Ligand-free Suzuki-Miyaura coupling reaction of an aryl chloride using a continuous irradiation type microwave and a palladium nanoparticle catalyst: Effect of a co-existing solid

Article abstract of DOI:10.1039/c9gc01043b

We have explored the effect of a co-existing metal in the ligand-free Suzuki-Miyaura coupling reaction of an aryl chloride, which is promoted by a "continuous irradiation type microwave" and a "palladium nanoparticle catalyst", and found that the co-existing metal affects this reaction due to its absorption ability of microwave energy in the reaction system. We also observed that spiking occurred more frequently in the presence of a co-existing metal.

Full text of DOI:10.1039/c9gc01043b

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Article
DOI: 10.1039/C9GC01043B
Ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using a continuous irradiation
type microwave and palladium nanoparticle catalyst: Effect of a co-existing solid
a
a
a
b
c
Makito Yamada , Yasunori Shio , Toshiki Akiyama , Tetsuo Honma , Yuuta Ohki , Naoyuki
c
a
a
Takahashi ,Kenichi Murai , and Mitsuhiro Arisawa*
a
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka
5
65-0871 Japan.
b
Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo
6
79-5198 Japan.
c
Tokyo Rikakikai Co., Ltd. (Brand: EYELA), TN Koishikawa Bldg. 1-15-17 Koishikawa Bunkyo-ku,
Tokyo 112-0002 Japan.
*
Corresponding Author. Phone: +81-6-6879-8226, Fax: +81-6-6879-8229,
E-mail: arisaw@phs.osaka-u.ac.jp
Abstract
We have explored the effect of a co-existing metal in the ligand-free Suzuki–Miyaura coupling
reaction of an aryl chloride, which is promoted by a “continuous irradiation type microwave” and
“palladium nanoparticle catalyst”, and found that the co-existing metal affects this reaction due to its
absorption ability of microwave energy in the reaction system. We also observed that spiking
occurred more frequently in the presence of a co-existing metal.
Introduction
In the synthesis of functional organic molecules, such as pharmaceuticals, agrochemicals, and
semi-conductor monomers, using a transition metal catalyst in carbon–carbon bond forming
1
reactions is extremely important. Aryl bromides, iodides, and triflates have been extensively
investigated for use as substrates in the Suzuki-Miyaura coupling, since they are easily activated by
2
active Pd(0) species. On the other hand, aryl chlorides, which are more economical and accessible
than the previously mentioned species, have rarely been used in Pd-catalysed Suzuki coupling due to
1

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the high activation barriers associated with the difficult oxidative insertion of Pd(0)
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Ar−Cl bond. A large amount of studies have focused primarily on designing electron-rich catalytic
sites on homogeneous catalysts by introducing special and costly ligands, such as sterically hindered
4
and electron-rich phosphanes and N-heterocyclic carbenes or palladacycles that facilitate activation
of the C−Cl bond. However, the contamination of the products by Pd residues, even after the
5
purification step, poses an acute problem, particularly for the pharmaceutical industry. To solve this
6
problem, ligand-free heterogeneous Pd-based catalysts have attracted much attention. However,
recyclable and low-leaching ligand-free Pd protocols that catalyse Suzuki–Miyaura cross-coupling
with aryl chlorides have been challenging to study.
Scheme 1. Preparation of ruthenium nanoparticle catalyst supported on gold, SARu, sulfur-modified
Au-supported ruthenium.
Scheme 2. SARu-catalysed ligand-free Suzuki–Miyaura coupling of 1a with 2a.
Under these circumstances, we recently developed ligand-free Suzuki–Miyaura coupling of aryl
chloride using a "continuous irradiation microwave" and a "proprietary ruthenium nanoparticle
catalyst supported on gold, named SARu, sulfur-modified Au-supported ruthenium" (Schemes 1, 2;
7
Table 1). SARu can be used repeatedly as a ruthenium reservoir, and the “continuous irradiation
type microwave” drastically changes the product yield. Although microwaves have been used to
8
accelerate Suzuki–Miyaura coupling or other metal catalysed reactions, in our experiments, a
"continuous irradiation microwave" worked more efficiently than a conventional microwave or
conventional heating. We considered what was activated by a "continuous irradiation microwave" in
2

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the reaction mixture and reached three possibilities: 1) the C–Cl bond on Ar–Cl, 2
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nanoparticle (SARu), 3) or the gold as a solid support.
