Amphipathic monolith-supported palladium catalysts for chemoselective hydrogenation and cross-coupling reactions

Article abstract of DOI:10.1039/c6ra24769e

A palladium catalyst immobilized on an amphipathic and monolithic polystyrene-divinylbenzene polymer bearing strongly acidic cation exchange functions (sulfonic acid moieties) (Pd/CM) was developed. It was used as a catalyst for hydrogenation and ligand-free cross-coupling reactions, such as the Suzuki-Miyaura, Mizoroki-Heck, and copper- and amine-free Sonogashira-type reactions, together with a palladium catalyst supported on monolithic polymer (Pd/AM) bearing basic anion exchange functions (ammonium salt moieties), which has been in practical use for the decomposition of hydrogen peroxide produced as a byproduct during the manufacture of ultrapure water. While the Pd/CM was highly active as a catalyst for the hydrogenation and a variety of reducible functional groups could be reduced, the use of Pd/AM led to a unique chemoselective hydrogenation. Aromatic carbonyl groups were tolerant under the Pd/AM-catalyzed hydrogenation conditions, although benzyl esters, benzyl ethers, and N-Cbz groups could be smoothly hydrocracked. The cross-coupling reactions readily proceeded using either catalyst. The palladium leaching from the Pd/CM into the reaction media was never observed during the Sonogashira-type reaction, which was hardly achieved by other palladium-supported heterogeneous catalysts due to the good affinity of the palladium species with alkynes.

Full text of DOI:10.1039/c6ra24769e

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Amphipathic monolith-supported palladium
catalysts for chemoselective hydrogenation and
Cite this: RSC Adv., 2017, 7, 1833
cross-coupling reactions†
Yasunari Monguchi, Fumika Wakayama,a Shun Ueda,a Ryo Ito,a Hitoshi Takada,b
a
*
b
b
a
a
*
Hiroshi Inoue, Akira Nakamura, Yoshinari Sawama and Hironao Sajiki
A palladium catalyst immobilized on an amphipathic and monolithic polystyrene–divinylbenzene polymer
bearing strongly acidic cation exchange functions (sulfonic acid moieties) (Pd/CM) was developed. It was
used as a catalyst for hydrogenation and ligand-free cross-coupling reactions, such as the Suzuki–
Miyaura, Mizoroki–Heck, and copper- and amine-free Sonogashira-type reactions, together with
a palladium catalyst supported on monolithic polymer (Pd/AM) bearing basic anion exchange functions
(ammonium salt moieties), which has been in practical use for the decomposition of hydrogen peroxide
produced as a byproduct during the manufacture of ultrapure water. While the Pd/CM was highly active
as a catalyst for the hydrogenation and a variety of reducible functional groups could be reduced, the
use of Pd/AM led to a unique chemoselective hydrogenation. Aromatic carbonyl groups were tolerant
under the Pd/AM-catalyzed hydrogenation conditions, although benzyl esters, benzyl ethers, and N-Cbz
groups could be smoothly hydrocracked. The cross-coupling reactions readily proceeded using either
catalyst. The palladium leaching from the Pd/CM into the reaction media was never observed during the
Sonogashira-type reaction, which was hardly achieved by other palladium-supported heterogeneous
catalysts due to the good affinity of the palladium species with alkynes.
Received 5th October 2016
Accepted 10th December 2016
DOI: 10.1039/c6ra24769e
www.rsc.org/advances
Monolithic polymers are supposed to be good supports for
the palladium catalysts based on the effective incorporation of
Introduction
substrates into the porous supports, and such catalysts are ex-
pected to be used for ow reactions due to the excellent
permeability of the reaction solution without resistance to the
uid ow. Palladium catalysts immobilized on polystyrene-
based monolithic polymers bearing quaternary ammonium
salts as the anion exchange functions have been used under
ow conditions for the cross-coupling reactions, such as the
Suzuki–Miyaura, Mizoroki–Heck, and Sonogashira-type reac-
tions, and transfer hydrogenation in the absence of hydrogen
gas.10 Other types of palladium catalysts supported on mono-
lithic polymers derived from ferritin bionanoparticles,11
N-aminoethylamidine-bound polyacrylonitrile,12 and Shiff base-
bound acrylate13 were also reported as effective catalysts for the
Suzuki–Miyaura reaction11–13 under batch conditions and ow
hydrogenation.11
A polystyrene-based monolithic polymer bearing quaternary
ammonium moieties (AM) has been in practical use as
a support for the palladium catalyst (Pd/AM), which decom-
poses hydrogen peroxide produced as a byproduct during the
UV irradiation process to degrade contaminated trace organic
substances for manufacturing ultrapure water.14 The
polystyrene-based monolithic polymer bearing sulfonic acid
moieties as cationic exchange functions (CM) are also manu-
factured.15 We anticipated that the hydrophilic sulfonic acid
The development of heterogeneous palladium catalysts is an
important subject in organic chemistry from environmental
and economical viewpoints based on their recovery, reuse, and
non-metal residual property.1 A wide variety of organic polymers
possessing some functional groups within the molecule, which
could act as ligands toward palladium species, has been used as
supports for the heterogeneous palladium catalysts, especially
for cross-coupling reactions.2,3 The variation in the supports of
palladium catalysts is also known to affect the catalyst activity
for hydrogenation,4 and we have developed a variety of hetero-
geneous palladium catalysts for chemoselective hydrogenation,
such as palladium broin (Pd/Fib),5 palladium on synthetic
adsorbent (Pd/HP20),2b,c palladium on molecular sieves (Pd/
MS),6 palladium on boron nitride (Pd/BN),7 palladium on
chelate resin (Pd/CR11 and Pd/CR20),8 and palladium on
ceramic (Pd/ceramic).9
aLaboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4
Daigaku-nishi, Gifu 501-1196, Japan. E-mail: monguchi@gifu-pu.ac.jp; sajiki@
gifu-pu.ac.jp; Fax: +81 58 230 8109; Tel: +81 58 230 8109
bR & D Center, Organo Corporation, 4-4-1 Nishionuma, Minami-Ku, Sagamihara 252-
0332, Japan
† Electronic supplementary information (ESI) available: Experimental details,
spectral data and NMR spectra of products. See DOI: 10.1039/c6ra24769e
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 1833–1840 | 1833

View Article Online
RSC Advances
Paper
moieties would facilitate the incorporation of palladium species
on/in the porous monolithic polymer in analogy with Pd/AM.
