A highly effective azetidine-Pd(II) catalyst for Suzuki-Miyaura coupling reactions in water

Article abstract of DOI:10.1016/j.tet.2008.05.093

Readily-synthesised, water-stable Pd(II) complexes of azetidine-based tridentate ligands have been studied as catalysts for the Suzuki-Miyaura coupling reaction. They are highly active for the coupling of aryl bromides with aryl boronates and also effecti

Full text of DOI:10.1016/j.tet.2008.05.093

Tetrahedron 64 (2008) 7178–7182
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A highly effective azetidine–Pd(II) catalyst for Suzuki–Miyaura
coupling reactions in water
,
d
Dong-Hwan Lee a, Young Hoon Lee b, Dong Il Kim b, Yang Kim c , Woo Taik Lim ,
*
Jack M. Harrowfield e , Pierre Thuery , Myung-Jong Jin , Yu Chul Park , Ik-Mo Lee
,
f
g
b,
a,
*
*
*
´
a Department of Chemistry, Inha University, Incheon 402-751, South Korea
b Department of Chemistry, Kyungpook National University, Daegu 702-701, South Korea
c Department of Chemistry and Advanced Materials, Kosin University, 149-1, Dongsam-dong, Yeongdo-gu, Busan, South Korea
d Department of Applied Chemistry, Andong National University, Andong, Kyungpook, South Korea
e Institut de Science et d’Inge´nierie Supramole´culaires, Universite´ Louis Pasteur, 8, alle´e Gaspard Monge, 67083 Strasbourg, France
f CEA Saclay, DSM/IRAMIS/SCM (CNRS URA 331), 91191 Gif-sur-Yvette, France
g Department of Chemical Engineering, Inha University, Incheon 402-751, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Readily-synthesised, water-stable Pd(II) complexes of azetidine-based tridentate ligands have been
studied as catalysts for the Suzuki–Miyaura coupling reaction. They are highly active for the coupling of
aryl bromides with aryl boronates and also effective for the coupling of aryl chlorides.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 12 February 2008
Received in revised form 16 May 2008
Accepted 20 May 2008
Available online 23 May 2008
1. Introduction
The palladium-catalysed Suzuki–Miyaura cross-coupling re-
action of aryl halides with arylboronic acids is one of the most
valuable methods for the synthesis of biaryl derivatives developed
over the past decades.1 The traditional Suzuki–Miyaura reaction
usually employs palladium–phosphine complex catalysts.2–5
However, many of these complexes are sensitive to both air and
moisture, and inert-atmosphere techniques are generally required
for their efficient manipulation and use. Moreover, their cost and
toxicity limit any large-scale industrial applications.6 Hence, the
development of efficient, phosphine-free catalysts is of current
interest. Water-solubility is another desirable characteristic for real
applications due to the facts that water is cheap, readily available,
nonflammable and nontoxic.7 The problem of low substrate solu-
bility in water can certainly be overcome to some extent by the use
of phase-transfer catalysts and mixed-aqueous solvent systems.8
Recently, non-phosphine Suzuki reaction catalysts involving li-
gands such as N-heterocyclic carbenes,9 some forming palladacycle
species,10 have been reported to be active in mixed-aqueous
solvents.10a,11,12 However, the activity of these systems remains too
low to be industrially viable. Herein we report the preparation of
palladium complexes containing the tridentate azetidine ligand, L1,
and some of its derivatives (Fig. 1), which are thermally stable,
Figure 1. The ligand 1-(2-aminoethyl)-3-methyl-3-(2-pyridyl)azetidine, L1, and its
derivatives discussed herein.
insensitive to oxygen and moisture and, which have proved to be
highly active catalysts for Suzuki–Miyaura reactions.
2. Experimental
2.1. Materials and equipment
All chemicals were purchased from Aldrich and used as-
received. NMR spectra were recorded in CD3OD on Varian Unity
Inova 400 (400.265 MHz) or Varian Gemini 2000 (199.976 MHz)
instruments. Elemental analysis was carried out with a Chem-
tronics TEA-3000 instrument.
2.2. Syntheses
The ligand 1-(2-aminoethyl)-3-methyl-3-(2-pyridyl)azetidine,
L1, was obtained by reaction of the bis(benzenesulfonate) of
2-methyl-2(2-pyridyl)propan-1,3-diol with 1,2-ethanediamine, as
described elsewhere.13
* Corresponding authors.
