Cobalt-catalyzed homo-coupling of aryl and alkenyl bromide using atmospheric oxygen as oxidant

Article abstract of DOI:10.1016/j.tetlet.2009.09.092

An efficient procedure for the synthesis of symmetric biphenyl and olefinic compounds was reported by cobalt-catalyzed direct homo-coupling reaction of aryl and alkenyl bromide in the presence of metallic magnesium using atmospheric oxygen as the oxidant. All tested aromatic bromides could give corresponding biaryls in good yields (up to 85%). Moreover, under the same conditions, β-bromostyrene could also afford the corresponding conjugated dienes in moderate yields, and the coupling is highly stereoselective to give trans-products. This mild and practicable method opened a new way to the preparation of symmetric biaryls and conjugated dienes.

Full text of DOI:10.1016/j.tetlet.2009.09.092

Tetrahedron Letters 50 (2009) 6795–6797
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cobalt-catalyzed homo-coupling of aryl and alkenyl bromide
using atmospheric oxygen as oxidant
*
Shan-Yong Chen, Ji Zhang, Ying-Hao Li, Jun Wen, Shao-Quan Bian, Xiao-Qi Yu
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient procedure for the synthesis of symmetric biphenyl and olefinic compounds was reported by
cobalt-catalyzed direct homo-coupling reaction of aryl and alkenyl bromide in the presence of metallic
magnesium using atmospheric oxygen as the oxidant. All tested aromatic bromides could give corre-
sponding biaryls in good yields (up to 85%). Moreover, under the same conditions, b-bromostyrene could
also afford the corresponding conjugated dienes in moderate yields, and the coupling is highly stereose-
lective to give trans-products. This mild and practicable method opened a new way to the preparation of
symmetric biaryls and conjugated dienes.
Received 15 August 2009
Revised 14 September 2009
Accepted 18 September 2009
Available online 25 September 2009
Keywords:
Homo-coupling
Biaryls
Ó 2009 Elsevier Ltd. All rights reserved.
Symmetric dienes
Cobalt
Grignard reagents
The biaryl motif plays a considerable role in organic chemistry
by its common presence in a vast array of natural products, phar-
maceuticals, agrochemicals, and materials.1 Increasing attentions
have been paid to the development of efficient synthetic methods
for biaryl formation. Homo- and cross-coupling are most com-
monly used methods to construct biaryl structure. Historically,
the copper-catalyzed coupling, known as Ullmann reaction, was
the first efficient method to synthesize symmetrical biaryls.2 Since
Ullmann reaction is always performed under tough conditions, var-
ious mild methods relying on the use of nickel or palladium have
been developed.3 Many symmetrical biaryls can be obtained by
the palladium- or nickel-catalyzed homo-coupling of ArX (X = I,
Br, Cl, OTf) in the presence of a reducing agent. However, the metal
catalysts together with the ligands are expensive and toxic. Re-
cently, such reaction was elevated to a high plateau by Gosmini
who reported an efficient procedure for reductive homo-coupling
of aryl halide catalyzed by CoBr2.4 In their reactions, excessive
Mn (6 equiv) was used as reducing agent, and besides, only low
yields were obtained when using substrates with electron-donat-
ing substituents.
halides. However, most homo-couplings involving Grignard
reagent need stoichiometric use of transition metal halides such
as TiCl4,5 TlCl,6 VO(OEt)Cl2,7 FeCl3,8 CoCl2,9 and CuCl2,10 making
the reactions neither atom-economical nor green. More recently,
Hayashi11 and Cahiez12 developed iron-catalyzed homo-couplings
Table 1
Cobalt-catalyzed homo-coupling of bromobenzenea
Mg, Cobalt Salts
Br
THF, RT
Entry
Cobalt salt
Catalyst amount (mol %)
Yieldb (%)
1
2
3
4
5
—
—
10
10
10
10
5
2.5
5
5
Trace
43
66
81
79
81
76
64
79
Co2O3
CoSO4
Co(acac)3
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
6
7
8c
9d
10e
11f
Oxidative homo-coupling of aryl-metal reagents is another effi-
cient synthetic method for the construction of symmetrical biaryls.
Although many organometallic reagents (ArM; M = B, Sn, Si, Zn,
Mn, and Mg) can be used for this reaction, Grignard reagent was
no doubt the best choice for large-scale preparation because of
their convenient and economical preparation directly from aryl
5
5
81
35
a
Bromobenzene, 1 mmol; Mg turnings, 1.2 mmol; anhydrous THF, 2 mL; under
dry air; and reaction time 3 h.
b
Isolated yields after column chromatography.
Mg, 0.75 equiv.
Mg, 1 equiv.
Mg, 2 equiv.
c
d
e
* Corresponding author. Tel.: +86 28 85460576; fax: +86 28 85415886.
E-mail address: xqyu@tfol.com (X.-Q. Yu).
f
Reaction under argon.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.092

