Polymer-supported electron-rich oxime palladacycle as an efficient heterogeneous catalyst for the Suzuki coupling reaction

Article abstract of DOI:10.1002/adsc.201300499

Various electron-rich oxime palladacycle resins designed as heterogeneous catalysts were employed for the Suzuki coupling reaction of aryl halides with arylboronic acids. The electron-richness of the oxime ligand was controlled by the substituted alkoxy groups. Evaluation based on the electronic effect of the catalysts revealed that the alkoxy-substituted oxime palladacycle resins showed better catalytic activity than palladated Kaiser oxime resin in the Suzuki coupling reactions and that the catalytic activity of oxime palladacycle resins increased as the electron-richness of oxime ligand increased. The most electron-rich oxime palladacycle resin exhibited an excellent catalytic performance for the synthesis of both biaryl and heterobiaryl compounds, despite its heterogeneous system. As a practical application of the catalyst, a valsartan precursor was synthesized in high yield under mild conditions. The electron-rich oxime resin could also be reused for up to 5 cycles while maintaining good catalytic activity in the Suzuki coupling reaction.

Full text of DOI:10.1002/adsc.201300499

FULL PAPERS
DOI: 10.1002/adsc.201300499
Polymer-Supported Electron-Rich Oxime Palladacycle as an
Efficient Heterogeneous Catalyst for the Suzuki Coupling
Reaction
a
b
a
a
Hong-Jun Cho, Sungwon Jung, Saerom Kong, Sung-Jun Park,
c,
a,
Sang-Myung Lee, * and Yoon-Sik Lee *
School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea
Fax : (+82)-2-880-1604; phone: (+82)-2-880-7073; e-mail: yslee@snu.ac.kr
Department of Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National
University, Suwon 443-270, Republic of Korea
Department of Chemical Engineering, Kangwon National University, Kangwon-Do 200-701, Republic of Korea
Fax : (+82)-33-251-3658; phone: (+82)-33-250-6335; e-mail: sangmyung@kangwon.ac.kr
a
b
c
Received: June 7, 2013; Revised: December 7, 2013; Published online: March 11, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300499.
Abstract: Various electron-rich oxime palladacycle an excellent catalytic performance for the synthesis
resins designed as heterogeneous catalysts were em- of both biaryl and heterobiaryl compounds, despite
ployed for the Suzuki coupling reaction of aryl hal- its heterogeneous system. As a practical application
ides with arylboronic acids. The electron-richness of of the catalyst, a valsartan precursor was synthesized
the oxime ligand was controlled by the substituted in high yield under mild conditions. The electron-
alkoxy groups. Evaluation based on the electronic rich oxime resin could also be reused for up to 5
effect of the catalysts revealed that the alkoxy-substi- cycles while maintaining good catalytic activity in the
tuted oxime palladacycle resins showed better cata- Suzuki coupling reaction.
lytic activity than palladated Kaiser oxime resin in
the Suzuki coupling reactions and that the catalytic
activity of oxime palladacycle resins increased as the Keywords: electron-rich ligands; heterogeneous cata-
electron-richness of oxime ligand increased. The lysts; oxime palladacycles; Suzuki coupling reaction;
most electron-rich oxime palladacycle resin exhibited valsartan synthesis
Introduction
Although oxime palladacycles were successfully
demonstrated in various homogeneous CÀC coupling
[
1]
In recent years, palladacycles have been developed reactions, they showed problems related to the sepa-
as efficient catalysts to increase the stability and activ- ration and recycling of the catalyst. It is therefore
ity of the palladium complex for CÀC coupling reac- necessary to develop a heterogeneous catalytic system
[2]
tions. Ever since phosphapalladacycles had been instead of a homogeneous one for the efficient recov-
[10]
highlighted by Herrmann for the Heck and Suzuki re- ery and reuse of the catalyst for green processes.
[3]
[4]
[5]
actions, various kinds of phosphorus-, nitrogen-,
Corma and co-workers covalently immobilized oxime
have palladacycles on solid supports of high surface area as
[6]
[7]
sulfur-,
and oxygen-derived palladacycles
emerged as promising catalysts with high turnover heterogeneous catalysts for the Suzuki reaction. On
numbers (TONs) in numerous CÀC coupling reac- silica supports, the oxime palladacycle complex was
tions. Nꢀjera and co-workers, in particular, reported covalently anchored, maintaining its catalytic activi-
[
11]
pioneering work on oxime palladacycles, which are ty.
