Aerobic ligand-free Suzuki coupling reaction of aryl chlorides catalyzed by in situ generated palladium nanoparticles at room temperature

Article abstract of DOI:10.1002/adsc.200700475

An aerobic, ligand-free Suzuki coupling reaction catalyzed by in situ generated palladium nanoparticles in polyethylene glycol with an average molecular weight of 400 Da (PEG-400) at room temperature has been developed. This catalytic system is a very simple and highly active protocol for the Suzuki coupling of aryl chlorides with arylboronic acids, which proceed smoothly in excellent yields in short times using low catalyst loadings. Control experiments demonstrated that the Suzuki reaction catalyzed by the in situ generated palladium nanoparticles can be carried out much quicker than that using the preprepared particles under the same conditions. The formation of palladium nanoparticles in PEG-400 was promoted by arylboronic acids.

Full text of DOI:10.1002/adsc.200700475

FULL PAPERS
DOI: 10.1002/adsc.200700475
Aerobic Ligand-Free Suzuki Coupling Reaction of Aryl Chlorides
Catalyzed by In Situ Generated Palladium Nanoparticles at
Room Temperature
Wei Han,a Chun Liu,a,* and Zilin Jina
a
State Key Lab of Fine Chemicals, Dalian University of Technology, Zhongshan Road 158, Dalian 116012, Peopleꢀs
Republic of China
Fax : (+86)-411-8899-3854; e-mail: chunliu70@yahoo.com
Received: September 26, 2007; Revised: December 10, 2007; Published online: February 6, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: An aerobic, ligand-free Suzuki coupling re- ments demonstrated that the Suzuki reaction cata-
action catalyzed by in situ generated palladium nano- lyzed by the in situ generated palladium nanoparti-
particles in polyethylene glycol with an average mo- cles can be carried out much quicker than that using
lecular weight of 400 Da (PEG-400) at room temper- the preprepared particles under the same conditions.
ature has been developed. This catalytic system is a The formation of palladium nanoparticles in PEG-
very simple and highly active protocol for the Suzuki 400 was promoted by arylboronic acids.
coupling of aryl chlorides with arylboronic acids,
À
which proceed smoothly in excellent yields in short Keywords: biaryls; C C coupling; nanotechnology;
times using low catalyst loadings. Control experi- palladium; Suzuki reaction
Introduction
challenging fields in organic chemistry, although only
a few examples have been successful up to now.[11] In
The palladium-catalyzed Suzuki coupling reaction of 2001, Sowa et al. reported a ligand-less Pd/C catalyst
aryl halides with arylboronic acids for the construc- for the Suzuki coupling of aryl chlorides and found
tion of the aryl-aryl bond is one of the most general that the solvent system had a great effect on the cata-
and powerful tools for the synthesis of pharmaceuti- lytic activity.[11a] Later, Choudary et al. described a
cals, herbicides, polymers, liquid crystals, natural ligand-free heterogeneous layered double hydroxide-
products, ligands for catalysis and advanced materi- supported nanopalladium catalyst for the Suzuki reac-
als.[1] Since the first report of the Suzuki reaction in tion of chloroarenes.[11b] Recently, Wang et al. demon-
1979,[2] a great number of monographs and review ar- strated a ligand-free system of PdCl2/PEG-300 for the
ticles on this topic have been published. In the last Suzuki coupling of aryl chlorides at room tempera-
decade, there has been an increasing research interest
A
in the Suzuki reaction of aryl chlorides since these dium nanoparticles supported on polyaniline nanofib-
substrates are cheaper and more widely available ers were active catalysts for the Suzuki coupling of
than aryl bromides and iodides.[3] However, they are aryl chlorides using low palladium loadings in water
much more difficult to activate than aryl bromides and air.[11d] Although the above-mentioned examples
and iodides. Among the approaches described in the were carried out either using high palladium load-
literature, numerous efforts have been devoted to the
C
achieved significant success.
using a suitable combination of palladium species
However, most of ligands are not only sensitive to with solvents.
air and/or moisture but also comparatively difficult to
The metal nanoparticles offer high catalytic effi-
prepare or rather expensive; attempts have also been ciency due to their large surface area-to-volume
made to develop “ligand-free” catalytic systems for ratio[12] and have been widely applied in the Suzuki
activating aryl chlorides, which is one of the most reaction.[11b,d,13] Although some important advances
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Wei Han et al.
