Newly-generated Al(OH)3-supported Pd nanoparticles-catalyzed Stille and Kumada coupling reactions of diazonium salts, (Het)aryl chlorides

Article abstract of DOI:10.1016/j.tet.2015.10.069

A ligand-free Pd/Al(OH)₃ nano-catalyst which is prepared by one-pot three-component method using Pd(PPh₃)₄, tetra (ethylene glycol), and aluminum tri-sec-butoxide exhibits excellent catalytic activity in Stille cross-couplings of (Het)aryl chlorides, arenediazonium tetrafluoroborate salts with phenyltributylstannane, respectively, and Kumada couplings of (Het)aryl chlorides with various Grignard reagents. More importantly, these two processes show excellent functional group compatibility with moderate to good yields and they are also versatile with respect to not only (Het)aryl chlorides, but also diazonium salts, and heteroaryl Grignard reagents. The nano-catalyst could also be recycled and reused 5 times without loss of activity and decrease of yield.

Full text of DOI:10.1016/j.tet.2015.10.069

Accepted Manuscript
Newly-generated Al(OH) -supported Pd nanoparticles-catalyzed Stille and Kumada
3
coupling reactions of diazonium salts, (Het)aryl chlorides
Xing Li, Tingting Zhu, Zhongqi Shao, Yingjun Li, Honghong Chang, Wenchao Gao,
Yongli Zhang, Wenlong Wei
PII:
S0040-4020(15)30169-1
10.1016/j.tet.2015.10.069
TET 27241
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 August 2015
Revised Date: 21 October 2015
Accepted Date: 26 October 2015
Please cite this article as: Li X, Zhu T, Shao Z, Li Y, Chang H, Gao W, Zhang Y, Wei W, Newly-
generated Al(OH) -supported Pd nanoparticles-catalyzed Stille and Kumada coupling reactions of
3
diazonium salts, (Het)aryl chlorides, Tetrahedron (2015), doi: 10.1016/j.tet.2015.10.069.
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Newly-generated Al(OH)3-supported Pd
nanoparticles-catalyzed Stille and Kumada
coupling reactions of diazonium salts,
(Het)aryl chlorides
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Xing Li, Tingting Zhu, Zhongqi Shao, Yingjun Li, Honghong Chang, Wenchao Gao, Yongli Zhang and
Wenlong Wei
Department of Chemistry and Chemical Engineering, Taiyuan University of Technology, 79 West Yingze Street,
Taiyuan 030024, People’s Republic of China.
Nano Pd/Al(OH)3
+
(Het)Ar
X
Y
Ar'(Het)
(Het)Ar Ar'(Het)
52 examples
up to 94% yield
X = Cl, N2BF4
Y = Bu3Sn, MgBr, MgCl
Pd (PPh3
HO-(CH2CH2O)4-H
)
4
(sec-BuO)3Al/BuOH

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Tetrahedron
journal homepage: www.elsevier.com
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Newly-generated Al(OH)3-supported Pd nanoparticles-catalyzed Stille and Kumada
coupling reactions of diazonium salts, (Het)aryl chlorides
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Xing Li,* Tingting Zhu, Zhongqi Shao, Yingjun Li, Honghong Chang, Wenchao Gao, Yongli Zhang and
Wenlong Wei*
Department of Chemistry and Chemical Engineering, Taiyuan University of Technology, 79 West Yingze Street, Taiyuan 030024, People’s Republic of China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A ligand-free Pd/Al(OH)3 nano-catalyst which is prepared by one-pot three-component method
using Pd(PPh3)4, tetra (ethylene glycol) and aluminum tri-sec-butoxide exhibits excellent
catalytic activity in Stille cross-couplings of (Het)aryl chlorides, arenediazonium
tetrafluoroborate salts with phenyltributylstannane, respectively, and Kumada couplings of
(Het)aryl chlorides with various Grignard reagents. More importantly, these two processes show
excellent functional group compatibility with moderate to good yields and they are also versatile
with respect to not only (Het)aryl chlorides, but also diazonium salts, and heteroaryl Grignard
reagents. The nano-catalyst could also be recycled and reused 5 times without loss of activity
and decrease of yield.