E-mail addresses: ykim@kosin.ac.kr (Y. Kim), harrowfield@isis.u-strasbg.fr (J.M.
Harrowfield), ychpark@knu.ac.kr (Y.C. Park), imlee@inha.ac.kr (I.-M. Lee).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.093

D.-H. Lee et al. / Tetrahedron 64 (2008) 7178–7182
7179
2.2.1. 1-(2-Benzylaminoethyl)-3-methyl-3-(2-pyridyl)azetidine, L2
Ligand L1 (0.5 g, 2.6 mmol) and benzaldehyde (0.28 g, 2.6 mmol)
were dissolved in absolute ethanol (100 mL) and heated at 60 ꢀC
under nitrogen for 24 h. The solvent was removed under vacuum and
the residue redissolved in methanol (100 mL) before NaBH4 (0.2 g,
5.2 mmol) was added and the mixture stirred for 12 h at room tem-
perature. HCl (2 mol Lꢁ1, 10 mL) was added to destroy any excess
borohydride, then the solvent was removed under vacuum. The
residue was dissolved in NaOH (2 mol Lꢁ1, 50 mL) and the solution
extracted with CH2Cl2 (3ꢂ50 mL). The combined extracts were
washed with water (3ꢂ50 mL), dried over Na2SO4 and the solvent
evaporated off to yield a colourless residue (0.7 g) of L2 used directly
in the preparation of its Pd(II) complex 2. Purification of the ligand
itself was most readily conducted by formation and crystallisation of
its Cu(II) complex, followed by treatment with HCl to isolate the li-
gandhydrochlorideasadeliquescent,whitesolid.1HNMR(400 MHz)
NMR (100 MHz in CD3OD)
130.2,125.1,125.0, 72.31, 71.01, 62.30, 56.40, 51.02, 42.97, 22.21 ppm.
d
164.7, 155.7, 141.8, 136.1, 131.3, 130.3,
2.2.5. Chloro{1-{2-(2-pyridylmethylamino)ethyl}-3-methyl-3-
(2-pyridyl)azetidine}palladium(II) perchlorate, [Pd(L3)Cl]ClO4, 3
Substituting ligand L3 for L2, the procedure above was repeated
to provide yellow crystals of 3, [Pd(L3)Cl]ClO4. 1H NMR (400 MHz in
CD3OD)
d
8.61 (d, J¼8.0 Hz, 1H), 8.17 (t, J¼8.0 Hz, 1H), 7.86 (d, J¼8.0
Hz,1H), 7.70 (d, J¼8.0 Hz, 2H), 7.64 (t, J¼6.0 Hz,1H), 7.48 (m, 2H), 5.00
(q, 1H), 4.46 (m, 2H), 4.19 (d, J¼15.2 Hz, 1H), 3.56 (d, J¼15.2 Hz, 1H),
3.44 (m, 2H), 3.10 (m, 2H), 2.95 (m, 1H), 1.77 (s, 3H) ppm. 13C NMR
(100 MHz in CD3OD)
d 164.8, 155.9, 154.0, 141.9, 139.9, 137.3, 132.3,
131.2,127.1,127.0, 73.41, 72.83, 62.30, 56.92, 52.14, 44.07, 22.90 ppm.
2.3. Crystallography
in 1 M DCl/D2O:
d
8.50 (d, 1H, J¼4.8 Hz), 8.11 (t, 1H, Japp¼7.9 Hz), 7.74
The data for compound 1 were collected on a Nonius Kappa-CCD
(t,1H, Japp¼7.9 Hz), 7.56 (t,1H, Japp¼6.4 Hz), 7.35, 7.33 (overlappingm,
6H), 3.85 (s, 2H, benzyl CH2), 3.69, 3.49 (dd, JAB¼13 Hz, 4H, azetidine
CH2), 3.45 (br, 4H, ethylene), 1.55 (s, 3H, methyl).
area detector diffractometer14 using graphite-monochromated Mo
Ka
radiation (l¼0.71073 Å). The crystal was introduced in a glass
capillary with a protecting ‘Paratone-N’ oil (Hampton Research)
coating. The unit cell parameters were determined from 10 frames,
2.2.2. 1-{2-(2-Pyridylmethylamino)ethyl}-3-methyl-3-(2-pyridyl)-
azetidine, L3
then refined on all data. The data (4- and u-scan) were processed
with HKL2000.15 The structure was solved by direct methods with
SHELXS-97 and subsequent Fourier-difference synthesis and
refined by full-matrix least-squares on F2 with SHELXL-97.16 Ab-
sorption effects were corrected empirically with the program
SCALEPACK.15 All non-hydrogen atoms were refined with aniso-
tropic displacement parameters. The hydrogen atoms bound to N3
were found on a Fourier-difference map and all the others were
introduced at calculated positions; all were treated as riding atoms
with a displacement parameter equal to 1.2 (NH, CH, CH2) or 1.5
(CH3) times that of the parent atom.