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Table 1. Suzuki coupling reactions of aryl chlorides with
have been achieved in the palladium nanoparticles-
catalyzed Suzuki reaction in recent years, it still
needed harsh conditions to activate aryl chlor-
phenylboronic acid in PEG-400 under different conditions.[a]
A
pared by a complicated process in the presence of re-
ducing agents and stabilizers in advance and are used
to catalyze a reaction thereafter. However, the small
nanoparticles could be aggregated to reduce their sur-
face energy to the state of stabilization in this
manner.[14]
Entry[a]
R
Conditions
Time
Yield [%][b]
1a
1b
2a
2b
3a
3b
4a
4b
4-CF3
4-CF3
4-MeCO
4-MeCO
2-CN
2-CN
2-NO2
2-NO2
Air
N2
Air
N2
Air
N2
Air
N2
2 h
2 h
2 h
2 h
5 h
5 h
1.5 h
4 h
96
40[c]
97
54[c]
90
For economic and environmental concerns and
good solubility to organic compounds as well, poly-
ethylene glycol (PEG) as a green and easily available
solvent has been used in the Suzuki reaction in the
last two years.[11c,15] PEG enables the reduction of
Pd(II) to Pd(0) while its hydroxy groups are oxidized
into aldehyde groups,[16] which makes it possible to
prepare palladium nanoparticles easily in PEG in the
absence of the normally adopted reducing agents. Fur-
thermore, PEG has been widely used to stabilize
nanoparticles in many types of transformations due to
its special molecular structure. Therefore, it is possible
to make use of the unique advantages of PEG to pre-
pare palladium nanoparticles easily in situ for the
ligand-free Suzuki coupling reaction of aryl chlorides
under mild conditions.
60[c]
96
88[c]
[a]
Reaction conditions (not optimized): aryl halides
(0.5 mmol), phenylboronic acid (0.75 mmol), Pd(OAc)2
ACHTREUNG
(2 mol%), K2CO3 (1 mmol), PEG-400 (4 g), 458C. The
reactions were monitored by GC.
Isolated yields.
[b]
[c]
PEG-400 was degassed.
Table 2. Effect of palladium species on the Suzuki coupling
reaction of 4-chloronitrobenzene with phenylboronic acid in
PEG-400.[a]
In a recent preliminary communication,[17] we pre-
sented an oxygen-promoted ligand-free Suzuki cou-
pling reaction of aryl chlorides with phenylboronic
acid catalyzed by the in situ generated palladium
nanoparticles in PEG-400 at 458C. Herein, we report
a detailed study of an aerobic ligand-free Suzuki cou-
pling reaction catalyzed by the in situ generated palla-
dium nanoparticles in PEG-400 at room temperature.
To our knowledge, this is the first example of a palla-
dium nanoparticles-catalyzed, aerobic, ligand-free
Suzuki coupling reaction of aryl chlorides at room
temperature. Moreover, control experiments have
been designed for the first time to investigate the cat-
alytic property differences between the in situ gener-
ated palladium nanoparticles and the preprepared
Entry
Pd Species
Pd(OAc)2
Time
Isolated Yield [%]
1
2
3
A
1 h
1 h
1 h
94
Pd2(dba)3
A
no reaction
no reaction
Pd/C
[a]
Reaction conditions: 4-chloronitrobenzene (0.5 mmol),
phenylboronic acid (0.75 mmol), Pd (1 mol%), K2CO3
(1 mmol), PEG-400 (4 g), room temperature. The reac-
tion was monitored by TLC.
ones in the aerobic, ligand-free Suzuki reaction of nitrogen. These results were consistent with what
aryl chlorides.
