Copper-free Sonogashira reaction using gold nanoparticles supported on Ce2O3, Nb2O5 and SiO2 under microwave irradiation

Article abstract of DOI:10.1055/s-2008-1078565

In the present communication we wish to report a copper-free Sonogashira reaction catalyzed by gold-supported catalysts under microwave irradiation. Aryl and alkyl acetylenes were used and good yields were obtained with short reaction times when DMF was u

Full text of DOI:10.1055/s-2008-1078565

LETTER
1777
Copper-Free Sonogashira Reaction Using Gold Nanoparticles Supported on
Ce2O3, Nb2O5 and SiO2 under Microwave Irradiation
C
opper-Free Son
o
d
ction using
S
r
upporte
i
d Gold
g
N
anoparticl
o
Victor Teixeira da Silva,b O. A. C. Antunes*a
a
Instituto de Química, CT Bl. A 641, Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
Fax +55(21)25627559; E-mail: octavio@iq.ufrj.br
NUCAT/PEQ/COPPE/UFRJ, CT Bl. G, Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
b
Received 1 February 2008
Cu(I) and Pd(0) in the catalytic cycle is very attractive,5a,b
particularly if these gold-supported catalysts act as
sources of soluble species as widely demonstrated in
Pd(0) chemistry by our6 and other groups.7
Abstract: In the present communication we wish to report a cop-
per-free Sonogashira reaction catalyzed by gold-supported catalysts
under microwave irradiation. Aryl and alkyl acetylenes were used
and good yields were obtained with short reaction times when DMF
was used as solvent. Three different supported gold catalysts were
used and Au/SiO2 gave the best result for both aryl and alkyl acety-
lenes.
Since the conditions to carry out this reactions involved
temperatures of about 130 °C and reaction times of 24–48
hours, the use of microwave irradiation emerged as a pos-
sibility to save time and increase yields.
Key words: Sonogashira reaction, gold nanoparticles, supported
catalyst
Use of microwaves (MWs) as an alternative energy source
is becoming widespread in organic chemistry, as demon-
strated by the rapidly growing number of annual publica-
tions on this topic. Of course the main reason for using
MW is related to the fact that it is a very fast way of ener-
gy transfer.8 Moreover, the reaction temperature can easi-
ly go above the solvent boiling point and the effect on
improving reaction rates is dramatic.9
The Sonogashira reaction1 is a carbon–carbon coupling
reaction between terminal alkynes and aryl or vinyl ha-
lides. This reaction has been widely applied in different
areas such as natural product synthesis and material sci-
ence. The reaction generally proceeds in the presence of a
palladium catalyst and a co-catalyst. The most widely em-
ployed co-catalysts are Cu(I) salts (Scheme 1). The origi-
nal Sonogashira reaction was performed in the presence of
large amounts of Pd(0) and Cu2I2 under inert conditions.
These conditions of course are not presently acceptable
from economic and environmental points of view.
The most significant improvement in this reaction2 has
been based on the omission of Cu2I2, not only because of
environmental concerns but also because it can induce the
formation of oxidatively homocoupled byproducts of
acetylenes that are difficult to separate from the desired
product and because Cu2I2 has also been shown to inhibit
the Sonogashira reaction.
Herein, we report copper-free Sonogashira reactions be-
tween aryl halides and phenylacetylene or 1-octyne cata-
lyzed by gold under microwave irradiation.
We first investigated the effect of various solvents on the
model reaction between iodobenzene (1) and phenylacet-
ylene (2) catalyzed by 3 mol% of supported Au/SiO2 in
the absence of Cu2I2. K2CO3 was used as base in this reac-
tion (Table 1).