PS (polystyrene)- and PEA [poly(ethylene
robust and highly active palladium catalysts for vari- glycol) dimethacrylate]-supported oxime palladacycles
[
12]
ous coupling reactions, such as the Heck, Suzuki, were also prepared by radical polymerization. Very
Stille, Sonogashira, Ullmann, and cycloannulation re- recently, Nꢀjera and co-workers prepared a polymer-
[8]
actions. These oxime palladacycles possess remark- supported oxime palladacycle using Kaiser oxime
[
13]
able air, moisture, and thermal stability with excellent resin for the Heck reaction. The palladated Kaiser
[
9]
TONs in organic and aqueous solvent systems.
oxime resin could be reused with low Pd leaching. In
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Polymer-Supported Electron-Rich Oxime Palladacycle
different approaches, a coordination method on PVP palladacycles. To this end, a series of electron-rich
resin and a self-supporting method via star-shaped li- oxime palladacycles immobilized on PS resin was syn-
gands through Pd-chloro bridges were utilized to im- thesized as heterogeneous catalysts for the efficient
[
14]
mobilize oxime palladacycles.
Suzuki coupling reaction. Unlike palladated Kaiser
[
13]
In order to enhance the catalytic activity of Pd oxime resin, alkoxy-substituted oxime groups were
complexes for coupling reactions, new ligand systems used for the electron-rich palladated oxime resin. The
have been developed, or the conventional ligands degree of electron-richness of the oxime ligand was
[
15]
have been modified.
The bulkiness and electron- controlled by the number of alkoxy groups. The cata-
richness of the ligands play important roles in achiev- lytic activity of the palladated oxime resins was evalu-
ing efficient catalytic activity with Pd. In the Suzuki– ated in the Suzuki coupling reaction of aryl halides
Miyaura reaction, bulky ligands accelerate the reduc- (Cl, Br, I) with phenylboronic acid. Furthermore,
tive elimination step, while an electron-rich ligand im- a three-alkoxy-substituted oxime palladacycle resin
proves the insertion ability of Pd in the oxidative ad- was applied to the synthesis of a valsartan precursor
dition step, which is a key step in the catalytic as a synthetic drug with a biaryl moiety. Lastly, the re-
[16]
cycle.
As these two factors promote the catalytic usability of the catalysts was examined by carrying
performance and increase the stability of Pd in the out the Suzuki coupling reaction of 4-bromoanisole
Suzuki coupling reactions, various combinations of with phenylboronic acid five times.
bulky and electron-rich ligands such as aryl-substitut-
ed NHCs and bulky biarylphosphine ligands have
[17]
been developed. In an oxime palladacycle system, Results and Discussion
the electron-richness of the ligand can be tuned with
modifications of the substituents on acetophenone or Preparation of Electron-Rich Oxime Palladacycle
benzophenone moieties. Although the catalytic effects Resins
of substituents at the para position of acetophenone
[
9a]
oxime or benzophenone oxime have been reported,
Three types of hydroxyacetophenones were chosen as
an in-depth study on oxime palladacycles for CÀC oxime precursors to prepare polymer-supported
coupling reactions has never been reported in terms oxime palladacycles with different degrees of elec-
of electronic effects.
tron-richness. As shown in Scheme 1, hydroxyaceto-
We have focused on the synthesis of electron-rich phenone derivatives were immobilized on chloro-
oxime ligands on resin supports and supported oxime methyl-polystyrene (CM PS) in the presence of
Scheme 1. Preparation of palladated oxime resins from CM PS resin.
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Figure 1. SEM images of CM PS resin, Kaiser oxime resin, and palladated oxime resins (4a–4d).
NaOCH . The ketone group was converted to an these results by indicating that the oxidation state of
3
oxime group by reaction with excess hydroxylamine Pd is +2 on the resins. A Pd peak (Pd 3d5) was found
and pyridine. The resulting oxime group mainly exist- at 337.77 eV, which corresponds to Pd(II) (see the
[
20]
ed as the (E)-isomer which is thermodynamically Supporting Information).
more stable than the corresponding (Z)-isomer.
