L. Geng et al. / Catalysis Communications 82 (2016) 24–28
27
catalyst Pd@NPad2-1.0 can be detected by 31P NMR at 42 ppm, which is
Table 3
Suzuki-Miyaura coupling of aryl bromides and phenylboronic acid.a
in agreement with the -P(Ad)2 group on phenyl group (see Fig. S8).
The Pd@NPad2-1.0 was studied for the Suzuki-Miyaura reaction of 4-
chloroanisole with phenylboronic acid and the results are listed in
Table 1. Solvents and bases were optimized for the reaction of 4-
chloroanisole with phenylboronic acid. Several solvents were tested,
and i-PrOH with water (i-PrOH/water, 1/1) was found to be the best sol-
vent, and 4-methoxybiphenyl was obtained in 94% yield (Table 1, en-
tries 1–13). Carbonate bases, such as K2CO3, Na2CO3 and Cs2CO3 are
suitable bases, and K3PO4 and NaOH were less effective for the transfor-
mation (Table 1, entries 1 and 14–17). The loading of catalyst Pd@
NPad2-1.0 was also tested and only 0.02% of Pd (Pd@NPad2-1.0) was re-
quired for the transformation, and 4-methoxybiphenyl was obtained in
92% yield within 18 h (Table 1, entries 18–20). The catalysts Pd@NPad2-
0.5 and Pd@NPad2-2.0 (contained 0.38 wt% and 1.7 wt% of Pd respec-
tively) were found to be similarly active and selective for the coupling
reaction of 4-chloroanisole with phenylboronic acid (Table 1, entries
21, 22). For comparison, the commercial Pd/C was found to be not active
under the same reaction conditions (Table 1, entry 23).
Entry
R
Yield(%)b
TONc
1
2
3
4
5
6
4-MeO
4-NO2
4-Me
4-CHO
4-MeCO
4-CN
4-tert-Butyl
2-MeO
2-Me
100
100
90
100
100
100
100
99
250,000
250,000
225,000
250,000
250,000
250,000
25,000
24,750
24,750
24,750
24,750
7d
8d
9d
10d
11d
99
99
99
2-CN
2-NO2
a
Reaction conditions: aryl bromides, 25.0 mmol; phenylboronic acid, 37.5 mmol;
Pd@NPad2–1.0 catalyst, 1.35 mg; Pd, 4.0 ppm; K2CO3, 50.0 mmol; i-PrOH/H2O, 20 mL; at
100 °C; 6 h; under argon.
b
Isolated yield, based on aryl bromide.
Turn over number, suppose every Pd atom is accessible for the reaction.
Pd@NPad2-1.0 catalyst, 14.0 mg; Pd, 40 ppm; 10 h.
c
d
Using the optimized reaction conditions, we tested the application
scope of the Pd@NPad2-1.0 for the coupling of aryl chlorides with aryl
boronic acids, and various aryl chlorides were used for the Pd@NPad2–
1.0 catalyzed Suzuki-Miyaura reaction. The results are listed in
Table 2. The coupling reaction of aryl chlorides with phenylboronic
acid gave the corresponding biphenyl compounds in excellent yields
with 0.02 mol% Pd loading of Pd@NPad2-1.0 under mild conditions
(Table 2, entries 1–9). Electron-donating and electron-withdrawing
groups, such as methyl, methoxyl, nitro, nitrile, acyl and formyl groups
were well tolerated, and the corresponding products were obtained in
high yields (Table 2, entries 1–9). Moreover, substituted phenylboronic
acids such as 4-methylphenylboronic acid and 4-methoxylphenylboronic
acid, can also be used for the coupling reaction with high yields of the
corresponding products (Table 2, entries 10–12). Interestingly, the cou-
pling of 2-chlorobenzonitrile with 4-methylphenylboronic acid gave
sartanbiphenyl in 100% yield, as sartanbiphenyl is a significant interme-
diate for the production of sartans, which are used widely as hyperten-
sion drugs.
para-substituents, including methoxyl, nitrile, methyl, nitro, tert-butyl,
formyl and acyl groups were well tolerated under the reaction condi-
tions. The corresponding biphenyls were obtained in good to excellent
yields, and the maximum of TON was up to 250,000 (Table 3, entries
1–6). The coupling of ortho-substituted aryl bromides with
phenylboronic acid also afforded the corresponding biphenyls in excel-
lent yields with increased Pd loading (Table 3, entries 7–11).
