Suzuki cross-coupling of aryl halides with aryl boronic acids catalyzed by phosphine-free NiCl2·6H2O

Article abstract of DOI:10.1016/S0040-4039(02)00716-5

Aryl bromides and iodides can be coupled with phenylboronic acid in good yields using NiCl₂·6H₂O as a catalyst precursor. This nickel complex is cheap, widely available and can be used without any auxiliary ligand or reducing agent.

Full text of DOI:10.1016/S0040-4039(02)00716-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4009–4011
Suzuki cross-coupling of aryl halides with aryl boronic acids
catalyzed by phosphine-free NiCl2·6H2O
Danilo Zim and Adriano L. Monteiro*
Laboratory of Molecular Catalysis, Instituto de Qu´ımica, UFRGS, Av. Bento Gonc¸alves, 9500 Porto Alegre 91501-970
CP 15003 RS, Brazil
Received 27 March 2002; revised 10 April 2002; accepted 11 April 2002
Abstract—Aryl bromides and iodides can be coupled with phenylboronic acid in good yields using NiCl2·6H2O as a catalyst
precursor. This nickel complex is cheap, widely available and can be used without any auxiliary ligand or reducing agent. © 2002
Elsevier Science Ltd. All rights reserved.
The transition metal-catalyzed Suzuki cross-coupling
reaction is one of the most efficient methods for the
construction of CarylꢀCaryl bonds.1 Indeed, various
efficient Pd catalyst precursors have been developed in
the last several years that allow aryl iodides, bromides,
triflates and chlorides to be effectively coupled with aryl
boronic acids under mild reaction conditions.2 More-
over, Ni-based catalysts have also been successfully
used for the Suzuki reaction of aryl chlorides.3
Recently, we have demonstrated that the NiCl2(PCy3)2
complex promotes the selective cross-coupling of aryl
tosylates with arylboronic acids under relatively mild
reaction conditions, tolerating a variety of functional
groups in both arenes.4 During these studies we have
observed in control experiments, that for some aryl
halides, the complex NiCl2·6H2O (a cheap and readily
available compound) is active in the Suzuki cross-cou-
pling reaction. More interestingly, these reactions were
performed without adding any auxiliary ligand or
reducing agent. From a synthetic point of view, it
would be important to determine in which cases we can
use this catalyst precursor. Here we demonstrate the
application of NiCl2·6H2O as a one component catalyst
precursor for the Suzuki cross-coupling reaction of aryl
halides.
optimized conditions developed earlier for aryl tosylates
(Table 1).4
The Suzuki reaction carried out using 0.5 mol% of
NiCl2·6H2O furnished 4-methoxybiphenyl in 74% yield
(Table 1, entry 1). Biphenyl generated from the homo-
coupling of phenylboronic acid was obtained in less
than 1% yield. Higher concentrations of nickel (Table
1, entries 2–4) do not improve the conversion and yields
of biaryl product. Low conversion was obtained using
0.01 mol% of Ni (entry 5) although this result repre-
sents a turnover number of 1300. A temperature of
130°C is the optimal temperature for this reaction
(compare Table 1, entries 1, 6 and 7). The low conver-
sion obtained at 170°C could be associated with rapid
catalyst decomposition under these conditions (Table 1,
entry 6). When the reaction temperature was lowered to
Table 1. NiCl2·6H2O-catalyzed Suzuki cross-coupling of 4-
bromoanisole with phenylboronic acida
Entry
NiCl2·6H2O (%)
Temp. (°C)
Yield (%)b
1
2
3
4
5
6
7
0.5
1
3
130
130
130
130
130
170
100
74
63c
60
64
14
30c
6c
5
0.01
0.5
0.5
Initially, we examined the coupling of 4-bromoanisole
with phenylboronic acid using NiCl2·6H2O under the
a Reactions conditions: 1.0 mmol of 4-bromoanisole, 1.5 mmol of
phenylboronic acid, 2.0 mmol of K3PO4, dioxane (5 mL), 19 h
(entries 2–5), 60 h (entries 1, 6 and 7).
* Corresponding author. Tel.: +55 51 33166303; fax: +55 51
33167304; e-mail: almonte@iq.ufrgs.br
b GC yield based on 4-bromoanisole.
c Average of two runs.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00716-5