Available online
Keywords:
Pd/Al(OH)3
Nanoparticles
Stille
2009 Elsevier Ltd. All rights reserved.
Kumada
Diazonium salts
1. Introduction
renders the couplings of these heterocycles relatively difficult.
Given the practicability of aryl chlorides and the importance of
The palladium-catalyzed Stille1,2 and Kumada3,4 cross-
coupling reactions represent two of the most versatile tools in
modern reliable methods for C-C bond formation. In the past few
years, numerous kinds of palladium catalysts have been
extensively investigated and some new catalysts are gradually
developed which have enabled these two transformations to be
applied with better catalytic results. Among these palladium
catalysts, although the combination of palladium salts with
various ligands provides excellent yields and high turnover
numbers,5-7 ligand-free catalysts,8, 9 especially nano-catalysts are
more practical, efficient and promising due to their advantages.
Recently, some progresses have been made about them. In terms
of the Stille cross-coupling reaction, tremendous attention and
efforts have been devoted to developing various nano-catalysts
which show enhanced reactivity with low catalyst loadings under
mild conditions.10 Despite the significant progresses and creative
efforts, the design and synthesis of versatile palladium nano-
catalysts would represent important advances and the
development of novel and green methods with wider substrate
scope still remain highly desirable. In contrast, few reports on the
use of nano-Pd catalysts in Kumada coupling reactions exist.
heteroaryl compounds in medicinal chemistry, biological, and
material sciences, the development of general, environmentally
friendly, and practical protocols for the couplings of aryl and
heteroaryl chlorides is still highly demanded.11 In addition,
diazonium salts are frequently used as the electrophiles in Pd-
catalyzed cross-coupling reactions due to their relatively high
reactivity. However, there is no report about nano-palladium-
catalyzed Stille coupling reactions of arenediazonium
tetrafluoroborate salts to date.
Pd(PPh3)4
+
110 o
air
C
110 oC
H2O
1) filtration
2) wash with acetone Pd/Al(OH)3
HO-(CH2CH2O)4-H
+
(sec-BuO)3Al
+
10 h
30 min 3) dry
nano-Pd
catalyst 1
BuOH
Scheme 1. Preparation of Pd nano-catalyst 1.
Recently, we have reported effective cross couplings of
arenediazonium salts using aluminum hydroxide-supported nano-
palladium catalyst12 which was prepared by a simple one-pot
three-component method (See Scheme 1). Herein, we will report
our efforts in catalyst development for the Stille and Kumada
coupling reactions and want to present the efficiency and
recovery of the palladium nanoparticles. With the catalyst, a wide
range of aromatic substrates, especially including diazonium salts,
heteroaryl chlorides and Grignard reagents can afford moderate
Although the cross couplings of inert aryl chlorides, which are
the most practical aryl halides, can be smoothly accomplished
with good results, their application as electrophilic coupling
partners still represent
a big challenge in nanoparticles
palladium-catalyzed cross-couplings. At the same time, the
couplings involving heteroaryl chlorides are still limited because
the presence of heteroatoms capable of coordinating to the metal
center can lead to catalyst inhibition and deactivation which

2
Tetrahedron
ACCEPTED MANUSCRIPT
to good results under non-anhydrous and non-degassed
However, KOH and K PO were totally ineffective (Table 1,
3 4
conditions.
entries 6-7). After the effects of solvent dosage, the amount of
base, catalyst loading, the amount of chlorobenzene and reaction
temperature on the coupling reaction were examined (See Table
8 in Supporting Information), the optimized reaction conditions
obtained were 0.2 mmol phenyltributylstannane, 1.5 equiv. of
chlorobenzene, 0.7 mol% Pd catalyst 1 and 1.0 equiv. of K2CO3
in 1.0 mL DMF under air atmosphere at 120 oC for 48 h (Table 1,
entry 5).
