Homocoupling of aryl iodides and bromides using a palladium/indium bimetallic system

Article abstract of DOI:10.1081/SCC-200063990

Homocoupling of aryl iodides and bromides using catalytic amounts of palladium and stoichiometric amounts of indium proceeded smoothly to afford the corresponding biaryls in good to high yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200063990

This article was downloaded by: [University of Illinois Chicago]
On: 15 April 2013, At: 10:10
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Homocoupling of Aryl
Iodides and Bromides Using a
Palladium/Indium Bimetallic
System
a
a
b
Yu Mi Chang , Seung Hwan Lee , Min Young Cho
,
b
c
a
Byung Woo Yoo , Hak June Rhee , Sang Ho Lee
&
b
Cheol Min Yoon
a
Graduate School of Biotechnology, Korea
University, South Korea
b
Department of New Material Chemistry, Korea
University, South Korea
c
College of Science and Technology, Hanyang
University, South Korea
Version of record first published: 15 Aug 2006.
To cite this article: Yu Mi Chang , Seung Hwan Lee , Min Young Cho , Byung Woo
Yoo , Hak June Rhee , Sang Ho Lee & Cheol Min Yoon (2005): Homocoupling of
Aryl Iodides and Bromides Using a Palladium/Indium Bimetallic System, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:13, 1851-1857
To link to this article: http://dx.doi.org/10.1081/SCC-200063990
PLEASE SCROLL DOWN FOR ARTICLE

Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

w
Synthetic Communications , 35: 1851–1857, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200063990
Homocoupling of Aryl Iodides and
Bromides Using a Palladium/Indium
Bimetallic System
Yu Mi Chang and Seung Hwan Lee
Graduate School of Biotechnology, Korea University, South Korea
Min Young Cho and Byung Woo Yoo
Department of New Material Chemistry, Korea University, South Korea
Hak June Rhee
College of Science and Technology, Hanyang University, South Korea
Sang Ho Lee
Graduate School of Biotechnology, Korea University, South Korea
Cheol Min Yoon
Department of New Material Chemistry, Korea University, South Korea
Abstract: Homocoupling of aryl iodides and bromides using catalytic amounts of
palladium and stoichiometric amounts of indium proceeded smoothly to afford the
corresponding biaryls in good to high yields.
Keywords: Aryl halide, homocoupling, indium, palladium
Biaryl compounds play important roles in organic chemistry because of a
variety of physical and chemical properties, and they have a broad range of
applications in various areas such as intermediates for natural product
Received in Japan January 11, 2005
Address correspondence to Cheol Min Yoon, Department of New Material
Chemistry, Korea University, Jochiwon, Chungnam 339-700, South Korea.
Tel.: þ82 2 3290 3433; Fax: þ82 2 3290 3433; E-mail: cmyoon@korea.ac.kr
1
851

1852
Y. M. Chang et al.
[1]
synthesis, monomers for conducting polymers, chiral phosphine ligands for
[
2]
[3]
organometallic catalysis, and core structures of liquid crystal. Since
Ullmann has developed the homocoupling of two aryl halides in the
[4]
presence of stoichiometric amounts of copper salts, many procedures
[5]
including palladium-catalyzed protocols have been developed.
example, biphenyls have been prepared by the palladium-catalyzed homocou-
For
[
6]
[7]
[8]
pling of arylboronic acids, arylstannanes, and arylzinc reagents. These
methods are efficient but their major drawback is the requirement of stoichio-
metric amounts of organometallic reagents generally prepared from aryl
halides. The transition-metal-catalyzed direct coupling of aryl halides could
be a convenient and straightforward method for the preparation of
[
9]
[10]
biphenyls. Indeed, various nickel and palladium
catalyst precursors
have been reported to promote the homocoupling of aryl halides under
relatively mild reaction conditions. For this, a combination of palladium
coupled with inorganic reducing agents such as aluminum, zinc, copper,
and magnesium has been developed, in which system reactivity and selectivity
highly depend on the components of the system, that is, transition-metal
[11]
reagents, electron sources, and solvents.
However, these reducing
reagents have their own problems, undesired reactions, caused by the in situ
generated Lewis acids from these metals. Herein, we report homocoupling
of aryl iodides and bromides in the presence of palladium as a catalyst
using indium as metallic reducing reagent to afford the corresponding
biaryls in good to high yields (Scheme 1). Indium as a reducing metal
might be a better metal or at least an alternative metal because of the
[
12]
several its own advantages.
(Indium powder (99.99% purity, 100 mesh,
product number 27,795–9) was purchased from Aldrich Co., Ltd.)
Initially we examined the homocoupling reaction of 4-iodoanisole as a
model in various solvent systems using Pd(PPh ) (4 mol%) and indium (1
3
4
equiv.) under the conditions mentioned in Table 1, and DMF was identified
to be the best solvent in yield and reaction time. The reaction in DMF was
complete in 3 h to give a biphenyl in 81.1% isolated yield (entry 6). The
reactions in THF or methanol at reflux did not proceed at all (entries 1 and
4) and those in acetonitrile, toluene, or DCM proceeded incompletely even
after 24 h of refluxing (entries 2, 3, and 5).
Among various palladium catalysts tested in the reaction using indium at
008C, Pd(PPh ) was identified to be the choice of palladium based on the
1
3
4
results listed in Table 2. The control tests revealed that the reactions did not
proceed at all in the absence of the palladium catalyst or indium after 24 h
at 1008C under the reaction conditions (entries 1 and 10). The optimum
Scheme 1.

