICB-NHC-Pd catalyst showed excellent activity in the Suzuki-Miyaura coupling reaction without leaching of Pd. Excellent results were obtained in gram-scale synthesis, and catalyst recovery/reuse experiments were completed without loss of catalyst activity.

Full text of DOI:10.1246/cl.160369

Received: April 15, 2016 | Accepted: April 30, 2016 | Web Released: May 11, 2016
CL-160369
N-Heterocyclic Carbene Coordinated Heterogeneous Pd Nanoparticles
as Catalysts for Suzuki­Miyaura Coupling
Hyemin Min, Hiroyuki Miyamura, and Shū Kobayashi*
The Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
(
E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp)
Palladium nanoparticle (Pd NP) catalysts immobilized in a
polymer with an N-heterocyclic carbene (NHC) moiety (PICB-
NHC-Pd) have been developed, wherein the NHC moiety plays
dual roles as a crosslinker and a ligand to activate the Pd NPs. The
presence of both Pd NPs and NHC was confirmed by STEM/EDS
and SR-MAS NMR analyses, respectively. This PICB-NHC-Pd
catalyst showed excellent activity in the Suzuki­Miyaura coupling
reaction without leaching of Pd. Excellent results were obtained
in gram-scale synthesis, and catalyst recovery/reuse experiments
were completed without loss of catalyst activity.
lized by N-heterocyclic carbene (NHC)-containing copolymers.
The catalysts showed an outstanding ligand acceleration effect in
the Corriu­Kumada­Tamao coupling reaction.11 The NHC moie-
ties in this catalyst have dual roles as a ligand for Ni NPs and a
crosslinker of the polymer support. The copolymer used for the
preparation of this catalyst contains imidazole moieties, which
are converted into NHC during catalyst preparation by simple
operations. They are relatively stable; thus, this catalyst can
compensate for the shortcomings noted above. Herein, we expand
this strategy to Pd NP catalysts and describe the preparation of
immobilized Pd NP catalysts in polymers containing NHC
moieties as ligands and crosslinkers.3
d,12
This catalyst showed
Keywords: Pd nanoparticle catalyst
|
N-Heterocyclic carbene
|
Suzuki–Miyaura cross-coupling reaction
excellent activity in the Suzuki­Miyaura cross-coupling reaction,
wherein the effect of the embedded NHC moieties was critical.
We started with the preparation of Pd NP catalyst in an
imidazole-bearing polymer by following a previously reported
procedure for the formation of the PI(CB)-NHC-Ni catalyst, with
slight modifications (Scheme 1).11 The catalyst was prepared
from two different copolymers: (1) copolymer 1, which contains
styrene and a 1-(4-vinylbenzyl)imidazole moiety; (2) copolymer 2,
comprised of styrene and the alkyl bromide group. Pd(OAc)2
and NaBH4 were used for NP formation as a metal source and
reductant, respectively. After microencapsulation and filtration,
crosslinking between the imidazole moiety and alkyl bromide was
conducted at elevated temperature under neat conditions. This
material was then treated with 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) to generate the NHC (by deprotonation), and synthesize
PICB-NHC-Pd catalyst 3. Swollen-resin magic angle spinning
(SR-MAS) NMR analysis was conducted to probe the formation of
the NHC after DBU treatment using d8-THF as a swelling solvent,
and from the signal change between the catalysts before and after
DBU treatment, the generation of NHC was confirmed (based on
the signals of the imidazolium proton and benzylic proton of
copolymer 1, see the Supporting Information (SI)).1 It was also
confirmed by scanning transmission electron microscopy (STEM)/
energy-dispersive X-ray spectroscopy (EDS) (mapping, area)
analysis that Pd was present as NPs in the polymer support;
mostly as small NPs around 2­3 nm, but small amounts of larger
NPs (10­20 nm) were present (see the SI).
Metal nanoparticles (NPs) are widely used as heterogeneous
catalysts because of their robustness and intrinsic characteristics,
which differ from those of bulk metals and metal complexes. A
diverse range of activities that are derived from many factors such
as support, size, oxidation state, and shape have been noted.1
Among the various kinds of metal NPs, Pd NPs have attracted
much attention as very powerful catalysts because they can be
widely used in a range of reactions, including hydrogenation and
2
cross-coupling reactions.