Ligand L1 (0.6 g, 3.1 mmol) and pyridine-2-carboxaldehyde
(0.35 g, 3.2 mmol) were reacted together following an identical
procedure to the above to give 0.81 g of crude ligand (an oil), again
used directly for preparation of the Pd(II) complex 3. Again, the li-
gand itself was most conveniently purified through formation of its
Cu(II) complex. Here, the NMR spectrum was recorded on the free
base ligand after extraction from its basic aqueous solution with
CHCl3.1HNMR(400 MHz)inCDCl3:
d8.44(unresolvedm, 2H), 7.57(t,
2H, Japp¼7.9 Hz), 7.27 (d, 1H, J¼5 Hz), 7.08 (m, 3H), 7.35, 7.33 (over-
lapping m, 6H), 3.85 (s, 2H, benzyl CH2), 3.52, 3.41 (dd, JAB¼7 Hz, 4H,
azetidine CH2), 2.61 (br, 4H, ethylene), 1.60 (s, 3H, methyl).
X-ray diffraction data for compound 2 were collected at 294(1) K
using an ADSC Quantum210 detector at Beamline 4A MXW at The
Pohang Light Source. Crystal evaluation and data collection were
2.2.3. Chloro{1-(2-aminoethyl)-3-methyl-3-(2-pyridyl)-
azetidine}palladium(II) trifluoromethanesulfonate,
[Pd(L1)Cl]CF3SO3, 1
done using
l
¼0.76999 Å radiation with
a detector-to-crystal
distance of 6.0 cm. Preliminary cell constants and an orientation
matrix were determined from 36 sets of frames collected at scan
intervals of 5ꢀ with an exposure time of 1 s per frame. The basic
scale file was prepared using the program HKL2000.15 The re-
flections were successfully indexed by the automated indexing
routine of the DENZO program.14 The 8750 reflections (see Table 1)
were harvested by collecting 72 sets of frames with 5ꢀ scans and an
exposure time of 1 s per frame. This highly redundant data set was
corrected for Lorentz and polarisation effects; negligible correc-
tions for crystal decay were also applied. The space group P21/n was
determined by the program XPREP.17 The structure was solved by
direct methods18 and refined on F2 by full-matrix least-squares
procedures.16 The hydrogen atoms were placed geometrically, with
N–H distances in 0.91 Å and C–H distances in 0.97 Å, and these
atoms were refined using a riding model.
A mixture of ligand L1 (0.30 g, 1.6 mmol) and PdCl2 (0.30 g,
1.7 mmol) in methanol (100 mL) was heated at reflux for 24 h under
nitrogen. Undissolved PdCl2 was filtered off and the filtrate taken to
dryness under vacuum to give a yellow-brown, hygroscopic solid
(0.51 g). This was dissolved in methanol (50 mL) containing excess
LiCF3SO3 and the solution allowed to slowlyevaporate to give yellow
crystals of 1, [Pd(L1)Cl]CF3SO3. Anal. Calcd for C12H17ClF3N3O3PdS:
C, 29.89; H, 3.55; N, 8.71. Found: C, 29.7; H, 3.5; N, 8.8%. 1H NMR
(400 MHz in CD3OD)
d
9.53 (d, J¼8.0 Hz, 1H), 8.14 (t, J¼8.0 Hz, 1H),
7.81 (d, J¼8.0 Hz, 1H), 7.51 (t, J¼8 Hz, 1H), 5.31 (br, 2H), 4.41 (d,
J¼10.0 Hz, 2H), 3.86 (d, J¼10.0 Hz, 2H), 3.03 (t, J¼6.0 Hz, 2H), 2.83 (m,
2H), 1.83 (s, 3H) ppm. 13C NMR (100 MHz in CD3OD)
d 164.7, 155.1,
141.7, 125.1, 124.9, 71.66, 64.71, 46.54, 43.14, 22.30 ppm.
Table 1 containssummary datarelating tothe crystalstructures and
their refinements. Full details have been depositedwith the Cambridge
Crystallographic Data Base under deposition numbers 669731 and
669732 and can be obtained through deposit@ccdc.cam.ac.uk.