Hence, Pd atoms were
[
18]
immobilized successfully on the oxime palladacycle
Loading levels of the oxime group, which were deter- resin as a chloro bridged complex in the +2 state.
À1
mined by nitrogen analysis, were 1.50 mmolg (3a), The amount of immobilized Pd on the palladated
À1
À1
1
.50 mmolg (3b), and 0.96 mmolg (3c), respective- oxime resins was quantified by ICP-AES. The loading
ly. The chemical conversions from CM PS to the levels of Pd on each resin and the loading yields were
À1
À1
oxime resin were verified by FT-IR analysis (2a–2c: 4a: 0.11 mmolg (29%), 4b: 0.14 mmolg (72%), 4c:
À1
À1
ketone band, 3a–3c: hydroxy band and oxime band, 0.13 mmolg (67%), and 4d: 0.05 mmolg (13%)).
see the Supporting Information).
Although 4a and 4d resins showed over 90% of Pd
adsorption, low Pd loading yields were obtained (see
[
19]
The oxime resins (3a–3c) and Kaiser oxime resin,
as a control, were treated with lithium tetrachloropal- the Supporting information). The reason for the dif-
ladate (Li PdCl ) in THF, and were shaken at room ference between Pd adsorption and final Pd loading
2
4
temperature for 6 h. During the formation of Pd com- yield is that unbound Pd or weakly coordinated Pd
plex, resin 3c showed the fastest absorption rate of Pd might be removed during the Soxhlet washing pro-
(
see the Supporting Information). This implies that cess. These results also support electronic effects of
the three alkoxy groups attached to the oxime ligand the oxime ligand on Pd coordination.
helped the ligand to coordinate Pd atoms more effi-
ciently than the others due to a good s-donor effect
of the electron-rich ligand. The resulting palladated Suzuki Coupling Reaction Catalyzed by Palladated
oxime resins (4a–4d) were analyzed by FE-SEM to Oxime Resins
examine any external morphology changes during the
reaction. The FE-SEM images clearly exhibited that Before the application of palladated oxime resins to
the surface morphology of the resins was unchanged the Suzuki coupling reaction, the reaction conditions,
during the reactions (Figure 1). The existence of Pd including the solvent and base, were optimized using
on the resin was verified by EDX and XPS analyses. palladated oxime resin (4a), which contained one
It is clear from the EDX spectrum that the oxime li- alkoxy group. Firstly, various solvent systems were ex-
gands formed a Pd complex via the chloro bridge amined in the Suzuki coupling reaction of 4-bromo-
form, due to the detection of Cl and Pd atoms (see
ACHTUNGTRENNUNG
[
9a]
2
3
2
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Polymer-Supported Electron-Rich Oxime Palladacycle
the highest yield of 4-methoxybiphenyl among the Table 3. Suzuki coupling reaction of various aryl halides
with phenylboronic acid in the presence of oxime palladacy-
cle resins (4a, 4b, 4c, and 4d).
several solvents (Table 1). In the results of the solvent
[a]
system screening (entries 6–11 in Table 1), we found
that a delicate balance of the solvent system is an im-
portant factor for the Suzuki coupling reaction in the
heterogeneous catalytic system when an inorganic
base is used, as a heterogeneous reaction requires
both the compatibility of the solid support and the
solubility of the organic and inorganic reagents. For Entry Substrate
base screening, the Suzuki coupling reactions with
various organic and inorganic bases were evaluated in
[
b]
Base
Yield [%] with
4
a
4b
4c
4d
Cs CO
84
40
92
63
99
99
1
-
2
3
3
H O/DMF (1:1) under heating (808C) using catalyst
1
2
3
4
[c]
[c]
[c]
[c]
2
K CO
2
3
4
a. The Suzuki coupling reaction in this solvent
[
c]
[c]
K CO
2
32
48
85
50
99
96
99
-
-
-
system did not progress well with organic bases, such
as triethylamine, tributylamine, pyridine, and
3
Cs CO
58
88
2
CH COONa. As shown in Table 2, the inorganic
3
K CO
2
3
3
Table 1. Effect of solvent systems in the Suzuki coupling re-
[a]
action of 4-bromoanisole with phenylboronic acid.
