NiII-(σ-Aryl) complex catalyzed suzuki reaction of aryl tosylates with arylboronic acids

Article abstract of DOI:10.1002/ejoc.201000147

A practical, efficient protocol was developed for the Suzuki reaction of aryl tosylates with arylboronic acids. The process was promoted by a nickel-based catalyst system consisting of the easily available Ni ^II-(σ-aryl) complex and the simple ligand PPh3 in toluene in the presence of the base K₂CO₃. The convenient operation, high yield, generality, and low cost make this method viable for most common laboratories and applicable in large-scale preparations.

Full text of DOI:10.1002/ejoc.201000147

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201000147
NiII–(σ-Aryl) Complex Catalyzed Suzuki Reaction of Aryl Tosylates with
Arylboronic Acids
Xin-Heng Fan[a,b] and Lian-Ming Yang*[a]
Keywords: Synthetic methods / Cross-coupling / Nickel / Boron / Biaryls
A practical, efficient protocol was developed for the Suzuki
reaction of aryl tosylates with arylboronic acids. The process
was promoted by a nickel-based catalyst system consisting
of the easily available NiII–(σ-aryl) complex and the simple
ligand PPh3 in toluene in the presence of the base K2CO3.
The convenient operation, high yield, generality, and low
cost make this method viable for most common laboratories
and applicable in large-scale preparations.
of aryl tosylates (electron-deficient ones) were studied, they
gave good yields under the conditions reported. Hu et al.
Introduction
The transition-metal-catalyzed Suzuki cross-coupling re-
action has become a powerful and routine tool in organic
synthesis for the construction of biaryl motifs commonly
found in natural products, pharmaceuticals, and material
chemicals. Over the past decades, palladium-based catalyst
systems have been fully developed that allow aryl halides/
pseudohalides to be effectively coupled with arylboronic ac-
ids under mild reaction conditions.[1] On the other hand,
the use of cheaper nickel complexes as catalysts has also
been attracting considerable interest. Since the first report
by Percec in 1995,[2] remarkable advance has been made in
the nickel-catalyzed version of the Suzuki reaction.[3–9] One
of the advantages of Ni systems over Pd is their high reac-
tivity toward relatively inert substrates such as aryl chlo-
rides and sulfonates without the need of special ligands that
are often expensive and/or air sensitive. For the cross-cou-
pling reactions, aryl sulfonates, particularly tosylates, are
very attractive as electrophilic substrates in place of haloar-
enes because of their ease of preparation and handling, pro-
nounced stability to air and moisture, as well as low cost.
Several examples of the nickel-catalyzed Suzuki aryl–aryl
couplings of aryl tosylates have been reported. Monterio et
al.[5] reported the first active and efficient nickel catalyst
system based on the expensive and air-sensitive ligand
PCy3. Percec et al.[6a] made a systematic investigation into
the effects of NiCl2R2 precatalysts (R = PPh3, PCy3, 1/
2dppf, and 1/2dppe), phosphane-type ligands, and solvents
on the reactions, and although only a very limited number
demonstrated the room-temperature Suzuki reaction of aryl
[7a]
tosylates based on the Ni(cod)2/PCy3
or Ni(cod)2/Fc-
MP[7b] system. Despite their high catalytic activities, the Ni0
precursor is not only costly (more expensive than normal
Pd sources) but also hard to handle because of its toxicity
and high instability in air. Very recently, Doi described
NHC-derived NiII pincer complexes as precatalysts in Su-
zuki aryl–aryl couplings; but this system is effective only for
electron-poor aryl tosylates.[8] Accordingly and considering
the need for large-scale or even industrial preparation, it
remains highly desirable to develop more practical proto-
cols (i.e., cost efficient, convenient, and general) for Suzuki
aryl–aryl cross-coupling reactions.
Recently, we have been exploring the possibility of em-
ploying NiII–(σ-aryl) complexes, trans-haloarylbis(triphen-
ylphosphane)nickel(II) (Figure 1), as catalysts in cross-cou-
pling reactions,[10] which turned out to be efficient for some
C–C/C–N bond-forming coupling reactions.[3g,11] These
nickel complexes, easily prepared from cheap and commer-
cially available starting materials,[12] display good stability
to air and moisture, making them highly applicable catalyst
precursors. Herein, we wish to disclose our new findings
concerning the NiII–(σ-aryl) complex-catalyzed Suzuki re-
action of aryl tosylates with arylboronic acids.
[a] Beijing National Laboratory for Molecular Sciences (BNLMS),
Laboratory of New Materials, Institute of Chemistry, Chinese
Academy of Sciences,
Figure 1. NiII–(σ-aryl) complexes.
Beijing 100190, China
Fax: +86-10-62559373
E-mail: yanglm@iccas.ac.cn
Results and Discussion
[b] Graduate School of Chinese Academy of Sciences,
Beijing 100049, China
Initially, a combination of the simple ligand PPh3 and
different NiII complexes was chosen as catalyst system, and
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000147.
Eur. J. Org. Chem. 2010, 2457–2460
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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X.-H. Fan, L.-M. Yang