Although many reactions have been reported with Pd NP
catalysts, ligands are often required to enhance the activity or
3
selectivity for a desired reaction. When ligands are externally
added to Pd NP catalysts, the subsequent recovery of the ligand
is generally difficult and significant leaching problems sometimes
occur because of strong interactions between the ligands and Pd
species. To compensate for these defects, systems that immobilize
the ligands together with Pd NPs on the same support have been
designed.4 When active ligands are immobilized together with
Pd NPs, subsequent recovery of the ligands with the Pd NP
catalysts after the reaction is facilitated, and leaching of Pd can be
suppressed. However, tedious procedures are required to introduce
ligands in supports, especially when the immobilized ligands are
not stable under catalyst preparation steps or during the recovery
processes; for example, phosphine ligands, which may be easily
oxidized. In these cases, additional treatment would be required
­7
1,13
5
a­5c
to regenerate the catalyst;
therefore, development of a stable
and active ligand immobilized catalytic system is challenging
work. Recently, various ligand immobilized Pd NP catalysts were
reported in the Suzuki­Miyaura coupling reaction, which is very
a useful and well-known carbon­carbon bond forming reaction.
In those reports, ligand immobilized Pd NP catalysts showed
higher and enhanced activity compared with the results for Pd NPs
2
m
m
2n
n
Et
2
O
(
dropwise)
then filtration
Pd(OAc)
2
NaBH
reduction
4
+
+
CB
coacervation
Br
O
1
50 oC, neat, Ar
overnight
170 oC, neat
Ar, 6 h
N
O
3
N
wash & dry
crosslinking
water, THF
DCM
Copolymer 1
Copolymer 2
4
,7b,8
without an immobilized ligand.
(
in diglyme)
DBU in THF wash & dry
We have developed polymer-incarcerated metal NP catalysts
PI catalysts) by using polystyrene-based copolymers containing
PICB-NHC-Pd (3)
NHC formation
THF
DCM
(
9
,10
crosslinker moieties with several metals.
Recently, we reported
the synthesis and use of heterogeneous Ni NP catalysts immobi-
Scheme 1. Catalyst preparation.
Chem. Lett. 2016, 45, 837–839 | doi:10.1246/cl.160369
© 2016 The Chemical Society of Japan | 837

Table 1. Screening conditions
Table 2. Substrate scope
Br
PICB-NHC-Pd (3)
Ph
R2
(
x mol% Pd)
X
B(OH)
2
PICB-NHC-Pd (0.25 mol% Pd)
A: K CO (1 equiv), EtOH
C, Ar balloon, 36 h
+
PhB(OH)2
R1
+
R
2
R1
K2CO3 (z equiv), Solvent
o
2
3
80
B : K
50
o
80 C, Ar, 24 h
4
5 (1.2 equiv)
2
CO
3
(2 equiv), DMF
6
4a
5a (y equiv)
6aa
1
o
C, Ar balloon, 36 h
Entry Solvent
x
y
z
6aaa
Leachingb
X = Br (Method A)
OMe
1
Tol/H2O (4:1)
1
1
1.7
1.5
78%
®
OMe
2; 6ab; 82%
OMe
OMe
OMe
2
3
4
5
EtOH/H2O (4:1)
1.7
1.5
99%
97%
96%
87%
ND
ND
ND
ND
0.5
0.25
0.1
1; 6aa; 96%
3; 6bb; 87%
4; 6cb; 66%
5; 6ac; 85%
O
O
6
EtOH
EtOH
0.25
0.25
1.7
1.2
1.5
1
97%
ND
ND
ND
MeO
6
; 6ad; 94%
7; 6cd; 72%
8; 6da; 89%
9; 6eb; 88%
CF
3
10; 6fa; 89%
OMe
7
93%
Quant.
96%)
49%
16%
29%
8c
OMe
OMe
OMe
(
NC
O N
Cl
2
c,d
11; 6gb;79%
12; 6hb; 93%
13; 6ib; 93%
9
0
1
0.49%
5.36%
0.47%
14; 6ja; Quant.
c,e
1
1
c,f
OMe
OMe
OMe
O
2
H N
a
Yield was determined by GC analysis with dodecane as internal
standard; the isolated yield is given in parentheses. Pd leaching was
determined by ICP analysis (detection limit: 0.1­0.5%). Reaction
time: 36 h. PICB-Pd was used instead of PICB-NHC-Pd. PICB-
18; 6kb; Quant.
21; 6mb; 80%
O
15; 6ka; Quant.
O
O
19; 6lb; 76%
b
16; Quant. (gram-scale)
7; 96%~Quant. (recovery and reuse
20; 87% (1.5 equiv Ar-B(OH)2)
1
c
until 3rd run)
d
e
f
OMe
OMe
Pd + IMes¢HCl (1 mol %). PICB-Pd + IPr¢HCl (1 mol %).
