Highly efficient palladium-catalyzed suzukiMiyaura cross-coupling with 9,10-dihydro-9,10-ethanoanthracene-11,12-diimine ligands under mild aerobic conditions

Article abstract of DOI:10.1246/cl.160057

A novel 9,10-dihydro-9,10-ethanoanthracene-11,12-diimine/ Pd(OAc)₂system has been demonstrated to form a highly efficient catalyst for the SuzukiMiyaura cross-coupling of various aryl bromides and activated aryl chlorides with arylboronic acids

Full text of DOI:10.1246/cl.160057

CL-160057
Received: January 20, 2016 | Accepted: February 2, 2016 | Web Released: February 11, 2016
Highly Efficient Palladium-catalyzed Suzuki-Miyaura Cross-coupling
with 9,10-Dihydro-9,10-ethanoanthracene-11,12-diimine Ligands
under Mild Aerobic Conditions
Ping Huo,1 Jingbo Li,1 Wanyun Liu,*1 Xiaohui He,2 and Guangquan Mei*1,3
1Key Laboratory of Jiangxi University for Applied Chemistry and Chemical Biology, Yichun University, Yichun 336000, P. R. China
2School of Materials Science and Engineering, Nanchang University, Nanchang 330031, P. R. China
3State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, P. R. China
(E-mail: liuwanyun@ycu.jx.cn, yc_mgq@ycu.jx.cn)
A
novel 9,10-dihydro-9,10-ethanoanthracene-11,12-di-
imine/Pd(OAc)2 system has been demonstrated to form a
highly efficient catalyst for the Suzuki-Miyaura cross-coupling
of various aryl bromides and activated aryl chlorides with
arylboronic acids in high yields at room temperature in ethanol/
aqueous media under ambient atmosphere.
Keywords: Suzuki–Miyaura cross coupling
| Palladium |
Anthracene-diimine ligand
The Suzuki-Miyaura cross-coupling reaction, involving the
coupling of an arylboronic acid with an organohalide, has proven
to be an extremely useful synthetic tool for the construction of
biaryls,1 which are present in a wide range of natural products,
pharmaceuticals, agrochemicals, functional polymer materials,
and liquid crystals.2 It is well known that the Suzuki-Miyaura
cross-coupling reaction can be efficiently carried out using
phosphine ligands/palladium complex. Because of the superior
donor capability and stabilization effects, the bulky and electron-
rich phosphine ligands are outstanding in the palladium-
catalyzed Suzuki cross-coupling reaction.3 However, serious
drawbacks still exist in most phosphines, such as highly toxic
and air- and moisture-sensitive.4 These drawbacks severely
hinder its usage. Therefore, in the past few years, great advances
have been made in developing active and efficient catalysts by
modifying traditional ligands and discovering phosphine-free
ligands.5
Recently, phosphine-free ligands, such as heterocyclic
carbenes,6 β-ketoamine,7 2-aryl-2-oxazolines,8 and other
amines,9 have also emerged for use in the Suzuki-Miyaura
cross-coupling reaction. Among them, α-diimine ligands, pre-
viously used as excellent candidates for olefin and α-alkene
polymerization, have been applied to Suzuki cross-coupling.
The Pd(OAc)2/N,N¤-dicyclohexyl-1,4-diazabutadiene system
has been successfully developed by Nolan and his collaborators,
which show high catalytic activity for cross-coupling of aryl
halides with arylboronic acids.10 Sun and co-workers found that
water-soluble diimine ligands exhibited moderate activity
toward the Suzuki reaction of arylbromide.11 Subsequently, the
utilization of α-diimine ligand/Pd for cross-coupling reaction
has attracted much interest in both academic and industrial
fields. Considering that both the backbone and the aryl ring have
profound effects on the catalytic properties of the palladium
complexes, herein we present a series of α-diimine ligands, the
9,10-dihydro-9,10-ethanoanthracene-11,12-diimine with bulky
backbones and substituted aniline moieties generated in situ.
The coordination versatility of these ligands, a consequence of
Scheme 1. 9,10-Dihydro-9,10-ethanoanthracene-11,12-diimine
ligands.
the flexibility of the NCCN backbone and the strong σ-donor
and π-acceptor properties, reflects a very important feature of
α-diimine ligand-metal complexes,12 which might assist in
stabilizing catalytic species. Meanwhile, bulky backbones could
increase the steric hindrance on the ligands, which could further
facilitate reductive elimination and facilitate cross-coupling.13
Therefore, desired products can be obtained in high yields under
aerobic conditions, with a great tolerance of raw material for a
broad range of functional groups on the aryl bromides.
As shown in Scheme 1, the target α-diimine ligands with
various steric and electronic substituents such as methyl,
isopropyl, bromine, and chlorine were prepared according to
the previously reported method.14 At first, 10 mmol of 9,10-
dihydro-9,10-ethanoanthracene-11,12-dione was reacted with
30 mmol of aniline by a catalytic amount of p-toluenesulfonic
acid in refluxing toluene. After 24 h, the reaction mixture was
cooled to room temperature, and then was evaporated at
reduced pressure. The residual solids were further purified by
silica column chromatography (v/v, 20/1, petroleum ether/ethyl
acetate) to get ligands (L1-L5) as yellow crystals in high yield.
The catalytic activity of L1-L5 in Suzuki cross-coupling
reactions was then evaluated. In an effort to understand how the
ligands would promote this coupling reaction most efficiently, a
reaction in which K2CO3 was used as a base and ethanol/water
was a cosolvent in the reaction of phenylboronic acid with 4-
bromoacetophenone at room temperature under air conditions
was examined. As shown in Table 1, the data revealed that the
α-diimine ligands were effective ligands for palladium-catalyzed
Suzuki cross-coupling. For a comparison, in the absence of
ligands, only 30% yield of product was produced in the presence
of 0.025 mol % of Pd(OAc)2 (Entry 1, Table 1). However, when
ligands were added in the system, the yield of the product
increased dramatically up to 80-99% (Entries 2-6, Table 1),
454 | Chem. Lett. 2016, 45, 454–456 | doi:10.1246/cl.160057
© 2016 The Chemical Society of Japan