Corma et al. reported.[15b] Therefore, we carried out
all reactions in air for the study.
The next investigation of this study was to optimize
the conditions of the Suzuki coupling reaction in
terms of palladium species and bases. A model cou-
pling reaction between 4-chloronitrobenzene and phe-
nylboronic acid in PEG-400 at room temperature was
Results and Discussion
Optimization of Reaction Conditions
Generally, the palladium-catalyzed Suzuki coupling chosen to study the catalytic activity of palladium spe-
reaction is performed under an inert atmosphere be- cies (Table 2).
cause the catalytic species are sensitive to oxygen or
The reaction catalyzed by Pd(OAc)2 resulted in an
A
moisture. In this study, we first investigated the effect excellent yield in 1 h (Table 2, entry 1). It was surpris-
of the atmosphere on the Suzuki reaction catalyzed ing that the cross-coupling reaction did not occur
by the PEG-400/Pd
shown in Table 1. To our surprise, the reactions per- (Table 2, entry 3) under the same reaction conditions.
formed in open air were much quicker than those in The reason for this was that both Pd2(dba)3 and Pd/C
A
G
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Aerobic Ligand-Free Suzuki Coupling Reaction of Aryl Chlorides
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Table 3. The effect of base on Suzuki coupling reaction of 4-
Table 4. PEG-400/Pd
ACHTREUNG
chloronitrobenzene with phenylboronic acid in PEG-400.[a]
Entry
Base
Time
Isolated Yield [%]
Entry
R
Time
Isolated Yield [%]
1
2
3
4
5
6
7
8
K2CO3
1 h
1.5 h
5 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
94
92
90
73
1
2
3
4
4-NO2
4-CHO
4-CF3
4-CN
4-COMe
2-NO2
H
1 h
2 h
2 h
4 h
6 h
1.5 h
3 h
3 h
94
98
93
85
87
96
91
82
KF·2H2O
K3PO4·3H2O
NaOH
LiOH·H2O
Ba(OH)2·8H2O
Na2CO3
NaHCO3
Li2CO3
HCOONa·2H2O
CH3COONa·3H2O
t-BuONa
CH3ONa
6
5
trace
27
11
trace
10
52
trace
88
trace
no reaction
no reaction
trace
6[b]
7[b]
8[b]
3-OMe
9
[a]
10
11
12
13
14
15
16
17
Reaction conditions: aryl chloride (0.5 mmol), phenylbor-
onic acid (0.75 mmol), Pd(OAc)2 2 mol% [for 4-chloroni-
trobenzene, Pd(OAc)2 1 mol%], K2CO3 (1 mmol), PEG-
AHCTREUNG
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400 (4 g), room temperature.
[b]
NEt3
HMTA
NH3·H2O
Na2SO3
458C.
Scope and Limitations of Substrates
[a]
Reaction conditions: 4-chloronitrobenzene (0.5 mmol),
phenylboronic acid (0.75 mmol), Pd(OAc)2 (1 mol%),
base (1 mmol), PEG-400 (4 g), room temperature. The
reaction was monitored by TLC.
AHCTREUNG
We explored the scope and limitations of substrates
for the Suzuki coupling reaction under the optimized
conditions using 1–2 mol% Pd
K2CO3 as a base at room temperature. The results are
were not activated at room temperature, because the illustrated in Table 4.
reaction only occurred at 808C. Thus, we selected Pd- A wide range of aryl chlorides gave the cross-cou-
(OAc)2 as the catalyst for our research. pling products with excellent isolated yields in the
Further investigation was carried out to study the system of PEG-400/Pd(OAc)2. Moreover, various
(OAc)2 in PEG-400,
ACHTREUNG
AHCTREUNG
influence of the bases on the same model reaction. functional groups such as nitro, aldehyde, cyano,
The results are summarized in Table 3. The use of in- acetyl, trifluoromethyl, and methoxy groups were tol-
organic bases such as K2CO3, KF·2H2O, K3PO4·3H2O, erated in the reaction and not affected. The substrates
NaOH or CH3ONa, gave the cross-coupling products with electron-withdrawing groups or electron-donat-
in good to excellent yields (Table 3, entries 1, 2, 3, 4, ing groups were all achieved in good yields (Table 4).