2. Results and Discussion
1
2
3
4
5
6
7
8
9
Because of the importance of surface area for the catalytic
activity, the N2 sorption analysis of samples prepared by the two
methods was done to demonstrate that the preparation methods of
the catalyst exerted an important impact on its surface area. As
seen from Figure 1, the BET surface area of the Pd nanoparticles
Cat. 1 prepared by one-pot three-component method displayed
the large specific surface area of 612 m2 g−1, a pore volume of
1.16 cm3/g, and an average pore size of 5.89 nm calculated from
the adsorption branch using the Barrett–Joyner–Halenda (BJH)
model. However, the BET surface area of the catalyst Cat. 2
prepared by co-precipitation were smaller than 70 m2 g−1 with a
pore volume of 0.16 cm3/g and an average pore size of 7.95 nm.
Owing to the larger BET surface area and pore volume of the
catalyst Cat. 1, it should possess higher catalytic activity.
Catalytic activity of the two catalysts was next examined through
the Stille coupling of iodobenzene and phenyltributylstannane.
The results demonstrated that the Cat. 1 exhibited higher catalytic
activity and produced diphenyl in 87% yield, and the Cat. 2 only
provided 62% yield under the same reaction conditions.
Table 1
Screening of solvents and bases on the Stille coupling reaction of
phenyltributylstannane with chlorobenzene a
Cat.1, 120 o
Base, Solvent
C
Cl Bu3SnPh
10
11
12
13
14
15
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1a
2
3a
Entry
Solvent
DMSO
H2O
Base
Yield (%) b
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
3
2
29
3
Toluene
CH3CN
DMF
38
4
51
5[c]
80
6
DMF
Trace
Trace
41
7
DMF
K3PO4
Et3N
800
700
600
500
400
8
DMF
9
DMF
NaHCO3
57
a
300
Reaction conditions: phenyltributylstannane (0.2 mmol), chlorobenzene
Cat.1
200
(1.5 equiv.), Pd catalyst 1 (0.7 mol% Pd), base (1.0 equiv.), solvent (1.0 mL),
temperature (120 oC), time (48 h).
100
80
b Isolated yield.
60
c
Reaction conditions: DMF (1.0 mL), base (K2CO3, 1.0 equiv.), Pd
40
o
Cat.2
catalyst 1 (0.7 mol% Pd), chlorobenzene (1.5 equiv.), temperature (120 C),
time (48 h).
20
0
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Relative pressure (P/P0)
To demonstrate the efficiency of this protocol, we investigated
the generality of this methodology for the cross-coupling
reactions of a variety of substituted chlorobenzene under the
optimal conditions. As shown in Table 2, it was noteworthy that
all reactions gave good results for substrates with electron-poor
or electron-rich functional groups (Table 2, entries 1-8). In
addition, heteroaryl chlorides could also provide moderate to
good yields (Table 2, entries 9-13).
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Cat.1
Table 2
The couplings of aryl chlorides and phenyltributylstannane a
Cat.1 (0.7 mol% Pd)
R1
R1 Cl Bu3Sn
K2CO3, DMF, 120 o
C
Cat.2
1
2
3
R1 = aryl, heteroaryl
0
5
10
15
20
25
30
35
t
Yield
(%) b
R1Cl
Product
Pore diameter (nm)
Entry
1
(h)
Figure 1. N2 adsorption/desorption isotherm and the pore size distribution
curve of the catalyst Cat.1 and Cat 2.
Subsequently, we initiated the research by testing a series of
solvents for the Stille coupling reaction between chlorobenzene
and phenyltributylstannane in the presence of 0.7 mol%
Cl
48
48
80
3a
3b
3c
O2N
O2N
2
87 c
Cl
o
Pd(PPh3)4-derived catalyst 1 and 1.0 equiv. of K2CO3 at 120 C,
NO2
NO2
and the results are outlined in Table 1. Out of these solvents,
DMF showed good catalytic activity and provided the product in
80% yield. Unfortunately, DMSO, H2O, Toluene and CH3CN led
to a significant decrease in the yield (Table 1, entry 5 vs. 1-4).
The type of bases had a significant effect on the yield, too.
Among the tested bases, K2CO3 proved to be the most efficient
affording the product in the 80% yield (Table 1, entry 5). Et3N
and NaHCO3 showed moderate yields (Table 1, entries 8 and 9).
