producers. Recently, polyethylene glycol (PEG) as a green
and easily available solvent has been widely used in the
Table 2. Control Experiments of Suzuki Coupling of
3
g,4
Suzuki reaction. PEG enables the reduction of Pd(II) to
Pd(0), and its hydroxyl groups are oxidized into aldehyde
2
-Bromo-m-xylene with Phenylboronic Acid in Different
a
Conditions by Palladium Nanoparticles in PEG-400
5
groups, which makes it possible to prepare palladium
entry
conditions
time
isolated yield (%)
nanoparticles easily in PEG in the absence of normally
6
1
2
3
air
O2
N2
50 min
50 min
6.5 h
91
93
92
adopted reducing agents such as hydrazine, hydrogen,
sodium borohydride, etc. To our knowledge, no reactions
catalyzed by the in situ generated palladium nanoparticles
in PEG have been reported.
b
a
Reaction conditions (not optimized): 2-bromo-m-xylene (0.5 mmol),
phenylboronic acid (0.75 mmol), Pd(OAc)2 (1 mol %), K2CO3 (1 mmol),
In this paper, we report a ligand-free Suzuki coupling
reaction catalyzed by the in situ generated palladium nano-
particles in PEG-400 under aerobic conditions. A very simple
and highly efficient approach for Suzuki coupling of aryl
chlorides with phenylboronic acid, the TOF was reached up
PEG (4 g), rt. The reactions were monitored by GC. b PEG-400 was
degassed.
preparing palladium nanoparticles in more than 2 h at 80
-1
to 196 h (Table 1, entry 9). Furthermore, the results showed
°C in PEG with an average molecular weight range from
5
6
00 to 4000 g/mol for a Heck reaction, Reetz and Wester-
mann generated in situ nanosized palladium colloids, which
7
needed an induction period of about 1 h. This means in our
Table 1. Suzuki Coupling Reactions of Aryl Halides with
Phenylboronic Acid in PEG-400 under Different Conditionsa
case the formation of the palladium nanoparticles was much
faster, which is supposed to be due to the reduction of
phenylboronic acid.
entry
R
X
conditions
time
yield (%)b
91
1a
1b
2a
2b
3a
3b
4a
4b
5a
5b
6
7
8
9
2-Me, 6-Me
2-Me, 6-Me
4-CF3
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
air
N2
air
N2
air
N2
air
N2
air
N2
air
air
air
air
50 min
6.5 h
2 h
2 h
2 h
2 h
5 h
5 h
1.5 h
4 h
c
92
96
40
c
4-CF3
4-COMe
4-COMe
2-CN
97
54
c
90
60
c
2-CN
2-NO2
2-NO2
H
3-MeO
4-NO2
4-NO2
96
88
c
3 h
3 h
20 min
1 h
91
82
96
Figure 1. TEM micrographs showing the in situ generated
palladium nanoparticles in PEG-400: (a) 5 min after reaction in
air, (b) 75 min after reaction in air, and (c) 75 min after reaction in
nitrogen. Reaction conditions: 4-chlorobenzotrifluoride (0.5 mmol),
d
e
98
a
phenyl boronic acid (0.75 mmol), Pd(AcO)
mmol), PEG-400 (4 g), rt.
2 2 3
(2 mol %), K CO (1
Reaction conditions (not optimized): aryl halides (0.5 mmol), phenyl
boronic acid (0.75 mmol), Pd(OAc)2 (2 mol %) (1 mol % for entries 1a
and 1b), K2CO3 (1 mmol), PEG (4 g), 45 °C (rt for entries 1a and 1b). The
b
c
reactions were monitored by GC. Isolated yields. PEG-400 was degassed.
d
1
-Chloro-4-nitrobenzene (10 mmol), phenyl boronic acid (15 mmol),
Pd(OAc)2 (2 mol %), K2CO3 (20 mmol), PEG (50 g), rt. Pd(OAc)2 (0.5
mol %). Other conditions were the same as entry 8.
e
It was worth noting that the system possessed excellent
catalytic activity for coupling aryl chlorides or unactivated
aryl bromides with phenylboronic acid using low catalyst
loadings in short times under mild conditions (Table 1, entries
that this approach was oxygen-promoted (Tables 1 and 2).
The first challenge was to generate palladium nanoparticles
in situ under aerobic conditions in PEG-400 without ad-
ditional ligands, reductants, and stabilizers. The transmission
electron microscopy (TEM) micrograph showed that pal-
ladium nanoparticles with an average size of ca. 1.5 nm were
formed within 5 min at room temperature or even at a lower
temperature accompanying the Suzuki coupling reaction
2
a, 3a, 4a, and 5a). Excitingly, the reactions performed in
open air were much quicker than those in nitrogen (Table
(6) (a) Choudary, B. M.; Madhi, S.; Chowdari, N. S.; Kantam, M. L.;
Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127. (b) Dams, M.;
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F. J. Org. Chem. 2005, 70, 6040. (g) Axel, H.; Rapha e¨ l, S.; Denis, B.;
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(
4) (a) Li, J. H.; Liu, W. J.; Xie, Y. X. J. Org. Chem. 2005, 70, 5409.
(
b) Liu, L.; Zhang, Y. H.; Wang, Y. G. J. Org. Chem. 2005, 70, 6122. (c)
Yin, L.; Zhang, Z. H.; Wang, Y. M. Tetrahedron 2006, 62, 935. (d) Li, J.
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(
5) Luo, C. C.; Zhang, Y. H.; Wang, Y. G. J. Mol. Catal. A: Chem.
2
005, 229, 7.
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Org. Lett., Vol. 9, No. 20, 2007