FeCl3 catalyzed barbier homocoupling reaction for synthesis of symmetric biaryls

Article abstract of DOI:10.1002/jccs.201100679

Aseries of biaryls and biheteroaryls were synthesized by the Barbier reaction of aryl bromide withmagnesium powder and 1,2-dibromoethane in the presence of FeCl3 in THF under reflux reaction condition. The catalytic system differentiates itself fromother homocoupling reactions catalyzed by iron salts in that it requires neither the preliminary preparation of Grignard reagent nor the addition of an oxidant.

Full text of DOI:10.1002/jccs.201100679

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
.
FeCl3 Catalyzed Barbier Homocoupling Reaction for Synthesis of Symmetric Biaryls
Adam Shih-Yuan Lee,* Pin-Lung Chen, Yu-Ting Chang and Heng-Tser Tsai
Department of Chemistry, Tamkang University, New Taipei, Taiwan 251, R.O.C.
(Received: Nov. 22, 2011; Accepted: Jan. 13, 2011; Published Online: Jan. 19, 2012; DOI: 10.1002/jccs.201100679)
Aseries of biaryls and biheteroaryls were synthesized by the Barbier reaction of aryl bromide with magne-
sium powder and 1,2-dibromoethane in the presence of FeCl3 in THF under reflux reaction condition. The
catalytic system differentiates itself from other homocoupling reactions catalyzed by iron salts in that it re-
quires neither the preliminary preparation of Grignard reagent nor the addition of an oxidant.
Keywords: Biaryl; Barbier homocoupling reaction; Iron salt.
INTRODUCTION
Biaryls constitute core structural motifs for a wide
catalyzed by iron salts in that it requires neither the prepa-
ration of Grignard reagent nor the addition of an oxidant.
The first feasibility of our approach was tested by
adding 1,2-dibromoethane (1.0 mmol) to a mixture of 3-
bromotoluene (1.0 mmol), magnesium powder (2.5 mmol),
CuCl (0.05 mmol) in THF (5 mL) and the reaction mixture
was refluxed for 15 hours (Scheme II). The expected prod-
uct biphenyl was only obtained with 40%. Others copper
salts such as CuBr, CuI, CuCl2, CuBr2 and Cu(OAc)2 also
were investigated and CuBr2 as catalyst improved the bi-
phenyl formation yield to 72%. The formation yield of bi-
range of functional molecules and their potential applica-
tions in optoelectronic materials and molecular devices are
well-recognized.1 The original and most widely used route
to biaryls is the copper-mediated homocoupling reactions
of aryl halides (Ullmann reaction).2 The need to avoid the
harsh reaction conditions typically required for Ullmann
couplings has motivated the search for milder variations.
The iron-catalyzed homocoupling reaction of aryl halides
has recently received considerable attention because the re-
actions proceed under milder reaction conditions which
compared to the classical Ullmann reaction conditions.3
Homocoupling reactions of aryl Grignard reagents are an
easy and efficient access to symmetrical Biaryls. Hayashi
and co-worker have demonstrated the efficiency of the
iron-catalyzed homocoupling of aryl Grignard reagents us-
ing stoichiometric amount of 1,2-dichloroethane as an oxi-
dant.4 However, for industrial applications, these methods
are limited since they require preparation of Grignard re-
agent and a stoichiometric amount of organic oxidant.5
Herewith, we wish to report a simple method for synthesis
of biaryls from aryl bromide with a catalytic amoumt of
FeCl3 under Barbier reaction condition (Scheme I).6 This
homocoupling reaction of aryl bromide was performed in
one pot by a combination of unactivated magnesium pow-
der7 and a catalytic amount of iron salt. The catalytic sys-
tem differentiates itself from other homocoupling reactions
Scheme II
Scheme I
5% FeCl3, Mg, BrCH2CH2Br,
Ar-Ar
Ar-Br
THF, reflux
Dedicated to the memory of Professor Yung-Son Hon (1955–2011).
* Corresponding author. Tel.: +8862-26215656#2543; Fax: +8862-26223830; E-mail: adamlee@mail.tku.edu.tw
452
© 2012 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2012, 59, 452-454