Such ammonium and sulfonic acid moieties were expected to
function as ligands for cross-coupling reactions and also as
catalyst poisons for chemoselective hydrogenation based on the
appropriate coordination to palladium metals.4a Furthermore,
the amphipathic and porous nature of the supports would
provide a broad substrate scope due to an easy access of both
hydrophobic and hydrophilic substrates to the catalyst met-
als.3e,16 In this paper, we demonstrate the development of
a novel palladium catalyst supported on CM (Pd/CM) as well as
the application of both Pd/AM and Pd/CM to several organic
reactions; i.e., hydrogenation and cross-coupling reactions
under batch conditions.
Scheme 1 Preparation of 5% Pd/monolith-SO3H (Pd/CM).
Results and discussion
Preparation of palladium on monolith-SO3H (Pd/CM)
The unfunctionalized monolithic polymer was rst prepared
through the two successive polymerization processes from
styrene and divinylbenzene using sorbitan fatty acid ester as an
emulsier, radical initiators, such as 2,20-azobis(isobutyroni-
trile), and water according to a previously reported method
(Fig. 1).14 Subsequently, the sulfonic acid function was intro-
duced to the resulting plain monolithic polymer by the general
method for the preparation of a strongly acidic cation exchange
resin using chlorosulfuric acid.15 The colorless monolith-SO3H
polymer (CM) was cut into 1 mm cubes using a ceramic knife,
then immersed in a reddish Pd(OAc)2 solution of MeOH. Aer
the mixture was stirred at room temperature under an Ar
atmosphere for 24 h, the solution became colorless, and the
colorless CM was time-dependently changed to brown by the
absorption of divalent palladium species. The brown CM was
treated with hydrazine hydrate in water to give the zero valent
palladium-supported black CM, which was collected on lter
paper, washed with MeOH and water, and dried in vacuo to give
the 5% Pd/monolith-SO3H (5% Pd/CM) (Scheme 1).17
Fig. 2 TEM image of 5% Pd/CM.
were revealed to be evenly distributed from the surface of the
5% Pd/CM to the inside by an electron probe microanalysis
(EPMA) (Fig. 3). The aggregation pattern of palladium species as
well as the palladium lording on 5% Pd/CM was quite similar to
the case of 3.9% Pd/AM.18
ꢀ
Pd/monolith-NMe3+NO3 (Pd/AM)- and Pd/monolith-SO3H
(Pd/CM)-catalyzed hydrogenation
The catalytic activity of the 3.9% Pd/monolith-NMe3+NO3ꢀ (Pd/
AM)19 and 5% Pd/CM for the hydrogenation of various reducible
functionalities was rst evaluated (Table 1). Alkyne (entries 1, 2,
29, and 30), alkene (entries 3, 4, 13–20, 25, and 26), azido
(entries 5 and 6), and nitro (entries 7 and 8) functionalities were
readily reduced to the corresponding products in good yields by
either catalyst. These catalysts can also be used for the depro-
tection of aromatic (entries 9 and 10) and aliphatic N-Cbz
groups (entries 11–16), benzyl esters (entries 17, 18, 21, and 22),
A transmission electron microscope (TEM) image of the 5%
Pd/CM shows that the palladium nanoparticles (approximately
5–10 nm) aggregate to form 5–30 nm size clusters (Fig. 2), which
Fig. 1 SEM image of unfunctionlized monolithic polymer.
1834 | RSC Adv., 2017, 7, 1833–1840
Fig. 3 EPMA of 5% Pd/CM.
