Oxygen-promoted Pd/C-catalyzed Suzuki-Miyaura reaction of potassium aryltrifluoroborates

Article abstract of DOI:10.1016/j.cclet.2015.12.022

A simple and highly efficient protocol has been developed for the Pd/C-catalyzed ligand-free Suzuki-Miyaura reaction of potassium aryltrifluoroborates. In this catalytic system, the results demonstrate that oxygen plays a positive role in the cross-coupling reaction. In addition, this catalytic system could be successfully applied to synthesize biaryl compounds containing a carbazole moiety and the catalyst was recycled seven times without significant loss of catalytic activity.

Full text of DOI:10.1016/j.cclet.2015.12.022

Chinese Chemical Letters 27 (2016) 631–634
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Chinese Chemical Letters
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Original article
Oxygen-promoted Pd/C-catalyzed Suzuki–Miyaura reaction
of potassium aryltrifluoroborates
*
Chun Liu , Chao Liu, Xin-Min Li, Zhan-Ming Gao, Zi-Lin Jin
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A simple and highly efficient protocol has been developed for the Pd/C-catalyzed ligand-free Suzuki–
Miyaura reaction of potassium aryltrifluoroborates. In this catalytic system, the results demonstrate that
oxygen plays a positive role in the cross-coupling reaction. In addition, this catalytic system could be
successfully applied to synthesize biaryl compounds containing a carbazole moiety and the catalyst was
recycled seven times without significant loss of catalytic activity.
Received 19 October 2015
Received in revised form 14 December 2015
Accepted 23 December 2015
Available online 6 January 2016
ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Pd/C
Oxygen-promoting effect
Suzuki–Miyaura reaction
Potassium aryltrifluoroborates
Carbazole derivatives
1. Introduction
Significant efforts have been focused on the development of
efficient systems for the Suzuki–Miyaura reaction of potassium
In recent years, potassium organotrifluoroborates have been
used in the Suzuki–Miyaura reaction, which is one of the most
versatile and powerful methods for the carbon–carbon bond
formation in the synthesis of biaryl compounds and has been
widely developed for its highly efficient and green characteristics
[1–4]. Nucleophilic partners of this cross-coupling reaction, the
arylboronic acids are not monomeric species, but rather exist as
dimeric and cyclic trimeric anhydrides [5]. Moreover, protodebor-
onation and homocoupling have been prone to competing with the
cross-coupling process, particularly for electron-poor arylboronic
acids [6,7]. Fortunately, potassium organotrifluoroborate salts
offer solutions for these problems. Unlike arylboronic acids, the
potassium organotrifluoroborates are monomeric solids, easily
prepared from organoboronic acids or esters by the addition of
inexpensive potassium hydrogen fluoride (KHF2) [8]. With very
few exceptions, potassium organotrifluoroborates show high
stability toward air and water and can be stored indefinitely at
room temperature without any precaution [9]. It is an ideal
organoboron reagent for organic synthesis.
organotrifluoroborates [10–13], but most of the reported protocols
are homogeneous catalytic systems, in which the palladium
catalysts are usually not recoverable, and the residual Pd metal in
the product could induce serious problems. Therefore, a number of
heterogeneous catalysts, which are easily separated and recycled,
have come to our attention. Among them, Pd/C is one of the most
common heterogeneous catalysts [14,15]. In 2009, LeBlond et al.
reported the Pd/C-catalyzed cross-coupling of aryl halides with
potassium p-tolyltrifluoroborate, although longer reaction time and
a high loading of catalyst were required [16]. Joucla et al. reported a
Pd/C-catalyzed approach for the vinylation of aryl halides using
potassium vinyltrifluoroborates in N-methyl-2-pyrrolidone [17,18].
In the past several years, a series of highly efficient and ligand-
free protocols for the Suzuki–Miyaura reaction of aryl boronic acids
with aryl halides have been developed by our group [19–22]. In
this paper, we describe a simple and efficient approach for the Pd/
C-catalyzed ligand-free Suzuki–Miyaura reaction of potassium
aryltrifluoroborates with aryl halides in aqueous media. This
catalytic system can be successfully applied to synthesize biaryl
compounds containing a carbazole moiety, which are important
building blocks for the construction of advanced photoelectric
materials [23,24]. Importantly, an oxygen-promoting effect was
observed in the Pd/C-catalyzed Suzuki–Miyaura reaction of
potassium aryltrifluoroborates.
*
Corresponding author.
E-mail address: cliu@dlut.edu.cn (C. Liu).
http://dx.doi.org/10.1016/j.cclet.2015.12.022
1001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