3
4
5
48
48
50
86 c
91 c
79
Cl
Cl
NO2
NO2
3d
Cl
3e

3
OMe
OMe
ACCEPTED MANUSCRIPT
6
50
83
1
2
3
4
5
23
18
35
23
23
76
93 c
71
86
66
Cl
Cl
N2BF4
3f
3n
1
2
3
4
5
6
7
7
8
50
48
86
88
MeO
Me
MeO
Me
N2BF4
3g
3o
O
H
O
H
Cl
Cl
3h
3i
N2BF4
3f
9
54
54
74
79
Me
N
N
Me
N2BF4
8
9
3g
3p
3q
F
Cl
N
N
F
10
3j
10
11
12
13
14
15
16
17
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20
21
22
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30
31
32
33
34
35
36
37
38
39
N2BF4
63 c
54
S
11
12
56
56
F
F
F
F
Cl
S
6
7
8
21
20
19
78
3k
3l
N2BF4
88
N2BF4
N
N
Cl
3r
Cl
Cl
69 d
Cl
N2BF4
3s
13
58
57
N
NO2
Cl
Cl
N
NO
2 3m
9
28
71
N2BF4
a
Reaction conditions: phenyltributylstannane (0.2 mmol), aryl chloride
(1.5 equiv.), Pd catalyst 1 (0.7 mol% Pd), K2CO3 (1.0 equiv.), DMF (1.0 mL),
3t
3u
3v
temperature (120 oC).
Cl
Br
10
20
20
81
72
Cl
Br
N2BF4
b
Isolated yield.
c
0.5 mol% Pd was used.
11
N2BF4
Generally, the aryl electrophilic reagents are limited to the use
of aryl halides13 or triflates14 in the Stille coupling reactions. Only
few examples which diazonium salts were used as electrophilic
partners have been reported.15 To the best of our knowledge, the
nano-catalyst has never been utilized to date for the Stille
reactions of diazonium salts. Subsequently, we will report the
application of the Pd catalyst 1 in the Stille coupling of
arenediazonium tetrafluoroborate salts with tributylphenyltin.
With the optimal conditions established,16 the scope of the
Stille reactions with respect to various diazonium salts was
examined (Table 3). To our delight, this catalyst exhibited the
remarkably broad substrate scope and the corresponding coupling
a
Unless otherwise noted, the reaction was carried out with Pd catalyst 1
(0.3 mol% Pd), diazonium salt (0.2 mmol), and tributylphenyltin (1.2 equiv)
in CH3CN (1.2 mL) at 35 oC for 18–35 h.
b
Isolated yield.
c
0.2 mol% Pd catalyst 1, 1 mL of CH3CN and room temperature was
utilized.
d
55 oC was used.
To demonstrate the generality of this nanoparticles pd catalyst
1, an examination of Kumada cross-coupling reactions of a series
of (hetero)aryl chlorides with Grignard reagents was performed.
Under the optimal experimental conditions obtained through the
screening and optimization selecting the reaction of
chlorobenzene with phenylmagnesium bromide as the model
reaction,17 various aryl chlorides were firstly examined. As
summarized in Table 4, this method was applicable for various
functionalized aryl chlorides. For substrates bearing an electron-
donating or electron-withdrawing group, the reactions smoothly
were carried out and afforded the desired products in high yields
(Table 4, entries 1–8). It was noted that 94% yield could be
obtain with 1-chloronaphthalene (Table 4, entry 9).
40 products were obtained in moderate to good yields (66–93%).
The electronic nature of substituents on the diazonium salts had
little effect on the yield. For example, the diazonium salts having
an electron-withdrawing or electron-donating group on the same
position of the phenyl ring were well tolerated and showed
similar catalytic reactivity (Table 3, entries 5-11 vs. 3-4).
Surprisingly, diazonium salts with methoxyl supplied better
results than those with methyl group (Table 3, entries 1 and 2 vs.
3 and 4). It was noteworthy that steric hindrance played an
important role on the yield. The para-substituted diazonium salts
afforded the better results than ortho- and meta-substituted ones
(Table 3, entries 7 and 10 vs. 5-6 and 8-9, entry 2 vs. 1 and entry
4 vs. 3).