This journal is © The Royal Society of Chemistry 2017

View Article Online
Paper
RSC Advances
Table 1 3.9% Pd/AM- and 5% Pd/CM-catalyzed hydrogenations
Entry
Substrate
Catalyst
Time (h)
Product
Yield (%)
1
2
3.9% Pd/AM
5% Pd/CM
3
100
99
2.5
3
3.9% Pd/AM
2
100
4
5
6
7
8
9
5% Pd/CM
3.9% Pd/AM
5% Pd/CM
3.9% Pd/AM
5% Pd/CM
3.9% Pd/AM
2
98
1.5
1.5
4
97
89
97
1.5
2
100
100
10
11
5% Pd/CM
3.9% Pd/AM
4
4
100
100
12
5% Pd/CM
3.9% Pd/AM
5% Pd/CM
3.9% Pd/AM
17.5
6.5
6.5
1
90
13a
14
98
96
15a
100b
16a,c
17
5% Pd/CM
3.9% Pd/AM
1
24
100b
100
18
5% Pd/CM
5.5
3.5
100 (44 : 56)
19
3.9% Pd/AM
100
20
21
22
23
24
5% Pd/CM
3.9% Pd/AM
5% Pd/CM
3.9% Pd/AM
5% Pd/CM
1
96
16.5
24
24
10
100
100
d
—
100
100
25
26
3.9% Pd/AM
5% Pd/CM
24
24
95
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 1833–1840 | 1835

View Article Online
RSC Advances
Paper
Table 1 (Contd.)
Entry
Substrate
Catalyst
Time (h)
Product
Yield (%)
e
27
28
3.9% Pd/AM
5% Pd/CM
24
2
—
94
29
3.9% Pd/AM
5% Pd/CM
24
24
100
30a
100b
a
The reaction was carried out at 40 ꢁC. b The reaction was carried out in CD3OD due to the volatility of the substrate/product, and 100% conversion
to the product was conrmed by 1H NMR aer removal of the catalyst by ltration. c 2 mol% of the catalyst was used. d A mixture of the starting
material and product was obtained in 98% yield in the ratio of 99 : 1, respectively. e A mixture of the starting material and product was obtained in
100% yield in the ratio of 97 : 3, respectively.
and aryl benzyl ethers (entries 19–22), although the benzyl ester
underwent partial transesterication with MeOH to afford the
methyl ester due to the strong acidity of the support (CM) of Pd/
CM (entry 18). While the Pd/CM effectively catalyzed the
hydrogenolysis of aromatic ketones (entries 24 and 26) and
benzyl alcohols (entries 24, 26, 28, and 30) to give the corre-
sponding deoxygenated products, these reducible functional-
ities were virtually untouched under the Pd/AM-catalyzed
conditions (entries 23, 25, 27, and 29). An exposition of benz-
hydrol under the Pd/AM-catalyzed hydrogenation conditions
afforded a very small amount of the dehydrogenated product,
benzophenone (entry 27). The different chemoselectivity toward
Fig. 4 Chemoselectivity of 3.9% Pd/AM- and 5% Pd/CM-catalyzed
the hydrogenolysis of aromatic carbonyls and benzyl alcohols,
i.e., higher activity of 5% Pd/CM compared with 3.9% Pd/AM,
would be attributed to the strong Brønsted acidity of CM;
thus, the activation of carbonyl groups and benzyl alcohols by
the protonation would promote the reactions.
The catalyst activities of the 3.9% Pd/AM and 5% Pd/CM
together with catalysts previously developed by us are summa-
rized in Fig. 4. The reducible functional groups in the specic
frameworks could be reduced using the corresponding catalysts.
While 5% Pd/CM can catalyze the hydrogenation of a wide range
of reducible functionalities as with Pd/C and Pd/HP20,2b the use
of 3.9% Pd/AM makes it possible to undergo a novel hydroge-
nation, i.e., aromatic carbonyl groups are tolerant, while N-Cbz,
benzyl ester, and aryl benzyl ether can be hydrocracked.
hydrogenation.
could be smoothly obtained using either 3.9% Pd/AM or 5% Pd/
CM at room temperature as is the case in 10% Pd/C that we have
previously reported.20 The phenylation of the non-protected free
bromoaniline was completed within only 1.5 h (entries 10 and
11), while 24 h was not long enough for the reaction completion
by 10% Pd/C (entry 12). These results were probably caused by
the hydrophilicity of the amino group, and the bromoaniline
could be more effectively absorbed into the amphipathic
monolith.
