Amine-bridged bis(phenol) ligands for efficient Pd-catalyzed aqueous C-C coupling reactions

Article abstract of DOI:10.1002/aoc.3033

The influence of ring size (5 or 6), chain length (1, 2 or 3) and bulkiness of N-aryl substituents in amine-bridged bis(phenol) ligands (1, 2, 3) on palladium-catalyzed aqueous C-C coupling reactions were revealed. The homocoupling of arylboronic acid can be completed in neat water with the aid of a catalytic amount of p-toluenesulfonyl chloride (TsCl) in a very short time under anaerobic or aerobic conditions. Interestingly, the same catalytic system was efficient for Suzuki-Miyaura reaction in aqueous acetone under aerobic conditions in the absence of TsCl. The crystal structures of ligand 1 and three unsymmetrical fluorine-substituted biaryl derivatives were also reported. Copyright

Full text of DOI:10.1002/aoc.3033

Full Paper
Received: 7 April 2013
Revised: 18 June 2013
Accepted: 18 June 2013
Published online in Wiley Online Library: 27 August 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3033
Amine-bridged bis(phenol) ligands for efficient
Pd-catalyzed aqueous C-C coupling reactions
Zhonggao Zhoua*, Minyan Liua, Xiaoli Wua, Hongwei Yub, Guohai Xua
and Yongrong Xiea*
The influence of ring size (5 or 6), chain length (1, 2 or 3) and bulkiness of N-aryl substituents in amine-bridged bis(phenol)
ligands (1–3) on palladium-catalyzed aqueous C-C coupling reactions were revealed. The homocoupling of arylboronic acid
can be completed in neat water with the aid of a catalytic amount of p-toluenesulfonyl chloride (TsCl) in a very short time
under anaerobic or aerobic conditions. Interestingly, the same catalytic system was efficient for Suzuki–Miyaura reaction in
aqueous acetone under aerobic conditions in the absence of TsCl. The crystal structures of ligand 1 and three unsymmetrical
fluorine-substituted biaryl derivatives were also reported. Copyright © 2013 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: water; N,O-ligands; palladium; homocoupling; Suzuki reaction
yield of coupling products.[47,48] Ligand structure defines the
steric and electronic properties of the palladium catalyst and thus
Introduction
Water, being cheap, non-flammable, non-toxic and environ-
mentally benign, has been recognized as perhaps the ultimate
green solvent. To date, development of green chemistry
through organic reactions conducted in water and aqueous
solution has become one of the most exciting research en-
deavors in organic synthesis.[1–3] Palladium catalysts are
critically important in numerous chemical processes including
C-C bond formation reactions.[4–6] The symmetrical and unsym-
metrical substituted biaryl motif is found in a range of pharma-
ceuticals, herbicides and natural products as well as in
conducting polymers and liquid crystalline materials.[7–16]
Among the developed reactions, the homocoupling reactions
of arylboronic acid is a good method to obtain symmetrical
substituted biaryls from just a single precursor since the first
example in 1987 studied by Suzuki.[17,18] A striking advantage
of this reaction is that the products are easily separated by
simple filtration.[14,19] The Suzuki–Miyaura reaction is undoubt-
edly the most powerful tool to selectively generate unsymmet-
rical substituted biaryls,[5] and is an excellent example which
has strongly benefited from aqueous chemistry.[20–33] Improve-
ments in the activity, selectivity and scope of the catalysts
could drastically reduce the environmental impact, and
increase the sustainability of chemical reactions.[34] Recent
advances in novel catalyst development have enabled this
transformation to be applied with a broad substrate scope, a wide
functional group tolerance, low catalyst loadings, etc.[6,35–41]
The development of amine-bridged bis(phenol) ligands that
have a rigid framework with bulky N-aryl substituents on the ring
nitrogen to restrict the rotation of the coordination group has
rarely been explored.[42–44] The presence of the nitrogen atom
on the amine bridge seems to have a significant effect on the
catalytic activity of the corresponding ligands.[43,45,46] Previously,
we also found that Pd/2- and Pd/3-catalyzed arylhalides with
arylboronic acid in methanol aqueous afford good to excellent
plays a crucial role in the efficiency of the Pd-catalyzed reaction.
The amine-bridged bis(phenol) rigid ligands (Fig. 1, 1–3), which
contain a well-defined orientation of the N,O-chelate for metal
coordination, have provided different steric and electronic
properties through slight diversity of the amine bridge. It is of
particular interest to explore the influence of ring size, chain
length and bulkiness of N-aryl substituents in these ligands
on the catalytic properties of palladium complexes in C-C
coupling reactions.