2.2.4. Chloro{1-(2-benzylaminoethyl)-3-methyl-3-(2-pyridyl)-
azetidine}palladium(II) perchlorate, [Pd(L2)Cl]ClO4, 2
A mixture of crude ligand L2 (0.70 g, 2.5 mmol) and PdCl2 (0.50 g,
2.8 mmol) in methanol (100 mL) was heated at reflux for 24 h under
nitrogen. Undissolved PdCl2 was filtered off and the filtrate taken to
dryness under vacuum to give a yellow, hygroscopic solid (0.80 g).
This was dissolved in methanol (50 mL) and mixed with methanolic
NaClO4 to provide yellow crystals of 2, [Pd(L2)Cl]ClO4. Anal. Calcd
for C18H23Cl2N3O4Pd: C, 41.36; H, 4.44; N, 8.04. Found: C, 40.9; H,
2.4. General procedure for the conduct of Suzuki coupling
Reactions were carried out in a glass ampoule equipped with
a Teflon screw cap. Aryl halide (1.0 mmol), phenylboronic acid
(1.1 mmol), Na2CO3 (2.0 mmol), TBAB(1.0 mmol) and n-dodecane
(15–20 mg) as an internal GC standard were dispersed in H2O
(3 mL) and then a solution of the catalyst, e.g., 1, [Pd(L1)Cl]CF3SO3,
4.5; N, 8.1%.1H NMR(400 MHzin CD3OD)
d
9.64 (d, J¼7.2 Hz,1H), 8.14
(t, J¼8.0 Hz,1H), 7.79 (d, J¼8.0 Hz,1H), 7.62 (d, J¼8.8 Hz, 2H), 7.52 (t,
J¼6.4 Hz, 1H), 7.46 (m, 3H), 4.60 (q, 1H), 4.38 (d, J¼13.6 Hz, 1H), 4.23
(d, J¼13.6 Hz, 1H), 4.04 (q, 1H), 3.78 (d, J¼9.2 Hz, 1H), 3.64 (d, J¼9.2
in H2O (1.0 m
mol mLꢁ1) was added to the mixture. The resulting
mixture was stirred at the appropriate temperature (see Tables 2
and 3). Samples were withdrawn periodically and analysed by
Hz,1H), 3.11 (m,1H), 2.87 (m, 2H), 2.56 (m,1H),1.78 (s, 3H) ppm; 13
C

7180
D.-H. Lee et al. / Tetrahedron 64 (2008) 7178–7182
Table 1
Crystal and refinement data
combined filtrates was separated and dried over MgSO4, and the
solvent was evaporated under reduced pressure. The product was
isolated by column chromatography on silica gel.
Compound
Chemical formula
M/g molꢁ1
Crystal system
Space group
a/Å
[Pd(L1)Cl]CF3SO3
C12H17ClF3N3O3PdS
482.20
Orthorhombic
Pbca
16.2206(6)
10.0931(4)
20.4040(7)
[Pd(L2)Cl]ClO4
C18H23Cl2N3O4Pd
522.69
Monoclinic
P21/c
11.491(2)
13.081(3)
13.646(3)
3. Results and discussion
The complexes 1, [Pd(L1)Cl]CF3SO3, 2, [Pd(L2)Cl]ClO4 and 3,
[Pd(L3)Cl]ClO4, are all easily prepared from the reactions of PdCl2
with the free ligand in methanol, followed by precipitation with an
appropriate poorly-coordinating anion, the limiting factor probably
being the slow rate of dissolution of polymeric PdCl2 in the solvent.
They are all, even the perchlorate 2, thermally stable to at least
90 ꢀC and do not appear to be sensitive to either oxygen or water.
The crystal structure determinations on the complexes 1 and 2
confirm both the expected nature of the ligands (Fig. 2) and the
expected square planar geometry of the PdN3Cl units (Table 1). In
both cases, the ligand adopts a chiral conformation and the
complex ion units are devoid of symmetry but centrosymmetric
enantiomer pairs can be identified in the lattices. In complex 2, the
benzyl substituent is axially disposed on the five-membered che-
late ring and the complicated but well-resolved 1H NMR spectrum
obtained when the complex is dissolved in CD3OD is consistent
with retention of this configuration in solution. Lattice interactions
are different in the two systems and may be significant in indicating
reasons for the differences in catalytic activity of the two com-
plexes, though the exact nature of the catalytically active species
has not been established. In complex 1, the centrosymmetric cation
pairs observed in the lattice are linked by reciprocal NH/Cl
interactions (N/Cl 3.449(3) Å), which involve the axial NH atoms
of the terminal amino group of the ligand, the equatorial NH atoms
being involved in hydrogen bonds to triflate-O (N/O 2.995(4) Å).