The 0.2 mol% of 3.9% Pd/AM- or 5% Pd/CM-catalyzed Miz-
oroki–Heck reaction of aryl iodides with benzyl acrylate (1.2
equiv.) in the presence of Bu3N (1.1 equiv.) in N,N-dimethyla-
cetamide (DMA) at 100 ꢁC efficiently proceeded regardless of the
electronic property of the substituent on the benzene ring of the
aryl iodides to give the corresponding butyl cinnamate deriva-
tives in excellent yields (Table 3, entries 1, 2, 4, 5, 7, 8, 10, and
11). The 3.9% Pd/AM or 5% Pd/CM catalyzed the cross-coupling
between iodobenzene and styrene in a manner similar to 10%
Pd/HP20 (entries 13–15).2c It is notable that both catalysts
Pd/AM- and Pd/CM-catalyzed cross-coupling reactions
The Suzuki–Miyaura coupling reaction between aryl bromides
and arylboronic acids (1.5 equiv.) were carried out using 0.5
mol% Pd/AM or Pd/CM and Na3PO4$12H2O (3.5 equiv.) in 50%
aqueous iPrOH (Table 2). Although the reaction time was
dependent on the kind of aryl bromides, the desired biaryls
1836 | RSC Adv., 2017, 7, 1833–1840
This journal is © The Royal Society of Chemistry 2017

View Article Online
Paper
RSC Advances
Table
2
3.9% Pd/AM- and 5% Pd/CM-catalyzed Suzuki–Miyaura Table
3
3.9% Pd/AM- and 5% Pd/CM-catalyzed Mizoroki–Heck
reactions
reactions
Entry R1
R2
Catalyst
Time (h) Yield (%)
1
4-NO2 CO2Bu 3.9% Pd/AM
5% Pd/CM
10% Pd/HP20
3-NO2 CO2Bu 3.9% Pd/AM
5% Pd/CM
5.5
24
4
5
6
80
88
81
84
75
98
92
99
93
100
91
95
52
61
64
93
2a
Entry
R1
R2
H
Catalyst
Time (h)
Yield (%)
3b
4
1
NO2
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
24
6
3.5
24
2
6
7
7
3.5
0.5
1.5
24
24
19
24
24
24
3.5
12
4
93
92
93
99
96
99
96
100
100
95
84
65
94
97
93
94
96
91
86
94
90
98
88
91
2
5
3a
6b
10% Pd/HP20 24
4
CO2Et
CO2H
NH2
H
7
4-Me
H
CO2Bu 3.9% Pd/AM
5% Pd/CM
10% Pd/HP20 24
CO2Bu 3.9% Pd/AM
7
4
5
8
6a
9b
7
H
10
11
12b
13a
14a
15b
16a
17a
18b
19c
20c
21b,c
4
3
4
24
24
8
5% Pd/CM
9a
10% Pd/HP20
3.9% Pd/AM
5% Pd/CM
10b
11b
12b,c
13
14
15a
16
17
18a
19d
20d
21a
22
23
24c
H
H
Ph
10% Pd/HP20 24
OMe
OH
H
H
CONH2 3.9% Pd/AM
5% Pd/CM
17.5
9
88
65
10% Pd/HP20 24
H
H
CN
3.9% Pd/AM
5% Pd/CM
24
6.5
94 (E/Z ¼ 85 : 15)
88 (E/Z ¼ 86 : 14)
73 (E/Z ¼ 86 : 14)
10% Pd/HP20 12
OMe
NO2
2-OMe
4-Ac
a
80 ꢁC. b Results from ref. 2c. c 2 mol% of catalyst was used.
6
23
2
temperature, the palladium species leached into the ltrate
were measured by atomic absorption spectrometry. In each
case, no palladium species were observed in the ltrate within
the detectable limits (<1 ppm). Therefore, the hydrogenation
would be expected to cause no or little degradation to the Pd/AM
and Pd/CM, and they could be reused until at least the 5th run
without any loss of catalyst activities (Table 5).
We have previously reported that approximately 25% of the
palladium metal was leached from 10% Pd/C during the copper-
and amine-free Pd/C-catalyzed Sonogashira-type reaction
between 40-iodoacetophenone and 3-butyn-1-ol [inductively
coupled plasma-atomic emission spectrometry (ICP-AES)],21 and
the catalyst could be reused only once. The use of simple poly-
styrene–divinylbenzene copolymer-supported 10% Pd/HP20 for
the reaction of 40-iodoacetophenone with ethynylbenzene led to
a reduction in the palladium leaching ratio to 2.4% probably
due to the relatively strong interaction between the palladium
species and aromatic rings of HP20.2c Since no detectable
palladium leaching from Pd/C and Pd/HP20 has been observed
in the cases of other cross-coupling reactions, such as the
Suzuki–Miyaura2c,20 and Mizoroki–Heck2c reactions, the signi-
cant palladium leaching during the copper-free, heterogeneous
Sonogashira-type reaction is an important issue that needs to be
12
a
Results from ref. 20. b 80 ꢁC. c Results from ref. 2c. d The reaction was
carried out in H2O.
effectively worked for the b-phenylation of the acryl amide and
acrylonitrile (entries 16, 17, 19, and 20), the catalyst efficiency of
which was quite low under the Pd/HP20-catalyzed conditions
(entries 18 and 21). The polarity of the functional groups (tri-
methylammonium and sulfonic acid) on the monolith resin
would increase the affinity for polar substrates in comparison to
the simple polystyrene–divinyl benzene-based polymer of HP20
thus leading to the enhanced reaction efficiency.
The 3.9% Pd/AM and 5% Pd/CM could be used for the copper-
and amine-free Sonogashira-type reaction in the absence of
ligands (Table 4). A wide variety of aryl iodides coupled with
aromatic or aliphatic alkynes (1.2 equiv.) in the presence of 0.4
mol% of 3.9% Pd/AM or 5% Pd/CM in 50% aqueous iPrOH at
80 ꢁC afforded the corresponding disubstituted alkynes.