Table 1 Effect of Different Solvents on the Reaction between
Iodobenzene (1) and Phenylacetylene (2) Catalyzed by Supported
Au/SiO2 (3% mol) under Microwave Irradiation
The use of gold in catalysis has received increased atten-
tion recently. Previously considered catalytically inac-
tive,3 gold is now widely used in catalytic processes and
in organic synthesis.4 Corma’s group has successfully ap-
plied Au/Ce2O3 among other gold-supported catalysts in
different processes, in particular in the Sonogashira cou-
pling.5 Corma’s hypothesis that Au(I) can replace both
Palladium catalyst
I
Au/SiO2
+
solvent, K2CO3
MW
1
2
3
Entry
Solventa
THF
Time
1 h
Yieldb
R2
X
R1
H
R1
R2
+
Cu+ Y–
base
1
2
3
4
68% (59)c
15%
H2O
1 h
Scheme 1 The Sonogashira cross-coupling reaction
DMF
EtOH
1 h
87% (81)c
no reaction
1 h
SYNLETT 2008, No. 12, pp 1777–1780
Advanced online publication: 02.07.2008
DOI: 10.1055/s-2008-1078565; Art ID: D03808ST
© Georg Thieme Verlag Stuttgart · New York
1
6
.0
7
.2
0
0
8
a The solvent volume used was 5 mL.
b Based on GC analysis.
c Isolated yield.

1778
R. O. M. A. de Souza et al.
LETTER
mately the same particle size, the slight difference in
TONs can be attributed only to the difference in the sur-
face area presented by the support, SiO2 (200 m2/g),
Nb2O5 (49 m2/g) and Ce2O3 (20 m2/g).
Table 2 The Use of Different Gold-Supported Catalysts in the
Reaction between Iodobenzene (1) and Phenylacetylene (2) under
Microwave Irradiation
I
Au-supported
We next investigated the copper-free Sonogashira reac-
tions of a variety of aryl iodides and bromides 4–7 with
phenylacetylene (1) in DMF under Au/SiO2 catalysis and
microwave irradiation. As summarized in Table 3, the re-
action between 4-nitroiodobenzene (4) and phenylacet-
ylene (2) led to the reaction product in 84% yield (entry
2). However, aryl iodides with electron-donating groups
such as 4-OMe (entry 3), gave moderate yields after 3.5
hours of reaction. When less reactive aryl bromides were
used in the copper-free reaction, the coupling products 10
and 11 were also obtained in moderate yields after a reac-
tion time of 3.5 hours (entries 4 and 5) and no yield im-
provement was observed after this time.
+
DMF, K2CO3
MW
3
1
2
Entry
Catalysta
Au/SiO2
Time
1 h
Yieldb
87% (81%)c
66%
TONs
29
1
2
3
Au/Nb2O5
Au/Ce2O3
1 h
22
1 h
52%
17
a The amount of catalyst used was 3% mol.
b Based on GC analysis.
c Isolated yield.
Finally, we explored the reaction between aryl iodides and
bromides 4–7 with 1-octyne (12) in DMF under Au/SiO2
catalysis and microwave irradiation (Table 4). Iodoben-
zene (1) and 4-nitroiodobenzene gave good yields in short
reaction times. The less activated aryl bromides and aryl
iodides substituted with an electron-donating group led to
moderate yields with longer reaction times.
As shown in Table 1, the use of DMF gave the highest
yield (entry 3, 87%) after one hour under microwave irra-
diation in the reaction of iodobenzene (1) with phen-
ylacetylene (2). The yield of the cross-coupled product
was reduced in the presence of protic (entries 2 and 4) and
low-polarity solvents (entry 1). This result can be related
to the fact that as DMF is a dipolar aprotic solvent it is ex-
pected to be a very good absorber of MW irradiation.