5
K CO
2
99
99
99
56
[b]
Entry
Solvent
Yield [%] with 4a
[a]
Conditions: aryl halides (1 mmol), phenylboronic acid
(1.2 mmol), palladated oxime resins (4a, 4b, 4c, and 4d,
1
2
3
4
5
6
7
8
9
H O
toluene
DMF
–
3
21
-
2
53
19
40
32
26
36
2
1 mol%), bases (1.5 mmol), in H O/DMF (1:1, v/v,
2
5 mL), at 508C, for 2 h.
Isolated yields by column chromatography.
Reaction time: 0.5 h.
[
[
b]
c]
H O/THF (4:1)
2
H O/dioxane (1:1)
2
H O/DMF (1:1)
2
H O/DMF (2:1)
2
H O/DMF (2:3)
2
bases generally exhibited good performance in the
Suzuki coupling reaction of 4-bromoanisole with phe-
H O/DMF (3:2)
2
1
1
0
1
H O/DMF (3:5)
2
nylboronic acid (91–96%). Consequently, H O/DMF
2
H O/DMF (5:3)
2
(
1:1) as a solvent and K CO , K PO , or Cs CO as
2 3 3 4 2 3
[
a]
Conditions: 4-bromoanisole (1 mmol), phenylboronic a base were chosen for the following the Suzuki cou-
acid (1.2 mmol), palladated oxime resins (4a, 1 mol%), pling reactions.
Cs CO3 (1.5 mmol), in diverse solvent systems (v/v,
2
Suzuki coupling reactions of several aryl halides
with phenylboronic acid were performed under mild
conditions to observe the apparent differences in the
catalytic performance among the palladated oxime
resins (Table 3). The electron-richness of palladated
oxime resins increased in the order of 4a<4b<4c, as
the number of alkoxy groups on the oxime ligand in-
creased. The palladated Kaiser oxime resin (4d) had
the lowest electron-richness compared to the other
alkoxy-substituted oxime resins due to the nitro
group on the Kaiser oxime ligand. As shown in
Table 3, palladated oxime resins (4a–4c) afforded
much better catalytic performances than the palladat-
ed Kaiser oxime resin (4d). The alkoxy-substituted
oxime palladacycle resins (4a–4c) could provide
better stabilities of Pd and catalytic activities due to
the electron-rich oxime ligands. Furthermore, as the
electron-richness of the palladated oxime resins in-
creased, the catalytic activity in the Suzuki coupling
reaction increased in the order of 4a<4b<4c
5
mL), at room temperature, for 2 h.
[
b]
GC yields.
Table 2. Effect of various bases in the Suzuki coupling reac-
tion of 4-bromoanisole with phenylboronic acid.
[
a]
[b]
Entry
Base
Yield [%] with 4a
1
2
3
4
5
6
7
8
9
Na CO
91
96
96
95
92
95
4
1
1
–
2
3
K CO
2
3
Cs CO
2
3
K PO ·H O
3
4
2
KOH
Na PO ·H O
3
4
2
CH COONa
3
triethylamine
tributylamine
pyridine
1
0
[
a]
Conditions: 4-bromoanisole (1 mmol), phenylboronic
acid (1.2 mmol), palladated oxime resins (4a, 1 mol%),
various bases (1.5 mmol), in H O/DMF (1:1, v/v, 5 mL),
at 808C, for 2 h.
GC yields.
(
Table 3). This indicates that the electron-richness of
2
the ligand promoted the ability for oxidative addi-
[
b]
[16]
tion, which is a crucial step in enhancing the cata-
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lytic activity of a palladacycle catalyst in the Suzuki Table 4. Suzuki coupling reaction of various aryl halides and
heterocyclic halides with phenylboronic acid in the presence
of oxime palladacycle resin (4c).
coupling reaction.
[a]
The three-alkoxy-substituted oxime palladacycle
resin (4c), which has the most electron-rich oxime
ligand, was evaluated with regard to its catalytic activ-
ity in the Suzuki coupling reaction of various sub-
strates with phenylboronic acid. Deactivated aryl bro-
mides as well as activated aryl chlorides were convert-
[b]
ed to the corresponding biaryl compounds in excel- Entry Substrate
lent yield by catalyst 4c (entries 1–9 in Table 4). Al-
Base
Temp
8C]
Yield [%] with
4c
[
though the Suzuki coupling reaction of deactivated
aryl chlorides did not give good yields (entries 6 and 7
in Table 4), the coupling reaction could be optimized
by changing the reaction conditions. The catalyst 4c
1
K CO 50
96
92
2
3
2
K CO 50
2 3
(
0.0033 mol%) gave a high TON of up to 30,000 for
the coupling reaction of 4-iodoacetophenone with
phenylboronic acid (entry 10 in Table 4). We conclud-
ed that the three-alkoxy-substituted oxime palladacy-
cle resin afforded a highly efficient catalytic activity,
despite the heterogeneous system in the Suzuki cou-
pling reaction, due to its electron-rich oxime ligand.