Reuse test of Pd/AM and Pd/CM for hydrogenation and
Sonogashira-type reaction
Aer the Pd/AM- and Pd/CM-catalyzed hydrogenations of 1,2- addressed. While a very small amount of palladium leaching
dimethoxy-4-(1-propenyl)benzene
in
MeOH
at
room (1.9%) was observed when 3.9% Pd/AM was used for the cross-
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 1833–1840 | 1837

View Article Online
RSC Advances
Paper
Table 4 3.9% Pd/AM- and 5% Pd/CM-catalyzed Sonogashira-type Table 6 Reuse test of 5% Pd/CM for Sonogashira-type reaction
reactions
Run
Yield (%) of producta
Recovered Pd/CM (%)
Entry
R1
Ac
R2
Catalyst
Time (h)
Yield (%)
1st
100
>100
91
95
2nd
3rd
4th
100
1
Ph
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
10% Pd/C
3.9% Pd/AM
5% Pd/CM
1
1
99
100
95
61
61
51
56
64
66
87
84
90
79
76
85
94
80
95 (5)b
93 (7)b
2
3a
4
0.5
17.5
24
0.5
1
1
0.5
1
1
1
7
1
88
OMe
H
Ph
a
Determined by 1H NMR using 1,4-dioxane as the internal standard.
Yield of recovered 40-iodoacetophenone.
5b
6a
7
b
Ph
8
9a
10
11
12a
13
14
15a
16
17
used for the second run without any further acid treatment, and
no increase in the weight of the recovered catalyst was observed
aer the second run. Although the catalyst activity only slightly
decreased aer the fourth run, the catalyst could be reused
without any signicant decrease in the catalyst activity. The
palladium leaching-free and reusable properties of the copper-
and amine-free Sonogashira-type reaction are remarkable
advantages of the 5% Pd/monolith-SO3H.
Ac
2-CF3C6H4
(CH2)2OH
4-MeC6H4
Ac
1
4
4
Ac
a
Results from ref. 21. b 2 equiv. of ethynylbenzene were used.
Conclusions
coupling reaction between 40-iodoacetophenone and ethy-
nylbenzene, palladium species were never detected by ICP-AES
in the case of the 5% Pd/CM. The less palladium leaching
would be arisen from the good interaction of palladium metals
with functional groups on the highly porous monolithic poly-
mer. Hence, the reuse test of the 5% Pd/CM was investigated
(Table 6). The weight of the recovered Pd/CM aer the rst run
increased compared to the initial use probably because of the
partial or full exchange of protons of the monolith-SO3H to the
sodium cations of Na3PO4$12H2O. The recovered catalyst was
A palladium catalyst supported on the amphipathic, monolithic
polystyrene–divinylbenzene polymer bearing ammonium func-
tions (Pd/AM) as well as a newly-developed sulfonic acid-bound
monolithic polymer-supported palladium (Pd/CM) could be
used for hydrogenation reactions. It is noteworthy that a novel
chemoselective hydrogenation was successively achieved under
the Pd/AM-catalyzed conditions; aromatic ketones could not be
reduced to the corresponding benzyl alcohols, and benzyl
alcohols were also intact, while Pd/CM catalyzed the hydroge-
nation of various reducible functionalities. Both catalysts were
applicable for the ligand-free cross-coupling reactions, Suzuki–
Miyaura, Mizoroki–Heck, and copper- and amine-free
Sonogashira-type reactions. When Pd/CM was used for the
Sonogashira-type reaction, no palladium leaching into the
reaction media was observed despite the use of an alkyne as
a substrate. Furthermore, Pd/CM could be recovered and reused
for the Sonogashira-type reactions for at least four runs. The
application of these catalysts for the ow reactions is now
ongoing in our laboratory.
Table 5 Reuse test of Pd/AM and Pd/CM for hydrogenation
3.9% Pd/AM
5% Pd/CM
Yield (%)
of product
Recovered
catalyst
Yield (%)
of product
Recovered
catalyst
Experimental
Preparation of 5% Pd/CM (Scheme 1)
Run
1st
100
97
100
99
96
97
99
96
100
94
99
100
100
100
100
99
99
99
100
The monolith-SO3H polymer (CM) was cut into 1 mm cubes
using a ceramic knife, washed with H2O and MeOH, and dried
overnight under reduced pressure. The dried CM (1.00 g) was
immersed in a solution of Pd(OAc)2 [111 mg, 495 mmol
2nd
3rd
4th
5th
100
1838 | RSC Adv., 2017, 7, 1833–1840
This journal is © The Royal Society of Chemistry 2017

View Article Online
Paper
RSC Advances
(52.6779 mg for Pd)] in MeOH (30 mL), and stirred at room (2 mL) in a test tube under an Ar atmosphere was stirred at
temperature under an Ar atmosphere for 24 h. The resulting 100 ꢁC or 80 ꢁC. Aer complete consumption of the aryl iodide
brown polymer was collected on a Kiriyama funnel (1 mm), was conrmed by TLC analyses or aer 24 h (if the reaction was
washed with MeOH (5 ꢂ 20 mL) and H2O (5 ꢂ 20 mL), then incomplete), the mixture was passed through a cotton lter to
MeOH (5 ꢂ 20 mL), and dried under vacuum for 12 h. The remove the catalyst. To the ltrate were added EtOAc (20 mL)
ltrate was concentrated in vacuo, then transferred to a 100 mL and saturated aqueous NH4Cl (20 mL), then the layers were
volumetric ask with H2O. Its atomic absorption analysis indi- separated. The organic layer was washed with saturated aq.