In summary, in the present letter it has been shown that the
use of gold-supported catalysts under microwave irradia-
tion is a very convenient way to carry out copper-free So-
nogashira coupling.10 It has been demonstrated that, in
contrast to the very long reaction times previously report-
ed, one to 3.5 hours were needed under the present condi-
tions with at least similar yields. The Au/SiO2-supported
catalyst provided the best yields, although similar TONs
were obtained with all the three catalytic sources. The fact
that reaction was carried out in DMF, a good MW absorb-
er, perhaps contributed to the formation of soluble spe-
cies, Au(III), upon oxidative addition and that of Au(I)
after reductive elimination, perhaps also leading to the
After selecting DMF as the optimal solvent, we investi-
gated the effect of other gold-supported catalysts on the
copper-free Sonogashira reaction of iodobenzene (1) with
phenylacetylene (2), under microwave irradiation. Ac-
cording to the results shown in Table 2, Au/SiO2 gave the
best yield (entry 1, 87%), when compared to the other cat-
alysts, Au/Ce2O3 and Au/Nb2O5 (entries 2 and 3, respec-
tively). However, it is very important to emphasize that
there is no significance difference in the turnover numbers
(TONs), between these three catalytic sources. As the
three catalytic sources tested, Au/SiO2 (4.2 nm), Au/
Nb2O5 (4.9 nm) and Au/Ce2O3 (5.9 nm) have approxi-
Table 3 Reaction of Aryl Iodides and Bromides 4–7 with Phenylacetylene (1) Catalyzed by Supported Au/SiO2 (3 mol%) in DMF under
Microwave Irradiation
X
Au/SiO2
R
+
DMF, K2CO3
MW
R
3, 8, 9
1, 4–7
2
Entry
R
X
I
Timea
1 h
Yieldb
1
2
3
4
5
H
3, 87% (81)c
8, 84% (80)c
9, 56% (50)c
3, 61%
NO2
OMe
H
I
1 h
I
3.5 h
3.5 h
3.5 h
Br
Br
OMe
9, 43%
a No further improvement was observed.
b Based on GC analysis.
c Isolated yield.
Synlett 2008, No. 12, 1777–1780 © Thieme Stuttgart · New York

LETTER
Copper-Free Sonogashira Reaction Using Supported Gold Nanoparticles
1779
Table 4 Reaction of Aryl Iodides and Bromides 4–7 with 1-Octyne (12) Catalyzed by Supported Au/SiO2 (3 mol%) in DMF under Microwave
Irradiation
X
Au/SiO2
DMF, K2CO3
+
4
R
5
R
1, 4–7
12
13–15
Entry
R
H
X
I
Timea
1 h
Yieldb
1
2
3
4
5
13, 66% (60)c
14, 78% (75)c
15, 59% (50)c
13, 52%
NO2
OMe
H
I
1 h
I
3.5 h
3.5 h
3.5 h
Br
Br
OMe
15, 32%
a No further improvement was observed.
b Based on GC analysis.
c Isolated yield.
J.-H.; Frost, T. M. Angew. Chem. Int. Ed. 2000, 39, 2285.
(q) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem. Int.
Ed. 1998, 37, 1415.
formation of Au(I) acetylides, and very fast catalytic cy-
cles in solution.
(5) (a) Corma, A.; Gonzalez-Arellano, C.; Iglesias, M.; Perez-
Ferreras, S.; Sanchez, F. Synlett 2007, 1771. (b) González-
Arellano, C.; Abad, A.; Corma, A.; Garcia, H.; Iglesias, M.;
Sánchez, F. Angew. Chem. Int. Ed. 2007, 46, 1536.
Acknowledgment
We are grateful to the FAPERJ, the CAPES and the CNPq for finan-
cial support.
(c) González-Arellano, C.; Corma, A.; Iglesias, M.;
Sánchez, F. J. Catal. 2006, 238, 497. (d) Carrettin, S.;
Guzman, J.; Corma, A. Angew. Chem. Int. Ed. 2005, 44,
2242. (e) Carrettin, S.; Corma, A.; Iglesias, M.; Sánchez, F.
Appl. Catal. A: Gen. 2005, 291, 247.
References and Notes
(1) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467. (b) Hierso, J. C.; Doucet, H. Angew.
Chem. Int. Ed. 2007, 46, 835.
(2) Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874.
(3) (a) Haruta, M. Cattech 2002, 6, 102. (b) Ishida, T.; Haruta,
M. Angew. Chem. Int. Ed. 2007, 46, 7154. (c) Haruta, M.
Nature (London) 2005, 437, 1098.
(4) (a) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
(b) Marion, N.; Nolan, S. P. Angew. Chem. Int. Ed. 2007, 46,
2750. (c) Bond, G. C.; Louis, C.; Thompson, D. T. Catalysis
by Gold; Imperial College Press: London, 2006.
(6) (a) Coelho, A. V.; Souza, A. L. F.; Lima, P. G.; Wardell, J.