Table 1. Liquid phase combinatorial synthesis using SARu and aryl chlorides.
Ar–Cl
Ar–Cl
Entry
1
Yield
Entry
Yield
a
a
(
%)
(%)
Cl
Cl
3a (93)
3b (60)
3g (52)
3d (84)
5
6
7
8
3e (76)
3f (83)
3g (70)
3h (65)
N
1
a
1e
Cl
Cl
2 MeO
N
1
b
1f
Cl
Cl
3
4
Me
S
1
c
1g
Cl
Cl
N
O N
2
1
d
H
1h
a
Isolated yields.
Scheme 3. Preparation of palladium nanoparticle catalyst supported on glass, SGlPd, sulfur-modified
glass-supported palladium.
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In this paper, we studied whether there was a third possibility, effect of a co-existing solid; we were
interested in whether the ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using this
continuous irradiation type microwave proceeds even when SARu with gold as a solid support is
1
0
substituted with SGlPd, sulfur-modified glass-supported palladium (Scheme 3) using glass as a
solid support. Furthermore, as re-confirmation, a metal solid was added to the ligand-free Suzuki–
Miyaura coupling reaction of aryl chloride using SGlPd and a continuous irradiation type
microwave.
Results and Discussion
Ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using a continuous irradiation
type microwave and SGlPd.
In the beginning, we tried the ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using a
continuous irradiation type microwave and SGlPd under the conditions listed in Table 1, and we
knew that no reaction proceeded. Then, we continued our experiments to find reaction conditions for
this reaction using solvents with higher boiling points than dimethoxyethane (DME) (Table 2).
When the reaction was carried out using toluene or 1-BuOH, the reaction hardly proceeded (entries 1,
2
). On the other hand, when using p-xylene, which is known for its low microwave absorption ability,
the expected coupling product 3a was obtained in 96% yield (entry 3). Next, using a non-continuous
irradiation type microwave device under the same conditions as listed in entry 3, the yield of 3a
decreased to 5% (entry 4). In addition, when dimethylformamide (DMF), ethylene glycol (EG),
glycerol, ionic liquid, or natural deep entectic solvents were used, which have higher boiling points
than p-xylene, large amounts of Pd nanoparticles leaked from SGlPd and agglomerated, and the
reaction did not proceed at all (entries 5-10) because SGlPd cannot stand these highly polar solvents.
The reaction did not proceed without base (entry 11) and requires an apporopriate base (entries
1
2-16). From these results, the condition described in entry 3 using p-xylene was optimized, and we
confirmed that gold is not needed as a solid support for the ligand-free Suzuki–Miyaura coupling
reaction of aryl chloride to proceed using a continuous irradiation type microwave and Pd
nanoparticle.
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Table 2. Suzuki–Miyaura coupling between 1a and 2a using SGlPd under high tempe
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conditions.
a
b
Entry Solvent
base
Temp. 1 MW1
°C)
Temp. 2 Yield (%)
(°C)
(
(W)
70
70
70
400
70
70
70
70
70
70
70
70
70
70
70
70
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
toluene
K
3
PO
PO
PO
PO
PO
PO
PO
PO
PO
PO
4
4
4
4
4
4
4
4
4
4
110
117
128
128
120
100
128
128
128
128
128
128
128
110
117
130
130
120
100
130
130
130
130
130
130
130
130
130
130
trace
2
t-BuOH
p-xylene
p-xylene
K
3
K
3
96
5
c
K
3
dimethylformamide,DMF K
3
nr
d
ethyleneglycol, EG
glycerol
K
3
nr
K
3
nr
e
MBITFB
K
3
nr
f
deep eutectic solvent 1
deep eutectic solvent 2
p-xylene
K
3
nr
g
0
1
2
3
4
5
6
K
3
nr
-
nr
p-xylene
K
2
CO
3
92
21
73
92
68
p-xylene
Na
2
CO
3
t
p-xylene
BuOK 128
p-xylene
Cs
2
CO
3
128
128
p-xylene
NaOH
a
b
c
Microwave power in the first step. Isolated yields. The reaction was performed using Anton-paar’s
d
Micromodel 3. The reaction time in step 1 was shortened to 5 min due to substantial Pd leaching.