Substituted heterocyclic compounds are important
in the pharmaceutical industry for developing new
3
4
Cs CO 50
99
99
2
3
Cs CO 50
2
3
5
6
Cs CO 100
92
55
2
3
Cs CO 100
2
3
[21]
drugs. Due to its useful features, catalyst 4c was ap-
plied to the synthesis of heterocyclic biaryl com-
pounds via the Suzuki coupling reaction of various
heterocyclic halides with phenylboronic acid. 2-Bro-
mopyridine and 2-iodothiophene were well converted
to the corresponding biaryl compounds at 508C for
7
Cs CO 100
40
2
3
8
9
1
Cs CO 100
70
79
2
2
3
3
Cs
CO
100
2
h (entries 13 and 15 in Table 4). While a high yield
[
c]
0
Cs CO 50
99
was obtained in the coupling 2-bromothiophene and
phenylboronic acid at high temperature, the coupling
reaction of the heterocyclic chloride proceeded with
moderate yield (entries 14 and 16 in Table 4).
2
3
[
[
d]
e]
1
1
1
2
Cs CO 50
62
97
2
3
Cs CO 50
2
3
For the practical application of Pd catalysts, a valsar-
tan precursor, which is known as a potent angiotensin
[
22]
13
Cs
2
CO
3
50
84
58
II receptor antagonist,
was synthesized using the
most electron-rich palladated oxime resin (4c). As the
synthesis of valsartan requires aryl-aryl bond forma-
tion, which is a key step in the synthesis of valsar-
1
4
Cs CO 100
2
3
[23]
tan, a precursor of valsartan (6) was synthesized via 15
Cs
2
CO
50
99
90
3
the Suzuki coupling reaction of 2-bromobenzonitrile
1
6
Cs CO 100
2 3
with arylboronate (5) at 508C for 2 h (Scheme 2). The
valsartan precursor synthesized by 4c catalyst was ob-
tained in higher yield (92%) in comparison with pre-
[a]
Conditions: aryl halides (1 mmol), phenylboronic acid
(1.2 mmol), palladated oxime resins (4c, 1 mol%), bases
1.5 mmol), in H O/DMF (1:1, v/v, 5 mL), for 2 h.
Isolated yields by column chromatography.
Catalyst 4c (0.0033 mol%), reaction time: 24 h.
Catalyst 4c (0.1 mol%), reaction time: 12 h.
Homogeneous catalyst corresponding to 4c (0.1 mol%),
reaction time: 12 h
[24]
vious reports. This result showed that the valsartan
precursor containing a biaryl moiety could be effi-
ciently synthesized under mild conditions via the
Suzuki coupling reaction using the three-alkoxy-sub-
stituted oxime palladacycle resin (4c).
(
2
[b]
[c]
[d]
[e]
To compare the catalytic activities of homogeneous
and heterogeneous catalysts, the electron-rich oxime
palladacycle which corresponds to the 4c catalyst was oxime palladacycle afforded a better coupling yield,
[9]
synthesized. This homogeneous oxime palladacycle as compared to that of the heterogeneous catalyst
0.1 mol%) was applied to the Suzuki coupling reac- (4c) (entries 11 and 12 in Table 4). However, as ex-
(
tion of 4-bromoanisole with phenylboronic acid. Be- pected, it was difficult to isolate the homogeneous Pd
cause of the same phase reaction, the homogeneous catalyst after the Suzuki coupling reaction.
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Polymer-Supported Electron-Rich Oxime Palladacycle
Scheme 2. Synthesis of a valsartan precursor via the Suzuki coupling reaction.
