Nickel(II)-aryl complexes as catalysts for the Suzuki cross-coupling reaction of chloroarenes and arylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2007.01.175

A series of air- and moisture-stable Ni(II)-(σ-aryl) complexes, Ni(PPh₃)₂(aryl)X (X = Cl, Br), were employed as catalyst precursors in the Ni-catalyzed Suzuki cross-coupling reaction. These pre-catalysts easily form the catalytically active Ni(0) species in situ without the need of additional reducing agents. A general catalytic system involving Ni(PPh₃)₂(1-naph)Cl and PPh₃ proved to be highly effective for the Suzuki reaction of aryl chlorides under mild conditions (at 60 °C in THF in the presence of K₂CO₃ as the base).

Full text of DOI:10.1016/j.tetlet.2007.01.175

Tetrahedron Letters 48 (2007) 2427–2430
Nickel(II)–aryl complexes as catalysts for the Suzuki
cross-coupling reaction of chloroarenes and arylboronic acids
a,b
Chen Chen and Lian-Ming Yang
a,
*
a
Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of New Materials,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
b
Graduate School of Chinese Academy of Sciences, Beijing 100049, China
Received 1 November 2006; revised 31 December 2006; accepted 4 January 2007
Available online 4 February 2007
3 2
Abstract—A series of air- and moisture-stable Ni(II)–(r-aryl) complexes, Ni(PPh ) (aryl)X (X = Cl, Br), were employed as catalyst
precursors in the Ni-catalyzed Suzuki cross-coupling reaction. These pre-catalysts easily form the catalytically active Ni(0) species
in situ without the need of additional reducing agents. A general catalytic system involving Ni(PPh ) (1-naph)Cl and PPh proved to
3
2
3
2 3
be highly effective for the Suzuki reaction of aryl chlorides under mild conditions (at 60 °C in THF in the presence of K CO as the
base).
Ó 2007 Elsevier Ltd. All rights reserved.
The palladium-catalyzed Suzuki cross-coupling reaction
represents a powerful and versatile methodology for the
ity and non-hygroscopicity. Since the active Ni(0) species
is essential for the Ni catalysis, the Ni(II) pre-catalysts
need to be activated, that is, in situ reduction of Ni(II)–
Ni(0). Unlike the Pd(II), the Ni(II) generally cannot be
reduced to Ni(0) by the added base and/or solvent in
the reaction system. A solution to this problem was that
Ni(II) complexes were treated with additional reducing
1
,2
construction of Caryl–Caryl bonds.
During the past
decades, various Pd catalytic systems have been devel-
oped that allow aryl iodides, bromides, triflates, and
chlorides to be effectively coupled with arylboronic acids
2
,3
under mild reaction conditions. Considering the high
cost of palladium, the use of much cheaper Ni catalysts
has attracted considerable interests. Since Percec’s
4
5
agents such as Zn or n-BuLi for in situ generating
Ni(0). Afterwards, it was found that Ni(0) was more con-
veniently generated in situ from Ni(II) at elevated tem-
peratures (80–130 °C) by the homocoupling of the
4
a
first report in 1995, remarkable advance has been
made in the Ni-catalyzed version of Suzuki cross-
4
–9
6
couplings.
The key advantage of Ni-based catalysts
reactant arylboronic acid. Also, the Ni(0) on charcoal
over Pd systems lies in their high reactivity toward
readily available but normally unreactive substrates
pre-treated from Ni(II) with n-BuLi was elaborated and
7
then the reaction was conducted at 135 °C. The simplest
8
a
8b
(
such as aryl chlorides or sulfonates) without the need
nickel salts, NiCl and NiCl Æ6H O, were also used as
2 2 2
of special ligands that are often electron rich (hence air
sensitive) and expensive.
the pre-catalyst for the Suzuki reaction, with nitrogen-
containing ligands and with no ligand respectively,
although they were effective only for aryl iodides and
bromides and the elevated temperature (95–130 °C) was
required. More recently, the room-temperature Ni-cata-
For the Ni-catalyzed Suzuki aryl–aryl cross-coupling, the
Ni(0) species is generally regarded as being catalytically
active and the mechanism follows a Ni(0)–Ni(II)
catalytic cycle. The most commonly used Ni sources
are the phosphine-coordinated nickel(II) halides, such as
NiCl (PPh ) , NiCl (PCy ) , NiCl (dppf), and NiCl (dppe).
lyzed Suzuki reaction has been demonstrated based on
9
the direct use of Ni(COD) . However, such Ni(0) source
2
would be difficult to handle in practice due to its high air
sensitivity. Besides, we noticed that K PO (anhydrous
2
3 2
2
3 2
2
2
3
4
These Ni(II) complexes are readily available and conve-
niently manipulated due to their air- and thermal-stabil-
or hydrated) seemed to be a sole effective base in almost
all the reported Ni-catalyzed Suzuki reactions.