Interestingly, the coordinated chlorine atoms are only marginally
more distant (Cl/C 3.454(3) Å) from methyl carbon atoms in ad-
jacent, homochiral cations than from N of enantiomeric species. In
complex 2, the axial hydrogen of the terminal amino of 1 has been
replaced by the benzyl unit but the equatorial NH retains its ability
to interact with O, this time from perchlorate (N/O 3.052(4) Å).
Centrosymmetric cation pairs may still be identified but here they
are associated with Cl/C(aromatic) contacts w3.6 Å. As there are
no contacts indicative of significant axial coordination to Pd(II) in
either structure, these coordinated-Cl contacts may be indicative of
primary interactions of the complexes with reaction substrates,
which initiate formation of catalytic intermediates.
b/Å
c/Å
ꢀ
ꢀ
a
/
b/
93.06(3)
ꢀ
g
/
V/Å3
3340.5(2)
8
1.918
2048.3(7)
4
1.695
Z
Dcalcd/g cmꢁ3
m
/mmꢁ1
1.444 (Mo K
1920
a
)
1.196 (
1056
l 0.77 Å)
F(000)
T/K
Reflections collected
Independent reflections
‘Observed’ reflections (I>2
Rint
Parameters refined
R1
100(2)
57,088
3170
2801
0.017
293(2)
8533
4741
4480
0.055
255
0.051
0.141
1.023
ꢁ1.24
1.82
s
(I))
218
0.025
0.063
1.292
ꢁ0.61
0.83
wR2
S
Drmin/e Åꢁ3
Drmax/e Åꢁ3
Table 2
Geometry of the primary coordination spheres in complexes
[Pd(L1)Cl]CF3SO3
[Pd(L2)Cl]ClO4
Distance/Å
Pd–Cl1
Pd–N1
Pd–N2
Pd–N3
Angle/ꢀ
Cl1–Pd–N1
N1–Pd–N2
N2–Pd–N3
N3–Pd–Cl1
2.3093(8)
2.079(3)
2.020(3)
2.020(3)
2.3007(8)
2.032(2)
2.031(2)
2.061(2)
96.78(8)
90.15(10)
84.06(11)
89.03(8)
89.30(7)
84.52(9)
90.07(9)
96.18(7)
Table 3
Suzuki–Miyaura coupling of bromobenzene with phenylboronic acida
Catalyst , H2O
Br
B(OH)2
+
Na2CO3, TBAB
To characterise a reference reaction, initial studies were made of
the coupling of bromobenzene and phenylboronic acid with
0.01 mol % of 2 as catalyst in the presence of Na2CO3 and tetrabu-
tylammonium bromide (TBAB) (see Table 3). The reaction pro-
ceeded to completion at 70 ꢀC within 1 h (entry 1). When the
catalyst loading was decreased to 0.001 mol %, high conversion was
still achieved (entries 3). Indeed, the reaction remained efficient
even when using a much lower catalytic loading of 0.0005%, for
which an ultra-high TOF of 592,000 hꢁ1 was obtained (entry 4).
Further optimisation of the reaction conditions was not attempted.
Catalyst 2 still showed outstanding performance at lower temper-
atures of 25–50 ꢀC (entry 5–8), its activity at 25 ꢀC (entry 8) being
particularly noteworthy. In the absence of TBAB, the reaction was
inefficient, giving only 28% yield (entry 13). The poor dispersion of
the hydrophobic substrate in water in the absence of a surfactant
might be the reason. Various roles for TBAB, including possibly
stabilisation of a species [R4N]þ[ArB(OH)3]ꢁ may in fact be antici-
pated. Improved dispersion of the organic substrates in the water
would result effectively in increased concentrations of reactants
and the formation of a complex between the boronic acid and the
ammonium salt would favour Suzuki coupling over hydro-
deboronation.19 The catalyst was found to be very stable to oxygen
and moisture, only very minor changes in its activity being
Entry
Catalyst (mol %)
Temperature (ꢀC)
Time (h)
Yieldc (%)
1
2
3
4
5
6
7
8
2 (0.01)
2 (0.005)
2 (0.001)
2 (0.0005)
2 (0.01)
2 (0.01)
2 (0.01)
2 (0.1)
3 (0.01)
3 (0.01)
1 (0.01)
1 (0.01)
2 (0.01)
70
70
70
70
50
40
25
25
70
40
70
40
70
1
1.5
5
24
2
5
24
10
1
5
1.5
98
97
90
71
93 (90)
95 (90)
41
92 (90)
91
9
10
11
12
13b
86
92
72
43
5
3
a
Molar ratio: bromobenzene (1.0 mmol), phenylboronic acid (1.1 mmol), Pd
complex (0.1–0.0005 mol %), TBAB(1.0 mmol) and Na2CO3 (2.0 mmol).
