The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder

Article abstract of DOI:10.1039/b314246a

The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder has been developed; terminal alkynes couple with aryl, alkenyl iodide and aryl bromide in the presence of cuprous iodide, triphenylphosphine, potassium hydroxide and ultrafine particle nickel(0) to provide the corresponding cross-coupling products with high yields.

Full text of DOI:10.1039/b314246a

The Sonogashira coupling reaction catalyzed by ultrafine nickel(0)
powder
Lei Wang,*ab Pinhua Lia and Yicheng Zhanga
a Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, P. R. China;
Fax: 86-561-309-0518; Tel: 86-561-380-2069. E-mail: leiwang@hbcnc.edu.cn
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, P. R. China
Received (in Cambridge, UK) 15th November 2003, Accepted 15th December 2003
First published as an Advance Article on the web 27th January 2004
The Sonogashira coupling reaction catalyzed by ultrafine
nickel(0) powder has been developed; terminal alkynes couple
with aryl, alkenyl iodide and aryl bromide in the presence of
cuprous iodide, triphenylphosphine, potassium hydroxide and
ultrafine particle nickel(0) to provide the corresponding cross-
coupling products with high yields.
Aromatic terminal alkynes and aliphatic terminal alkynes were
successfully coupled with aromatic, heteroaromatic and vinyl
iodides. Aryl bromides with terminal alkynes formed moderate to
good yields of coupling products under unoptimized reaction
conditions. Substituent effects of aromatic terminal alkynes and
aromatic iodides were also examined. The results indicate that the
reaction is relatively insensitive to the electronic characteristics of
a substituent as well as its location.
Since potassium hydroxide is an effective desilylating reagent
for trimethylsilyl-substituted acetylene,5 we used the trimethylsilyl
derivatives of aryl terminal alkynes as starting materials to react
with aromatic iodides in a one-pot Sonogashira coupling reaction.
1-Phenyl-2-(trimethylsilyl)acetylene coupled with p-iodotoluene to
generate the corresponding cross coupling product in excellent
yield (95%) under the reaction conditions. We also investigated the
Sonogashira coupling-cyclization of o-iodophenol with phenyl-
acetylene to produce a 75% yield of 2-phenylbenzo[b]furan
(Scheme 1).
The recyclability of the nickel(0) powder catalyst was also
examined. After carrying out a reaction and isolating the product,
additional potassium hydroxide, cuprous iodide and triphenylphos-
phine were added to the nickel catalyst and the reaction repeated.
Only minor decreases in product yields were observed through
seven repetitive cycles.
In conclusion, a novel and reliable procedure for the synthesis of
arylacetylenes via a Sonogashira coupling reaction has been
developed which involves the use of ultrafine nickel(0) powder as
catalyst. The reaction is an inexpensive alternative to the palla-
dium-catalyzed process, and results in high yields of the desired
product.
Transition metal-catalyzed cross-coupling reactions of organome-
tallic compounds with organic electrophiles rank among the most
useful processes for forming carbon–carbon bonds.1 The palla-
dium-catalyzed coupling of terminal acetylenes with aryl and vinyl
halides (the Sonogashira reaction) is one of the important and
widely used procedures for the preparation of terminal and internal
alkynes in organic syntheses.2 The reaction generally proceeds in
the presence of a homogeneous palladium catalyst, which makes
the recovery of the metal tedious if not impossible and might result
in high palladium contamination of the product. Because of its
cheap availability and high catalytic activity, Ni(0) has been used in
Suzuki coupling, Negishi reaction, Kumada coupling, and amina-
tion reactions in the last two decades.3 To the best of our
knowledge, there is one report on the Sonogashira reaction
catalyzed by Ni(PPh3)2Cl2, but this approach is limited by the
narrow choice of reactants (only aryl iodides and aromatic terminal
alkynes).4 Here, we report an ultrafine particle nickel(0) catalyzed
Sonogashira reaction of terminal alkynes with aryl iodides, vinyl
iodide and aryl bromides in heterogeneous catalytic conditions, and
the Ni(0) catalyst can be recycled without change of activity.
First, our studies were directed towards exploring the reaction
conditions for the reaction of aryl iodides with terminal alkynes
catalyzed by nickel(0).† The results are summarized in Table 1.
Phenylacetylene and p-iodotoluene were chosen as model com-