e
f
1
-butyl-3-methylimidazolium tetrafiuoloborate. choline chloride : phenylpropionic acid = 1 : 1.
g
choline chloride : urea = 1 : 2.
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Figure 1. Temperature of SGlPd and glass (control experiment) as well as reaction mixture solution
determined by infrared camera
We measured temperature of SGlPd and glass (control experiment) as well as reaction mixture
solution using infrared camera, FLIR CHINO CPA-T540S (Figure 1). As far as these results, no
significant temperature difference could be confirmed.
Subsequently, when SGlPd was repeatedly used 10 times for the Suzuki–Miyaura coupling under the
conditions listed in Table 2 (entry 3), in each case, the coupling product was obtained in high yield.
Therefore, the amount of Pd leaking into each reaction solution was measured by inductively
coupled plasma mass spectrometry (ICP-MS) (Table 3). As a result, it was found that up to 93 ng
(
7.14 ppm) of Pd leaked into the reaction solution. A high yield of product 3a was maintained for
each repeated use.
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Table 3. Ligand-free Suzuki–Miyaura coupling between 1a and 2a using SGlPd and c
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irradiation microwave: repeatedly use and it’s Pd leakage in the reaction solution.
b
c
d
Run
Yield of 3a Amount of released Pd (ng , mmol% , % ,
a
e
-1 f
(
%)
TON , TOF h )
1
2
st
98
97
93, 0.35, 0.13, 28571, 1120
nd
27, 0.10, 0.037, 100000, 3922
3
4
5
6
7
8
9
1
rd
th
th
th
th
th
th
0th
98
96
96
94
92
90
89
90
87, 0.33, 0.12, 30303, 1188
34, 0.13, 0.047, 76923, 3017
27, 0.10, 0.037, 100000, 3922
29, 0.11, 0.040, 90909, 3565
15, 0.056, 0.021, 178571, 7003
5.3, 0.020, 0.0073, 500000, 19608
4.7, 0.018, 0.0065, 555556, 21786
11, 0.040, 0.015, 250000, 9804
b
Total released
350
g)
b
Used SGlPd
30333
a
Yields were determined by HPLC, high-performance liquid-chromatography, and are average
b
values of three sets of reactions. The amount of Pd released into the reaction mixture is the average
c
d
value of three sets of reactions. mmol% of Pd species in the reaction mixture. % of Pd employed in
e
f
the catalysis. Turn over number based on the amount of released Pd Turn over frequency calculated
g
by TOF/25.5 h The amount of Pd on SGlPd after 10 cycles of Suzuki–Miyaura coupling. The
amount of Pd on SGlPd before Suzuki–Miyaura coupling is 36666 ng.
Next, the valency of Pd on SGlPd was measured by XAFS, x-ray absorption fine structure analysis
(
Figure 2). As a result, the graph of SGlPd (before green use, after purple use) before and after use
almost agreed with the graph (blue) of zero valent Pd foil. From this, it was found that Pd supported
on SGlPd had zero valence before and after use. Next, we examined the substrate adaptation range of
this reaction condition.
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Figure 2. XANES, x-ray absorption fine structure analysis, spectrum of the Pd–K edge.