and 13). However, some inorganic bases of For example, 4-chloronitrobenzene was more reactive
LiOH·H2O, Na2CO3, NaHCO3, HCOONa·2H2O or than other substrates and 94% isolated yield was ob-
CH3COONa·3H2O resulted in lower yields (Table 3, tained using a Pd(OAc)2 loading of 1 mol% (Table 4,
G
entries 5, 7, 8, 10, and 11). Other inorganic bases like entry 1). Steric hindrance due to the ortho substitu-
Li2CO3, t-BuONa, NH3·H2O, Na2SO3, and organic ents on the aryl chlorides affected the reaction prog-
bases such as NEt3, hexamethylenetetraamine ress. Thus, 2-chloronitrobenzene needed a higher tem-
(HMTA) were completely ineffective in the catalytic perature (458C) and a two-fold higher catalyst load-
system (Table 3, entries 9, 12, 16, 17, 14, and 15). The ing (2 mol%) than 4-chloronitrobenzene (Table 4,
best result was obtained with K2CO3, which provided entry 6). Excitingly, the non-activated aryl chlorides
the highest cross-coupling yield of 94% in 1 h such as chlorobenzene and 3-chloroanisole were con-
(Table 3, entry 1).
sumed in 3 h (Table 4, entries 7 and 8).
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Wei Han et al.
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Table 5. PEG-400/Pd
of aryl chlorides with arylboronic acids at room tempera-
ture.[a]
A
the nucleophilicity. As for the 3,5-difluoro substitu-
ents, they increase the nucleophilicity by presenting
d-transfer due to the participation of the lone-pair
electron.[20]
ACHTREUNG
Control Experiments of In Situ and Preprepared
Palladium Nanocatalysis
Entry R1
R2
Time
Isolated Yield [%]
Generally, transition metal nanoparticles are prepre-
pared for nanocatalysis. There are only a few exam-
ples of in situ nanocatalysis.[21] To our knowledge, the
present work was the first example of the in situ gen-
erated palladium nanoparticles-catalyzed Suzuki reac-
tion at room temperature. To disclose the catalytic
properties of the in situ generated palladium nanopar-
ticles and the preprepared ones[22] in the aerobic
ligand-free Suzuki coupling reaction of aryl chlorides,
control experiments were carried out under the same
reaction conditions, respectively. The catalytic results
are shown in Table 6 and the average sizes of the pal-
ladium nanoparticles were characterized by the trans-
mission electron microscopy (TEM). As expected, the
catalytic properties were quite different. The in situ
generated palladium nanoparticles showed much
higher activity than the preprepared ones (Table 6).
The results were consistent with the TEM micro-
graphs: the average diameters of the in situ generated
1
2
3
4
5
6
7
8
9
10
4-NO2
4-NO2
4-NO2
2-OMe
4-OMe
3-OMe
50 min 93
50 min 95
6 h
6 h
3 h
1 h
1.5 h
50 min 96
84
85
87
95
91
4-COMe 3-OMe
4-CF3
4-NO2
4-NO2
4-NO2
4-NO2
4-NO2
3-OMe
2-Me
3-Me
4-Me
3-F, 5-F 50 min 96
4-CF3 8 h 85
[a]
Reaction conditions: aryl chloride (0.5 mmol), arylboron-
ic acid (0.75 mmol), Pd(OAc)2 1 mol% [for entries 4 and
5, Pd(OAc)2 2 mol%], K2CO3 (1 mmol), PEG-400 (4 g),
room temperature. The reaction was monitored by TLC.