4
–9
Recently, we became interested in exploring Ni-based
catalysts applicable in the cross-coupling reactions.
The principle of choice is both convenient-to-handle
*
Corresponding author. Tel.: +86 10 62565609; fax: +86 10
2559373; e-mail: yanglm@iccas.ac.cn
6
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.01.175

2428
C. Chen, L.-M. Yang / Tetrahedron Letters 48 (2007) 2427–2430
and easy-to-activate. We paid attention to a class of
(1-naph)Cl, the Suzuki reaction can be initiated, albeit
in only 24% yield (entry 3). In this case, the color change
of the reaction solution, turning dark-red and then black
immediately after the addition of THF to the reaction
mixture, clearly indicated that the Ni(II)–aryl complex
is much easily activated. At the same time, the low con-
version in the reaction also suggested that the in situ
generated Ni(0) could not be stabilized very well in the
absence of additional ligands. Indeed, the reaction yield
isolatable Ni(II)–(r-aryl) complexes that were earlier
1
0
established but have rarely been successfully applied
1
1
in the catalytic coupling reactions. The Ni(II)–aryl
complex is assumed to be an intermediate in the
Ni(0)–Ni(II) catalytic cycle involving sequential oxida-
tive addition, transmetalation, and reductive elimina-
4
a,5b,6c
tion.
Thus, these complexes could undergo a
process of sequential transmetalation and reductive
elimination, prior to the normal cross-coupling reaction,
to afford the active Ni(0) species (Scheme 1). A compa-
rable protocol has been carried out in Pd-catalyzed
cross-couplings, where the Pd(II)–(p-allyl) complex gen-
erates the active Pd(0) in situ by a sequential procedure
increased drastically as extra two equiv of PPh (per
3
equiv of Ni) was added to stabilize the labile Ni(0)
species (entry 4). It was found that moisture had no
influence on this coupling reaction. Rather, the reaction
was accelerated when little amounts of H O were added.
2
3
of nucleophilic attacking at the g -coordinating allyl
This was likely because the added water increased
the solubility of the base K CO (entry 5 vs entry 4).
1
2
moiety and then reductive elimination. Herein, we re-
port our results on the use of simple and easily available
Ni–(r-aryl) complexes as pre-catalysts for the Suzuki
cross-coupling reaction of aryl chlorides.
2
3
Attempts either to reduce catalyst loading or to lower
reaction temperature led to the decreased yields (entries
6 and 7). For the other nickel–aryl complexes,
Ni(PPh ) (phenyl)Br and Ni(PPh ) (1-naph)Br were
3
2
3 2
Four Ni(II)–aryl complexes, Ni(PPh ) (1-naph)Cl,
also effective but slightly inferior to Ni(PPh3)2-
3
2
Ni(PPh ) (o-tol)Cl, Ni(PPh ) (1-naph)Br, and Ni(PPh ) -
(1-naph)Cl (entries 9 and 10), while Ni(PPh ) (o-tol)Cl
3
2
3 2
3 2
3 2
(
phenyl)Br were synthesized according to the literature
gave only a moderate yield of 62% (entry 8). The reason
is yet unclear at the moment. For weak bases, Na CO
1
0,11a
procedures.
The effects of the catalyst, ligand, base
2
3
and temperature on the cross-coupling reaction were
first investigated using a model reaction of m-chloro-
toluene and phenylboronic acid in THF. The results
are shown in Table 1. Normal Ni(II) catalysts such as
NiCl (PPh ) and NiCl (dppe) did not mediate the reac-
resulted in a yield of 75% (entry 11), and an excellent
yield was obtained using K PO Æ7H O as the base (entry
3
4
2
13). On the other hand, some stronger bases, CsCO and
3
KOH, did not promote the reaction (entries 12 and 14).
At room temperature, the coupling reaction proceeded
rather sluggishly even though K PO was employed as
2
3 2
2
tion at 60 °C in the presence of K CO as the base at all
2
3
3
4
(
entries 1 and 2). After being replaced by Ni(PPh ) -
the base (entries 15 and 16).