N
N
OMe
OMe
22; 6na; 97%
23; 6ob; Quant.
24; 6pb; Quant.
25; 6qb; Quant.
3-Bromotoluene (4a) and phenylboronic acid (5a) were
X = I (Method A)
selected as model substrates, and the Suzuki­Miyaura coupling
reaction was conducted with the prepared catalyst PICB-NHC-Pd
OMe
OMe
OMe
OMe
H
2
N
NC
2
O N
(
3) (Table 1).
Firstly, we conducted screening of bases in a toluene/water
26; 6bb; 91%
27; 6mb; Quant.
28; 6hb; Quant.
29; 6ib; 96%
X = Cl (Method B)
OMe
mixed solvent system at 120 °C, and K2CO3 was found to be a
suitable base (see the SI). When the reaction temperature was
decreased to 80 °C, the yield of the desired product 6aa was 78%
OMe
Cl
O
2
N
O
2
N
2
O N
30; 6ja; Quant.
31; 6ib; 95%
32; 6ia; Quant.
33; 6ic; Quant.
(
Table 1, Entry 1). An almost quantitative yield was obtained
when an ethanol/water mixed solvent system was used at the same
temperature, and Pd leaching did not occur (Entry 2). The use of
an ethanol/water (4:1) solvent system was very effective in this
reaction, and excellent results were obtained even when the catalyst
loading was decreased to 0.25 mol % (Entries 3 and 4). With
First, a range of aryl bromide substrates was examined. When
meta-, para-, and ortho-bromotoluenes 4a­4c, respectively, were
used as substrates, differences in the activities were observed
depending on the position of the substituents, but good-to-
excellent yields of the products were observed in all cases
(Table 2, Entries 2­4). Substituents on the boronic acid also
affected the rate of the reactions. When an electron-withdrawing
substituent was present at the para-position (5d), a higher yield
was obtained than with boronic acids substituted in the meta-
and para-positions with an electron-donating group (5b and 5c)
(Entry 2 vs. 6, and Entry 5 vs. 6). The use of 4-acetylphenyl-
boronic acid (5d) gave an increased yield of the coupling product
with ortho-bromotoluene (4c), compared with that obtained with
3-methoxyphenylboronic acid (5b) (Entry 4 vs. 7). In terms of the
electronic effect on the aryl bromide, the reactions proceeded well
with both electron-donating and electron-withdrawing groups
(Entries 8­13); however, slightly better results were obtained with
electron-withdrawing groups (Entries 12 and 13). When 1-bromo-
4-chlorobenzene (4j) was used as a substrate, only the bromide
moiety reacted and the chloride moiety remained unchanged
(Entry 14). A range of functional groups such as ketone (4k), ester
(4l), and amine (4m) were tolerated in this reaction system (Entries
15 and 18­21). Naphthalene (4n), pyridine (4o), and quinoline
(4p) derivatives also showed excellent yields (Entries 22­24).
When dibromo-containing substrate 4q was used with twice the
0
.1 mol % catalyst, a slight decrease in the yield was observed
(
Entry 5). This reaction also proceeded well in ethanol (Entry 6).
Taking the optimal catalyst loading to be 0.25 mol %, we attempted
to decrease the number of equivalents of phenylboronic acid and
K2CO3. As a result, a yield of 93% was obtained with only 1.2
equivalents of phenylboronic acid and 1 equivalent of K2CO3
(
Entry 7). Furthermore, a quantitative yield of the product was
formed by extending the reaction time to 36 h (Entry 8). For
comparison, when PICB-Pd catalyst, which does not contain an
NHC moiety, was used under the optimized reaction conditions,
only 49% yield of the product was obtained, and a small amount of
Pd leaching was measured (Entry 9). Two types of NHC (IMes¢HCl
and IPr¢HCl) were externally added in the latter reaction with the
PICB-Pd catalyst. In both cases, low yields and Pd leaching were
observed (Entries 10 and 11). From these results, we could confirm
the significant advantages of using the NHC-immobilized catalyst,
not only because the catalyst can be easily recovered and reused,
but also because of the excellent catalytic activity and suppression
of metal leaching achieved using this immobilized system.
Based on the optimized conditions, the substrate scope of the
reaction was surveyed (Table 2).
838 | Chem. Lett. 2016, 45, 837–839 | doi:10.1246/cl.160369
© 2016 The Chemical Society of Japan

amount of boronic acid, a high yield of the disubstituted product
was observed (Entry 25). In the case of aryl iodide, high yields
were obtained with substrates bearing either electron-donating (4b
and 4m) or electron-withdrawing (4h­4j) groups (Entries 26­30).