In the continuation of our interest in the development of
new ligands for Pd-catalyzed C-C bond formation reactions,
here we report the catalytic activity of ligands 1–3 in Pd-
catalyzed aqueous C-C coupling reactions. More specifically,
the same catalytic system was efficient for Pd-catalyzed
homocoupling of arylboronic acids in neat water and Suzuki–
Miyaura reaction in aqueous acetone with or without TsCl
(Fig. 2). Thus these results would be complementary to those
known catalytic systems.
Experimental
General Considerations
All chemicals employed in the synthesis were analytical grade,
obtained commercially, and used as received without further
*
Correspondence to: Zhonggao Zhou and Yongrong Xie, College of Chemistry and
Chemical Engineering, Gannan Normal University, Ganzhou 341000, People's Republic
of China. E-mail: zhgzhou@foxmail.com; yongrongxie@foxmail.com
a College of Chemistry and Chemical Engineering, Gannan Normal University,
Ganzhou 341000, People's Republic of China
b School of Chemical Engineering, Shijiazhuang University, Shijiazhang 050035,
People's Republic of China
Appl. Organometal. Chem. 2013, 27, 562–569
Copyright © 2013 John Wiley & Sons, Ltd.

Efficient green protocol of Pd-catalyzed aqueous C–C coupling
Figure 1. Amine-bridged bis(phenol) N,O-ligands 1, 2 and 3.
Figure 2. Pd-catalyzed aqueous C-C coupling reactions.
purification. Ligands 1,[42] 2[43] and 3[44] were prepared as
reported. NMR spectra were performed on a Bruker Avance III
400 MHz spectrometer (tetramethylsilane as internal standard)
and coupling constants (J values) are given in hertz. Analyses
by gas chromatography–mass spectrometry (GC-MS) were
carried out on an Agilent 6890 gas chromatograph with 5973
mass spectral detector, using an AT.SE-30 column of 50 m
length, 0.32 mm diameter and 0.5 μm film thickness.
Mo-Kα radiation (λ = 0.71073 Å). Intensity data were collected
using φ and ω scans at 296 K. Datasets were corrected for
Lorentz and polarization factors as well as for absorption by
SADABS program.[49] Structures were solved by the direct
method and refined by full-matrix least-squares fitting on F2
by SHELX-97.[50,51] All non-hydrogen atoms were refined an-
isotropically except for the water molecules in 1. All H atoms
were refined using a riding model. Three F atoms on the -CF3
group of 4 are disordered over two positions (F1/F1′, F2/F2′
and F3/F3′) with equal populations for each orientation.
Experimental details of the X-ray analyses are provided in
Table 1.
Single-Crystal Structure Determination
Data collections for crystals were performed on a Bruker Smart Apex
II CCD diffractometer equipped with graphite-monochromated
Table 1. Crystal data collection and structure refinements for compounds 1 and 4–6
Compound
1
4
5
6
Formula
C
34H55N2O3
539.8
C15H11F3O1
264.2
C14H10F2O1
232.2
C14H9F3O1
250.2
Formula weight
Crystal size (mm)
0.40 × 0.36 × 0.28
Pnma
0.50 × 0.46 × 0.37
P21/c
0.45 × 0.40 × 0.35
P21/c
0.35 × 0.30 × 0.26
P212121
7.396(5)
12.594(5)
12.770(5)
90.000(5)
90.000(5)
90.000(5)
1189.5(10)
4
space group
a (Å)
8.8194(3)
37.3103(14)
10.2814(4)
90.00
11.431(5)
11.431(5)
13.715(5)
90.000(5)
105.968(5)
90.000(5)
1269.1(10)
4
10.244
12.444
9.814
b (Å)
c (Å)
α (°)
β (°)
90.00
90.00
115.03
90.00
γ (°)
90.00
V (Å3)
3383.1(2)
8
1133.6
4
Z
Rint
0.0515
0.0231
0.0280
480
0.0116
F(000)
1188
544
512
Reflections collected
GOF on F2
R1 [I > 2σ(I)]
wR2
3893/2304
1.021
2996/2059
1.038
2520/1826
1.086
2691/1942
1.032
0.070
0.070
0.079
0.058
0.245
0.137
0.189
0.111
Formula weight
Goodness-of-fit on F2
Appl. Organometal. Chem. 2013, 27, 562–569
Copyright © 2013 John Wiley & Sons, Ltd.
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Z. Zhou et al.
Figure 3. ORTEP view of molecular structure of ligand 1.