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Table 4
The couplings of aryl chlorides and phenylmagnesium bromidea
R3
R3
Cat.1 (0.4 mol% Pd)
toluene, 140 oC, N2
Cl +
BrMg
Table 3
The Stille coupling reactions for diazonium saltsa
1
5a
3
R2
R2
Yield (%) b
94
Cat.1 (0.3 mol% Pd)
Entry
1
Aryl chloride
Product
t (h)
N2BF4
Bu3SnPh
+
CH3CN
4
2
3
Cl
Entr
y
t
Yield
36
Diazonium salt
Product
(h) (%) b
3a

4
Tetrahedron
ACCEPTED MANUSCRIPT
Cl
S
S
Cl
2
3
4
5
6
7
40
40
36
36
30
28
89
91
93
90
84
85
3
4
5
6
50
51
51
50
31
61
45
39
3k
3e
1
2
3
4
5
6
7
8
9
Cl
Cl
N
N
Cl
3f
3l
CH3
N
CH3
N
Cl
3g
3x
Cl
10
11
12
13
14
15
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65
Cl
OMe
OMe 3o
N
CH3
NO2
Cl
N
N
CH3
3y
NO2
Cl
NO2
Cl
3b
7
8
50
48
51
62
N
NO2
O2N
O2N
Cl
Cl
3m
3z
NO2
O2N
O2N
3c
N
N
8
28
36
87
94
a Reaction conditions: heteroaryl chloride (0.2 mmol), phenylmagnesium
bromide (1.5 equiv.), Pd catalyst 1 (0.45 mol% Pd), toluene (2 mL),
NO
2 3d
temperature (140 oC), N2.
b Isolated yield.
Cl
9
Furthermore, we explored the Kumada couplings of various
Grignard reagents with chlorobenzene in the presence of the
palladium catalyst 1. As shown in Table 6, various Grignard
reagents substituted with an electron-donating or electron-
withdrawing group could be employed in the coupling to produce
desired products in good yields (Table 6, entries 1–6). Excitedly,
heteroaryl Grignard reagents afforded the products in moderate to
good yields (Table 6, entries 7–8). Good yields were also
obtained about aryl magnesium chlorides (Table 6, entries 9-11).
3w
a
Reaction conditions: aryl chloride (0.2 mmol), phenylmagnesium
bromide (1.5 equiv.), Pd catalyst 1 (0.4 mol% Pd), toluene (2 mL),
temperature (140 oC), N2.
b Isolated yield.
In addition, the Kumada reactions of heteroaryl chlorides with
phenylmagnesium bromide could be carried out using 0.45 mol%
Pd catalyst 1 and 140 C. Moderate yields might be attained
o
about various Cl-substituted heteroaryl compounds. It was found
that 3-chloro-pyridine exhibited better yield than 4-chloro-
pyridine, which revealed the steric hindrance have little influence
on the reaction yields (Table 5, entry 1 vs. 2). 31% and 61%
yields were obtained with 2-chlorothiophene and 2-
chloroquinoline, respectively (Table 5, entries 3 and 4). Nitro-
substituted chloropyridine could offer higher yields than methyl-
substituted chloropyridine (Table 5, entries 7-8 vs. 5-6).
Table 6
The couplings of chlorobenzene and various Grignard reagents a
Cat.1 , T
YMg R5
+
R5
Cl
toluene, N2
1a
Y= Br, Cl
R5 = aryl, heteroaryl
5
3
Entry
1
Grignard reagent
Product
Yield (%) b
Table 5
MgBr
The couplings of heteroaryl chlorides and phenylmagnesium bromide a
80
82
86
75
Cat.1 (0.45 mol% Pd)
toluene, 140 oC, N2
R4 Cl + BrMg
R4
3e
1
5a
3
MgBr
MgBr
Heteroaryl
chloride
Entry
1
Product
t (h) Yield (%) b
2
3
4
3f
3g
3q
N
N
50
50
46
39
N
Cl
3i
3j
N
F
MgBr
2
F
Cl

5
strategies for the synthesis of various biaryls. In terms of a
ACCEPTED MANUSCRIPT
MgBr
range of aryl chlorides, it could show remarkable catalytic
reactivity and good to high yields. More importantly, this catalyst
has also proved to be highly efficient for various diazonium salts,
heteroaryl chlorides and Grignard reagents.