cated that 0.32224 mg Lꢀ1 (32.224 mg) of palladium species was NH4Cl (2 ꢂ 20 mL) and brine (20 mL), dried over MgSO4, and
present. To a suspension of the collected solid in H2O (20 mL) concentrated in vacuo. The residue was puried by silica gel
was added NH2NH2$H2O (74.3 mg, 1.47 mmol), and the mixture ash column chromatography (n-hexane/EtOAc) to give the
was stirred at room temperature under an Ar atmosphere for corresponding disubstituted alkene derivative. The spectral
24 h. The black solid was collected on a Kiriyama funnel (1 mm), data of the product were identical to those in the literature. For
washed with H2O (5 ꢂ 20 mL) and MeOH (5 ꢂ 20 mL), then entries 19 and 20, the reactions were performed using 2 mol%
dried under vacuum for 24 h to produce the Pd/CM (1.05 g). The of Pd/AM (27.3 mg, 10.0 mmol) or Pd/CM (21.3 mg, 10.0 mmol).
ltrate was concentrated in vacuo, then transferred to a 100 mL
volumetric ask with H2O. Its atomic absorption analysis indi-
Typical procedure for the 3.9% Pd/AM- and 5% Pd/CM-
catalyzed Sonogashira-type reactions (Table 4)
cated that 0.82912 mg Lꢀ1 (82.912 mg) of the palladium species
was present. The palladium amount, which was not captured
A mixture of the aryl iodide (500 mmol), the mono-substituted
on the CM, was found to be 115.136 mg (32.224 + 82.912 mg),
which means that the palladium ratio of Pd/CM was 5.0%
[(52.6779 ꢀ 0.115136)/1050 ꢂ 100].
ꢁ
stirred at 80 C. Aer complete consumption of the aryl iodide
Typical procedure for the 3.9% Pd/AM- and 5% Pd/CM-
catalyzed hydrogenation (Table 1)
alkyne (600 mmol), Na3PO4$12H2O (380 mg, 1.00 mmol) and
Pd/AM (5.5 mg, 2.00 mmol) or Pd/CM (4.3 mg, 2.00 mmol) in H2O
(1 mL)–iPrOH (1 mL) in a test tube under an Ar atmosphere was
was conrmed by TLC analyses, the mixture was passed through
a cotton lter to remove the catalyst. To the ltrate were added
EtOAc (20 mL) and saturated aqueous NH4Cl (20 mL), then
the layers were separated. The organic layer was washed with
A mixture of the substrate (200 mmol) and 3.9% Pd/AM (5.5 mg,
2.00 mmol) or 5% Pd/CM (4.3 mg, 2.00 mmol) in MeOH (1 mL)
was stirred under an H2 atmosphere (balloon) at room
temperature for a specic time, then passed through a cotton
saturated aqueous NH4Cl (2 ꢂ 20 mL) and brine (20 mL), dried
over MgSO4, ltered, and concentrated in vacuo. The residue
lter to remove the catalyst. The ltrate was concentrated in
was puried by ash silica gel column chromatography
vacuo to give the analytically pure product. The spectral data of
(n-hexane/EtOAc) to give the corresponding disubstituted
alkyne. The spectral data of the product were identical to those
the product were identical to those in the literature.
in the literature. For entry 5, the reaction was performed using 2
equiv. of ethynylbenzene (102 mg, 1.00 mmol).
Typical procedure for the 3.9% Pd/AM- and 5% Pd/CM-
catalyzed Suzuki–Miyaura reactions (Table 2)
A mixture of the aryl halide (500 mmol), arylboronic acid (550
mmol), Na3PO4$12H2O (665 mg, 1.75 mmol) and Pd/AM (6.8 mg,
Notes and references
2.50 mmol) or Pd/CM (5.3 mg, 2.50 mmol) in H2O (1 mL)–iPrOH
(1 mL) or in H2O (2 mL) in a test tube under an Ar atmosphere
was stirred at room temperature or 80 ꢁC. Aer complete
1 (a) L. Yin and J. Liebscher, Chem. Rev., 2007, 107, 133; (b)
M. J. Climent, A. Corma and S. Iborra, Chem. Rev., 2011,
111, 1072.
consumption of the aryl halide was conrmed by TLC analyses
2 For unfunctionalized polymer as the support: (a) R. Akiyama
or aer 24 h (if the reaction was incomplete), the mixture was
and S. Kobayashi, Angew. Chem., Int. Ed., 2001, 40, 3469;
passed through a cotton lter to remove the catalyst. To the
Angew. Chem., 2001, 113, 3577; (b) Y. Monguchi, Y. Fujita,
ltrate were added EtOAc (20 mL) and saturated aqueous NH4Cl
K. Endo, S. Takao, M. Yoshimura, Y. Takagi, T. Maegawa
and H. Sajiki, Chem.–Eur. J., 2009, 15, 834; (c) Y. Monguchi,
K. Sakai, K. Endo, Y. Fujita, M. Niimura, M. Yoshimura,
(20 mL), then the layers were separated. The organic layer was
washed with saturated aqueous NH4Cl (2 ꢂ 20 mL) and brine
(20 mL), dried over MgSO4, ltered, and concentrated in vacuo.