Encouraged by the above results, SGlPd was repeatedly used for the Suzuki–Miyaura coupling of
aryl chlorides 1 and phenyl boronic acid 2a. SGlPd was taken from the reaction solution with a pair
of tweezers after completion of the first step of the reaction. Then, the surface was washed with
ethanol, dried under reduced pressure, and repeatedly used. As a result, it was confirmed that the
corresponding coupling were efficiently proceeded, with arylbenzoyl chloride 1b, 1i, 1d, and 1k in
which the electron-donating group and the electron-withdrawing group are substituted on the
benzene ring. Also ortho-substituted aryl chloride 1c was converted to the corresponding
compound 3c in 92% yield. In addition, the objective coupled product was obtained in good yield
from bicyclic compound 1j and aryl chloride 1f, 1e, and 1g, having a hetero atom (Table 4). In the
case of using a substrate substituted with an electron-withdrawing group or pyridine (entries 5-8), the
yield of the coupled product tended to be low (starting material remained), but more Pd NPs leaked
from the SGlPd surface due to chemical etching by oxidative addition of the substrate. It is
considered to have aggregated/inactivated.
This was likewise the case when the boronic acid derivative was changed. SGlPd was also repeatedly
used for the Suzuki–Miyaura coupling of aryl chloride 1a and phenyl boronic acids 2 (Table 5).
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Table 4. Ligand-free Suzuki–Miyaura coupling between 1 and 2a using SGlPd and co
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irradiation microwave: application to liquid phase combinatorial synthesis.
a
Ar–Cl
Ar–Cl
Entry
Yield
Entry
Yield (%)
a
(
%)
1
2
3
3b (91)
3i (98)
3c (92)
5
6
7
3d (60)
3k (80)
3f (72)
1
1
b
i
1d
1k
1
1
1
f
1
1
c
j
4
3j (98)
8
9
3e (65)
3g (84)
e
g
a
Isolated yields.
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Table 5. Ligand-free Suzuki–Miyaura coupling between 1a and 2 using SGlPd and continuous
irradiation microwave: application to liquid phase combinatorial synthesis (2).
a
a
ArB(OH)
2
ArB(OH)
-naphthyl
B(OH)
2
Entry
1
Yield (%) Entry
Yield (%)
1
3b (94)
5
2
3j (82)
2
f
2
2
2
b
c
2
3
3i (90)
3k (93)
6
7
3g (90)
3c (88)
2g
2h
d
4
3d (98)
8
9
3f (89)
3e (87)
2
e
2i
2
j
a
Isolated yields.
Ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using a continuous irradiation
type microwave and SGlPd with a co-existing metal (aluminium foil).
Experimental results thus far have revealed that the co-existing metal (gold) plays some role in the
ligand-free Suzuki–Miyaura coupling reaction of an aryl chloride using a continuous irradiation type
microwave and SGlPd. We also found that Suzuki–Miyaura coupling of an aryl chloride using
SGlPd proceeds under harsher reaction conditions than when using SARu. It is expected that
microwave absorption will change depending on whether gold or glass is present during microwave
irradiation, and this will affect reactivity.
1
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Therefore, when a metallic solid is added to the reaction solution, the reaction of SGlPDO
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completed under milder conditions than when no metallic solid is added. First, aluminium foil, which
is most easily available and cheaper than gold, was added to the first stage of the optimum conditions
listed in Table 4, and the absorption of microwaves was compared. As a result, it was confirmed that
the amount of microwave absorption increased in the reaction system with added aluminium foil
(
Figure 3). Furthermore, under the conditions with aluminium foil, we observed more frequent
spiking. Higher microwave energy was absorbed for a short period.
Figure 3. Difference in microwave absorption amount depending on the presence/absence of Al foil.
Next, the reaction time in the second step was fixed at 9 h, and the reaction condition in the first step
was examined (Table 6). In Entry 1, when the output of the microwave was weak, the yield of the
corresponding coupled product 3a was as low as about 40%. Therefore, in Entry 2, when the
microwave output was increased to 50 W, 3a was quantitatively obtained. Therefore, in Entry 3, the
reaction time was shortened to 1 h while the microwave output was maintained at 50 W. As a result,
the yield of 3a was maintained at 98%. In Entry 6, the reaction time was further shortened, but the
yield decreased to 43%. Finally, in Entry 5, the reaction was carried out under the conditions of
Entry 3 using a microwave device that was not continuously irradiated. However, in this case, sparks
occurred in the reaction system, SGlPd was pulverized, and a large amount of Pd leaked; therefore,
the reaction did not proceed. Based on the above results, the condition of Entry 3 was optimized.