Table 1. Screening of reaction conditions for the NiII-catalyzed Suzuki reaction of aryl tosylate and phenylboronic acid.[a]
SHORT COMMUNICATION
Entry
[NiII][b] (mol-%)
Ligand (mol-%)
Base
Solvent
Temp. [°C]
Time [h]
Yield[c] [%]
1
2
3
4
5
6
7
8
Ni(acac)2 (5)
Ni(PPh3)2Cl2 (5)
1 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
none
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
KOH
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
THF
100
100
100
100
100
100
100
100
100
100
100
100
100
100
70
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
51
50
65
83
66
71
67
16
8
70
26
20
36
6
2 (5)
3 (5)
3 (5)
3 (5)
PPh3 (10)
IPrHCl[d] (2.5)
bipy[e] (2.5)
phena[f] (2.5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (3)
3 (5)
9
3 (5)
10
11
12
13
14
15
16
17
3 (5)
3 (5)
3 (5)
3 (5)
3 (5)
3 (5)
3 (5)
toluene
toluene
80
100
50
79
3 (3)
[a] Reagents: p-anisyl tosylate (1 mmol), phenylboronic acid (1.5 mmol), K2CO3 (4 mmol), toluene (5 mL). [b] 1: Ni(PPh3)2(1-naphthyl)-
Br; 2: Ni(PPh3)2(phenyl)Br; 3: Ni(PPh3)2(1-naphthyl)Cl. [c] Isolated yield. [d] IPrHCl: 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride.
[e] bipy: 2,2Ј-bipyridine. [f] phena: 1,10-phenanthroline.
the reaction of p-anisyl tosylate with phenylboronic acid in a negative effect (Table 1, Entry 17 vs. 5). Finally, the
was performed to optimize the reaction conditions optimal reaction conditions were set as Entry 5 in Table 1.
(Table 1). The effect of the source of NiII on the reaction is
Next, a wide range of aryl tosylates was coupled with
significant: the use of Ni(acac)2 led to only 5% yield several representative arylboronic acids under the optimized
(Table 1, Entry 1); Ni(PPh3)2Cl2 promoted substantially the reaction conditions to examine the substrate scope of this
reaction with 51% yield (Table 1, Entry 2); Ni(PPh3)2(1- reaction (Table 2). Generally, electron-neutral (Table 2, En-
naphthyl)Br (1) and Ni(PPh3)2(phenyl)Br (2) provided com- tries 6, 10, 11, and 16–18), -poor (Table 2, Entries 7–9),
parable yields (Table 1, Entries 3 and 4); and Ni(PPh3)2- and -rich (Table 2, Entries 1–5, 14, 15, 22, and 23) aryl tosy-
(phenyl)Cl (3) was found to display the highest activity, giv- lates were coupled smoothly in high isolated yields. Al-
ing a high isolated yield of 83% (Table 1, Entry 5).
though the electronic effect of the substituents did not ham-
After NiII–(σ-aryl) complex 3 was determined as the pre- per the reaction substantially, aryl tosylates with electron-
ferred precatalyst, a further investigation was made into withdrawing groups (Table 2, Entries 2, 7–9) were more re-
other factors that would affect the reaction, such as ligands, active than those with electron-donating groups (Table 2,
bases, solvents, and the like (Table 1). Without the help of Entries 1, 5, 14, and 23). However, 4-nitrophenyl tosylate
additional PPh3 ligand (Table 1, Entry 6), the reaction yield (Table 2, Entry 12) and p-tosyloxybenzaldehyde (Table 2,
decreased substantially. Interestingly, the use of an excess Entry 13) indeed quenched the reaction due to the role of
amount of PPh3 did not favor this reaction (Table 1, En- the nitro[13a] and formyl[13b] groups, as is well documented.
try 7). The N-heterocyclic carbene ligand IPrHCl did not The ortho substituents of the tosylate substrate seemed to
seem to be superior to PPh3 (Table 1, Entry 8), whereas the be favorable, or they, at least, do not impose a detrimental
nitrogen-based bidentate ligands 2,2Ј-bipyridine (Table 1, effect on the reaction (Table 2, compare Entries 3, 10, 15,
Entry 9) and 1,10-phenanthroline (Table 1, Entry 10) were and 22 to Entries 1, 11, 14, and 23). The nickel-based cata-
almost ineffective for this reaction. For the bases used, lyst, different from other transition-metal systems, is not
K3PO4 (Table 1, Entry 11) was not as effective as K2CO3, sensitive to the steric hindrance of the electrophilic sub-
although it has been the most commonly used base in strates, as recorded earlier.[14] In addition, the reaction was
nickel-catalyzed Suzuki reactions;[3–9] strongly basic KOH highly tolerable to some sensitive functional groups such as
(Table 1, Entry 12) or the weak base Na2CO3 (Table 1, En- ester (Table 2, Entry 7) and acetal (Table 2, Entries 14 and
try 13) was far inferior to K2CO3. Toluene seemed to be the 15) with excellent yields of the desired products. For aryl-
solvent of choice for the reaction. For example, a consider- boronic acid substrates, both electronic and steric effects
ably low yield was afforded upon replacing toluene with slightly disfavored the reaction under the standard reaction
dioxane (Table 1, Entry 14) or THF (Table 1, Entry 15). conditions (Table 2, compare Entry 6 with Entries 16–18).
Additionally, lowering the reaction temperature caused a Further, double cross-coupling proceeded in excellent yields
substantial decrease in the yield (Table 1, Entry 16 vs. 5), under similar conditions when phenylene-bistosylates were
and an attempt to reduce the catalyst loading also resulted treated with phenylboronic acid (Table 2, Entries 19 and
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Eur. J. Org. Chem. 2010, 2457–2460