L.; Antunes, O. A. C. Appl. Organomet. Chem. 2008, 22,
39. (b) Coelho, A. V.; Souza, A. L. F.; Lima, P. G.; Wardell,
J. L.; Antunes, O. A. C. Tetrahedron Lett. 2007, 48, 7671.
(c) Senra, J. D.; Malta, L. F. B.; Souza, A. L. F.; Medeiros,
M. E.; Aguiar, L. C. S.; Antunes, O. A. C. Tetrahedron Lett.
2007, 48, 8153. (d) Oliveira, B. L.; Antunes, O. A. C. Lett.
Org. Chem. 2007, 4, 13. (e) Estrada, G. O. D.; Souza, A. L.
F.; Silva, J. F. M.; Antunes, O. A. C. Catal. Commun. 2008,
9, 1734. (f) Souza, A. L. F.; Silva, L. C.; Oliveira, B. L.;
Antunes, O. A. C. Tetrahedron Lett. 2008, 49, 3895.
(7) (a) Andrews, S. P.; Stepan, A. F.; Tanaka, H.; Ley, S. V.;
Smith, M. D. Adv. Synth. Catal. 2005, 347, 647. (b) Ji, Y.;
Jain, S.; Davis, R. J. J. Phys. Chem. B 2005, 109, 17232.
(c) Cassol, C. C.; Umpierre, A. P.; Machado, G.; Wolke, S.
I.; Dupont, J. J. Am. Chem. Soc. 2005, 127, 3298. (d) Yu,
K.; Sommer, W.; Richardson, J.; Weck, M.; Jones, C. W.
Adv. Synth. Catal. 2005, 347, 161. (e) Weck, M.; Jones, C.
W. Inorg. Chem. 2007, 46, 1865. (f) Alimardanov, A.;
Schmieder-van de Vondervoort, L.; de Vries, A. H. M.;
de Vries, J. G. Adv. Synth. Catal. 2004, 346, 1812.
(8) (a) Martins, D. L.; Alvarez, H. M.; Aguiar, L. C. S.; Antunes,
O. A. C. Lett. Org. Chem. 2007, 4, 253. (b) Alvarez, H. M.;
Malta, L. F. B.; Herbst, M. H.; Horn, A. Jr.; Antunes, O. A.
C. Appl. Catal. A: Gen. 207, 326, 82. (c) Valdés, R. H.;
Aranda, D. A. G.; Alvarez, H. M.; Antunes, O. A. C. Lett.
Org. Chem. 2007, 4, 35. (d) Pimentel, L. C. F.; Souza, A. L.
F.; Fernández, T. L.; Wardell, J. L.; Antunes, O. A. C.
Tetrahedron Lett. 2007, 48, 831. (e) Alvarez, H. M.;
Barbosa, D. P.; Fricks, A. T.; Aranda, D. A. G.; Valdés, R.
H.; Antunes, O. A. C. Org. Process Res. Dev. 2006, 10, 941.
(d) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006,
4555. (e) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem.
Int. Ed. 2006, 45, 7896. (f) Hashmi, A. S. K. Angew. Chem.
Int. Ed. 2005, 44, 6990. (g) Astruc, D.; Lu, F.; Aranzes, J. R.
Angew. Chem. Int. Ed. 2004, 44, 7852. (h) Schrekker, H. S.;
Gelesky, M. A.; Stracke, M. P.; Schrekker, C. M. L.;
Machado, G.; Teixeira, S. R.; Rubim, J. C.; Dupont, J.
J. Colloid Interface Sci. 2007, 316, 189. (i) Schelwies, M.;
Dempwolff, A. L.; Rominger, F.; Helmchen, G. Angew.
Chem. Int. Ed. 2007, 46, 5598. (j) Hashmi, A. S. K.;
Schäfer, S.; Wölfle, M.; Gil, C. D.; Fischer, P.; Laguna, A.;
Blanco, M. C.; Gimeno, M. C. Angew. Chem. Int. Ed. 2007,
46, 6184. (k) Deng, X.; Baker, T. A.; Friend, C. M. Angew.
Chem. Int. Ed. 2006, 45, 7075. (l) Brouwer, C.; He, C.
Angew. Chem. Int. Ed. 2006, 45, 1744. (m) Han, X.;
Widenhoefer, R. A. Angew. Chem. Int. Ed. 2006, 45, 1747.
(n) Lemière, G.; Gandon, V.; Agenet, N.; Goddard, P.;
de Kozak, A.; Aubert, C.; Fernsterbank, L.; Malacria, M.