General Procedure for the Homocoupling
of Arylboronic Acids
(3) 4-methoxy-1,1′-biphenyl (Table 5, entry 4)[54]
(4) 4-acetyl-1,1′-biphenyl (Table 5, entry 5)[43]
(5) 2-methyl-1,1′-biphenyl (Table 5, entry 6)[55]
Appropriate amounts of ligand and metal precursor and 3.0 ml
solvent were placed in a two-necked round-bottom flask with a
magnetic stir bar at 0 °C. After stirring for 5 min, arylboronic
acids (2.0 mmol) and base (2.0 mmol) were added to the flask.
The reaction mixture was stirred under nitrogen or air atmo-
sphere at ice-water temperature then at room temperature.
The course of the reaction was monitored by GC-MS analysis
and yields were calculated against n-dodecane. The solvent
was removed under reduced pressure after the reaction was
completed. The pure products were obtained through a short
column chromatography using petroleum ether as eluent from
any arylboronic acid. The organic solvent was evaporated un-
der reduced pressure. Products were characterized by compar-
(6) 4-trifluoromethyl-1,1′-biphenyl (Table 5, entry 9)[47]
(7) 2-methoxy-1,1′-biphenyl (Table 5, entry 10)[56]
(8) 4-acetyl-3′,4′,5′-trifluoro-1,1′-biphenyl (Table 5, entry 11)[55]
(9) 4-acetyl-3′,5′-difluoro-1,1′-biphenyl (Table 5, entry 12)[56]
(10) 4-acetyl-4′-trifluoromethyl-1,1′-biphenyl (Table 5, entry 13)[57]
Results and Discussion
The colorless crystals of 1, suitable for X-ray diffraction analysis,
were grown by the slow evaporation of methanol at room
temperature. A perspective view of the molecular structure of
compound 1 with atom numbering scheme is shown in Fig. 3.
In the asymmetric unit of 1, there is only half a ligand molecule.
The C16 and C18 atoms reside on a mirror plane with half a
population so that another symmetry-related half is gener-
ated. In the molecular structure of 1 the amine bridge moiety
possesses a stable chair conformation. The chair conforma-
tion of 1 was due to the weak hydrogen bonding between
the tertiary nitrogen atom and hydrogen atom of the
phenoxy groups; the bond distance of H1O-N is 1.888(4) Å.
The C-N bond distances of 1 are 1.473(3) Å (N-C15), 1.451(2) Å
(N-C16) and 1.465(4) Å (N-C17), whereas the bond length of
1
ison of H NMR spectroscopic data with those in the literature:
(1) biphenyl (Table 3, entry 1, Table 5, entry 7)[47]
(2) 4,4′-dichlorobiphenyl (Table 3, entry 2)[15]
(3) 4,4′-difluorobiphenyl (Table 3, entry 3)[16]
(4) 4,4′-dicyanobiphenyl (Table 3, entry 4)[16]
(5) 4,4′-dinitrobiphenyl (Table 3, entry 5)[16]
(6) 4,4′-dimethylbiphenyl (Table 3, entry 6)[12]
(7) 9,9′-biphenanthrene (Table 3, entry 8)[16]
(8) 3,3′-bipyridine (Table 3, entry 8)[16]
(9) 2,2′-bithiophene (Table 3, entry 9)[52]
(10) 4,4′-dimethoxybiphenyl (Table 3, entry 10)[52]
General Procedure for the Suzuki Reaction
The appropriate amounts of ligand 1 and metal precursor
were added to the required solvent (3.0 ml). The mixture
was stirred for 5 min, then the aryl halide (0.5 mmol),
phenylboronic acid (0.75 mmol) and base (1.0 mmol) were
added, and the mixture was stirred under air. The course
of the reaction was monitored by GC-MS analysis, and yields
were calculated against the aryl halides. On completion of
the reaction, the solvent was removed under reduced pres-
sure. The residue was dissolved with H2O (3.0 ml) and Et2O
(3.0 ml), followed by extraction with Et2O (2 × 3.0 ml). The
organic fraction was dried over anhydrous MgSO4, then
filtered, and the solvent was evaporated under reduced
pressure. The crude product was purified by column chroma-
tography using 200-300 mesh silica gel and the purified
products were characterized by comparing their NMR spec-
tra (1H or 1H, 13C or 1H, 13C and heteronuclear single quan-
tum coherence (HSQC) with those found in the literature:
4
5
6
(1) 4-methyl-1,1′-biphenyl (Table 5, entries 1, 2 and 8)[43]
(2) 4-cyano-1,1′-biphenyl (Table 5, entry 3)[53]
Figure 4. ORTEP view of unsymmetrical fluorine-substituted biaryl
derivative.