pounds for the initial investigation.
Table 1 Optimization reaction conditions for Sonogashira couplinga
Entry
Solvent (T/°C)
Base
Yieldb (%)
As can be seen from Table 1, the solvent plays a very important
role in the coupling reaction. A low yield of coupled product was
obtained in THF (entry 6, Table 1), and moderate to good yields
were obtained in DMSO, dioxane, acetonitrile and DMF (entries
2–5, Table 1). When isopropanol serves as solvent, and potassium
hydroxide as base, a quantitative yield of product was isolated
(entry 1, Table 1). In addition, the Sonogashira reaction requires the
presence of a base. Of the bases, including organic and inorganic
bases we tested, potassium hydroxide was the most effective
(entries 7–12, Table 1). The ultrafine nickel(0) powder (ca. 100 nm
diameter), triphenylphosphine and cuprous iodide are all essential
to the reaction. No reaction occurs in the absence of nickel(0)
powder, triphenylphosphine or cuprous iodide. Meanwhile, the
particle size of metallic nickel powder has a strong effect on the
reaction. When 100 mesh nickel(0) powder was used for the
reaction, only a trace of the product was generated, and when a
submicron nickel(0) powder was used, 57% yield of the product was
obtained (entries 13–14, Table 1).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Isopropanol (80)
DMSO (120)
Dioxane (100)
DMF (100)
Acetonitrile (80)
THF (70)
Acetonitrile (80)
Isopropanol (80)
Isopropanol (80)
Isopropanol (80)
Isopropanol (80)
Isopropanol (80)
Isopropanol (80)
Isopropanol (80)
KOH
KOH
KOH
K2CO3
KOH
KOH
K3PO4
KF
NaOH
K3PO4
K2CO3
(C2H5)3N
KOH
98
58
70
80
75
23
82
25
89
80
71
10
Tracec
57d
KOH
a Phenylacetylene (102 mg, 1.00 mmol), p-iodotoluene (218 mg, 1.00
mmol), Ni (ca. 100 nm activated powder from Aldrich, 6 mg, 0.10 mmol),
CuI (10 mg, 0.052 mmol), triphenylphosphine (79 mg, 0.30 mmol), and
base (3 mmol) in solvent (4 mL) for 5 h. b Isolated yield. c Ni (100 mesh)
was used instead of Ni (ca. 100 nm) powder. d Ni (submicron powder) was
used instead of Ni (ca. 100 nm) powder.
Under optimized conditions, the coupling results of a variety of
terminal alkynes with organic halides are shown in Table 2.
514
C h e m . C o m m u n . , 2 0 0 4 , 5 1 4 – 5 1 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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Table 2 Ultrafine nickel(0) powder catalyzed Sonogashira coupling reactiona
Entry
R1X
R2C·CH
Solvent/base (T/°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
p-CH3C6H4I
C6H5I
C6H5I
p-CH3C6H4I
p-CH3OC6H4I
p-H2NC6H4I
p-O2NC6H4I
o-FC6H4I
p-CH3COC6H4I
C6H5I
C6H5I
C6H5I
2-Iodothiophene
n-C8H17C·CH
n-C6H13C·CH
C6H5C·CH
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/K2CO3 (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
Isopropanol/KOH (80)
94
92
95
98
96
90
88
93
92
91
95
90
89
C6H5C·CH
C6H5C·CH
C6H5C·CH
C6H5C·CH
n-C8H17C·CH
n-C8H17C·CH
p-CH3C6H4C·CH
p-FC6H4C·CH
o-ClC6H4C·CH
C6H5C·CH
14
C6H5C·CH
Isopropanol/KOH (80)
85
15
16
17
p-CNC6H4Br
2-Bromopyridine
3-Bromopyridine
n-C8H17C·CH
C6H5C·CH
n-C8H17C·CH
DMF/K2CO3 (120)
DMF/K2CO3 (120)
DMF/K2CO3 (120)
56
71
63
a Terminal alkyne (1.00 mmol), organic halide (1.00 mmol), Ni (ca. 100 nm diameter size activated powder, 6 mg, 0.10 mmol), CuI (10 mg, 0.052 mmol),
triphenylphosphine (79 mg, 0.30 mmol), and base (3 mmol) in solvent (4 mL) at the given reaction temperature with stirring for 5 h. b Isolated yields.
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Scheme 1
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We thank the National Natural Science Foundation of China (No.
20372024, 20172018) and the Excellent Scientist Foundation of
Anhui Province, China (No. 2001040) for support of this
research.
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Notes and references
† The synthesis of phenyl-p-tolylacetylene is representative. Phenyl-
acetylene (102 mg, 1.00 mmol), p-iodotoluene (218 mg, 1.00 mmol), nickel
(ca. 100 nm diameter activated powder from Aldrich, 6 mg, 0.10 mmol),
triphenylphosphine (79 mg, 0.30 mmol), cuprous iodide (10 mg, 0.052
mmol), and potassium hydroxide (168 mg, 3.00 mmol) were added in a
round-bottomed flask containing isopropanol (4 mL). The reaction mixture
was stirred at 80 °C for 5 h. After complete reaction, the mixture was
vacuum filtered using a sintered glass funnel and the product was purified
by flash chromatography to generate 188 mg of phenyl-p-tolylacetylene
(98% yield).
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C h e m . C o m m u n . , 2 0 0 4 , 5 1 4 – 5 1 5
515