3
2
Next, the cross-coupling reaction of several representa-
tive arylboronic acids with various aryl chlorides was
carried out to determine the generality of our standard
protocol (Table 2). As shown in Table 2, this transfor-
mation, generally, was very clean and highly efficient.
ortho-Substituted aryl chlorides or arylboronic acids
2
Ar B(OH)2
1
1
2
(
PPh ) Ni(II)Ar Cl
(PPh3)2Ni(II)Ar Ar
3
2
base
PPh3
Ni(0)(PPh3)n Ar1 Ar2
Scheme 1. Possible pathway for activation of the Ni(II)–aryl complex.
a
Table 1. Reaction conditions for Ni(II)-catalyzed Suzuki reactions of m-chlorotoluene and phenylboronic acid
Ni(II) Cat.
Cl
B(OH)2
Base
b
Entry
Catalyst (mol %)
Ligand (mol %)
Solvent
Temperature (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
NiCl
NiCl
2
(PPh
(dppe) (5)
3
)
2
(5)
PPh
dppe (5)
No
3
(10)
K
K
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
THF
THF
THF
THF
THF–H
THF–H
THF–H
THF–H
THF–H
THF–H
THF–H
THF
60
60
60
60
60
60
40
60
60
60
60
60
60
60
rt
5
5
5
5
3
10
10
3
3
3
3
3
3
3
24
24
No reaction
No reaction
2
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
3
)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(1-naph)Cl (5)
(1-naph)Cl (5)
(1-naph)Cl (5)
(1-naph)Cl (2.5)
(1-naph)Cl (5)
(o-tol)Cl (5)
(1-naph)Br (5)
(phenyl)Br (5)
(1-naph)Cl (5)
(1-naph)Cl (5)
(1-naph)Cl (5)
(1-naph)Cl (5)
(1-naph)Cl (5)
(phenyl)Br (5)
24
95
96
68
72
62
83
83
75
15
94
12
23
34
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
3
3
3
3
3
3
3
3
3
3
3
3
3
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
(10)
2
2
2
2
2
2
2
O
O
O
O
O
O
O
1
1
1
1
1
1
1
NaCO
CsCO
PO
KOH
3
3
K
3
4
Æ7H
2
O
THF
THF
THF
THF
K
K
3
PO
PO
4
3
4
rt
a
Reaction conditions: m-Chlorotoluene (1.0 equiv), phenylboronic acid (1.2 equiv), base (3 equiv), THF (3 mL) or THF (3 mL)–H
Isolated yields (average of two runs).
2
O (0.15 mL).
b

C. Chen, L.-M. Yang / Tetrahedron Letters 48 (2007) 2427–2430
Table 2. Ni(II)–Aryl complex-catalyzed Suzuki cross-couplings of Table 2 (continued)
2429
a
chloroarenes and arylboronic acids
b
Entry
ArX
ArB(OH)
2
Yield (%)
Ni(PPh ) (naph)Cl
3
2
OH
OH
R
R`
PPh3
R
R`
c
Cl
(HO)2B
13
O
Cl
O
B
92
THF-H O; K CO
2
2
3
b
Entry ArX
ArB(OH)
2
Yield (%)
OH
OH
OH
OH
1
Cl
Cl
Cl
B
B
99
14
Cl
Cl
91
88
B
B
OH
OH
2
91
96
OH
OH
1
5
a
Reaction conditions: aryl chlorides (1.0 equiv), arylboronic acids
(1.2 equiv), Ni(PPh (1-naph)Cl (5 mol %), PPh (10 mol %), K CO
3 equiv), THF (3 mL)–H O (0.15 mL), 60–70 °C, 2.5–3 h.
OH
OH
3
4
B
B
B
B
3
)
2
3
2
3
(
2
b
c
Isolated yields (average of two runs).
Arylboronic acids 1.4 equiv.