5
6
77
F
F
3r
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
MgBr
75
4. Experimental Section
H3CO
S
OCH3
3o
4.1. General
MgBr
S
7
8
61
75
All reagents were purchased from commercial sources and
used without further purification, unless otherwise indicated.
Deuterated solvents were purchased from Aldrich. Column
chromatography was performed on silica gel (200-300 mesh)
with petroleum ether /ethyl acetate gradients, unless otherwise
specified. All yields were referred to isolated yields (average of
two runs) of compounds. The known compounds were partly
characterized by melting points (for solid samples), 1H NMR, and
compared to authentic samples or the literature data. Melting
points were measured with a RD-II digital melting point
3k
N
N
MgBr
3i
MgCl
MgCl
9
74
79
87
3a
3f
3g
1
apparatus and are uncorrected. H NMR data were acquired at
10
11
300 K on a Bruker Advance 600 MHz spectrometer or Avarian
Inova 500 MHz spectrometer using CDCl3 as solvent. Chemical
shifts are reported in ppm from tetramethylsilane with the solvent
resonance as the internal standard (CDCl3 = 7.26). Spectra are
reported as follows: chemical shift (δ = ppm), multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet),
coupling constants (Hz), integration, and assignment.
MgCl
a Reaction conditions: chlorobenzene (0.2 mmol), Grignard reagent (1.5
equiv.), Pd catalyst 1 (0.4 mol% Pd), toluene (2 mL), temperature (140 oC), t
(48 h).
4.2. General reaction procedures
4.2.1. General procedure for Stille couplings of
aryl chlorides
To a tube equipped with a magnetic stir bar were added the Pd
catalyst 1 (19.6 mg, 0.7 mol% Pd), 1.0 equiv. of K2CO3 (27.6 mg,
0.2 mmol) and 1.5 equiv. of aryl chloride (0.3 mmol) in turn.
b Isolated yield.
We further explored the recovery and reuse of the catalyst 1
through the Stille coupling reaction of chlorobenzene with
phenyltributylstannane and the results are listed in Table 7. The
31 catalyst could be recovered through membrane filtration and
Subsequently,
the
solvent
(DMF,
1.0
mL)
and
reused in the next reaction with freshly added chlorobenzene,
phenyltributylstannane and K2CO3. The experimental results
showed that the catalytic activity of the catalyst did not obviously
decrease after the sixth consecutive cycles, and it could be reused
five times without a significant reduction in the yield (Table 7,
runs 2-6).
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
phenyltributylstannane (0.2 mmol) were added under air
atmosphere, respectively. The reaction was then heated to 120 °C
and stirred until aryl chloride was completely consumed as
determined by TLC. At last, the reaction mixture was purified by
silica gel column chromatography to afford the desired pure
coupling product.
Table 7
4.2.2. General procedure for Stille couplings of
diazonium salts with phenyltributylstannane
Recycling and reuse of the Pd catalyst 1.
Cat.1 (0.7 mol% Pd)
Cl
Bu3SnPh
K2CO3, DMF, 120 o
C
Phenyltributylstannane (81 µL, 1.2 equiv) was added to the
mixture of the Pd catalyst 1 (8.4 mg, 0.3 mol% Pd) and
diazonium salt (0.2 mmol, 44.4 mg) in acetonitrile (1.2 mL) at
room temperature. The reaction mixture was stirred in a test tube
under air atmosphere at 35 oC until the diazonium salt was
consumed fully as determined by TLC. The reaction mixture was
concentrated and then purified by column chromatography on
silica gel.