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Appl. Organometal. Chem. 2013, 27, 562–569

Efficient green protocol of Pd-catalyzed aqueous C–C coupling
Appl. Organometal. Chem. 2013, 27, 562–569
Copyright © 2013 John Wiley & Sons, Ltd.
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Z. Zhou et al.
C1-O1 is 1.374(4) Å, which is slightly longer compared with the
piperazine moiety.[43] The bond angles around the nitrogen atom
vary from 110.15(1)° (C16-N-C17) to 110.95(1)° (C15-N-C16). The
bond angle around C15-N-C17 is 112.33(2)°, which is slightly larger
compared with the literature value.[43]
Several palladium sources were tested, and the best results
were obtained for Pd(OAc)2 (Table 2, entries 14, 18–21); when
Pd(PPh3)4 was used as catalyst without addition of any other
ligands, the catalytic activity was similar to Pd(OAc)2/1 (Table 2,
entry 20).
Three unsymmetrical fluorine-substituted biaryl derivatives
(Fig. 4, compounds 4, 5 and 6) all gave yellow crystals by the
slow evaporation of dichloromethane and petroleum ether
mixture at room temperature. Further, their molecular struc-
tures were confirmed by single-crystal X-ray diffraction study
The catalytic activity of the Pd(OAc)2 was investigated with
respect to loadings. After many studies on the homocoupling
reaction, we found that the best Pd/L molar ratio was 1:1 (Table 2,
entries 22–35), and when less than 0.05 mol% Pd(OAc)2 was
applied, this resulted in slower speed or lower yield (Table 2,
entries 28–30).
1
in addition to H, 13C and HSQC spectra. A perspective view of
these single crystals with atom numbering scheme is shown in
Fig. 4.
To evaluate the scope and limitations of this procedure, the
reactions of a wide variety of arylboronic acids were examined in
the presence of 0.05 mol% Pd/L (L= 1, 2 or 3) under optimal
conditions in neat water (Table 3). Arylboronic acids with either
electron-withdrawing or electron-donating substituents all gave
excellent yields (86–99%). The homocoupling of heteroarylboronic
acids (3-pypridylboronic acid, 2-thienylboronic acid) gave corre-
sponding products in good isolated yields (88–92%) (Table 3, entries
8 and 9). In concluded, the homocoupling reaction of aryl boronic
acids can accelerate by Pd/L system with the aid of a catalytic
amount of TsCl in neat water under anaerobic or aerobic conditions.
The present procedure involved mild reaction conditions within just
15 min compared with Zhang (0.5–3.0 mol% Pd)[14] or Smith (5.0 mol
% Pd),[8] who obtained only moderate yields, even when prolonging
the reaction time to 24 h.
The effectiveness of ligand 1 observed in the homocoupling of
arylboronic acids encouraged us to study its catalytic activity in
the Suzuki reaction. The reaction parameters were investigated
in detail, as illustrated in Table 4. Ligand 1 is capable of catalyzing
the coupling of 4-bromotoluene with phenylboronic acids to
form unsymmetrical biaryl products in excellent yields in acetone
aqueous (acetone/water = 1/1) under air within just 1 h (0.1 mol%
Pd/1). Investigation of reaction temperature revealed that room
temperature (r.t.) was not an efficient temperature (Table 4,
entries 1–5), and the reaction can proceed smoothly under
reflux. A similar study was undertaken to determine whether
solvent polarity played a significant role in the reaction outcome
As fluorine is a small, highly polar and almost non-polarizable
atom, it is more accurate at close interatomic distances ri and
also the charge on the substituent atom (e.g. F) will vary
depending on the chemical environment of the substituent as
opposed to a fixed C-F dipole. In particular the charge on a
fluorine atom decreases in the order CH2F > CHF2 > CF3; thus
the electric field contribution will decrease in this order also.
Their C1-C9 bond distances are 1.490(2) Å (4), 1.490(2) Å (5)
and 1.479(2) Å (6) respectively, whereas the bond length of
compound 6 is slightly longer compared with the others. The
C-F bond lengths for these compounds were 1.288(4) Å
(4, C15-F1), 1.271(6) Å (4, C15-F2), 1.245(6) Å (4, C15-F3), 1.311
(2) Å (5, C11-F1), 1.312(2) Å (5, C11-F2), 1.351(3) Å (6, C11-F1),
1.360(2) Å (6, C11-F2), 1.351(3) Å (6, C11-F3), which were slightly
less than the experimental values (cf. fluoroethane 1.372 vs.