Phenylboronic acid 2.4 equiv.
d
OH
OH
c
Cl
94
were coupled smoothly (entries 2, 14, and 15), indicating
that the steric hindrance of coupling partners had less
influence on this coupling reaction. On the other hand,
the electronic effects of either coupling partner also pro-
duced no significant impact on the reaction yields (Table
2). The chloride bearing ester group reacted with phen-
ylboronic acid to give an almost quantitative yield (entry
OH
OH
5
6
H CO C
Cl
98
3
2
5
), demonstrating the tolerance of the reaction toward
OH
OH
functional groups. For aryl chlorides bearing electron-
donating groups at the para position, excellent yields
could be obtained by addition of a little more excess
of arylboronic acids (1.4 equiv vs 1.2 equiv) (entries 4,
c
O
Cl
90
6, 7, 10, 11, and 13). For arylboronic acids bearing elec-
tron-donating groups at the para position, the reaction
proceeded smoothly under the standard conditions (en-
tries 9–13). Although the cross-coupling reaction of p-
chloroaniline (with free amino group) was not achieved
at this time, (4-chlorophenyl)diphenylamine was cou-
pled smoothly (entries 7 and 11). Finally, p-terphenyl
was easily synthesized in high yield via the double
coupling of p-dichlorobenzene with phenylboronic acid
OH
OH
c
7
B
B
87
N
Cl
OH
OH
d
8
9
0
Cl
Cl
88
(entry 8).
OH
OH
In summary, Ni(II)–(r-aryl) complexes have first been
successfully applied in the Ni-catalyzed Suzuki cross-
coupling reaction. Ni(II)–(r-aryl) complexes seem to
be activated conveniently and easily, hence this coupling
reaction of aryl chlorides and arylboronic acids proceeds
under very mild conditions with excellent yields.
Ni(PPh ) (1-naph)Cl was the most efficient pre-catalyst
Cl
B
B
96
OH
OH
c
1
1
1
Cl
92
3
2
and K CO was an effective base. These Ni(II)–aryl
2
3
complexes are readily prepared and manipulated due
to their stability toward air and moisture. This new pro-
tocol provides a very convenient, highly efficient and less
expensive alternative for the synthesis of biaryls. Further
work to extend this type of Ni catalysts to other catalytic
cross-coupling reactions, for instance the C–N coupling
reaction, is underway in our laboratory.
OH
OH
c
1
2
B
92
N
Cl
OH
Cl
O
B
94
General procedure: An oven-dried 50-mL three-necked
OH
flask was charged with Ni(PPh ) (1-naph)Cl (5 mol %,
3
2

2430
C. Chen, L.-M. Yang / Tetrahedron Letters 48 (2007) 2427–2430
relative to aryl chloride), PPh (10 mol %, relative to
Gruber, A. S.; Ebeling, G.; Dupont, J.; Monteiro, A. L.
Org. Lett. 2000, 2, 2881–2884; (h) Willis, M. C.; Mori, L.;
Yamaguchi, K.; Hara, T.; Mizugaki, T.; Ebitani, K.;
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Gst o¨ ttmayr, C. W. K.; B o¨ hm, V. P. W.; Herdtweck, E.;
Grosche, M.; Herrmann, W. A. Angew. Chem., Int. Ed.
3
aryl chloride), K CO (3.0 mmol), the arylboronic acid
2
3
(
1.2 mmol). The aryl halide (1.0 mmol) was added at this
time if it is solid. The flask was evacuated and backfilled
with nitrogen, with the operation being conducted
twice. The aryl halide (1.0 mmol) was added at this time
via syringe if it is liquid. THF (3 mL) and degassed
water (0.15 mL) were added via syringe. The reaction
mixture was heated in an oil bath of 60–70 °C for 2.5–
2
002, 41, 1363–1365; (j) Altenhoff, G.; Goddard, R.;
Lehmann, C. W.; Glorius, F. Angew. Chem., Int. Ed. 2003,
2, 3690–3693; (k) Powell, H.; Claverie, C. K. Angew.
4
Chem., Int. Ed. 2004, 43, 1249–1251; (l) Walker, S. D.;
Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew.
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Soc. 2004, 126, 15195–15201; (n) Lebel, H.; Janes, M. K.;
Charette, A. B.; Nolan, S. P. J. Am. Chem. Soc. 2004, 126,
3
h. After being quenched with water, the reaction mix-
ture was extracted with ethyl acetate, and dried over
anhydrous Na SO . The solvent was evaporated under
2
4
reduced pressure, and then the residue was purified by
column chromatography on silica gel with hexane/ethyl
acetate as the eluent to give the desired product. Yields
are listed in Table 2.
5
046–5047; (o) Barder, T. E.; Walker, S. D.; Martinelli, J.
R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685–
696; (p) Anderson, K. W.; Buchwald, S. L. Angew.
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Acknowledgments
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The authors thank the National 863 Program of China
Z36-1-715-98) and the National Natural Science Foun-
dation of China (Project No. 20672116) for financial
support of this work.
1
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8
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Detailed experimental procedure and characterization
of the products. This material is available free of charge.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
7
8
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