Table 5. Reusability of the palladated oxime resins in the
After filtering the catalyst, the filtrate solution was al-
Suzuki coupling reaction of 4-bromoanisole with phenylbor-
lowed to react for another 1 h under the same reac-
tion conditions. No further reaction was observed in
the final solution. Based on these reusability results,
we confirmed that the three-alkoxy-substituted oxime
palladacycle resin is a stable and potent catalyst for
the successive Suzuki coupling reactions up to the
fifth cycle without significant Pd leaching.
onic acid in the presence of oxime palladacycle resins (4a,
[a]
4b, and 4c).
[
b]
Catalyst
Yield [%]
3
st
nd
rd
th
th
1
cycle
2
cycle
cycle
4
cycle
5
cycle
Conclusions
4
4
4
a
b
c
60
65
90
6
8
92
–
–
91
–
–
88
–
–
84
We have synthesized a series of electron-rich oxime
palladacycle resins as heterogeneous catalysts for the
Suzuki coupling reaction. The electron-richness of the
[
a]
Conditions: 4-bromoanisole (1 mmol), phenylboronic
acid (1.2 mmol), palladated oxime resins (4a, 4b, and 4c, oxime ligand was controlled by the number of alkoxy
1
mol%), K CO (1.5 mmol), in H O/DMF solvent (1:1, groups on the ligand. Compared to the palladated
2
3
2
v/v, 5 mL), at 508C, for 2 h.
Isolated yields by column chromatography
Kaiser oxime resin, the alkoxy-substituted oxime pal-
ladacycle resins showed good catalytic performance in
the Suzuki coupling reaction. It is noteworthy that the
catalytic activity of oxime palladacycle resins in-
[
b]
One of the advantages of a heterogeneous catalyst creased as the electron-richness of the oxime ligand
is that the catalyst can be easily isolated and reused. increased in the Suzuki coupling reaction. The most
To evaluate the reusability of electron-rich oxime pal- electron-rich oxime resin (4c), which contained three
ladacycle resins, a recycling test was carried out using alkoxy groups on the ligand, afforded the best catalyt-
the recovered catalysts for the Suzuki coupling reac- ic activity with high yield in the synthesis of biaryl
tion of 4-bromoanisole with phenylboronic acid and heterobiaryl compounds via the Suzuki coupling
(
Table 5). As the recycling number increased, the cat- reaction, in spite of the heterogeneous system. As
alytic activity of the palladated oxime resins (4a and a practical application, a valsartan precursor was suc-
b) decreased dramatically, even in the second cycle cessfully synthesized in high yield under mild condi-
Table 5). In contrast, the palladated oxime resin (4c) tions using the three-alkoxy-substituted oxime palla-
4
(
consistently gave 4-bromobiphenyl in high yield until dacycle resin (4c). Catalyst 4c could be reused for up
the fifth cycle, maintaining good catalytic activity. to 5 cycles without severe Pd leaching or losing cata-
After each cycle of the reaction, catalyst 4c was ana- lytic activity.
lyzed by HR-TEM and ICP-AES. From HR-TEM
images (see the Supporting Information), it was con-
firmed that deactivated Pd nanoparticles were not
Experimental Section
formed in the internal part of the resin as the recycle
was repeated. The ICP-AES results showed that Pd
leaching was insignificant during the reactions, main-
General Methods
À1
taining 0.10–0.13 mmolg of Pd loading in every
Unless otherwise noted, all solvents and reagents were ob-
tained from commercial suppliers and used without further
cycle. To support these results, the Suzuki coupling re-
action of 4-bromoanisole with phenylboronic acid was purification. Chloromethyl-polystyrene (CM PS) resin (1%
performed for 30 min in the presence of catalyst 4c. DVB-PS, 100–200 mesh, 2.19 mmolg ), Kaiser oxime resin
À1
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Hong-Jun Cho et al.