1.397 Å).[58] The bond angle around C6-C1-C2 is 117.45(1)°,
121.25(2)°, 120.57(2)°, and the bond angle around C6-C1-C9 is
121.23(1)°, 120.79(2)°, 121.40(2)° respectively. More details of
the crystallographic data are given in the X-ray crystallographic
files in CIF format (supporting information).
One area of research interest has been in the use of water and
aqueous solution as a solvent for many organic reactions over
the past decade.[31,59] The homocoupling of phenylboronic acid
in the presence of catalyst (PdCl2/1) was studied to identify
suitable bases and solvents. In acetone/water solvent, the bases
K2CO3, Cs2CO3, KOH, and Na2CO3 were found to be the best
(Table 2, entries 1, 2, 4 and 5). The synthesis of unsymmetrical
diaryl sulfones using the PdCl2-catalyzed coupling of aryl
boronic acids with TsCl has been developed by Bandgar,[60]
herein, just the product of homocoupling of phenylboronic acid
was found. A considerable improvement in the yield was
obtained when the reaction was carried out in protic solvents.
The solvents methanol, ethanol, ethanol (95%) and water
were found to be suitable (Table 2, entries 11–17). We found
that neat water can promote the reaction, and resulted in
excellent yield (Table 2, entry 14). When attempts were made
to carry out reactions in the absence of nitrogen atmosphere,
the homocoupling reactions proceeded smoothly. The reac-
tion mixture maintained a yellow under anaerobic or aerobic
conditions.
Table 3. Pd-catalyzed homocoupling of various arylboronic acidsa
Entry
Product
Yield (%)b
L1
99
L2
L3
93
1
2
Ph–Ph
93
95
93
88
96
94
87
89
90
96
p-Cl–Ph–Ph–Cl-p
p-F–Ph–Ph–F-p
94
95
90
97
96
90
91
92
98
92
92
90
95
90
86
90
88
94
3
4
p-CN–Ph–Ph–CN-p
p-NO2–Ph–Ph–NO2-p
p-Me–Ph–Ph–Me-p
9,9′-Biphenanthrene
3,3′-Bipyridine
5
Only trace products were detected by GC-MS in air without
TsCl (Table 2, entry 33); our results showed that a relatively
strong oxidizing agent was essential for this homocoupling
reaction, even in the presence of oxygen. Unlike the traditional
protocols during our experiments, a single product was
obtained by running the reaction directly in air or nitrogen
under ice/water, then at room temperature with the aid of TsCl.
In this way, we can further verify the developed mechanism of
this reaction.[13–15]
6
7
8
9
2,2′-Bithiophene
10
p-MeO–Ph–Ph–OMe-p
aReaction conditions: arylboronic acids (1.0 mmol), K2CO3 (2.0 mmol), water
(3.0 ml), catalyst Pd(OAc)2/L= 1:1 (0.05 mol%), TsCl (0.5 mmol), r.t., 15 min.
bIsolated yields.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 562–569

Efficient green protocol of Pd-catalyzed aqueous C–C coupling
Table 4. Investigation of Suzuki reaction of 4-bromotoluene and phenylboronic acida
Entry
Pd source
Pd(OAc)2
Base
K2CO3
Solvent
Ethanol
Conditions
Time (h)
Yield (%)b
1
r.t. N2
1
1
24
3
3
1
1
1
2
1
1
1
1
1
1
1
1
1
1
1
1
3
3
1
3
1
24
1
1
1
1
1
1
40
40
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
KOH
Methanol
r.t. N2
3
Water
r.t. air
40
4
Acetone
r.t. air
Trace
65
5
Toluene
r.t. air
6
Methanol
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
Reflux air
90
7
Toluene
85
8
Acetone
80
9
Water
85
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
Acetone/water (1/3)
Acetone/water (3/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
Acetone/water (1/1)
93
55
99
70
85
Cs2CO3,
NaHCO3
Na2CO3
K3PO4
TMEDA
TEA
97
70
95
96
Trace
42
None
Trace
97
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Pd(CF3COO)2
Pd(PPh3)4
Pd2(dba)3
Pd(COD)Cl2
None
95
85c
99
96
Trace
85d
95e
60f
70g
75h
45i
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
aReaction conditions: 4-bromotoluene (1.0 mmol), phenylboronic acid (1.25 mmol), base (2.0 mmol), solvent (3.0 ml), catalyst Pd/1 = 1:1 (0.1 mol%).
bDetermined by GC-MS.
cPd(PPh3)4 (0.1 mol%).
f
dPd/1 = 1:3; ePd/1 = 1:2; Pd/1 = 1:1.5; gPd/1 = 1:0.5.
hCatalyst 0.05 mol%.
iWithout ligand.