Homocoupling of Aryl Iodine and Bromides
Table 1. Homocoupling of 4-iodoanisole in various
1853
a
solvents
Temp
(8C)
Time
(h)
Yield
b
(%)
Entry
Solvent
THF
DCM
1
2
3
4
5
6
Reflux
Reflux
Reflux
Reflux
Reflux
100
24
24
24
24
24
3
0
14.6
57.9
0
Acetonitrile
Methanol
Toluene
DMF
71.4
81.1
a
4-Iodoanisole (93.6 mg, 0.4 mmol), Pd(PPh ) (18.5 mg,
.016 mmol, 4 mol%), and indium (45.9 mg, 0.4 mmol) were
3 4
0
dissolved in various solvents (2 ml) and heated at 1008C.
Isolated yields.
b
amount of indium for this homocoupling reaction in the presence of catalytic
amount of Pd(PPh ) was 1 equivalent (entries 9–13).
3
4
Under the optimum conditions, homocouplings of various aryl iodides
and aryl bromides were conducted to give the results shown in Table 3.
The reaction of iodobenzene under the reaction condition provided a
a
Table 2. Homocoupling of 4-iodoanisole using palladium and indium
Palladium
catalyst
Indium
(equiv.)
Time
(h)
Yield
b
(%)
Entry
1
2
3
4
5
—
1
1
1
1
1
24
24
24
21
24
0
PdCl2
Pd(PPh)
Pd (dba)
20.3
30.6
74.2
35.7
2
Cl
.
2
2
3
CHCl
3
Allylpalladium
chloride dimer
Pd(OAc)
6
7
8
9
2
1
24
21
24
3
71.2
75.9
56.5
81.1
0
Pd(CH
Pd(PhCN) Cl
3
CN)
2
Cl
2
1
1
2
2
Pd(PPh
Pd(PPh
3
)
)
4
4
1
1
1
1
1
0
1
2
3
3
—
0.5
1.5
2
24
24
3
Pd(PPh3)4
52.3
83.9
79.8
Pd(PPh
Pd(PPh
3
)
)
4
4
3
3
a
The reaction of 4-iodoanisole (93.6 mg, 0.4 mmol) in DMF (2 ml) at
1008C using palladium catalyst (0.016 mmol, 4 mol%) and indium
(
45.9 mg, 0.4 mmol, 1 equiv.).
b
Isolated yields.