AHCTREUNG
ACHTREUNG
Effect of Various Arylboronic Acids
The effect of the substituents in different positions of palladium nanoparticles in the whole reaction process
an arylboronic acid on the Suzuki coupling reaction were ca. 1.5 nm (Figure 1, top row), while the prepre-
was studied (Table 5). It was clear from the Table 5
that the cross-couplings of aryl chlorides with the ar-
ylboronic acids bearing either electron-rich or elec- Table 6. Control experiments of the in situ generated and
the preprepared[22] palladium nanoparticles-catalyzed Suzuki
tron-deficient functional groups were carried out
cross-coupling reaction in PEG-400 in air.[a]
smoothly in the catalytic system. In agreement with
the results reported by Sajiki et al.,[18] the coupling re-
actions of arylboronic acids containing electron-rich
groups such as 2-MeO, 4-MeO, and 4-Me (Table 5, en-
tries 1, 2, and 8; 50 min) proceeded more efficiently
than those of phenylboronic acid (Table 4, entry 1;
1 h), while the arylboronic acid with an electron-with-
drawing substituent needed a longer reaction time for
[b]
completion (Table 5, entry 10; 8 h). Interestingly, an
electron-donating group in the meta position of an ar-
ylboronic acid such as 3-MeO or 3-Me (Table 5, en-
tries 3 and 7) showed lower reactivity,[19] however, the
3,5-difluoro substituents promoted the reaction
(Table 5, entry 9). This is because of the effect of the
substituents on the nucleophilicity of arylboronic
acids. The stronger the nucleophilicity, the more
active is the arylboronic acid. An electron-donating
group in the ortho or para position of an arylboronic
acid increases the nucleophilicity of the carbon atom
bounded to the boron atom, while an electron-with-
drawing group in the same position decreases the nu-
cleophilicity. Comparably, an electron-donating group
in the meta position of an arylboronic acid decreases
Entry
R
Catalyst Type
Time [h]
Yield [%]
1a
1b
2a
2b
3a
3b
4
4-NO2
4-NO2
4-CF3
4-CF3
2-NO2
2-NO2
4-NO2
in situ
preprepared
in situ
preprepared
in situ
preprepared
10% Pd/C
1
12
2
12
1.5
12
1
94
82
93
49
96
76
no reaction
[a]
Reaction conditions: aryl chlorides (0.5 mmol), phenyl
boronic acid (0.75 mmol), Pd(OAc)2 2 mol% (1 mol%
for entries 1a and 1b, 1 mol% 10% Pd/C for entry 4),
K2CO3 (1 mmol), PEG-400 (4 g), room temperature
(458C for entries 3a and 3b). The reactions were moni-
tored by GC and TLC.
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[b]
Isolated yields.
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Figure 1. TEM micrographs of Pd nanoparticles; reaction conditions: 4-chlorobenzotrifluoride (0.5 mmol), phenylboronic
acid (0.75 mmol), Pd(OAc)2 (1 mol%), K2CO3 (1 mmol), PEG-400 (4 g) at room temperature for (a), (b), and (c): (a, top
left) 5 min after reaction in air, (b, top right) 75 min after reaction in air, (c, bottom left) preprepared Pd nanoparticles[22]
[Pd(OAc)2 2 mol%] in PEG-400 at room temperature in nitrogen, (d, bottom right) 75 min after preprepared Pd nanoparti-
AHCTREUNG
ACHTREUNG
cles catalyzed the reaction in air.
pared palladium nanoparticles were ca. 3.6 nm curred immediately. And in view of the molecular col-
(Figure 1, bottom left). It is known that nanoparticles lision theory, the reaction might be catalyzed by palla-
have a large surface to volume ratio leading to high dium at an atom level. However, the preprepared
energy surfaces and easy aggregation. In our manner, nanoparticles were easy to congregate to be in the
the formation of palladium nanoparticles in situ ac- state of stability to catalyze the reaction in a big di-
companied with the Suzuki coupling reaction oc- ameter and exhibited low activity. Surprisingly, there
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Wei Han et al.