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D. Zim, A. L. Monteiro / Tetrahedron Letters 43 (2002) 4009–4011
100°C, the yield also decreased (Table 1, entry 7). This
could be due to the decreased solubility of K3PO4
and/or decreased reactivity of 4-bromoanisole. Other
attempts to find reaction conditions that enabled the
complete conversion of 4-bromoanisole to product,
such as increased phenylboronic acid concentration or
the addition of more nickel catalyst or PhB(OH)2 dur-
ing the reaction, also failed. The reason for this incom-
plete reaction is not yet clear.5 However, the good
yields obtained using such a simple, inexpensive and
widely available catalyst precursor encouraged us to
investigate the extension of this reaction to other aryl
halides.
tron-donating groups were coupled to furnish the corre-
sponding biaryl products in good yields (61–87% yield,
Table 2, entries 2–7). Ni-catalyzed Suzuki reactions are
sensitive to steric hindrance and the coupling of bro-
momesitylene afforded very low yields of product
(entry 7).7 Attempts to perform the cross-coupling of
aryl chlorides and tosylates gave only modest yields.
For these substrates the addition of a phosphine ligand
is essential to achieve high yields.3,4 Substituted aryl-
boronic acids were also investigated. NiCl2·6H2O also
promotes the coupling of bromobenzene with 3-trifl-
uoromethylphenylboronic acid in 68% yield. However,
low yields in biaryl product are obtained when 4-
chlorophenylboronic acid (entry 10) and 4-
methoxyphenylboronic acid (entry 11) were used. It is
interesting to note that in these cases the cleavage of the
arylꢀboron bond, affording the arene product, was
observed in significant amounts (60% of chlorophenyl-
boronic acid is converted to chlorobenzene and 30% of
The coupling of several aryl halides with phenylboronic
acid was examined using NiCl2·6H2O (Table 2).6 4-
Iodoanisole was coupled with phenylboronic acid to
give 4-methoxybiphenyl in 65% yield (entry 1). Aryl
bromides containing electron-withdrawing and elec-
Table 2. NiCl2·6H2O-catalyzed Suzuki cross-coupling of aryl halides with arylboronic acidsa

D. Zim, A. L. Monteiro / Tetrahedron Letters 43 (2002) 4009–4011
4011
methoxyphenylboronic acid is converted to anisole).
Attempts to improve the cross-coupling reaction by
using a higher arylboronic acid concentration or adding
more aryl boronic acid during the reaction did not
increase the yield in byphenyl product. This secondary
reaction could be associated with the deactivation of
the nickel catalyst and the incomplete conversion of
aryl bromide observed in this system. A study of this
reaction is underway in our laboratory.
Am. Chem. Soc. 2000, 122, 4020–4028; (d) Littke, A. F.;
Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387; (e) Bei,
X.; Crevier, T.; Guran, A. S.; Jandeleit, B.; Powers, T. S.;
Turner, H. W.; Uno, T.; Weinberg, W. H. Tetrahedron
Lett. 1999, 40, 3855–3858; (f) Zhang, C. M.; Huang, J. K.;
Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64,
3804–3805; (g) Zim, D.; Gruber, A. S.; Ebeling, G.;
Dupont, J.; Monteiro, A. L. Org. Lett. 2000, 2, 2881–2884.
3. (a) Saito, S.; Oh-tani, S.; Miayaura, N. J. Org. Chem.
1997, 62, 8024–8030; (b) Indolese, A. F. Tetrahedron Lett.
1997, 38, 3513–3516; (c) Leadbeater, N. E.; Resouly, S. M.
Tetrahedron 1999, 55, 11889–11894; (d) Lipshutz, B. H.;
Sclafani, A.; Blomgren, P. A. Tetrahedron 2000, 56, 2139–
2144.
4. Zim, D.; Dupont, J.; Monteiro, A. L. Org. Lett. 2001, 3,
3049.
5. Incomplete conversion in nickel-catalyzed Suzuki cross-
coupling has been observed in several cases. See Refs. 3a,
3b, 4a and: Percec, V.; Bae, J. Y.; Hill, D. H. J. Org.
Chem. 1995, 60, 1060.
In summary, we have found that aryl bromides and
iodides can be coupled with phenylboronic acid in good
yields using NiCl2·6H2O as catalyst precursor. This
nickel complex is cheap, widely available and can be
used without any auxiliary ligand or reducing agent.
From a synthetic point of view this protocol is cheap
and an easy alternative for the synthesis of biaryls from
aryl bromides and iodides.
Acknowledgements
6. In a typical experiment an oven-dried resealable Schlenk
flask was evacuated and back-filled with argon and
charged with K3PO4 (2 mmol), arylboronic acid (1.5
mmol), and NiCl2·6H2O (0.005 mmol). The flask was
evacuated and back-filled with argon and then the aryl
halide (1 mmol) and dioxane (5 mL) were added. The
reaction mixture was stirred at the desired temperature
until the conversion of starting aryl halide stopped, as
judged by GC analysis. The solution was then taken up in
ether (20 mL) and washed with aqueous NaOH (1 M, 5
mL) and brine (2×5 mL), and then dried over MgSO4.
After purification by flash chromatography the biaryl
product was characterized by H and C NMR, IR and
GC–MS.
7. For an active Pd-catalyst for the synthesis of sterically
hindered biaryls see: Yin, J.; Rainka, M. P.; Zhang, X.-X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162–1163.
We thank PADCT-CNPq and FAPERGS for partial
financial support and CNPq (DZ) for a scholarship. We
also thank Professor Jairton Dupont for helpful discus-
sions and Dr. John Spencer (UK) for proof reading the
manuscript.
References
1. Suzuki, A. J. Organomet. Chem. 1999, 576, 147 and refer-
ences cited therein.
2. (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S.
L. J. Am. Chem. Soc. 1999, 121, 9550–9561; (b) Old, D.
W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722–9723; (c) Littke, A. F.; Da´ı, C.; Fu, G. C. J.
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