Sonogashira reaction of aryl halides with terminal alkynes catalyzed by cobalt hollow nanospheres

Article abstract of DOI:10.1055/s-2008-1072615

Sonogashira reaction catalyzed by cobalt hollow nanospheres has been developed. Coupling of alkynes with aryl iodide or aryl bromide in the presence of potassium carbonate, triphenylphosphine, and cuprous iodide provides the corresponding products with mo

Full text of DOI:10.1055/s-2008-1072615

LETTER
1415
Sonogashira Reaction of Aryl Halides with Terminal Alkynes Catalyzed by
Cobalt Hollow Nanospheres
S
onogashira Re
i
action
z
of Aryl Ha
l
h
ide
s
w
ith Te
eminal Alkynes Feng, Fangxian Liu, Peipei Sun,* Jianchun Bao*
Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Environmental Science, Nanjing Normal University,
Nanjing 210097, P. R. of China
Fax +86(25)83598280; E-mail: sunpeipei@njnu.edu.cn
Received 13 January 2008
neous catalysts for the Suzuki and Stille cross-coupling
Abstract: Sonogashira reaction catalyzed by cobalt hollow nano-
reactions of aryl halides carried out in ionic liquids.8
spheres has been developed. Coupling of alkynes with aryl iodide
or aryl bromide in the presence of potassium carbonate, triphen-
ylphosphine, and cuprous iodide provides the corresponding prod-
Hyeon and co-workers9 synthesized Pd/Ni bimetallic
nanoparticles with a cheap metal core (Ni) and a noble-
ucts with moderate to good yields, which reveals obvious metal shell (Pd), which can be used in Sonogashira cou-
advantages such as low-cost catalyst, the recyclability of the cata-
lyst, and simple experimental operation.
pling reactions. In our previous works, bimetallic hollow
palladium–cobalt nanoparticles have been prepared and
Key words: cobalt hollow nanospheres, catalysis, Sonogashira re-
action, cross-coupling, alkynes
successfully used as catalysts in aqueous media for the
coupling of aryl iodides or bromides and phenylacety-
lene.10 Instead of the costly palladium, nickel-catalyzed
Sonogashira couplings of activated aryl iodides and aro-
As a well-known sp2–sp coupling reaction between aryl or matic terminal alkynes were also reported in recent
alkenyl halides and terminal alkynes, the Sonogashira re- years.11 To our knowledge, as a well-established partner
action has become the most important method to prepare of nickel, especially as an inexpensive and relatively non-
arylalkynes and conjugated enynes,1 which are precursors toxic metal, metallic cobalt has not been as a catalyst used
for many natural products, pharmaceuticals, and molecu- in Sonogashira reaction.
lar organic materials.2 The Sonogashira reaction is usually
In our recent research, cobalt hollow nanospheres were
performed using a palladium–phosphine ligand complex
firstly prepared by a wet chemical method and used to cat-
as the catalyst in the presence of a catalytic amount of a
alyze the Heck reaction with a good result.12 The high sur-
copper(I) salt and an amine (as a solvent or in large ex-
face area of the hollow spheres resulting from the
cess) under homogeneous conditions. The traditionally
nanoparticulate nature of the shell, which is much larger
used catalysts are triphenylphosphine-related complexes,
than that of dense spheres of the same diameter, is respon-
Pd(PPh3)4, with the more stable and soluble Pd(PPh3)2Cl2
sible for the high catalytic activity. In this paper, these
being the most common. Although catalysts with biden-
hollow nanospheres were further successfully applied as
tate ligands such as Pd(dppe)Cl2, Pd(dppp)Cl2, or Pd(dp-
catalyst in the Sonogashira reaction (Scheme 1).
pf)Cl2 have also been employed. Most frequently, rather
high loadings of palladium (usually up to 5 mol%) and
nano-Co, Ph3P, CuI
ArX
R
Ar
R
larger amounts of the copper(I) salt are required when
these palladium species are employed. Numerous palladi-
um complexes have been employed to catalyze this trans-
formation in recent years, in which palladium–N
complexes,3 palladium–P,N complexes4 and palladium–
P,O complexes,5 as well as palladium–NHC (N-heterocy-
clic carbene) complexes6 were successfully used in these
procedures.
+
K2CO3, NMP
Scheme 1
The preparation of cobalt hollow nanospheres was de-
scribed in our previous report. It was found that the aver-
age diameter of the hollow spheres was about 50 nm with
mainly ranging from 50 nm to 60 nm, and the shell thick-
ness was about 10 nm. The ICP-MS analyses showed that
no palladium was detected in these hollow spheres, as
well as in K2CO3 and triphenylphosphine, which were
used in this coupling reaction. For investigating the reac-
tion conditions of these nanospheres-catalyzed Sonogash-
ira reaction, the coupling of phenylacetylene and p-
iodotoluene was chosen as a model reaction. The reaction
was carried out under a nitrogen atmosphere to avoid the
oxidative coupling of terminal alkynes which generally
takes place in the presence of oxygen.13 The experiment
indicated that 3 mol% of catalyst could catalyze the reac-
tion sufficiently. The reaction took place at 120 °C, and
Transition-metal nanoparticles are especially active cata-
lytic systems due to their large surface area. In recent
years, there has been growing interest in the fabrication of
Pd nanoparticles and their applications in organic reac-
tions, especially the formation of carbon–carbon bonds.7
For example, ligand-free Pd nanoparticles of about 3.3 nm
in size stabilized by tetraalkylammonium salts bearing
long alkyl chains were obtained and used as heteroge-
SYNLETT 2008, No. 9, pp 1415–1417
x
x.
x
x.
2
0
0
8
Advanced online publication: 07.05.2008
DOI: 10.1055/s-2008-1072615; Art ID: W01008ST
© Georg Thieme Verlag Stuttgart · New York