(Table 4, entries 1–12). We were pleased to observe that the re-
action could be efficiently conducted in a number of solvents,
and acetone/water (v/v = 1/1) was chosen as the best solvent.
Without the use of base as additive, only trace amount of
product was obtained (Table 4, entry 21). Therefore, a range of
bases including Cs2CO3, K2CO3, K3PO4, KOH, Na2CO3, NaOH and
NaHCO3 were screened (Table 4, entries 12–18); K2CO3 was found
to be the most suitable and gave the desired product in 99% yield.
The use of organic bases such as tetramethylethylenediamine
(TMEDA) and triethylamine led to much decreased yields, and
only trace and 42% yields were obtained, respectively (Table 4,
entries 19 and 20).
Next, we examined the range of catalysts that could be employed
by evaluating different palladium sources as well as ligand stoichiom-
etry (Table 4, entries 22–26 and 28–30). Rewardingly, only a minor
difference was observed when comparing reference conditions
(Table 4, entry 12); the catalytic activity of Pd/1 was higher than
commercially available palladium catalyst Pd(PPh3)4.
Maintaining the same Pd/L ratio but decreasing Pd(OAc)2 load-
ing to 0.05 mol% was less effective, providing lower conversion
within 1 h (Table 4, entry 32). Interestingly, maintaining the same
Pd loading but increasing the ligand 1 level to 0.12–0.3 mol%, as
described in an earlier report, led to lower conversion within the
same reaction time (Table 4, entries 28–30). Higher concentration
Appl. Organometal. Chem. 2013, 27, 562–569
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

Z. Zhou et al.
Table 5. Suzuki reactions of various aryl halides with arylboronic acidsa
Entry
Aryl halides
p-Me–Ph–I
Product
p-Me–Ph–Ph
Time (h)
Yield (%)b
1
0.5
1
99
99
99
98
99
92
99
95
96
60c
98
96
98
2
p-Me–Ph–Br
p-MeO–Ph–Br
p-CN–Ph–Br
p-MeCO–Ph–Br
o-Me–Ph–Br
Ph–Br
p-Me–Ph–Ph
3
p-MeO–Ph–Ph
p-CN–Ph–Ph
3
4
3
5
p-MeCO–Ph–Ph
o-Me–Ph–Ph
3
6
3
7
Ph–Ph
1
8
o-MeO–Ph–Br
p-CF3–Ph–Cl
p-Me-Ph-Cl
o-MeO–Ph–Ph
p-CF3–Ph–Ph
3
9
12
24
1
10
11
12
13
p-Me–Ph–Ph
p-MeCO–Ph–Br
p-MeCO–Ph–Br
p-MeCO–Ph–Br
p-MeCO–Ph–Ph–3F-m,m′,p
p-MeCO–Ph–Ph–2F-m,m′
p-MeCO–Ph–Ph–CF3-p
1
1
aReaction conditions: aryl halide (1.0 mmol), arylboronic acid (1.25 mmol), K2CO3 (1.0 mmol), acetone/water (v/v = 1/1, 3.0 ml), Pd(OAc)2/1 (0.1 mol
%), reflux, in air.
bIsolated yields.
c0.75 mmol TBAB.
of ligand 1 appears to either retard decomposition of the catalyst
or provide a less reactive coordinate complex. Decreasing the
ligand 1 level to 0.05 mol% also afforded lower conversion
(Table 4, entry 31).
In order to assess the scope of the aryl halide coupling partner,
we undertook a systematic study employing several arylboronic
acids to evaluate coupling with various aryl halides (Table 5).
Iodides, bromides, as well as activated chlorides were all found
to give the desired product in excellent yields (Table 5, entries
1–9). The reaction was tolerant to substituents present on the aryl
ring, affording the desired product in good to excellent yields.
the Key Laboratory of Jiangxi University for Functional Materials
Chemistry and Gannan Normal University.
References
[1] C. J. Li, Chem. Rev. 2005, 105, 3095.
[2] D. Dallinger, C. O. Kappe, Chem. Rev. 2007, 107, 2563.
[3] R. N. Butler, A. G. Coyne, Chem. Rev. 2010, 110, 6302.
[4] E.-I. Negishi, Angew. Chem. Int. Ed. 2011, 50, 6738.
[5] A. Suzuki, Angew. Chem. Int. Ed. 2011, 50, 6722.