NiII–(σ-Aryl) Complex Catalyzed Suzuki Reactions
Table 2. NiII–aryl complex catalyzed Suzuki cross-couplings of aryl 20), but the bistosylate of bisphenol-A, somehow, cannot
tosylates with arylboronic acids.[a]
afford a satisfactory result even upon increasing the catalyst
loadings (Table 2, Entry 21).
Conclusions
In summary, as part of our ongoing effort, we developed
a general, practical method for the Suzuki reaction of aryl
tosylates with arylboronic acids catalyzed by the simple
NiII–(σ-aryl) complex/PPh3 system. The advantages of con-
venient operation, high yield, milder conditions, generality,
and low cost make this protocol extremely attractive as an
alternative and complement to metal-catalyzed Suzuki
aryl–aryl cross-coupling reactions.
Experimental Section
Synthesis of Ni(PPh3)2(1-naphthyl)Cl (3) as a Representative Exam-
ple for the Synthesis of NiII–(σ-aryl) Complexes:[12] A stirred mix-
ture of NiCl2·6H2O (4.8 g, 0.02 mol), triphenylphosphane (11.53 g,
0.044 mol), and 95% ethanol (90 mL) was heated until a gentle
reflux started. 1-Chloronaphthalene (6.5 g, 0.04 mol, excess) was
then added, followed by zinc dust (1.3 g, 0.02 mol) over 5 min. The
dark-green mixture very soon turned yellow. After stirring and
heating under reflux for 1.5 h (under an atmosphere of nitrogen),
the mixture was cooled to room temperature. Hydrochloric acid
(30% aq., 4ϫ2 mL) was added over 15 min. After stirring for 1.5 h,
the solid was filtered off on a sintered-glass funnel and successively
washed with ethanol (20 mL), hydrochloric acid (1  aq.,
2ϫ20 mL), ethanol (2ϫ20 mL), petroleum ether (30–60 °C,
1ϫ20 mL). The yellow solid was dried in vacuo with a bath tem-
perature of not higher than 45 °C. The yield was above 80%.
General Procedure for the NiII–(σ-Aryl) Complex-Catalyzed Reac-
tion of Aryl Tosylates with Arylboronic Acids: An oven-dried 50-
mL, three-necked flask was charged with K2CO3 (4 mmol),
Ni(PPh3)2(1-naphthyl)Cl (0.05 mmol), and PPh3 (0.05 mmol).
Then, the aryl tosylate (1 mmol) and arylboronic acid (1.5 mmol)
were added. The flask was evacuated and backfilled with nitrogen,
with the operation being repeated twice. Dried PhMe (5 mL) was
added by syringe at this time. The reaction mixture was heated in
an oil bath of 100 °C for 5 h and then allowed to cool to room
temperature; it was then filtered through a silica gel pad that was
washed with ethyl acetate. The combined organic phase was evapo-
rated under reduced pressure, and the residue was purified by silica
gel column chromatography to give the desired products.
Supporting Information (see footnote on the first page of this arti-
cle): General considerations and characterization data of all com-
pounds prepared.
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[a] Reagents: aryl tosylate (1 mmol), arylboronic acid (1.5 mmol), 3
(0.05 mmol), PPh3 (0.05 mmol), K2CO3 (4 mmol), toluene (5 mL).
[b] Isolated yield. [c] Arylboronic acid (3.0 mmol). [d] 3 (0.1 mmol),
PPh3 (0.1 mmol).
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Eur. J. Org. Chem. 2010, 2457–2460
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X.-H. Fan, L.-M. Yang
SHORT COMMUNICATION
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Received: February 3, 2010
Published Online: March 23, 2010
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Eur. J. Org. Chem. 2010, 2457–2460