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
FeCl3 Catalyzed Barbier Homocoupling Reaction
phenyl was improved to 80% when FeCl3 was used as cata-
lyst under the reaction condition. The reaction time by us-
ing iron salt catalyst under the reaction condition was much
shorter than using copper salt catalyst.
coupling smoothly affording the corresponding symmetri-
cal biaryls in moderate to excellent yields. It is interesting
to know that 1H,1¢H-5,5¢-biindoyl compound was obtained
with the starting unprotected 5-bromoindole under the
Barbier reaction condition (Table 1, Entry 7).
In order to realize the optimized reaction condition of
this Barbier homocoupling reaction, 2-bromothiophene
was selected as the testing substrate for synthesis of bis-
thiophene which was well known as the important syn-
thetic intermediate of optoelectronic material.8 The intro-
ducing amount of FeCl3 in different solvent was investi-
gated and the results were shown in Scheme III.
A representative procedure for synthesis of a biaryl is
as follows: 1,2-Dibromoethane (2.0 mmol) was added to a
mixture of aryl bromide (2.0 mmol), magnesium powder
(5.0 mmol), FeCl3 (0.1 mmol) in anhydrous THF (10 mL)
and the reaction mixture was refluxed for 1 hour. The
cooled reaction mixture was filtrate by a paper filter and the
filtrate was extracted with ether (20 mL´ 3). The combined
organic layer was washed with brine (20 mL), dried with
MgSO4, filtered, and then the organic solvent was removed
under reduced pressure. Further purification was achieved
on a flash chromatograph with silica gel and ethyl acetate/
hexane as eluant.
Scheme III
As a conclusion, we demonstrate here an efficient
Table 1. Synthesis of biaryls
2.5 Mg, 1.0 BrCH2CH2Br
Ar
X
Ar Ar
5% FeCl3, THF, reflux, 1 hr
Product
Entry
1
Aryl-X
Yield(%)a
80
Br
2
80
H3C
Br
CH3
H3C
3
4
80
75
Br
MeO
MeO
OMe
NMe2
O
1,2-Dibromoethane (2.0 mmol) was added to a reac-
tion mixture of 2-bromothiophene (2.0 mmol), magnesium
powder (5.0 mmol), FeCl3 (0.1 mmol) in THF (10 mL) and
the reaction mixture was refluxed for 1 hour and the bis-
thiophene was obtained with 82% yield. Different intro-
ducing amount of catalyst FeCl3 was investigated and the
experimental results showed that 0.05 molar ratio of FeCl3
to substrate is the best choice for this Barbier homocou-
pling reaction. It should be noted that the Barbier homo-
coupling reaction did not proceed when toluene or hexane
was used as solvent.
Me2N
Br
Me2N
O
O
5
79
O
O
Br
O
Br
6
7
81
81
HN
HN
NH
Br
Br
S
S
8
9
82
40
49
S
S
S
S
N
RESULTS AND DISCUSSION
Cl
Br
To understand and expand the scope for synthesis of
biaryls by this Barbier homocoupling reaction, a series of
aryl bromides was investigated and the results are shown in
Table 1. Various aromatic bromides underwent the homo-
10
N
N
a Isolated yields were measured and based on introducing amount of Ar-X.
J. Chin. Chem. Soc. 2012, 59, 452-454
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Article
Lee et al.
method for the synthesis of symmetric biaryls under Bar-
bier reaction condition. The Barbier homocoupling reac-
tion of aryl bromides was successfully performed in one
pot by a combination of unactivated magnesium powder
and a catalytic amount of iron trichloride. This catalytic
system differentiates itself from other homocoupling reac-
tions catalyzed by iron salts in that it requires neither the
preliminary preparation of Grignard reagent nor the addi-
tion of an oxidant.
134.7, 134.8.
2,2¢-Bithiophene (Table 1, Entry 8)
1H-NMR: d 7.00 (2H, dd, J = 3.70, 4.95 Hz), 7.71-
7.26 (4H, m); 13C-NMR: d 123.9, 124.5, 127.9, 137.6.
2,2¢-Bipyridyl (Table 1, Entry 10)
1H-NMR: d 7.13 (2H, m, J = 7.2 Hz), 7.64 (2H, m, J =
7.2 Hz), 8.74 (2H, m, J = 7.5 Hz), 8.64 (2H, m J = 7.2 Hz);
13C-NMR: d 121.3, 123.9, 137.1, 149.4, 156.4.
ACKNOWLEDGEMENTS
EXPERIMENTAL
We thank the National Science Council in Taiwan
(NSC98-2119-M-032-002-MY3) and Tamkang University
for financial support.
Biphenyl (Table 1, Entry 1)
1H-NMR: d 7.34 (2H, t, J = 7.2 Hz), 7.44 (4H, t, J =
7.2 Hz), 7.60 (4H, d, J = 7.5 Hz); 13C-NMR: d 127.3, 127.4,
128.9, 141.4.
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J. Chin. Chem. Soc. 2012, 59, 452-454