[6] C. C. Johansson Seechurn, M. O. Kitching, T. J. Colacot, V. Snieckus,
Angew. Chem. Int. Ed. 2012, 51, 5062.
[7] M. Moreno-Mañas, M. Pérez, R. Pleixats, J. Org. Chem. 1996, 61, 2346.
[8] K. A. Smith, E. M. Campi, W. R. Jackson, S. Marcuccio, C. G. M. Naeslund,
G. B. Deacon, Synlett 1997, 1, 131.
[9] M. S. Wong, X. L. Zhang, Tetrahedron Lett. 2001, 42, 4087.
[10] H. Yoshida, Y. Yamaryo, J. Ohshita, A. Kunai, Tetrahedron Lett.
2003, 44, 1541.
[11] H. Tsunoyama, H. Sakurai, N. Ichikuni, Y. Negishi, T. Tsukuda,
Langmuir 2004, 20, 11293.
[12] S. Carrettin, J. Guzman, A. Corma, Angew. Chem. Int. Ed.
2005, 44, 2242.
Conclusions
A highly efficient green protocol for Pd-catalyzed aqueous C-C
coupling reaction under mild conditions has been developed. In
the homocoupling of arylboronic acid, Pd/1 was higher efficient,
with a catalytic amount of TsCl in neat water under anaerobic or
aerobic conditions. The same catalytic system was more efficient
for Suzuki–Miyaura reaction in aqueous acetone under air com-
pared with Pd/2 and Pd/3 in the absence of TsCl. In conclusion,
the steric hindrance of amine-bridged bis(phenol) ligands plays
a role in the coupling reaction.
[13] C. Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J. Am. Chem.
Soc. 2006, 128, 6829.
[14] Z. Xu, J. C. Mao, Y. W. Zhang, Catal. Commun. 2008, 9, 97.
[15] B. Mu, T. S. Li, Z. H. Fu, Y. J. Wu, Catal. Commun. 2009, 10, 1497.
[16] G. J. Cheng, M. M. Luo, Eur. J. Org. Chem. 2011, 2011, 2519.
[17] N. Miyaura, A. Suzuki, Main Group Met. Chem. 1987, 10, 295.
[18] D. V. Partyka, Chem. Rev. 2011, 111, 1529.
[19] T. Yokomatsu, B. Kaboudin, T. Haruki, Synthesis 2010, 2011, 91.
[20] N. E. Leadbeater, M. Marco, Org. Lett. 2002, 4, 2973.
[21] R. K. Arvela, N. E. Leadbeater, T. L. Mack, C. M. Kormos, Tetrahedron
Lett. 2006, 47, 217.
Supporting information
Supporting information may be found in the online version of
this article.
[22] J. W. Kim, J. H. Kim, D. H. Lee, Y. S. Lee, Tetrahedron Lett. 2006, 47, 4745.
[23] Y. Uozumi, Y. Matsuura, T. Arakawa, Y. M. Yamada, Angew. Chem. Int.
Ed. 2009, 48, 2708.
[24] C. C. Yang, P. S. Lin, F. C. Liu, I. J. B. Lin, G. H. Lee, S. M. Peng,
Organometallics 2010, 29, 5959.
Acknowledgments
Financial support for this work was provided by the National Nat-
ural Science Foundation of China (No. 21241005 and 21201040),
wileyonlinelibrary.com/journal/aoc
Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 562–569

Efficient green protocol of Pd-catalyzed aqueous C–C coupling
[25] B. Karimi, P. Fadavi Akhavan, Inorg. Chem. 2011, 50, 6063.
[26] N. Liu, C. Liu, Z. Jin, Green Chem. 2012, 14, 592.
[27] G. Sartori, G. Hervé, G. Enderlin, C. Len, Synthesis 2013, 45, 330.
[28] M. Bakherad, S. Jajarmi, J. Mol. Catal. A: Chem. 2013, 370, 152.
[29] A. Decottignies, A. Fihri, G. Azemar, F. Djedaini-Pilard, C. Len, Catal.
Commun. 2013, 32, 101.
[44] X. P. Xu, Y. M. Yao, Y. Zhang, Q. Shen, Inorg. Chem. 2007, 46, 3743.
[45] S. Mohanty, D. Suresh, M. S. Balakrishna, J. T. Mague, J. Organomet.
Chem. 2009, 694, 2114.
[46] Z. G. Zhou, Z. Y. Du, Q. S. Hu, J. C. Shi, Y. R. Xie, Y. L. Liu, Transition Met.
Chem. 2012, 37, 149.