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Table 7. Effect of the amount of phenylboronic acid on the
Suzuki reaction of 4-chloronitrobenzene in PEG-400 in
air.[a]
no reaction occurred on using 1 mol% 10% Pd/C
(Table 6, entry 4).
It was interesting that the average diameters of pal-
ladium nanoparticles became smaller (2.5 nm,
Figure 1, bottom right) than the original ones (3.6 nm,
Figure 1, bottom left), when the Suzuki reaction of 4-
chlorobenzotrifluoride with phenylboronic acid was
performed after 75 min catalyzed by the preprepared
palladium nanoparticles. This phenomena could be
explained by the Ostwald ripening process.[14] During
the reaction, the palladium nanoparticles were in a
growth phase and formed large palladium clusters.
Consequently, the larger palladium particles were ag-
gregated and precipitated out of the reaction solution,
while the smaller ones stayed in the solution. In fact,
Entry Molar Ratio of Phenylboronic
Acid to 4-Chloronitrobenzene
Time Isolated
[h]
Yield [%]
1
2
3
1.1
1.5
2.0
15
1
1
58
94
95
[a]
Reaction conditions: 4-chloronitrobenzene (0.5 mmol),
Pd(OAc)2 1 mol%, K2CO3 (1 mmol), PEG-400 (4 g),
AHCTREUNG
room temperature. The reactions were monitored by GC
and TLC.
we observed palladium black in the final reaction. formed much faster than the preprepared palladium
However, the system of the in situ generated palladi- nanoparticles under the same conditions. In fact, this
um nanoparticles in PEG-400 in air was stable for was confirmed by UV-vis spectroscopy (Figure 2).
months, and no palladium black was observed.
It was clear that there was a peak at 400 nm as-
signed to Pd(II) (Figure 2, a). In the presence of phe-
nylboronic acid, this peak completely disappeared, re-
vealing the full conversation of Pd(II) to Pd(0) within
2 h (Figure 2, b). In the case of the absence of phenyl-
Roles of Arylboronic Acids
In the preliminary communication,[17] we presented a boronic acid, a weak peak of the absorbance at
proposed mechanism of an oxygen-promoted, ligand- 400 nm was observed, showing that the Pd(II) could
free Suzuki coupling reaction catalyzed by the in situ not be reduced to Pd(0) totally even after 12 h
generated palladium nanoparticles in PEG-400. The (Figure 2, c). This was because the phenylboronic acid
PEG-400 played important roles as a reducing agent played a role as an associate reducing agent[11a] and
and stabilizer for the formation of palladium nanopar- quickened the formation of palladium nanoparticles
ticles. However, the reason why the palladium nano- in PEG-400. Moreover, arylboronic acids could act as
particles formed much quicker than those described stabilizers and keep the palladium nanoparticles con-
in literature[16] was unclear. In this work, we further stant in size.[14]
investigated the role of the phenylboronic acid in the
To further reveal the effect of phenylboronic acid
formation of the palladium nanoparticles. Control ex- on the Suzuki reaction, different molar ratios of phe-
periments have been carried out to prepare the palla- nylboronic acid to 4-chloronitrobenzene have been
dium nanoparticles in the presence or in the absence studied. The results shown in Table 7 demonstrate
of the phenylboronic acid, respectively. We found that that a suitable excess amount of the phenylboronic
the in situ generated palladium nanoparticles were acid was necessary to complete the reaction (Table 7,
entries 2 and 3). Lower amounts of the phenylboronic
acid resulted in incomplete reaction (Table 7, entry 1),
from which it was concluded that a portion of phenyl-
boronic acids was consumed for the formation of pal-
ladium nanoparticles.