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Table 6. Ligand-free Suzuki–Miyaura coupling between 1a and 2a using SGlPd, Al f
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continuous irradiation microwave; optimization of step 1 conditions.
Entry
MW (W)
30
Time (h)
Yield (%)
1
2
3
4
1.5
1.5
1
42
99
98
43
nr
50
50
50
0.5
-
a, b)
5
400
a
The reaction was performed using Anton Paar’s MW instrument.
a
A spark was caused.
Scheme 4. Ligand-free Suzuki–Miyaura coupling between 1a and 2a using SGlPd, Al foil, and
continuous irradiation microwave; control experiments with/without Al foil, a co-existing metal.
As a control experiment, differences in reactivity with and without aluminium foil were compared by
subjecting benzene chloride (1a) to the above optimum conditions without using aluminium foil
(
Scheme 4). As a result, almost no reaction proceeded when aluminium foil was not added, and it
was shown that the reaction was accelerated by adding aluminium foil.
In summary, based on our experiments investigating what is activated by a "continuous irradiation
microwave" in the ligand-free Suzuki–Miyaura coupling reaction of aryl chloride using a palladium
nanoparticle catalyst (SGlPd), we found that a co-existing metal plays some important role, even
though the reaction itself proceeds without a co-existing solid under harsher conditions (Tables 2–5),
and there is still the possibility that "continuous irradiation microwave" largely affects the “C–Cl
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bond on Ar–Cl” or the “metal nanoparticle”. In the presence of aluminium foil, the re
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proceeded efficiently under milder conditions than in the absence of aluminium foil because
microwave absorption and spiking increased in the presence of aluminium foil, as shown in Figure
3
.
Experimental
Preparation of SGlPd
2
A 10 × 10 mm sample of glass was placed in piranha solution for 15 min and then rinsed in
succession with H O (2 mL × 6) and EtOH (2 mL × 6). The sample was placed in a flask and dried
2
for 10 min under reduced pressure. The resulting sulfur-modified glass [S-Gl] was placed ins
solution of Pd(OAc)2 (5.3 mg, 0.024 mmol) in p-xylene (3.0 mL) and stirred at 100 ℃for 12 h
under a N atmosphere. Then the plate was rinsed with p-xylene (2 mL × 6) and dried under vacuum.
2
The obtained plate was placed in p-xylene (3 mL) and heated at 135 ℃for 12 h two times. The plate
was rinsed with p-xylene (2 mL × 6) and dried under vacuum for 10 min to give SGlPd (Pd: 36.7 ±
9
μg).
SGlPd-catalyzed ligand-free Suzuki-Miyaura coupling with continuously irradiating
microwave (Table 2, Entry 3)
A mixture of chlorobenzene (1a) (28.1 mg, 0.25mmol), phenylboronic acid (2a) (45.7 mg, 0.375
2
mmol), K
3
PO
4
(159.1 mg, 0.75 mmol) and SGlPd (10 × 10 mm , Pd: 36 ± 9 μg) was heated in a
p-xylene (2.0 mL) at 128 ℃ and irradiated by semi-conductor type microwave machine for 1.5 h.
After the reaction mixture had been cooled to room temperature, the SARu mesh was removed from
the reaction mixture and rinsed several times with EtOH. Then, H
reaction mixture and whole was stirred at 100 ℃ for 10 h. After the reaction mixture had been
cooled to room temperature, sat. NH Cl (4.0 mL) was added, and the reaction mixture was
concentrated in vacuo and extracted with AcOEt. The organic layer was washed with brine, dried
over anhydrous Na SO and concentration under reduced pressure. The resulting crude product was
purified by silica gel column chromatography (100% hexane) to provide a title compound, biphenyl
3a, 96%, 37.0 mg) as a colorless plate.