1416
L. Feng et al.
LETTER
solvents such as DMF or N-methyl-2-pyrrolidone (NMP) Under the selected reaction conditions, the cobalt-cata-
was chosen as the reaction media. In DMF, it gave a lower lyzed Sonogashira coupling of a series of aryl halides with
yield than in NMP. So NMP was adopted as the solvent of terminal alkynes was studied.15 The results are shown in
the reaction. As co-catalyst and ligand, cuprous iodide and Table 1. The reactions of aryl halides with electron-with-
triphenylphosphine were essential to the reaction. With- drawing or electron-donating groups did not show obvi-
out them, the reaction gave only traces of product. How- ous differences. This means that the reaction was
ever, the addition of copper salt as cocatalyst in this cross- relatively insensitive to the electronic characteristics of
coupling reaction also has drawbacks. The in situ genera- the substituents. The reaction of aryl iodides with aromat-
tion of copper acetylides under the reaction conditions ic or aliphatic terminal alkynes gave the corresponding
could generate homocoupling products of the terminal coupling products in higher yields than that of aryl bro-
alkyne (the so-called Glaser coupling),14 so the quantity of mides, while the reaction of aryl chloride gave only trace
cuprous iodide should be limited. The appropriate quanti- desired product. Furthermore, the reaction of aliphatic
ty of cuprous iodide in this reaction was 2 mol%. The alkynes with low boiling points proceeded at a lower tem-
yield of the reaction did not change significantly when the perature to avoid the volatilization of alkynes. A possible
amount of triphenylphosphine was at the range of 10 mechanism of this cobalt-catalyzed Sonogashira reaction
mol% to 20 mol%. As described previously in the litera- is shown in Scheme 2.
ture, a basic environment was also important for the Sono-
R2
R1
gashira reaction. As general bases, Na2CO3, K2CO3,
NaOH, and KOH were tested, and K2CO3 was found to be
the best. Potassium carbonate was therefore selected as
the base for our research. Another notable advantage of
this reaction was the recyclability of the Co catalyst. The
catalyst could be reused after being separated from the so-
lution and washed thoroughly with methanol and diethyl
ether. After being reused three times, the catalytic activity
did not decrease significantly.
R1X
Co0(Ln)
(Ln)
(Ln)
R1 Co
R1 Co
R2
X
Cu+X–
Cu
R2
Table 1 The Coupling of Aryl Halides with Terminal Alkynes Us-
HX
ing Cobalt Hollow Nanospheres as Catalyst
R2
Cu+X–
H
R2
H
Entry ArX
R
Time (h) Yield (%)a
1
2
PhI
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bu
Bu
Bu
Bu
Bu
Bu
Bu
20
20
22
24
20
24
28
30
20
20
20
24
20
24
30
90
Scheme 2
4-MeC6H4I
3-MeC6H4I
2-MeC6H4I
4-ClC6H4I
2-ClC6H4I
PhBr
85 (83, 83, 80)b
In conclusion, we have successfully used hollow cobalt
nanospheres in the Sonogashira reaction of aryl iodides
with alkynes. The obvious advantages of this method are
that the catalyst is much cheaper and easy to prepare as
compared to the conventional palladium catalysts, and the
catalyst can be reused for several times. The application of
this new catalyst in organic synthesis is under way in our
laboratory.
3
86
80
87
82
65
4
5
6
7
8
PhCl
Trace
85
Acknowledgment
9
PhI
This work was supported by the National Natural Science Founda-
tion of China (Project 20473038, 20772057), the Natural Science
Foundation of Jiangsu province (No. BK2005139), and the Natural
Science Foundation of the Education Committee of Jiangsu pro-
vince (No. 04KJB150066).
10
11
12
13
14
15
4-MeC6H4I
3-MeC6H4I
2-MeC6H4I
4-ClC6H4I
3-ClC6H4I
PhBr
88
86
82
88
82
33
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LETTER
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Sonogashira Reaction of Aryl Halides with Terminal Alkynes
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mmol, 3 mol%), Ph3P (0.1 mmol, 10 mol%), CuI (0.02
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80 °C (for aliphatic alkyne) with stirring under a nitrogen
atmosphere for the appropriate time (see Table 1, monitored
by TLC) until the reaction was complete, then centrifuged.
The solution was separated and the precipitate was washed
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column chromatography on SiO2 with hexane–EtOAc
(100:1) as eluent to yield the products. The precipitate was
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Synlett 2008, No. 9, 1415–1417 © Thieme Stuttgart · New York

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