Conclusions
We have developed an aerobic, ligand-free Suzuki
coupling reaction catalyzed by the in situ generated
palladium nanoparticles in PEG-400 at room temper-
ature, which was a very simple and highly active pro-
tocol for the Suzuki coupling of aryl chlorides with ar-
ylboronic acids in excellent isolated yields in short
times. Control experiments illustrated that the reactiv-
ity of the in situ palladium nanoparticles was much
higher than that of the preprepared ones. The arylbor-
onic acids played roles as both a substrate and an as-
Figure 2. UV-vis absorption spectra of (a) Pd
(0.2 mmol) in DMF, (b) Pd(OAc)2 (0.2 mmol) and phenyl-
boronic acid (1.5 mmol) in PEG-400 (4 g) was stirred 2 h at
room temperature in air, and (c) Pd(OAc)2 (0.2 mmol) in
PEG-400 (4 g) was stirred 12 h at room temperature.
A
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Aerobic Ligand-Free Suzuki Coupling Reaction of Aryl Chlorides
FULL PAPERS
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tekoven, A. Schnyder, Adv. Synth. Catal. 2004, 346,
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sistant reductant. It is noteworthy that the reaction
can be performed efficiently at room temperature in
air, which is of great interest for industrial applica-
tion.
Experimental Section
General Information
[2] N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett.
1979, 3437–3440.
[3] V. V. Grushin, H. Alper, Chem. Rev. 1994, 94, 1047–
1062.
All aryl halides and arylboronic acids were used as received
(Alfa Aesar, Avocado). The PEG-400 was purchased from
Acros. All other chemicals were purchased from commercial
sources and used without further purification. 1H NMR
spectra were recorded on a Varian Inova 400 spectrometer.
Chemical shifts are reported in ppm relative to TMS. Mass
spectra were obtained using a GCT(EI, 70 eV). Gas chro-
matography analyses were performed on a Tianmei 7890
Gas Chromatograph with a FID and 50-meter OV-101
column. Transmission electron microscopy (TEM) was per-
formed on a Tecnai 20 microscope operating at 200 kV. All
products were isolated by short chromatography on a silica
gel (200–300 mesh) column using petroleum ether (60–
908C), unless otherwise noted. UV-vis spectroscopy meas-
urements (300–700 nm) were performed on a Bejing Rui Li
UV-2100 using quartz cells.
[4] a) F. Gonzµlez-Bobes, G. C. Fu, J. Am. Chem. Soc.
2006, 128, 5360–5361; b) S.-Y. Liu, M. J. Choi, G. C.
Fu, Chem. Commun. 2001, 2408–2409; c) A. F. Littke,
C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020–
4028; d) A. F. Littke, G. C. Fu, Angew. Chem. 1998,
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General Procedure for the Suzuki Cross-Coupling of
Aryl Chlorides with Arylboronic Acids
A mixture of aryl chloride (0.5 mmol), arylboronic acid
(0.75 mmol), Pd(OAc)2 (2 mol%, 2.2 mg, 1 mol% for 4-
R
chloronitrobenzene), K2CO3 (1 mmol, 138 mg) and PEG-400
(4 g) was stirred at room temperature for the indicated time
until complete consumption of starting material as moni-
tored by GC. The mixture was added to brine (15 mL) and
extracted four times with diethyl ether (4 ”15 mL). The sol-
vent was concentrated under vacuum and the product was
isolated by short chromatography on a silica gel (200–300
mesh) column.
Supporting Information
Experimental details and characterization of the products
are given in the Supporting Information.
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Acknowledgements
We thank the financial support from Dalian University of
Technology (No. 893336, 893222, 0204–888X43) and the
State Key Labof Fine Chemicals of China (No. KF0510). We
also thank Dr. Hongwei Yu for the valuable discussions.
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[22] Method for preprepared palladium nanoparticles: Pd-
A
Table 6) was added into deoxygened PEG-400 (4 g) at
room temperature (458C for entries 3a and 3b in
Table 6) by magnetic stirring for 12 h (2 h at 458C)
under N2. During the process the colour of the solution
turned from light yellow to dark, indicating the genera-
tion of palladium nanoparticles. Then, the as prepared
palladium nanoparticles were used to catalyze Suzuki
cross-coupling reactions in air.
508
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Adv. Synth. Catal. 2008, 350, 501 – 508