1854
Y. M. Chang et al.
Table 3. Homocoupling reaction of aryl halide
Time
(h)
Yield
a
(%)
Entry
1
Aryl halides
1.5
82.3
81.1
85.6
2
3
2
10
4
24
77.5
5
6
21
24
80.7
82.6
7
24
77.3
8
9
4
4
91.7
80.6
1
0
1
20
34
90.7
56.4
1
(
continued)

Homocoupling of Aryl Iodine and Bromides
1855
Table 3. Continued
Time
(h)
Yield
a
(%)
Entry
Aryl halides
1
2
48
88.6
b
b
1
3
20 min
93.7
57.5
1
4
1
b
b
1
5
24
24
79.3
75.6
1
6
1
7
8
4
82.4
44.1
1
48
a
b
Isolated yields.
Reflux.
biphenyl in 82.3% yield after 1 h heating at 1008C (entry 1). The electron-
sufficient aryl iodides (entries 2–7), such as o- or m- or p-iodoanisoles,
3
-iodophenol, and 6-iodospiropyrans, and the electron-deficient aryl iodides
entries 8–11), such as 2- or 4-iodobenzoic acids, 5-iodosalicylaldehyde,
(
and 1-iodo-2-bromobenzene, underwent homocoupling reactions to give the
corresponding products in high yields. Biphenyls obtained from the reactions
are useful compounds by themselves or as a substrate for the useful
0
compound. For example, 2,2 -dibromobiphenyl, a coupling product of
1
-iodo-2-bromobenzene, has been known as a useful substrate for carbazoles

1856
Y. M. Chang et al.
[13]
(entry 11).
The electron-deficient and sufficient bromides also were homo-
coupled under the reaction conditions to afford the corresponding biphenyl in
good to high yields respectively (entries 12–17). This reaction condition was
applied to coupling of 1-chloroisoquinoline to afford bis-isoquinoline, each
enantiomer of which might be very useful as a chiral ligand for asymmetric
[
14]
synthesis (entry 18).
The low yields of the coupling reactions of 1-iodo-
2
1
-bromobenzene, 3-bromobenzaldehyde and 1-chloroisoquinoline (entries
1, 14, and 18) are due to the incomplete reaction. All of these reactions
conducted were clean and those observed on TLC were coupling product
and substrate. The reaction condition was compatible with the labile
aldehyde group (entries 13–15) and spiropyran ring system (entries 7 and
8
). However, the nitro group was susceptible for the reaction condition and
the reaction of 1-iodo-4-nitrobenzene under the reaction condition provided
complicated mixtures because of the reduction of nitro group. The ortho-,
meta-, and para-bromobenzaldehyde and 2-bromo-4-toluidine at reflux
underwent coupling reaction to give the corresponding biphenyls in good to
excellent yields. Homocoupling reaction by using indium metal under soni-
[
15]
cation condition became available for iodoarenes,
was widely effective for iodo-, bromo-, and chloroarenes.
but our Pd/In protocol
In conclusion, the homocoupling reactions of aryl halides in DMF using
Pd-In system under our conditions proceeded smoothly to afford the corre-
sponding biaryls. Indium metal was identified to be a nice reducing reagent
for these homocoupling reactions. We believe our method is a nice alternative
for the synthesis of a variety of biphenyls from aryl iodides and bromides.
EXPERIMENTAL
To a solution of aryl halide (0.4 mmol) in DMF (2 ml) was added Pd(PPh3)4
(18.5 mg, 0.016 mmol, 4 mol%) and indium (45.9 mg, 0.4 mmol, 1 equiv.) at
room temperature and the resulting mixture was heated at 1008C. The
reaction progress was monitored by TLC using n-hexane or an eluent of ethyl
acetate and n-hexane (1: 4 or 1 : 10, depending on the polarity of substrate).
After the reaction time specified in Table 3, the reaction was quenched with
saturated sodium bicarbonate solution (4 ml) and extracted with ethyl acetate
(10 ml). The ethyl acetate layer was washed with water (4 ml) twice and
brine (4 ml), and dried over MgSO . The concentrate was chromatographed
4
on silica gel using n-hexane or a solution of ethyl acetate and n-hexane,
depending on the polarity of product, to afford the corresponding biphenyls.
ACKNOWLEDGMENTS
The authors acknowledge the financial support of the Korea Research
Foundation (KRF-C00122) made in the program year 2004.