2
O (1.0 mL) were added into the
4
2
4
(
Recycling experiment of SGlPd-catalyzed ligand-free Suzuki-Miyaura coupling (Table 3, run
1
)
A mixture of chlorobenezene (1a) (28.1 mg, 0.25 mmol), phenylboronic acid (2a) (45.7 mg, 0.375
2
mmol), K
3
PO
4
(159.1 mg, 0.75 mmol) and SGlPd (10 × 10 mm , Pd: 36 ± 9 μg) in a p-xylene (2.0
mL) was heated and irradiated by semi-conductor type microwave machine at 70 W and 128 ℃ for
1
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1
.5 h. After the reaction mixture had been cooled to room temperature, the SGlPd plat
from the reaction mixture and rinsed several times with EtOH. Then, H O (2.0 mL) were added into
the reaction mixture and whole was stirred at 130 ℃for 24 h. The yield was measured using HPLC
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(
(
Condition: Mightysil-RP18 (150 mm, φ 4.6 mm, 3 μm, Kanto Chemical Co. Inc.), MeCN : H
75/25), 0.80 mL/min, 35 ℃, tR 9.8 min).
2
O
ICP-Mass analysis
The whole reaction mixture or SGlPd substrate was treated with concentrated nitric acid, and Pd
species in this mixture was examined by ICP-Mass.
Typical experimental procedure of successively SGlPd-catalyzed ligand-free Suzuki-Miyaura
coupling with continuously irradiating microwave heating (Table 4, Entry 1)
A mixture of 4-chloroanisole (1b) (35.6 mg, 0.25mmol), phenylboronic acid (2a) (45.7 mg, 0.375
2
mmol), K
3
PO
4
(159.1 mg, 0.75 mmol) and SGlPd (10 × 10 mm , Pd: 36 ± 9 μg) was heated in a
p-xylene (2.0 mL) and irradiated by semi-conductor type microwave machine at 70 W and 80 ℃for
.5 h. After the reaction mixture had been cooled to room temperature, the SARu mesh was removed
from the reaction mixture and rinsed several times with EtOH. Then, H O (2.0 mL) were added into
the reaction mixture and whole was stirred at 130 ℃ for 24 h. After the reaction mixture had been
cooled to room temperature, sat. NH Cl (4.0 mL) was added, and the reaction mixture was
concentrated in vacuo and extracted with AcOEt. The organic layer was washed with brine, dried
over anhydrous Na SO and concentration under reduced pressure. The resulting crude product was
purified by silica gel column chromatography (100% hexane) to provide a title compound, biphenyl
3b, 98%, 45.1) as a colorless plate. The recovered SGlPd plate was again subjected to the above
1
2
4
2
4
(
reaction as a next run. This procedure was repeated for a total 9 runs.
Measurement of microwave absorption (Figure 2)
A mixture of chlorobenzene (5a) (28.1 mg, 0.25 mmol), phenylboronic acid (2h) (45.7 mg, 0.375
2
mmol), K
3
PO
4
(159.1 mg, 0.75 mmol) and SGlPd (10 × 10 mm , Pd: 107 ± 63 μg) in p-xylene (2.0
2
mL) was heated with aluminum foil (14 × 12 mm , 5 mg) and irradiated by semi-conductor type
microwave machine at 70 W and 128 ℃for 1.5 h. In this occasion, microwave machine measured
quantity of microwaves as absorption quantities except a received microwave by a receiving antenna
and lost microwave via a reflection, transmission, and insertion loss.
Research the effect of coexisting metal in the SGlPd-catalyzed Suzuki-Miyaura coupling under
continuous microwave irradiation (Scheme 4)
1
4

Page 15 of 20
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A mixture of chlorobenezene (1a) (28.1 mg, 0.25 mmol), phenylboronic acid (2a) (45
D
.
O
7
I:
m
10
g
.10
,
3
0
9
.
