Use of ruthenium/alumina as a convenient catalyst for copper-free Sonogashira coupling reactions

Article abstract of DOI:10.1002/adsc.200404189

It has been found that a new and practical catalyst system of ruthenium-supported on alumina carries out copper-free Sonogashira coupling reactions with high efficiency over a wide range of substrates under mild and convenient conditions.

Full text of DOI:10.1002/adsc.200404189

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Use of Ruthenium/Alumina as a Convenient Catalyst for
Copper-Free Sonogashira Coupling Reactions
Soyoung Park, Min Kim, Dong Hyun Koo, Sukbok Chang*
Center for Molecular Design and Synthesis (CMDS), Department of Chemistry and School of Molecular Science (BK21),
Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
Fax: (þ82)-42-869-2810, e-mail: sbchang@kaist.ac.kr
Received: June 21, 2004; Accepted: August 23, 2004
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de.
Abstract: It has been found that a new and practical
catalyst system of ruthenium-supported on alumina
carries out copper-free Sonogashira coupling reac-
tions with high efficiency over a wide range of sub-
strates under mild and convenient conditions.
x H2O as precursor with a slight modification of the re-
ported procedures.[9] Reduction of the metal precursors
and subsequent immobilization of the resultant rutheni-
um(0) metal particles on a range of supports were car-
ried out either by a solution phase method or by a calci-
nation hydrogenation procedure, and their activities
were examined in a test reaction of 4-iodoacetophenone
with phenylacetylene (Table 1). Loaded metal contents
and their average sizes were measured by using induc-
tively coupled plasma (ICP) analysis and transmission
electron microscopic (TEM) images, respectively. Metal
contents on the supports were in the range of 2.2–
8.5 wt %, and ruthenium nanoparticles were uniformly
ꢀ
Keywords: alkynes; C C bond formation; copper-
free Sonogashira reaction; heterogeneous catalysis;
ruthenium
Alkynylation reactions of aryl and alkenyl (pseudo)ha- dispersed on the supports with an average diameter of
lides have been developed as one of the most useful syn- 2.3–10 nm, which varied depending on the supports em-
thetic methods for the preparation of acetylene deriva- ployed.
tives in such diverse areas as organic synthesis, materials
It was found that the nature and structure of the sup-
science, pharmaceutical and fine chemical industries.[1] porting materials play a crucial role in the catalytic activ-
The couplings are carried out most frequently by palla-
dium catalysts combined with a copper cocatalyst in an
Table 1. Catalytic activity of various supported Ru catalysts
amine, which was originally reported in 1975.[2] Al-
though several modified protocols have been revealed,
such as copper-free,[3] heterogeneous,[4] or bimetallic
systems,[5] there is still a need to develop more practical
and convenient catalytic systems that can be applied to a
broader range of substrates. During the course of our
studies on the development of metal-catalyzed, efficient
organic transformations, we have focused on the syn-
thetic utility of ruthenium catalysis.[6] Whereas support-
ed ruthenium systems can be conveniently prepared,
their use as a catalyst is rather limited, in most cases,
to the areas of either oxidation or hydrogenation reac-
tions.[7] Recently, however, we have demonstrated that
a heterogeneous Ru/alumina catalyst system performs
in alkynylation reaction.[a]
Entry
Support (wt %)[b]
Yield [%][b]
1
2
3
4
carbon (5.0)
MCM-48 (8.5)
CMK-5 (2.9)
MgO (2.2)
TiO2 (3.5)
Montmo K10 (3.4)
Al2O3 (5.0)
72
13
14
7.1
13
8.0
97
70
5
6[c]
7
8[d]
Al2O3 (5.0)
ꢀ
C C bond forming reactions such as olefination (Heck
reactions) and Suzuki–Miyaura cross-couplings with
high efficiency and selectivity.[8] Described herein are
our latest studies on the preparation of supported ruthe-
nium catalysts and their applications to alkynylation re-
actions.
[a]
Reaction conditions: 4-iodoacetophenone (0.5 mmol),
phenylacetylene (1.0 mmol), Ru/support (5 mol %),
CuCl2 (10 mol %), and triethylamine (1.0 mmol) in CH3
CN (1.0 mL).
NMR yields based on an internal standard (anisole).
Montmorillonite K10.
[b]
[c]
[d]
At the outset of our studies, we prepared a number of
supported ruthenium metal systems starting from RuCl3
In the absence of copper cocatalyst.
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ꢀ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200404189
Adv. Synth. Catal. 2004, 346, 1638–1640