6796
S.-Y. Chen et al. / Tetrahedron Letters 50 (2009) 6795–6797
of Grignard reagents using 1, 2-dihalogenoethanes as oxidant. Such
procedures may be attractive alternatives to those reactions using
stoichiometric amounts of metal salts. Cahiez et al. also developed
a more economical procedure for the homo-coupling catalyzed by
MnCl2 or FeCl3 by using atmospheric oxygen as oxidant.13 Similar
reactions were performed smoothly with FeCl3/bipyridine/O2 sys-
tem by Lei group.14 However, all the above methods require the
preparation of Grignard reagents, which make the reaction mois-
ture-sensitive and not easily handled.
To the best of our knowledge, direct oxidative homo-coupling of
aryl halide in the presence of metallic magnesium is rare, and only
two examples catalyzed by MnCl2 and FeCl3 were reported.15 Co-
balt, as an environmental friendly and inexpensive metal like iron
or manganese, has been widely used as catalyst in the coupling
reactions between organomagnesium halides and organohalides.16
Herein, we report the cobalt-catalyzed direct homo-coupling of
aryl bromides in the presence of metallic magnesium using atmo-
spheric oxygen as oxidant, and this method obviates the pre-prep-
aration of Grignard reagents. Furthermore, we also studied the
direct homo-coupling of alkenyl bromides, and the resulted conju-
gate olefins, which can be used in liquid crystal material,17 were
smoothly obtained.
use of CoCl2 or Co(acac)3 as catalysts could evidently increase the
chemical yield to around 80% (entries 4 and 5). CoCl2 was chosen
for subsequent optimization of reaction conditions for economic
consideration. It was found that the catalyst loading does not affect
the yields apparently, and only slight yield differences (76–81%)
were found in the reactions using 2.5–10 mol % of CoCl2 (entries
5–7). 1.2 equiv of magnesium might be a proper amount for this
reaction (entries 6 and 9), and the yield did not change by increas-
ing Mg to 2 equiv (entry 10), which is the amount chosen by Xu
and Yuan.15 On the other hand, a sharp decrease of yield was found
by reducing the amounts of Mg to 0.75 equiv, and only 64% yield
together with 20% of recovered substrate was obtained (entry 8).
These various yields caused by different Mg loadings suggest that
Grignard reagent species was involved in the reaction, and at least
1 equiv of Mg is needed for complete conversion.
When the reaction was performed under argon, only 35% homo-
coupling product was given (entry 11). We consider that, as Cahiez
reported,13 the atmospheric oxygen plays a key role as an oxidant
in the reaction. It was known that in the absence of any transition
metal salts, aryl Grignard reagents could be oxidized directly by
oxygen to give ArOH. However, little amount of phenol was ob-
served in our system. We speculate that the oxidation of Grignard
reagents to biphenyl products catalyzed by cobalt salts is much
faster than the oxidative formation of phenols.
Initially, the study was carried out by the direct homo-coupling
of bromobenzene catalyzed by different cobalt salts (10 mol %) in
tetrahydrofuran under dry air on 1 mmol scale at room tempera-
ture (Table 1). Only trace of the desired product was obtained in
the absence of catalyst, indicating that cobalt salt is essential to
this reaction (entry 1). The reactions catalyzed by CoSO4 or Co2O3
with poor solubility led to moderate yields (entries 2 and 3). The
When the reaction was carried out on a 5 mmol scale under
same conditions, the biphenyl product increased to 85%, indicating
that the reaction system may avail large-scale preparation. This
result also encouraged us to extend the scope of the reaction to
various bromide substrates, and the results are listed in Table 2.
Table 2
CoCl2-catalyzed homo-coupling of bromide compoundsa
X
R
R
Mg, CoCl2
THF, RT
R
1
2
Entry
1
Substrate
Product
Yieldb (%)
85
Br
2a
1a
Br
2
3
84
84
2b
1b
Br
2c
1c
Br
O
O
O
4
5
6
80
80
79
2d
H3CO
H3CO
1d
O
Br
1e
2e
Br
1f
2f

S.-Y. Chen et al. / Tetrahedron Letters 50 (2009) 6795–6797
6797
Table 2 (continued)
Entry
Substrate
Product
Yieldb (%)
70
Br
F
F
7
8
2g
F
1g
Br
75c
81
1h
2h
Br
9
1i
2i
Br
10
65 E/E:Z/E = 99:1d
1j
2j
Br
11
66 E/E:Z/E = 98.5:1.5d
1k
2k
a
Bromobenzene, 5 mmol; cobalt salt, 5 mol %; Mg turnings, 6 mmol; anhydrous THF, 10 mL; under dry air; and reaction time 4 h.
Isolated yields after column chromatography.
Recrystallized from ethanol.
b
c
d
The stereoselectivity was determined by GC–MS.
All tested aromatic bromides could give the corresponding biaryls
in good yields (entries 1–7). Strong electron-donating substituent
such as methoxy group on the phenyl ring has little effect on the
reaction (entries 4 and 5). The substituent at ortho-position de-
creased the yield (entry 2 and 6), which might be attributed to
the steric effect. For p-fluorophenyl bromide (entry 7), decreased
yield of homo-coupling product was obtained, while some ter-
phenyl compounds were obtained. This method also worked well
in the reaction of 2-bromonaphthalene, and 2,20-binaphthalene
was obtained with 75% yield after recrystallization from ethanol
(entry 8). Moreover, activated alkyl bromide such as benzyl bro-
mide could also be converted to 1,2-diphenylethane smoothly
through homo-coupling with 81% yield (entry 9). When ester or
nitrile substituents were present, no obvious conversion was
observed (data not shown), which was probably due to the surface
deactivation of Mg caused by the substituted groups.18 More inter-
estingly, under the same conditions, trans-b-bromostyrene also
afforded the corresponding conjugated dienes in moderate yields
(entries 10 and 11), and the coupling is highly stereoselective to
give trans-products. Such high stereoselectivity might be attrib-
uted to the fast coupling of alkenyl Grignard reagents.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.09.092.
References and notes
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Acknowledgments
The authors acknowledge the National Science Foundation of
China (Nos. 20702034 and 20725206) for financial support. The
authors also thank the Analytical & Testing Center of Sichuan
University for NMR analysis.