/C
3
9GC01043B
7
5
2
mmol), K
3
PO
4
(159.1 mg, 0.75 mmol), SGlPd (10 × 10 mm , Pd: 107 ± 63 μg) with or without
3
aluminum foil (12 × 14 × 0.05 mm ) in a p-xylene (2.0 mL) was heated and irradiated by
semi-conductor type microwave machine at 50 W and 128 ℃ for 1 h. After the reaction mixture had
been cooled to room temperature, the SGlPd plate and aluminum foil was removed from the reaction
mixture and rinsed several times with EtOH. Then, H
mixture and whole was stirred at 130 ℃for 9 h. After the reaction mixture had been cooled to room
temperature, sat. NH Cl (4.0 mL) was added, and the reaction mixture was concentrated in vacuum
and extracted with AcOEt. The organic layer was washed with brine, dried over anhydrous Na SO
2
O (2.0 mL) were added into the reaction
4
2
4
and concentration under reduced pressure. The resulting crude product was purified by silica gel
column chromatography (100% hexane) to provide a title compound, biphenyl (4g, with: 98%,
without: 2%) as a colorless plate.
1
1, 12
Biphenyl 3a
Mp. 70.0-70.5 ℃ (MeOH) (lit. 70.0-71.0 ℃, MeOH), colorless plate; H NMR (500 MHz, CDCl
2
1
3
)
δ: 7.58 (d, J = 8.0 Hz, 4H), 7.42 (dd, J = 8.0 and 7.4 Hz, 4H), 7.33 (dd, J = 7.4 and 7.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 141.2, 128.7, 127.2, 127.1.
1
1, 12
4
-Methoxybiphenyl 3b
Mp. 89.5-90.0 ℃ (MeOH) (lit. 90-91 ℃, MeOH), a colorless powder; H NMR (400 MHz, CDCl
δ: 7.59-7.50 (m, 4H), 7.42 (dd, J = 7.3 and 7.3 Hz, 2H), 7.30 (dd, J = 7.3 and 7.3 Hz, 1H), 6.98 (d, J
2
1
3
)
1
3
=
8.2 Hz, 2H), 3.85 (s, 3H); C NMR (100 MHz, CDCl ) δ: 140.8, 138.2, 133.7, 128.7, 128.1, 126.7,
3
1
26.6, 114.2, 55.3.
1
1, 13
4-Methylbiphenyl 3i
1
5

Green Chemistry
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3
1
Mp. 50.0-50.5 ℃ (EtOH) (lit. 49.0-50.0 ℃, EtOH), a colorless crystal; H NMR (40
D
0
O
M
I: 10
H
.1
z
03
,
9
C
/C
D
9G
C
C0
l
31 043B
)
δ: 7.58 (d, J = 7.3 Hz, 2H), 7.50 (d, J =7.8 Hz, 2H), 7.43 (dd, J = 7.8 and 7.3 Hz, 2H), 7.32 (dd, J =
1
3
7
1
.3 and 7.3 Hz, 1H), 7.25 (d, J = 7.8 Hz, 2H), 2.40 (s, 3H); C NMR (100 MHz, CDCl
3
) δ: 141.1,
38.3, 137.0, 129.4, 128.7, 128.6, 127.0, 126.9, 21.1.
1
4
2
-Methylbiphenyl 3c
1
A colorless oil; H NMR (400 MHz, CDCl
3
) δ: 7.44-7.38 (m, 2H), 7.36-7.30 (m, 3H), 7.29-7.21 (m,
13
4
H), 2.27 (s, 3H); C NMR (100 MHz, CDCl
3
) δ: 141.9, 135.3, 130.3, 129.8, 129.2, 128.0, 127.4,
1
26.7, 125.7, 20.5.
1
5, 16
1
-Phenylnaphthalene 3j
1
13
A colorless oil; H NMR (400 MHz, CDCl
3
) δ: 7.94-7.81 (m, 3H), 7.56-7.37 (m, 9H); C NMR (100
Hz, CDCl
3
) δ: 140.7, 140.2, 133.7, 131.6, 130.0, 128.23, 128.22, 127.6, 127.2, 126.9, 126.8, 126.0,
125.7, 125.3.