[47] Z. G. Zhou, J. C. Shi, Q. S. Hu, Y. R. Xie, Z. Y. Du, S. Y. Zhang, Appl.
Organomet. Chem. 2011, 25, 616.
[30] A. Fihri, D. Luart, C. Len, A. Solhy, C. Chevrin, V. Polshettiwar, Dalton
Trans. 2011, 40, 3116.
[48] J. Xue, Z. G. Zhou, Y. L. Liu, L. Huang, H. W. Yu, Y. R. Xie, C. Lai, Tran-
[31] V. Polshettiwar, C. Len, A. Fihri, Coord. Chem. Rev. 2009, 253, 2599.
[32] F. Hapiot, J. Lyskawa, H. Bricout, S. Tilloy, E. Monflier, Adv. Synth.
Catal. 2004, 346, 83.
[33] A. Cassez, A. Ponchel, F. Hapiot, E. Monflier, Org. Lett. 2006, 8, 4823.
[34] A. J. Hickman, M. S. Sanford, Nature 2012, 484, 177.
[35] W. Tang, A. G. Capacci, X. Wei, W. Li, A. White, N. D. Patel, J. Savoie,
J. J. Gao, S. Rodriguez, B. Qu, N. Haddad, B. Z. Lu, D. Krishnamurthy,
N. K. Yee, C. H. Senanayake, Angew. Chem. Int. Ed. 2010, 49, 5879.
[36] A. Fihri, M. Bouhrara, B. Nekoueishahraki, J.-M. Basset, V. Polshettiwar,
Chem. Soc. Rev. 2011, 40, 5181.
sition Met. Chem. 2012, 37, 331.
[49] S. APEX2, SAINT, Bruker AXS Inc., Madison, WI, 2008.
[50] G. Sheldrick, Program for X-ray crystal structure solution, University
of Göttingen, Germany, 1997.
[51] G. Sheldrick, Program for X-ray crystal structure refinement,
University of Göttingen, Germany, 1997.
[52] C. Gonzalez-Arellano, A. Corma, M. Iglesias, F. Sanchez, J. Catal.
2006, 238, 497.
[53] G. A. Grasa, M. S. Viciu, J. K. Huang, C. M. Zhang, M. L. Trudell,
S. P. Nolan, Organometallics 2002, 21, 2866.
[37] J. Qiu, L. Wang, M. Liu, Q. Shen, J. Tang, Tetrahedron Lett. 2011, 52, 6489.
[38] C. Gao, H. Zhou, S. Wei, Y. Zhao, J. You, G. Gao, Chem. Commun.
2013, 49, 1127.
[39] T. Mahamo, M. M. Mogorosi, J. R. Moss, S. F. Mapolie, J. C.
Slootweg, K. Lammertsma, G. S. Smith, J. Organomet. Chem.
2012, 703, 34.
[54] H. W. Yu, J. C. Shi, H. Zhang, P. Y. Yang, X. P. Wang, Z. L. Jin, J. Mol.
Catal. A: Chem. 2006, 250, 15.
[55] B. P. Morgan, G. A. Galdamez, J. R. J. Gilliard, R. C. Smith, Dalton Trans.
2009, 2020.
[56] A. N. Marziale, D. Jantke, S. H. Faul, T. Reiner, E. Herdtweck,
J. Eppinger, Green Chem. 2011, 13, 169.
[40] V. Polshettiwar, A. Decottignies, C. Len, A. Fihri, ChemSusChem
2010, 3, 502.
[57] B. J. Gallon, R. W. Kojima, R. B. Kaner, P. L. Diaconescu, Angew. Chem.
Int. Ed. 2007, 46, 7251.
[41] F. Hapiot, A. Ponchel, S. Tilloy, E. Monflier, C. R. Chimie 2011, 14, 149.
[42] J. R. Farrell, J. Niconchuk, C. S. Higham, B. W. Bergeron, Tetrahedron
Lett. 2007, 48, 8034.
[58] R. J. Abraham, M. A. Warne, L. Griffiths, J. Chem. Soc., Perkin
Trans. 2 1997, 203.
[59] A. Hassine, S. Sebti, A. Solhy, M. Zahouily, C. Len, M. N. Hedhili,
A. Fihri, Appl. Catal. A: Gen. 2013, 450, 13.
[43] S. Mohanty, D. Suresh, M. S. Balakrishna, J. T. Mague, Tetrahedron
2008, 64, 240.
[60] B. P. Bandgar, S. V. Bettigeri, J. Phopase, Org. Lett. 2004, 6, 2105.
Appl. Organometal. Chem. 2013, 27, 562–569
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