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À1
(
1% DVB-PS, 100–200 mesh, 1.52 mmolg ) were obtained
water, the filtrate was diluted to 25 mL with distilled water
and analyzed by ICP-AES. For obtaining similar Pd loading
levels, 3b and 3c resins were treated with Li PdCl (52 mg,
from BeadTech Inc. (Korea). The resins were characterized
by FT-IR (Bomem, FTLA2000) and elemental analysis (EA,
Leco, CHNS-932). The morphologies of the resins were in-
vestigated by field emission scanning electron microscopy
2
4
0.20 mmol) and Kaiser oxime resin was treated with
Li PdCl (105 mg, 0.40 mmol). Other palladated oxime
2
4
(
FE-SEM, Jeol Inc. JSM-6700F). The internal images of the
resins were prepared by the same procedure as 4a. The Pd
content on palladated oxime resins was determined by ICP-
AES, and the loading yield was calculated based on the
amount of Li PdCl and weight gain of the resins [Pd load-
oxime palladated resins were analyzed by high-resolution
transmission electron microscopy (HR-TEM, JEOL, JEM-
3
slicing them to ~50 nm using a microtome. Palladium immo-
bilized on the resin was detected by energy dispersive X-ray
spectrometer (EDX, Jeol Inc. JSM-6700F) and quantified by
inductively coupled plasma-atomic emission spectroscopy
010) after embedding the resins with epoxy resin (Spurr),
2
4
À1
ing level (yield) for 4a: 0.11 mmolg
(29%), for 4b:
À1
À1
0.14 mmolg (72%), for 4c: 0.13 mmolg (67%), and for
À1
4d: 0.05 mmolg (13%)].
(
ICP-AES, Shimadzu, ICPS-1000 IV). Palladium 3d binding
Synthesis of 3’,5’-Dimethoxy-4’-hydroxyacetophenone
Oxime
energy was investigated by X-ray photoelectron spectrosco-
py (XPS, ThermoVG, SIGMA PROBE). Gas chromatogra-
phy/mass spectrometry analysis was carried out on HP-6890
and HP-5973 instruments equipped with a capillary column
This oxime palladacycle was prepared by a modified litera-
[9]
ture method.
3’,5’-Dimethoxy-4’-hydroxyacetophenone
(
DB-5, 30 mꢂ0.320 mmꢂ0.25 mm). Mass spectra of the val-
(500 mg, 2.55 mmol) dissolved in MeOH (30 mL) was added
to hydroxylamine hydrochloride (354 mg, 5.10 mmol) and
sodium acetate (418 mg, 5.10 mmol) dissolved in distilled
water (30 mL). The mixture was stirred overnight at 608C.
After removing the solvent on an evaporator, the residue
was diluted with ethyl acetate and washed with distilled
sartan precursor were obtained by high-resolution electro-
spray ionization mass spectrometry (HR-ESI-MS, Thermo
Finnigan, LTQ-Orbitrap). The H and C nuclear magnetic
resonance spectroscopy (NMR) spectra were recorded on
a Bruker spectrometer at 400 MHz and 100 MHz, respec-
1
13
tively, using CDCl as a solvent and TMS as an internal
water. The organic layer was dried over MgSO and concen-
4
3
standard.
trated under reduced pressure. The crude product was puri-
fied by column chromatography on silica gel (eluent:
hexane and ethyl acetate, 1:1). The final compound was ob-
tained in 93% yield (501 mg) as a white powder.
Preparation of Palladated Oxime Resins
Immobilization of 4’-hydroxyacetophenone derivatives on
CM PS: CM PS resin (3 g, 2.19 mmolg ) was pre-swollen in
DMF (100 mL) and 4’-hydroxyacetophenone (1a, 1.79 g,
Suzuki Coupling Reaction Catalyzed by Palladated
Oxime Resins
À1
1
3.14 mmol) and sodium methoxide (0.71 g, 13.14 mmol)
Optimization of Suzuki coupling reaction: The Suzuki cou-
pling reaction of 4-bromoanisole (125 mL, 1 mmol) with phe-
nylboronic acid (146 mg, 1.2 mmol) was carried out using
were added to the resin. The mixture was stirred by an over-
head stirrer at 708C for 12 h. After cooling to room temper-
ature, the resin 2a was washed with H O, 1N HCl, DMF,
CH Cl , and MeOH (100 mLꢂ3) and dried under vacuum.
Resins 2b and 2c were also prepared using 4’-hydroxy-3’-me-
thoxyacetophenone (1b, 2.18 g, 13.14 mmol) and 3’,5’-dime-
thoxy-4’-hydroxyacetophenone (1c, 2.58 g, 13.14 mmol) by
the same procedure as 2a.