Ru/Alumina as Catalyst for Cu-Free Sonogashira Coupling Reactions
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Table 2. Ru-catalyzed copper-free Sonogashira reactions.[a]
ity of the corresponding impregnated ruthenium cata-
lysts. For example, while conversion of the reaction
was over 70% within 12 h in the presence of CuCl2 coca-
talyst when ruthenium on activated carbon was used as a
catalyst (5 mol %) in acetonitrile (entry 1), a change of
the template to silica-based materials such as MCM-
48[10] resulted in much poorer activity under otherwise
identical conditions (entry 2). Acetonitrile was the sol-
vent of choice and other solvents were less satisfactory
in the reaction. It is interesting that among the similar
carbon-based materials, use of mesoporous materials
such as CMK-5[11] brought about significantly lower ac-
tivity compared to an active charcoal template (com-
pare entries 1 and 3).[12] Ruthenium catalysts supported
on inorganic oxides such as MgO[13] and TiO2 dis-
[14]
played low reactivity on the alkynylation (entries 4
and 5, respectively). In addition, use of montmorillonite
K10[15] as a support did not improve the catalytic activity
of impregnated ruthenium catalyst (entry 6). On the
other hand, alumina turned out to be most effective
among the various supports investigated. The reaction
took place quantitatively with the use of a commercially
available Ru/alumina catalyst (entry 7). The high activ-
ity of the Ru/aluminacatalystsystem permitted the reac-
tion to proceed in acceptable yields even in the absence
of copper cocatalysts (entry 8). It should be mentioned
that this represents the first example of a heterogeneous
ruthenium catalyst system for the Sonogashira coupling
reactions without the need of copper cocatalysts.[16]
When longer reaction times were allowed, a complete
conversion was achieved even in the copper-free ruthe-
nium system (vide infra). On the other hand, no conver-
sion was observed when only alumina was employed
even in large excess, implying that no background reac-
tion took place with the alumina support. It turned out
[a]
Reaction conditions: aryl iodide (0.5 mmol), alkyne
(1.0 mmol), Ru/Al2O3 (5 wt %, 5 mol %), and triethyla-
mine (1.0 mmol) in CH3CN (1.0 mL).
Isolated yield.
Run at 1108C.
[b]
[c]
that triethylamine was the most efficient base among group was selectively coupled with phenylacetylene to
those examined thus giving a full conversion, and others give the corresponding alkynylchloropyridine adduct
were inferior: pyrrolidine (46%), Cs2CO3 (50%), and 2,6- in moderate yield (entry 10). Heteroaromatic acety-
lutidine (<5%).
lenes were coupled with aryl iodides in good to excellent
A wide array of substrates was subjected to the opti- yields albeit at higher reaction temperatures (entries 11
mized reaction conditions (Table 2). Using Ru/alumina and 12). A silyl-substituted acetylene was also smoothly
as a catalyst in the absence of the copper cocatalyst, coupled with 4-iodoacetophenone in good yield (en-
moderate to excellent product yields were obtained try 14). It is worthy of remark that the reaction condi-
from the coupling reactions. The electronic nature of tions are highly convenient so that a simple aqueous
the alkynyl substituents has little influence on the effi- work-up after the reactions provides the desired prod-
ciency of the couplings (entries 1–4) although those ucts with a high purity (>95%, 1H NMR) after removal
with electron-donating groups retarded slightly the re- of excess volatile starting materials, thus making the
action, requiring higher reaction temperatures to obtain present procedure highly practical. The coupling reac-
satisfactory results (entry 5). Electronic effects of aryl tions could be readily scaled up to gram scales while still
iodides on the coupling efficiency were also negligible maintaining the same efficiency as on the depicted scale
as in the cases of the acetylene counterparts. As a result, of Table 2. Moreover, the heterogeneous catalyst can be
good to excellent yields were obtained from the reac- recovered quantitatively after the coupling, and the cat-
tions of phenylacetylene with various aryl iodides re- alytic activity of thus recovered material remained al-
gardless the electronic nature of electrophilic reagents most unchanged in the second cycle reaction.[17]
(entries 6–8). It was observed that a conjugated enyne
In summary, we have demonstrated that ruthenium
was also readily participated in the reaction (entry 9). supported on alumina can be used as a convenient and
When 2-chloro-5-iodopyridine was used, only the iodo practical catalyst system for the Sonogashira reactions
Adv. Synth. Catal. 2004, 346, 1638–1640
asc.wiley-vch.de
ꢀ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1639

Soyoung Park et al.
COMMUNICATIONS
Buchmeiser, Bioorg. Med. Chem. Lett. 2002, 12, 1837–
1840; d) L. Djakovitch, P. Rollet, Tetrahedron Lett.
2004, 45, 1367–1370.
between terminal alkynes and iodoarenes. It was found
that efficiency of the reaction was influenced significant-
ly by the nature and structure of metal supports. The het-
erogeneous catalyst exhibits high activity and selectivity
over a range of substrates allowing the coupling reac-
tions to proceed efficiently even in the absence of cop-
per cocatalysts.
[5] S. U. Son, Y. Jang, J. Park, H. B. Na, H. M. Park, H. J.
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Org. Lett. 2001, 3, 2089–2091; e) S. H. Yang, S. Chang,
Org. Lett. 2001, 3, 4209–4211; f) S. Ko, Y. Na, S. Chang,
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[7] For selected recent examples, see: a) G. C. Bond, A. D.
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Experimental Section
Typical Procedure for Alkynylation of Iodoarenes
To a solution of 4-iodoacetophenone (123 mg, 0.50 mmol) in
acetonitrile (1.0 mL) was added phenylacetylene (102 mg,
1.0 mmol), Et3N (102 mg, 1.0 mmol), and Ru/Al2O3 (5 wt %,
52 mg, 0.025 mmol). The reaction mixture was stirred for
24 h at 908C and then was diluted with EtOAc (10 mL) fol-
lowed by water (10 mL). The organic layer was separated,
dried over anhydrousMgSO4, and filtered. After removal of or-
ganic solvent under reduced pressure, the residue was purified
by flash column chromatography (ethyl acetate/hexane, 1:20)
to give the desired product, 4-(phenylethynyl)acetophenone;
yield: 94 mg (85%).
[8] Y. Na, S. Park, S. B. Han, H. Han, S. Ko, S. Chang, J. Am.
Chem. Soc. 2004, 126, 250–258.
[9] For details of the preparative procedures, see the Sup-
porting Information.
[10] For examples of the use of MCM-48 as a support mate-
rial, see: a) M. Eswaramoorthy, Neeraj, C. N. R. Rao,
Chem. Commun. 1998, 615–616; b) C. D. Nunes, M. Pil-
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346, 459–466.
Acknowledgements
This research was supported by Korea Science & Engineering
Foundation (R02-2003-000-10075-0) through the Basic Re-
search Program.
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ˆ
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Adv. Synth. Catal. 2004, 346, 1638–1640