Angew. Chem. Int. Ed. 2006, 45, 7559. (o) Manea, F.;
Houillon, F. B.; Pasquato, L.; Scrimin, P. Angew. Chem. Int.
Ed. 2004, 43, 6165. (p) Hasmi, A. S. K.; Schwarz, L.; Choi,
Synlett 2008, No. 12, 1777–1780 © Thieme Stuttgart · New York

1780
R. O. M. A. de Souza et al.
LETTER
(9) (a) Loupy, A. Microwaves in Organic Synthesis, Vol. 1;
Wiley–VCH: Weinheim, 2006. (b) Loupy, A. Microwaves
in Organic Synthesis, Vol. 2; Wiley–VCH: Weinheim,
2006. (c) Kappe, C. O.; Stadler, A. Microwaves in Organic
and Medicinal Chemistry; Wiley–VCH: Weinheim, 2005.
(d) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563.
(e) Hosseini, M.; Stiasni, N.; Barbieri, V.; Kappe, C. O.
J. Org. Chem. 2007, 72, 1417. (f) Kremsner, J. M.; Stadler,
A.; Kappe, C. O. Top. Curr. Chem. 2006, 266, 233.
(g) Kappe, C. O.; Larhed, M. Angew. Chem. Int. Ed. 2005,
44, 7666. (h) Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43,
6250. (i) Desai, B.; Kappe, C. O. Top. Curr. Chem. 2004,
242, 177.
Compound 8: 1H NMR (300 MHz, CDCl3): d = 8.10 (m, 2
H), 7.95 (m, 2 H), 7.49–7.53 (m, 2 H), 7.20–7.25 (m, 3 H).
Compound 9: 1H NMR (300 MHz, CDCl3): d = 7.51 (m, 2
H), 7.46 (m, 2 H), 7.18–7.23 (m, 3 H), 6.84 (m, 2 H), 3.80 (s,
3 H).
Compound 13: 1H NMR (300 MHz, CDCl3): d = 7.25 (m, 1
H), 7.13 (m, 4 H), 2.38 (m, 2 H), 1.40 (m, 8 H), 0.89 (m, 3 H).
Compound 14: 1H NMR (300 MHz, CDCl3): d = 8.10 (m, 2
H), 7.89 (m, 2 H), 2.35 (m, 2 H), 1.33 (m, 8 H), 0.85 (m, 3 H).
Compound 15: 1H NMR (300 MHz, CDCl3): d = 7.36 (m, 2
H), 6.79 (m, 2 H), 3.55 (s, 3 H), 2.40 (m, 2 H), 1.45 (m, 8 H),
1.11 (m, 3 H).
Commercial Nb2O5 (49 m2/g1) and SiO2 (200 m2/g), kindly
provided by CBMM and DEGUSA, were used as received.
CeO2 (20m2/g) was obtained by calcination of Ce(III) nitrate
hexahydrate (ACROS, 99.5%) at 800 °C/h in a conventional
oven. Gold was incorporated into the supports using the
deposition–precipitation method at a constant pH of 8 by
addition of Na2CO3 and using a HAuCl4 (ACROS) solution
as gold source. Characterization of the catalysts by small-
angle X-ray scattering (SAXS) revealed gold particle sizes
of 4.9, 5.9 and 4.2 nm for Nb2O5, CeO2 and SiO2 supports,
respectively.
(10) A mixture of the aryl halide (1.00 mmol), Au-supported
catalyst (3 mol%), phenylacetylene or 1-octyne (1.00 mmol)
and K2CO3 (138 mg, 1.00 mmol) was mixed in DMF (5.0
mL). Microwave-assisted syntheses were conducted with a
CEM Discover focussed microwave oven (150 W). After the
reaction, usual aqueous workup and column chromatograph-
ic purification process on silica gel (hexanes–EtOAc, 9:1)
were carried out. The spectroscopic data of compounds 3, 8,
9, 13, 14 and 15 are as follows.
Compound 3: 1H NMR (300 MHz, CDCl3): d = 7.45–7.50
(m, 4 H), 7.20–7.25 (m, 6 H).
Synlett 2008, No. 12, 1777–1780 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.