Table 1. Influence of α-diimine ligands on the palladium-
catalyzed cross-coupling reaction of 4-bromoacetophenone with
phenylboronic acida
Table 3. Suzuki cross-coupling reaction of aryl halides with
phenylboronic acid under aerobic conditionsa
Entry
Ligand
Yield/%b
1
2
3
4
5
6
None
L1
L2
L3
L4
30
91
93
99
88
80
Time Yield
/h
Entry
Aryl halide
Arylboronic acid
/%b
97
Br
Br
B(OH)2
1
2
Me
2
L5
B(OH)2
B(OH)2
MeO
2
2
96
99
aReaction conditions: 1.0 mmol of 4-bromoacetophenone, 1.2 mmol of
phenylboronic acid, 2.0 mmol of K2CO3, 0.025 mol % Pd(OAc)2,
0.025 mol % ligand, 5 mL of EtOH/H2O (v/v, 1:1), room temperature,
O
C
H3C
Br
3
b
2 h. Isolated yields.
Br
Br
B(OH)2
B(OH)2
4
5
OHC
Cl
2
2
98
99
Table 2. Optimization of reaction conditions at room temperaturea
Entry
Solvent
Base
Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
EtOH
DMF
THF
Toluene
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
KOH
84
80
68
45
91
80
99
94
93
92
99
86
54
91
87
65
CH3
Br
B(OH)2
6
4
90
Br
DMF/H2O(v/v, 1:1)
THF/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 2:1)
EtOH/H2O(v/v, 1:2)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
EtOH/H2O(v/v, 1:1)
B(OH)2
B(OH)2
7
8
4
6
95
81
CH3
Br
CH3
H3C
O
C
H3C
B(OH)2
Br
Br
Br
H3C
9
10
11
2
2
2
98
97
99
Ca(OH)2
NaOEt
K3PO4
KF
O
C
H3C
B(OH)2
B(OH)2
H3CO
F
O
C
H3C
aReaction conditions: 1.0 mmol of 4-bromoacetophenones, 1.2 mmol
of phenylboronic acid, 2.0 mmol of base, 0.025 mol % Pd(OAc)2,
0.025 mol % ligand L3, 5 mL of solvent, 2 h. Isolated yields.
b
CH3
B(OH)2
CH3
O
C
H3C
12
13
Br
4
86
44
indicating the in situ formation of catalyst systems. Among the
α-diimines investigated, L3 with 2,4,6-trimethyl groups on the
aniline moiety (Entry 4, Table 1) afforded the highest activity. In
this case, the conversion of the product reached 99%. Compa-
ratively, L5 with an electron-withdrawing chloro group on the
para position of the aniline (Entry 6, Table 1) was less active
under the same conditions (80% yield). These results could be
ascribed to the increase in the electron-donating ability of the
aniline moieties of the ligand, leading to an increase in the rate of
oxidative addition and the stabilization of the palladium species.
As shown in Table 2, the effect of solvents on the coupling
reaction was also examined. The polarity of the solvent had a
profound effect on the yield. For instance, the nonpolar solvent
toluene gave a poor yield (45%), whereas the polar solvents,
such as N,N-dimethylformamide (DMF), tetrahydrofuran (THF),
and ethanol, provided the product in moderate yield (Entries 1-
3, Table 2). Meanwhile, reaction activities were dramatically
improved using organic/water cosolvents. EtOH/H2O (v/v, 1:1)
system afforded the highest yield (Entry 7, Table 2) among the
tested aqueous-organic solvents. In addition, an investigation
of the influence of the base suggested that the common and
CH3
Br
CH3
24
B(OH)2
H3C
O
C
H3C
14c
15c
12
12
75
35
Cl
B(OH)2
B(OH)2
Cl
Me
aReaction conditions: 1.0 mmol of aryl bromide, 1.2 mmol of
arylboronic acid, 2.0 mmol of K2CO3, 0.025mol % Pd(OAc)2,
0.025 mol % ligand, 5 mL of EtOH/H2O (v/v, 1:1), room temperature.
bIsolated yields. cReaction conditions: 1.0 mmol of aryl chloride,
1.2 mmol of arylboronic acid, 2.0 mmol of K2CO3, 0.25 mol %
Pd(OAc)2, 0.25 mol % ligand, 5 mL of EtOH/H2O (v/v, 1:1), reaction
temperature: 80 °C.
inexpensive inorganic bases, such as Cs2CO3 and K2CO3 are
more effective, while other bases such as Na2CO3, KOH,
Ca(OH)2, NaOEt, K3PO4, and KF gave slightly lower yields.
Chem. Lett. 2016, 45, 454–456 | doi:10.1246/cl.160057
© 2016 The Chemical Society of Japan | 455