Generally, cross-coupling reactions of aryl chlorides are
challenging because of the difficulty of achieving an oxidative
3
a) R. Akiyama, S. Kobayashi, Angew. Chem., Int. Ed. 2001, 40,
3469. b) R. Akiyama, S. Kobayashi, J. Am. Chem. Soc. 2003,
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Schäfer, F. Glorius, Angew. Chem., Int. Ed. 2010, 49, 7786.
For immobilized phosphine ligand with Pd NPs, see: a) T.
Shiomi, T. Nakahodo, H. Fujihara, Chem. Lett. 2012, 41, 1700.
b) R. Fareghi-Alamdari, M. G. Haqiqi, N. Zekri, New J. Chem.
4
5
8
a,14
addition step in a catalytic cycle.
Aryl chlorides showed very
low reactivity and almost no reaction occurred under the initially
optimized conditions. Therefore, we attempted to develop reaction
conditions suitable for aryl chlorides (see the SI). Optimal
conditions were found when the reaction was performed at a
higher reaction temperature (150 °C) in DMF (solvent) and with an
increased amount of base. Under these conditions, excellent yields
were obtained with 1-chloro-4-nitrobenzene substrate (4i) (Entries
2
016, 40, 1287.
For phosphinated PI-Pd catalysts, see: a) R. Nishio, M. Sugiura,
S. Kobayashi, Org. Lett. 2005, 7, 4831. b) R. Nishio, M.
Sugiura, S. Kobayashi, Org. Biomol. Chem. 2006, 4, 992. c) R.
Nishio, M. Sugiura, S. Kobayashi, Chem.®Asian J. 2007, 2,
9
2
83. d) T. Inasaki, M. Ueno, S. Miyamoto, S. Kobayashi, Synlett
007, 3209.
3
1­33).
Gram-scale synthesis and experiments focusing on the
recovery and reuse of the catalyst were conducted by using
¤-bromoacetophenone (4k) and phenylboronic acid (5a) as
6
7
For immobilized amine ligand with Pd NPs, see: a) H. Jiang,
X. Sun, Y. Du, R. Chen, W. Xing, Chin. J. Catal. 2014, 35,
1
990. b) M. Saikia, L. Saikia, RSC Adv. 2016, 6, 16937.
4
For amime ligand as stabilizer or capping agent, see: a) S.
Mandal, D. Roy, R. V. Chaudhari, M. Sastry, Chem. Mater.
substrates. Around 1 g of the product was formed under the
optimized conditions (slightly concentrated, Entry 16), and the
catalyst could be successfully recovered and reused. Excellent
yields were obtained until the third run, with outstanding activity
being maintained throughout (Entry 17).
2
004, 16, 3714. b) H. R. Choi, H. Woo, S. Jang, J. Y. Cheon, C.
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In summary, we have developed Pd NP catalysts immobilized
in a polymer with an NHC moiety as a crosslinker, wherein the
NHC moiety in the polymer played an important role as a ligand
to activate the Pd NPs. Both the immobilization and formation
of NHC were confirmed by SR-MAS NMR experiments, and the
formation of Pd NPs was confined by STEM/EDS analysis. This
Pd NP catalyst showed a much higher activity in the Suzuki­
Miyaura cross-coupling reaction than both an immobilized Pd NP
catalyst without a NHC moiety and Pd NP catalysts with externally
added NHC ligands. The PICB-NHC-Pd catalyst could be used for
aryl iodide, bromide, and chloride substrates. Excellent results
were also obtained in gram-scale synthesis and in recovery/reuse
of catalyst experiments. We envisage that this catalytic system
would be expanded to the application of other metal NP catalysts
prepared with NHC-containing copolymers. Detailed investiga-
tions on catalyst structure and the development of further
applications of NHC-containing metal NP catalysts are ongoing.
2
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9
1
This work was partially supported by a Grant-in-Aid for
Science Research from the Japan Society for the Promotion of
Science (JSPS), Global COE Program, The University of Tokyo,
the Ministry of Education, Culture, Sports, Science and Technol-
ogy (MEXT), and the Japan Science and Technology Agency
1
1 J.-F. Soulé, H. Miyamura, S. Kobayashi, J. Am. Chem. Soc.
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(
JST). We also thank Mr. Noriaki Kuramitsu (The University of
Commun. 2014, 50, 3204.
Tokyo) for STEM and EDS analysis.
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Chem. Lett. 2016, 45, 837–839 | doi:10.1246/cl.160369
© 2016 The Chemical Society of Japan | 839