Homocoupling of Aryl Iodine and Bromides
REFERENCES
1857
1
. (a) Schulz, E.; Fahmi, K.; Lemaire, M. Acros. Org. Acta 1995, 1, 10;
b) Papilon, J.; Schulz, E.; Gelinas, S.; Lessard, J.; Lemaire, M. Synth. Metals
998, 96, 155; (c) Zhu, S. S.; Swager, T. M. Adv. Mater. 1996, 8, 497;
d) Yamamoto, T.; Maruyama, T.; Zhou, Z.; Ito, T.; Fukada, T.; Yoneda, Y.;
(
1
(
Begum, F.; Ikeda, T.; Sasaki, S.; Takezoe, H.; Fukada, A.; Kubota, K. J. Am.
Chem. Soc. 1994, 116, 4832.
. Noyori, R. Chem. Soc. Rev. 1989, 18, 187.
. Yamamura, K.; Ono, S.; Tabushi, I. Tetrahedron Lett. 1988, 29, 1797.
. Ullmann, F. Ber. 1903, 36, 2389.
. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002,
2
3
4
5
102, 1359.
6
7
8
9
. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
. Farina, V. Pure Appl. Chem. 1996, 68, 73.
. Negishi, E. Acc. Chem. Res. 1982, 15, 340.
. (a) Massicot, F.; Schneider, R.; Fort, Y.; Illy-Cherrey, S.; Tillement, O.
Tetrahedron 2001, 57, 531; (b) Lin, G.-Q.; Hong, R. J. Org. Chem. 2001, 66,
2
877; (c) Howarth, J.; James, P.; Dai, J. Tetrahedron Lett. 2000, 41, 10319;
d) Massicot, F.; Schneider, R.; Fort, Y. J. Chem. Res. 1999, 664.
0. (a) Hassan, J.; Penalva, V.; Lavenot, L.; Gozzi, C.; Lemaire, M. Tetrahedron 1998,
(
1
54, 13793; (b) Luo, F.-T.; Jeevanandam, A.; Basu, M. K. Tetrahedron Lett.
1998, 39, 7939; (c) Venkatraman, S.; Li, C.-J. Org. Lett. 1999, 1, 1133;
(
(
d) Hennings, D. D.; Iwama, T.; Rawal, V. H. Org. Lett. 1999, 1, 1205;
e) Boger, D. L.; Goldberg, J.; Andersson, C.-M. J. Org. Chem. 1999, 64, 2422.
1
1
1. (a) Tanaka, H.; Sumida, S.; Kobayashi, N.; Komatsu, N.; Torii, S. Inorg. Chim.
Acta 1994, 22, 323; (b) Tanaka, H.; Kosaka, A.; Yamashita, S.; Morishita, K.;
Torii, S. Tetrahedron Lett. 1989, 30, 1261; (c) Roche, A. J.; Duan, J.-X.;
Dolbier, W. R., Jr.; Abboud, K. A. J. Org. Chem. 2001, 66, 7055.
2. An advantage of indium over the other metals such as zinc, tin, and magnesium is
that it is inert toward water and acid solutions, is low for the first ionization
potential, and is itself without apparent toxicity. For review (a) Nair, V.;
Ros, S.; Jayan, C. N.; Pillai, B. S. Tetrahedron 2004, 60, 1959; (b) Joachim, P.;
Thomas, C. M. Synthesis 2003, 633; (c) Miao, W.; Lu, W.; Chan, T. H. J. Am.
Chem. Soc. 2003, 125, 2412; (d) Khan, F. A.; Dash, J.; Sahu, N.; Gupta, S. Org.
Lett. 2002, 4, 1015; (e) Cho, S.; Kang, S.; Keum, G.; Kang, S. B.; Han, S.-Y.;
Kim, Y. J. Org. Chem. 2003, 68, 180; (f) Ranu, B. C.; Dutta, J.; Guchhait, S. K.
Org. Lett. 2001, 3, 2603; (g) Ranu, B. C.; Samanta, S.; Guchhait, S. K. J. Org.
Chem. 2001, 66, 4102; (h) Ranu, B. C.; Samanta, S.; Guchhait, S. K. Eur.
J. Org. Chem. 2000, 2347.
1
3. Nozaki, K.; Takahashi, K.; Nakano, K.; Hiyama, T.; Tang, H. Z.; Fujiki, M.;
Yamaguchi, S.; Tamao, K. Angew. Chem. Engl. Int. Ed., 2003, 42, 2051.
4. Busato, S.; Craig, D. C.; Judeh, Z. M.A.; Read, R. W. Tetrahedron 2003, 59, 461.
5. Ranu, B. C.; Dutta, P.; Sarkar, A. Tetrahedron Lett. 1998, 39, 9557.
1
1