632
C. Liu et al. / Chinese Chemical Letters 27 (2016) 631–634
Table 2
2. Experimental
The Suzuki–Miyaura reaction of aryl halides with potassium aryltrifluoroborates.a
2.1. General procedure for the Suzuki–Miyaura reaction of potassium
aryltrifluoroborates
A mixture of aryl halide (0.5 mmol), potassium aryltrifluor-
oborate (0.6 mmol), K2CO3 (1.0 mmol), Pd/C (0.5 mol%), ethanol
(3 mL), and distilled water (1 mL) was stirred at 80 8C in air for the
indicated time. The reaction mixture was added to brine (15 mL)
and extracted with ethyl acetate (4 Â 15 mL). The organic solvent
was removed under vacuum, and the product was isolated by
short-column chromatography.
Entry
R1
R2
Time (min)
Yield (%)b
1
4-CN
H
20
25
25
30
91
95
93
95
78
91
95
96
90
70
93
79
46
94
97
2
4-NO2
4-CHO
4-COCH3
4-OCH3
4-OH
H
3
H
4
H
5
H
50
6
H
30
7
4-CF3
4-CH3
4-CH3
4-OCH3
4-OCH3
4-CH3
3-CH3
2-CH3
H
27
35
30
8
4-CN
2.2. Recyclability tests of the Pd/C catalyst
9
4-CN
10
11
12
13
14
15
4-OCH3
4-NO2
4-NO2
4-NO2
2-CN
60
For the first run, a mixture of 4-nitrobromobenzene (0.5 mmol),
potassium 9-phenylcarbazolyltrifluoroborate (0.6 mmol), K2CO3
(1.0 mmol), Pd/C (1.0 mol%), ethanol (3 mL), and distilled water
(1 mL) was stirred at 80 8C in air. The reaction was monitored by
TLC. At the end of the reaction, the Pd/C catalyst was recovered by
simple filtration, washed with chloroform and water, and dried
under vacuum for the next run.
25
120
120
30
2-CN
4-CH3
25
a
Reaction conditions: aryl halide (0.5 mmol), potassium aryltrifluoroborate
(0.6 mmol), Pd/C (0.5 mol%), K2CO3 (1.0 mmol), EtOH/H2O (3 mL/1 mL), 80 8C, in air.
The reaction was monitored by TLC.
b
Isolated yield.
3. Results and discussion
(0.5 mol %) as catalyst at 80 8C in air. As shown in Table 2, in
general, most of the reactions gave biaryl derivatives in high yields.
The electronic nature of the substituent has some influence on the
reactivity of the cross-coupling reactions. It is clear that 4-
substituted aryl bromides containing electron-withdrawing
groups showed a slightly higher reactivity than those containing
electron-donating groups, due to the effect of these substituents on
the reactivity of C-Br bond (Table 2, entries 1–6). Either 4-methyl
or 4-methoxyl-substituted potassium phenyltrifluoroborates
could complete the reactions smoothly (Table 2, entries 7–9).
Increasing the steric effect could decrease the reactivity of the
substrates (Table 2, entries 12 and 13). Unexpectedly, the ortho-
substituted substrate, 2-bromobenzonitrile, reacted with potassi-
um phenyltrifluoroborate or potassium p-tolyltrifluoroborate,
providing the desired products in 94% and 97% yields, respectively
(Table 2, entries 14 and 15).
The present protocol was also extended to the synthesis of
useful nitrogen-based heterobiaryl compounds. The results are
summarized in Table 3. The cross-coupling of 5-bromo-2-
methoxypyridine with potassium p-tolyltrifluoroborate gave 5-
bromo-2-phenylpyridine in a 93% yield (Table 3, entry 2). Using
potassium o-tolyltrifluoroborate as the nucleophilic partner, the
cross-coupling was completed in 120 min, providing an 86% yield
(Table 3, entry 3). As for 6-substituted 2-bromopyridines, both 2-
bromo-6-methoxypyridine and 2-bromo-6-fluoropyridine provid-
ed good to excellent yields of the desired products (Table 3, entries
4–6). Other nitrogen-based heterobiaryls also achieved good
results (Table 3, entries 7–10), whereas 2-bromothiophene was
less active and generated the product in 44% yield (Table 3, entry
11). In this heterogeneous catalytic system, the reaction between
N-heteroaryl chloride and potassium phenyltrifluoroborate
achieved a moderate yield (Table 3, entry 12).
Our group has a long standing interest in the effects of different
atmospheres on the Suzuki–Miyaura reaction. Since 2007 we have
found that oxygen plays a positive role in the palladium-catalyzed
ligand-free Suzuki–Miyaura reaction of aryl boronic acids with aryl
halides in different solvents, including polyethylene glycol,
organic/water mixed solvents and pure water [4,25,26]. These
results inspired us to speculate whether oxygen could also
promote the Suzuki–Miyaura reaction of potassium phenyltri-
fluoroborates with aryl halides. Therefore, the Pd/C-catalyzed
Suzuki–Miyaura reaction of 4-nitrobromobenzene with potassium
phenyltrifluoroborate was performed in the different atmospheres
(Table 1). The cross-coupling gave the product in 51% yield in a
nitrogen atmosphere (Table 1, entry 2). However, the cross-
coupling performed in air provided a 91% yield within the same
reaction time, which is much faster than that in nitrogen (Table 1,
entry 1). Excitingly, the same cross-coupling reaction carried out in
an oxygen atmosphere was completed in 15 min (Table 1, entry 3).
It is clear that oxygen promotes the Pd/C-catalyzed Suzuki–
Miyaura reaction of potassium phenyltrifluoroborate under
aqueous conditions. Consequently, we carried out all the reactions
in air for the study.
After having optimized the reaction conditions such as solvents,
bases and catalysts (see Supporting information), we further
investigated the scope and limitations of substrates under the
conditions of 75% aqueous ethanol as solvent, K2CO3 as base, Pd/C
Table 1
The effects of different atmospheres on the Pd/C-catalyzed Suzuki–Miyaura
reaction of 4-nitrobromobenzene with potassium aryltrifluoroborate.a
In recent years, carbazole derivatives have been extensively
used as functional building blocks for the synthesis of small
molecules, oligomers or polymers, and also as host materials
because of their high triplet energy and good hole-transporting
ability [27,28]. In this catalytic system, a series of aryl substituted
9-phenylcarbazolyl derivatives have been successfully synthesized
via the Pd/C-catalyzed Suzuki–Miyaura reaction of aryl bromides
with potassium 9-phenylcarbazolyltrifluoroborate. The results
presented in Table 4 show that the aryl bromides bearing
Entry
Atmosphere
Time (min)
Yieldb (%)
1
2
3
Air
N2
O2
20
20
15
91
51c
98
a
Reaction conditions: 4-nitrobromobenzene (0.5 mmol), potassium phenyltri-
fluoroborate (0.6 mmol), Pd/C (0.5 mol%), K2CO3 (1.0 mmol), EtOH/H2O (3 mL/1mL).
b
Isolated yield.
c
The EtOH and H2O were degassed.