T. Mizusaki, Y. Sawama and H. Sajiki, ChemCatChem, 2012,
The residue was puried by ash silica gel column chroma-
4, 546.
tography (n-hexane/EtOAc or CH2Cl2/MeOH/AcOH) to give the
3 (a) D. Sengupta, J. Saha, G. De and B. Basu, J. Mater. Chem. A,
corresponding biaryl. The spectral data of the product were
2014, 2, 3986; (b) V. Pandarus, D. Desplantier-Giscard,
identical to those in the literature.
´
G. Gingras, F. Beland, R. Ciriminna and M. Pagliaro, Org.
Process Res. Dev., 2013, 17, 1492; (c) B. Tamami,
M. M. Nezhad, S. Ghasemi and F. Farjadian, J. Organomet.
Chem., 2013, 743, 10; (d) M. Bakherad, A. Keivanloo and
S. Samangooei, Tetrahedron Lett., 2012, 53, 5773; (e)
Y. M. A. Yamada, S. M. Sarkar and Y. Uozumi, J. Am. Chem.
Soc., 2012, 134, 3190; (f) G. Li, H. Yang, W. Li and
Typical procedure for the 3.9% Pd/AM- and 5% Pd/CM-
catalyzed Mizoroki–Heck reactions (Table 3)
A mixture of the aryl iodide (500 mmol), mono-substituted
alkene (600 mmol), Bu3N (102 mg, 550 mmol), and Pd/AM
(2.7 mg, 1.00 mmol) or Pd/CM (2.1 mg, 1.00 mmol) in DMA
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 1833–1840 | 1839

View Article Online
RSC Advances
Paper
G. Zhang, Green Chem., 2011, 13, 2939; (g) B. Karimi and
P. F. Akhavan, Inorg. Chem., 2011, 50, 6063; (h) P. Das,
D. Sharma, A. K. Shil and A. Kumari, Tetrahedron Lett.,
2011, 52, 1176; (i) M.-J. Jin and D.-H. Lee, Angew. Chem.,
Int. Ed., 2010, 49, 1119; Angew. Chem., 2010, 122, 1137; (j)
D.-H. Lee, M. Choi, B.-W. Yu, R. Ryoo, A. Taher, S. Hossain
and M.-J. Jin, Adv. Synth. Catal., 2009, 351, 2912; (k)
B. Basu, S. Das, P. Das, B. Mandal, D. Banerjee and
T. Yamada, S. Nagata, Y. Monguchi and H. Sajiki,
ChemCatChem, 2013, 5, 2360.
8 Y. Monguchi, T. Ichikawa, K. Nozaki, K. Kihara, Y. Yamada,
Y. Miyake, Y. Sawama and H. Sajiki, Tetrahedron, 2015, 71,
6499.
9 Y. Monguchi, T. Marumoto, T. Ichikawa, Y. Miyake, Y. Nagae,
M. Yoshida, Y. Oumi, Y. Sawama and H. Sajiki,
ChemCatChem, 2015, 7, 2155.
F. Almqvist, Synthesis, 2009, 7, 1137; (l) S. Schweizer, 10 (a) K. Mennecke and A. Kirschning, Beilstein J. Org. Chem.,
J.-M. Becht and C. L. Drian, Org. Lett., 2007, 9, 3777; (m)
R. Sayah, K. Glegola, E. Framery and V. Dufaud, Adv. Synth.
Catal., 2007, 349, 373; (n) L. Wu, B.-O. Li, Y.-Y. Huang,
H.-F. Zhou, Y.-M. He and Q.-H. Fan, Org. Lett., 2006, 8,
3605; (o) K. Okamoto, R. Akiyama, H. Yoshida, T. Yoshida
and S. Kobayashi, J. Am. Chem. Soc., 2005, 127, 2125; (p)
2009, 5, 21; (b) W. Solodenko, H. Wen, S. Leue,
¨
F. Stuhlmann, G. Sourkouni-Argirusi, G. Jas, H. Schonfeld,
U. Kunz and A. Kirschning, Eur. J. Org. Chem., 2004, 3601;
(c) K. Mennecke, R. Cecilia, T. N. Glasnov, S. Gruhl,
C. Vogt, A. Feldhoff, M. A. L. Vargas, C. O. Kappe, U. Kunz
and A. Kirschning, Adv. Synth. Catal., 2008, 350, 717.
A. N. Cammidge, N. J. Baines and R. K. Bellingham, Chem. 11 S. Kumari, A. Kulkarni, G. Kumarasawamy and S. S. Gupta,
Commun., 2001, 2588. Chem. Mater., 2013, 25, 4813.
4 (a) Y. Yabe, Y. Sawama, Y. Monguchi and H. Sajiki, Catal. Sci. 12 D. Kundu, A. K. Patra, J. Sakamoto and H. Uyama, React.
Technol., 2014, 4, 260; (b) H.-Y. Lee, S. Ryu, H. Kang, Y.-w. Jun Funct. Polym., 2014, 79, 8.
and J. Cheon, Chem. Commun., 2006, 1325; (c) H. Hagiwara, 13 M. Nandi and H. Uyama, RSC Adv., 2014, 4, 20847.