Therefore, K2CO3 as a base and EtOH/H2O (v/v, 1:1) as a
solvent were chosen for further study because they were readily
available, inexpensive, and had a higher efficiency.
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As illustrated in Table 3, high catalytic activity was
observed in the coupling of aryl halides with phenylboronic
acid at room temperature with ligand L3. These catalytic system
on cross-coupling reaction displayed remarkable tolerance
toward the electronic properties of the substrates. For both the
aryl bromides (Entries 1-8, Table 3) and aryl boronic (Entries 9-
11, Table 3) with different electronic effect substituent, there
were no significant difference in the yield or reaction time. Due
to retarding both the oxidative addition and transmetalation
processes, the aryl halides or aryl boronic with ortho-methyl
substituent had less active. However, in this study, they could
achieve high yield with a prolonged reaction time (Entries 6, 8,
and 12, Table 3). However, the phenylboronic with ortho-
substituents reacted with aryl bromide with ortho-substituents,
the catalytic system exhibited lower activity through prolonged
reaction time. For example, the larger hindered substrate 2-
bromo-1,3,5-trimethylbenzene and 2-tolylboronic acid was
coupled under the same reaction conditions for 24 h, the less
reactivity was obtained (Entry 13, Table 3). It was probable that
the steric effect might prevent its effective oxidative addition
process. Significantly, the relatively unactivated aryl chlorides
could react with phenylboronic acid when this catalytic system
was employed, which led to moderate to high yields (Entries 14
and 15, Table 3).
In summary, an unprecedented, general, and efficient
method based on the 9,10-dihydro-9,10-ethanoanthracene-
11,12-diimine/Pd(OAc)2 system has been developed for the
Suzuki-Miyaura cross-coupling reaction of aryl bromides with
arylboronic acids. The corresponding Suzuki coupling products
were obtained in excellent yields at room temperature in
ethanol/aqueous media under ambient atmosphere. In particular,
the experimental data shows that the α-diimine ligand with
2,4,6-trimethyl groups on the aniline moiety facilitates the cross-
coupling reaction. Future studies focused on the activation of
electron-rich and electron-neutral aryl chlorides by 9,10-di-
hydro-9,10-ethanoanthracene-11,12-diimine/Pd(OAc)2 systems
are ongoing.
2
3
4
5
6
7
8
9
This work was supported by the National Natural Science
Foundation of China (No. 21261024) and the Natural Science
Foundation of Jiangxi Province (Nos. 20151BAB206021 and
20132BAB203002).
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Supporting Information is available on http://dx.doi.org/
10.1246/cl.160057.
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456 | Chem. Lett. 2016, 45, 454–456 | doi:10.1246/cl.160057
© 2016 The Chemical Society of Japan