C. Liu et al. / Chinese Chemical Letters 27 (2016) 631–634
633
Table 3
Table 4
The Suzuki–Miyaura reaction of heteroaryl halides with potassium aryltrifluor-
oborates.a
Synthesis of aryl or heteroaryl substituted 9-phenylcarbazolyl derivatives.a
Entry
1
Heteroaryl halide
Product
Time (min)
120
Yield (%)b
79
Entry Aryl halides
1
Product
Time (min) Yield (%)b
60
93
2
3
120
120
93
86
2
60
95
4
5
180
78
89
97
3
60
90
97
97
Br
F C
O
4
Br
6
60
93
O
N
N
N
N
7
8
9
180
200
180
96
93
83
O
H
5
6
7
8
100
83
92
96
91
83
Br
O
H
F
Br
F
10
240
80
O N
120
120
NO
Br
11
12
120
240
44
61
Br
N
N
a
Reaction conditions: heteroaryl halide (0.5 mmol), potassium aryltrifluorobo-
rate (0.6 mmol), Pd/C (0.5 mol%), K2CO3 (1.0 mmol), EtOH/H2O (3 mL/1mL), 80 8C, in
air. The reaction was monitored by TLC.
CN
9
60
80
93
96
78
NC
b
Isolated yield.
Br
Br
electron-withdrawing groups were more effective. Among them,
the substrates bearing 4-NO2, 4-CN, or 4-CF3, provided the
corresponding products in excellent yields within 60 min
(Table 4, entries 1–3). Meanwhile, 4-COCH3, 4-CHO and 4-
fluoro-substituted aryl bromides were also successfully coupled
with 9-phenylcarbazolyltrifluoroborate in good yields (Table 4,
entries 4–6). Additionally, an 83% isolated yield was obtained in
120 min in the case of 4-bromotoluene (Table 4, entry 8). It is
noteworthy that the cross-coupling reaction between potassium
9-phenylcarbazolyltrifluoroborate and 3-nitrobromobenzene pro-
ceeded well, resulting in a 91% yield of the product within 120 min
(Table 4, entry 7). To our delight, ortho-substituted substrate
exhibited almost the same reactivity in terms of rate and yield
(Table 4, entry 9). Furthermore, the cross-couplings of 5-bromo-2-
methoxypyridine and 6-bromo-2-fluoropyridine also provided
good yields of the desired products (Table 4, entries 10 and 11).
10
11
a
N
N
F
N
F
Br
240
N
O
N
O
N
Reaction conditions: aryl or heteroaryl bromides (0.5 mmol), potassium 9-
phenylcarbazolyltrifluoroborate (0.6 mmol), Pd/C (0.5 mol%), K2CO3 (1.0 mmol),
EtOH/H2O (3 mL/1mL), 80 8C, in air. The reaction was monitored by TLC.
b
Isolated yield.

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C. Liu et al. / Chinese Chemical Letters 27 (2016) 631–634
100
90
80
70
60
50
40
30
20
10
0
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The authors thank the financial support from the National
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Appendix A. Supplementary data
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Supplementary material related to this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2015.12.
022.