T. Nakamura, T. Hoshi and T. Suzuki, Green Chem., 2011, 14 H. Inoue, H. Takada and M. Murayama, Kobunshi
¨
13, 1131; (d) M. Armbruster, M. Behrens, F. Cinquini,
Ronbunshu, 2011, 68, 320. Pd/AM was industrially
produced by Organo Corporation according to the
procedure described in Note and reference;14 palladium
¨
¨
K. Fottinger, Y. Grin, A. Haghofer, B. Klotzer, A. Knop-
Gericke, H. Lorenz, A. Ota, S. Penner, J. Prinz,
´
C. Rameshan, Z. Revay, D. Rosenthal, G. Rupperchter,
species
were
immobilized
on
the ammonium-
¨
´
P. Sautet, R. Schlogl, L. Shao, L. Szentmiklosi, D. Teschner,
D. Torres, R. Wagner, R. Widmer and G. Wowsnick,
ChemCatChem, 2012, 4, 1048; (e) M. V. Vasylyev, G. Maayan,
Y. Hovav, A. Haimov and R. Neumann, Org. Lett., 2006, 8,
functionalized monolithic polymer (AM), and then reduced
with NH2NH2. The palladium loading was determined to
be 3.9 weight% by the inductively coupled plasma-atomic
emission spectrometry (ICP-AES) aer the degradation of
Pd/AM using a microwave heating.
´
5445; (f) J. Le Bras, D. K. Mukherjee, S. Gonzalez,
ˇ
M. Tristany, B. Ganchegui, M. Moreno-Manas, R. Pleixats, 15 H. Inoue, K. Yamanaka, A. Yoshida, T. Aoki, T. Kaneko and
F. Henin and J. Muzart, New J. Chem., 2004, 28, 1550; (g) M. Teraguchi, Kobunshi Ronbunshu, 2004, 61, 301.
E. Thiery, J. Le Bras and J. Muzart, Green Chem., 2007, 9, 16 Reviews including transition metal catalysts immobilized on
´
´
326; (h) N. M. Callis, E. Thiery, J. Le Bras and J. Muzart,
Tetrahedron Lett., 2007, 48, 8128.
5 (a) H. Sajiki, T. Ikawa and K. Hirota, Tetrahedron Lett., 2003,
amphipathic supports: (a) A. Molnar, Chem. Rev., 2011, 111,
2251; (b) J. Lu and P. H. Toy, Chem. Rev., 2009, 109, 815; (c)
S. Ikegami and H. Hamamoto, Chem. Rev., 2009, 109, 583.
44, 171; (b) H. Sajiki, T. Ikawa and K. Hirota, Tetrahedron 17 4.6 mmol gꢀ1 of sulfonic acid groups are distributed evenly
Lett., 2003, 44, 8437; (c) T. Ikawa, H. Sajiki and K. Hirota,
Tetrahedron, 2005, 61, 2217; (d) Y. Kitamura, A. Tanaka,
on the polymer, see the ESI.† The molar ratio of sulfonic
acids to palladium metals is 9.8.
M. Sato, K. Oono, T. Ikawa, T. Maegawa, Y. Monguchi and 18 The TEM image of 3.9% Pd/AM indicates that 10–30 nm-Pd
H. Sajiki, Synth. Commun., 2007, 37, 4381; (e) T. Ikawa,
H. Sajiki and K. Hirota, J. Synth. Org. Chem., Jpn., 2005, 63,
1218.
clusters are formed by the aggregation of Pd nanoparticles
(approximately 5 nm). The palladium species were found
to be dispersed into the whole monolithic polymer by
EPMA, although a partial localization of the species inside
the monolithic polymer was also observed, see the ESI.†
6 (a) T. Maegawa, T. Takahashi, M. Yoshimura, H. Suzuka,
Y. Monguchi and H. Sajiki, Adv. Synth. Catal., 2009, 351,
2091; (b) T. Takahashi, M. Yoshimura, H. Suzuka, 19 4.3 mmol gꢀ1 of ammonium groups are distributed evenly
T. Maegawa, Y. Sawama, Y. Monguchi and H. Sajiki,
on the polymer, see the ESI.† The molar ratio of
Tetrahedron, 2012, 68, 8293.
ammonium functionalities to palladium metals is 10.5.
7 (a) Y. Yabe, T. Yamada, S. Nagata, Y. Sawama, Y. Monguchi 20 T. Maegawa, Y. Kitamura, S. Sako, T. Udzu, A. Sakurai,
and H. Sajiki, Adv. Synth. Catal., 2012, 354, 1264; (b)
Y. Yabe, Y. Sawama, Y. Monguchi and H. Sajiki, Chem.–Eur.
J., 2013, 19, 484; (c) A. Kawanishi, C. Miyamoto, Y. Yabe,
A. Tanaka, Y. Kobayashi, K. Endo, U. Bora, T. Kurita,
A. Kozaki, Y. Monguchi and H. Sajiki, Chem.–Eur. J., 2007,
13, 5937.
M. Inai, T. Asakawa, Y. Hamashima, H. Sajiki and T. Kan, 21 S. Mori, T. Yanase, S. Aoyagi, Y. Monguchi, T. Maegawa and
Org. Lett., 2013, 15, 1306; (d) Y. Yabe, Y. Sawama, H. Sajiki, Chem.–Eur. J., 2008, 14, 6994.
1840 | RSC Adv., 2017, 7, 1833–1840
This journal is © The Royal Society of Chemistry 2017