2
palladated oxime resin (1 mol% Pd, 4a: 91 mg) with Cs CO3
2
2
2
(489 mg, 1.5 mmol) in various solvent systems to investigate
the optimal conditions. The following solvent systems
(6 mL) were examined: H O, toluene, DMF, H O/THF
2
2
(4:1), H O/dioxane (1:1), H O/DMF (1:1), H O/DMF (2:1),
2
2
2
H O/DMF (2:3), H O/DMF (3:2), H O/DMF (3:5), and
2
2
2
Preparation of oxime resins: The excess amount of hy-
droxylamine hydrochloride (6.95 g, 100 mmol) and pyridine
H O/DMF (5:3). The mixture was stirred at room tempera-
ture for 2 h. For base screening, triethylamine, tributyl-
2
(
8.09 mL, 100 mmol) were added to the resins 2a–2c (3 g,
ACHTUNGTRENNUNGa mine, pyridine, CH COONa, Na CO , K CO , Cs CO ,
3 2 3 2 3 2 3
each) which were pre-swollen in EtOH (100 mL). The mix-
ture was heated under reflux with stirring for 24 h. After
cooling to room temperature, the resins were washed with
EtOH, DMF, CH Cl , and MeOH (100 mL ꢂ 3) and dried
K PO ·H O, KOH, and Na PO ·H O (1.5 mmol, each) were
3 4 2 3 4 2
used in H O/DMF (1:1) system. The reactions were per-
2
formed at 808C for 2 h. After filtration, the resin was
washed with distilled water (3 mLꢂ5) and diethyl ether
(3 mLꢂ5). The filtrate was diluted with diethyl ether, and
the organic solution was washed with water 3 times. The or-
2
2
under vacuum. The loading level of oxime was determined
by nitrogen analysis, and the loading yield was calculated
based on the amount of reactant hydroxyacetophenone de-
rivatives and weight gain of the resins [loading level (yield)
ganic layer was dried over MgSO and concentrated under
4
reduced pressure. The crude product was analyzed by gas
chromatography/mass spectrometry (GC-MS).
À1
À1
for 3a: 1.50 mmolg (86%), for 3b: 1.50 mmolg (90%),
À1
and for 3c: 0.96 mmolg (61%)].
Preparation of palladated oxime resins: Li PdCl (105 mg,
.40 mmol) dissolved in THF (10 mL) was added to the sus-
pension of oxime resin 3a (1 g, each) which was pre-swollen
in THF (10 mL). The mixture was stirred at room tempera-
ture for 6 h. After the reaction, the resin was washed with
THF in a Soxhlet system, and dried under vacuum. For ICP-
2
4
General Procedure for Suzuki Coupling Reaction of
Aryl Halides with Phenylboronic Acid
0
Aryl halide (1 mmol), phenylboronic acid (1.2 mmol,
1.2 equiv.), and a base (1.5 mmol, 1.5 equiv.) dissolved in dis-
tilled water and DMF (1/1, v/v, 5 mL) were added to palla-
dated oxime resins 4a–4d (1 mol% Pd, for 4a: 91 mg, for 4b:
71 mg, for 4c: 77 mg, and for 4d: 200 mg, 0.1 mol% Pd for
AES analysis, the resin was treated with HNO at 1008C for
3
4
h. After filtration and washing the resin with distilled
1062
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ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1056 – 1064

FULL PAPERS
Polymer-Supported Electron-Rich Oxime Palladacycle
4
1
c: 8 mg), suspended in distilled water and DMF (1/1, v/v, Acknowledgements
mL). For homogeneous reactions, 3’,5’-dimethoxy-4’-hy-
droxyacetophenone oxime palladacycle was prepared from
’,5’-dimethoxy-4’-hydroxyacetophenone oxime and Li PdCl
This work was supported by WCU (World Class University)
program (R32-2010-000-10213-0) through the National Re-
search Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology. Also, this research was
supported by the Pioneer Research Center Program through
the National Research Foundation of Korea funded by the
Ministry of Science, ICT & Future Planning (2013006141).
3
2
4
[9]
(
1 mol% Pd: 3.52 mg, 1 mol% Pd: 0.35 mg). The mixture
was stirred at 508C for 2 h. After filtration, the resin was
washed with distilled water (3 mLꢂ5) and diethyl ether
(
3 mLꢂ5). The filtrate was diluted with diethyl ether, and
the organic solution was washed with water 3 times. The or-
ganic layer was dried over MgSO and concentrated under
4
reduced pressure. The crude product was purified by
column chromatography on silica (eluent: hexane and ethyl
acetate or hexane and CHCl ) and the final product was
3
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ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1056 – 1064