1a
2
3a
Run
1
t (h)
48
48
50
50
52
52
Yield (%) a
97
97
96
95
93
92
2
3
4
4.2.3. General procedure for Kumada-Corriu
couplings of aryl chlorides
5
6
To a tube equipped with a magnetic stir bar were added the Pd
catalyst 1 (11.2 mg, 0.4 mol% Pd) and 1.0 equiv. of aryl chloride
(0.2 mmol) in turn. Subsequently, the solvent (toluene, 2.0 mL)
and Grignard reagent (0.3 mmol, 1.5 equiv) were added under N2
atmosphere, respectively. The reaction was then heated to 140 °C
and stirred until aryl chloride was completely consumed as
determined by TLC. At last, the reaction mixture was purified by
silica gel column chromatography to afford the desired pure
coupling product.
a Isolated yield.
3. Conclusion
In summary, we have reported the Stille cross-coupling
reactions of (hetero)aryl chlorides, and arenediazonium
tetrafluoroborate salts with phenyltributylstannane, respectively,
and Kumada cross-coupling reactions of (hetero)aryl chlorides
with various Grignard reagents catalyzed by a highly active, air-
stable, and readily-synthesized Pd nano-catalyst supported on
aluminum hydroxide, and developed two novel and efficient
4.2.4. General procedure for Kumada-Corriu
couplings of heteroaryl chlorides

6
Tetrahedron
ACCEPTED MANUSCRIPT
674–688; (f) Slagt, V. F.; de Vries, A. H. M.; de Vries, J. G.;
Kellogg, R. M. Org. Process Res. Dev. 2010, 14, 30–47; (g) See
Ref [1a].
To a tube equipped with a magnetic stir bar were added the
Pd catalyst 1 (12.6 mg, 0.45 mol% Pd) and 1.0 equiv. of
heteroaryl chloride (0.2 mmol) in turn. Subsequently, the solvent
(toluene, 2.0 mL) and phenylmagnesium bromide (0.3 mmol, 1.5
equiv) were added under N2 atmosphere, respectively. The
reaction was then heated to 140 °C and stirred until heteroaryl
chloride was completely consumed as determined by TLC. At
last, the reaction mixture was purified by silica gel column
chromatography to afford the desired pure coupling product.
4. For recent selected examples of Kumada-Corriu cross-coupling
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1
2
3
4
5
6
7
8
9
4.2.5. General procedure for recycled Stille
coupling of chlorobenzene and
phenyltributylstannane
To a tube equipped with a magnetic stir bar were added
potassium carbonate (27.6 mg, 0.2 mmol, 1.0 equiv.) and the
10
11
12 palladium catalyst 1 (19.6 mg, 0.7 mol% Pd) in turn.
Subsequently, the solvent (DMF, 1.0 mL), chlorobenzene (1.5
equiv.) and phenyltributylstannane (0.2 mmol) were added under
air atmosphere, respectively. The reaction mixture was then
stirred at 120 oC for the specified time. The corresponding
recycling reactions were carried out with the recovered Pd
catalyst 1 that determined the amount of the substrate and reagent
as reference at 120 °C. Reaction times were 48, 50, 50, 52 and 52
h for cycles 1, 2, 3, 4 and 5, respectively. After the reactions were
fully carried out as determined by TLC, 3 mL H2O and 5 mL
CH2Cl2 were added and the reaction system was shaken well.
Subsequently, the catalyst 1 was recovered through membrane
filtration and reused in the next reaction. After the organic phase
was separated from the reaction system, the water phase was
extracted with CH2Cl2 (2 × 5 mL). The organic layer was then
combined and dried over anhydrous Na2SO4. At last, the solvent
was removed in vacuum and the residue was purified by silica
gel column chromatography to afford the pure product.
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65
Acknowledgements
We appreciate gratefully the Natural Science Foundation of
Shanxi Province (No. 2012021007-2) for financial support.
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10
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16. Extensive screening showed that the optimized reaction conditions
were 0.2 mmol diazonium salt, 1.2 equiv. of tributylphenyltin and
0.3 mol% Pd catalyst 1 in 1.2 mL CH3CN at 35 oC.
17. The optimal reaction conditions screened were 0.2 mmol aryl
chlorides, 1.5 equiv. of phenylmagnesiu bromide and 0.4 mol% Pd
catalyst 1 under N2 atmosphere in 2.0 mL toluene at 140 oC.
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