To explore the Pd@NPad2-1.0 catalyst in industrial application, we
studied the coupling of 2-nitrochlorobenzene with 4-chloro-
phenylboronic acid (see Scheme 2), as the corresponding product 4′-
chloro-2-nitro-1,1′-biphenyl is a key intermediate for the production
of Boscalid (Bactericide). The coupling of 2-nitrochlorobenzene and 4-
chlorophenylboronic acid proceeded smoothly to the corresponding
product in 98% yield. Moreover, the Pd@NPad2-1.0 catalyst can be re-
covered easily by centrifugation and reused several times. And the reus-
ability of Pd@NPad2-1.0 catalyst was studied for the coupling of 2-
nitrochlorobenzene with 4-chloro- phenylboronic acid. As shown in
Fig. 2, the yield of the product was decreased slightly, and the deactiva-
tion may be due to oxidation of P ligand and the slightly aggregation of
the Pd nanoparticles. In order to examine the leaching of Pd from Pd@
NPad2-1.0 catalyst, Pd in the reaction solution was measured by ICP-
AES after removal of the Pd@NPad2-1.0 catalyst (stopped after 3 h),
and no Pd was detected in the solution (below detect limit, b7 ppb).
The solution was not active any more for the cross-coupling reaction.
It is indicated that the catalyst Pd@NPad2-1.0 is heterogeneous for
Suzuki-Miyaura reaction, and no contamination (ligand or Pd) was
found from the catalyst system, which is important for pharmaceutical
chemistry.
As some aryl bromides are also cheap and available widely, we in-
vestigated the coupling of aryl bromides and phenylboronic acid with
the Pd@NPad2-1.0 catalyst, and the results are listed in Table 3. The
Pd@NPad2-1.0 catalyst showed ultimate activity for the coupling of
aryl bromides and phenylboronic acid, and only 4 ppm Pd loading was
required under mild conditions (Table 3, entries 1–6). 4-Bromoanisole
was coupled smoothly with phenylboronic acid at 100 °C in 6 h. The
Table 2
Suzuki-Miyaura coupling reactions of aryl chlorides and phenylboronic acids.a
In the one-pot process, both Pd nanoparticles and
diadamantylphosphine ligand were immobilized and supported on
the polymers as heterogeneous catalysts. Evidently, more active Pd
nanoparticles were immobilized preferentially into the N contained
polymers, as the polymerization was catalyzed by the active Pd nano-
particles. Thus, we can obtain the highly active Pd@NPad2-1.0 catalyst.
As the surface of the Pd@NPad2-1.0 was low, the reaction solvent was
important for the Pd@NPad2-1.0 catalyzed Suzuki-Miyaura reaction.
Suitable solvent (i-PrOH with water) can enhance the movement of
aryl halides and aryl boronic acids into active nanoparticles.
Entry
R1
R2
Yield(%)b
TONc
1
2
3
4
5
6
7
8
4-MeCO
4-CH3
4-CHO
4-NO2
4-CN
2-CN
2-NO2
2-Me
2-MeO
H
H
H
H
H
H
H
H
H
99
99
99
99
99
99
99
92
92
90
90
100
4950
4950
4950
4950
4950
4950
4950
4600
4600
4500
4500
5000
9
H
10
11
12d
4-Me
4-MeO
4-Me
H
2-CN
a
Reaction conditions: aryl chlorides, 2.0 mmol; phenylboronic acids, 3.0 mmol;
Pd@NPad2-1.0 catalyst, 5.4 mg; Pd, 0.02 mol%; K2CO3, 4.0 mmol; i-PrOH/H2O, 4.0 mL; at
100 °C; 18 h; under argon.
b
Isolated yield, yield based on aryl chloride.
turn over number, suppose every Pd atom is accessible for the reaction.
For 7 h.
c
Scheme 2. Suzuki-Miyaura catalyzed coupling of 2-nitrochlorobenzene and 4-
chlorophenylboronic acid.
d