1
7, 18
4
Mp. 113.0-113.5 ℃ (MeOH) (lit. 113-115 ℃, MeOH), a yellow needle-like crystal; H NMR (400
MHz, CDCl ) δ: 8.31 (d. J = 8.2 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 7.3 Hz, 2H),
-Nitrobiphenyl 3d
7
1
3
1
3
7
.52-7.45 (m, 3H); C NMR (100 Hz, CDCl ) δ: 147.6, 147.0, 138.7, 129.1, 128.9, 127.8, 127.4,
3
1
24.1.
1
9, 20
4-Acetylbiphenyl 3k
1
6

Page 17 of 20
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9
1
Mp. 120.5-121.0 ℃ (MeOH) (lit. 120 ℃, EtOH), an off-white powder; H NMR (40
D
0
O
M
I: 10
H
.10
z
3
,
9
C
/C
D
9G
C
C0
l
13 043B
)
δ: 8.04 (d, J = 7.9 Hz, 2H), 7.69 (d, J = 7.9 Hz, 2H), 7.63 (d, J = 7.3 Hz, 2H), 7.48 (dd, J = 7.3 and
1
3
7
1
.3 Hz, 2H), 7.41 (dd, J = 7.3 and 7.3 Hz, 1H), 2.65 (s, 3H); C NMR (100 Hz, CDCl
3
) δ: 197.8,
45.8, 139.9, 135.8, 129.0, 128.9, 128.2, 127.3, 127.2 26.7.
2
1, 22
2
-Phenylpyridine 3f
1
A light yellow oil; H NMR (400 MHz, CDCl
3
) δ: 8.70 (d, J = 4.6 Hz, 1H), 8.03-7.94 (m, 2H),
1
3
7
1
.77-7.70 (m, 2H), 7.52-7.37 (m, 3H), 7.26-7.19 (m, 1H); C NMR (100 Hz, CDCl
3
) δ: 157.4, 149.6,
39.3, 136.7, 128.9, 128.7, 126.8, 122.0, 120.5.
2
1, 23
3
-Phenylpyridine 3e
1
A colorless oil; H NMR (400 MHz, CDCl
3
) δ: 8.85 (d, J = 2.3 Hz, 1H), 8.58 (dd, J = 4.8 and 1.6 Hz,
1
2
H), 7.84 (ddd, J = 7.8, 1.5 and 0.8 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 7.8 and 7.3 Hz,
1
3
H), 7.38 (dd, J = 7.6 and 7.1 Hz, 1H), 7.33 (dd, J = 7.6 and 5.3 Hz, 1H); C NMR (100 Hz, CDCl )
3
δ: 148.3, 148.2, 137.6, 136.4, 134.2, 128.9, 127.9, 127.0, 123.4.
1
1, 21
3-Phenylthiophene 3g
1
1
Mp. 89.5-90.0 ℃(EtOH) (lit. 89-91 ℃, EtOH), a colorless plate; H NMR (400 MHz, CDCl
3
) δ:
1
3
7
.60 (d, J = 7.3 Hz, 2H), 7.51-7.34 (m, 5H), 7.33-7.24 (m, 1H); C NMR (100 Hz, CDCl
3
) δ: 142.3,
1
35.8, 128.8, 127.1, 126.4, 126.3, 126.2, 120.2
Acknowledgements
The XAFS measurements were performed at beamlines BL14B2 of SPring-8, with the approval of
the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal nos. 2017A1793, 2017B1931,
2
017B1732, 2018A1727 and 2018A1793). This work was partially supported by a Grant-in-Aid
from JSPS KAKENHI for Precisely Designed Catalysts with Customized Scaffolding (Grant No. JP
1
7

Green Chemistry
Page 18 of 20
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A16H010260 and 18H04260), A262880510, T15K149760, and T15KT00630, by Pla
D
tf
O
o
I:
r
1
m
0.10
P
3
r
9
o
/C
j
9
e
GC01043B
c
t
for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug
Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP18am0101084,
by Shorai Foundation for Science and Technology and by TEPCO Memorial Foudation.
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Graphical Abstract
DOI: 10.1039/C9GC01043B
2
0