b
without TBAB.
c
GC yield determined using n-dodecane as an internal standard and based on the
amount of bromobenzene employed. Isolated yield is given in parenthesis.
GC/GC–MS. GC yields are based on the amount of aryl halide
employed. The reaction mixture was filtered and the filter washed
with H2O and Et2O several times. The organic phase in the

D.-H. Lee et al. / Tetrahedron 64 (2008) 7178–7182
7181
Figure 2. Cations present in the lattices of [Pd(L1)Cl]CF3SO3,1, and [Pd(L2)Cl]ClO4, 2.
observed on exposure of the system to air and water during the
Suzuki reaction. Functionalisation of the ligand has significant ef-
fects on the catalyst activity, the complexes 1 and 3 giving yields of
71 and 81% at 40 ꢀC, respectively. The complex 1, lacking a sub-
stituent on the terminal amino group, seems generally a slightly
inferior catalyst to 2 and 3, perhaps reflecting the greater ability of
a secondary N-donor to enhance electron density on Pd and thus to
facilitate intermediate oxidative addition steps. The additional
(pyridine-N) coordinating centre in 3 may have some influence,
though, as for the benzyl group in 2, it is possible that the influence
of the pendent arms is due to agostic CH/Pd interactions.
To further extend the scope of our Pd catalytic system, we next
investigated the coupling of various aryl halides with phenyl-
boronic acid. As shown in Table 4, high catalytic activity was
observed in the coupling of deactivated aryl bromides such as 2-
bromoanisole, 4-bromoanisole, 2-bromo-toluene, 4-bromotoluene
and 4-bromo phenol (entries 2–6) as well as activated 1-bromo-4-
nitro benzene (entry 1). Regardless of the substituents, all of the
aryl bromides were rapidly coupled in the presence of 1. A catalyst
loading of 0.01 mol % was sufficient to achieve high TOFs. Deacti-
vated aryl bromides possessing electron-donating groups showed
a slight drop in reactivity compared to those with electron-
withdrawing groups. However, all of the reactions were complete
at 50 ꢀC in less than 3 h. Encouraged by these results, we in-
vestigated the coupling of several aryl chlorides (entries 7–19). It is
well known that C–Cl is much less reactive than C–Br. Catalyst 1
showed outstanding performance at low temperatures of 50–90 ꢀC
(entries 7–13). The coupling of chlorobenzene at 50 ꢀC in the
presence of 1 mol % of 1 proceeded rapidly, giving 91% yield in 6 h,
although when the loading was decreased to 0.01 mol %, only 39%
yield was obtained in 24 h under otherwise identical conditions
(entry 7). Activated 1-chloro-4-nitrobenzene was coupled almost
quantitatively in 5 h at 90 ꢀC with 0.1 mol % catalyst (entry 14) but
this high temperature was necessary to reach satisfactory conver-
sion. Attempts to couple deactivated aryl chlorides were successful
to some extent. The reactions of 2-chloroanisole, 4-chloroanisole
and 4-chlorotoluene with phenylboronic acid proceeded smoothly
but required more extended reaction times to afford the same high
yields. Homocoupling products such as biphenyl were observed in
the reactions with 2-chloroanisole (entry 15) and 2-chlorotoluene
(entry 17) but a higher catalyst loading depressed the formation of
this byproduct (entry 18).
4. Conclusion
Table 4
Suzuki coupling of various aryl halides with arylboronic acida
New palladium(II) complexes containing functionalised pyridyl-
azetidine ligands can be used as highly efficient catalysts for Suzuki
coupling reactions in aqueous dispersions. Various aryl bromides
undergo coupling with phenylboronic acid under particularly mild
conditions and the catalyst system is also effective for the reactions
of aryl chlorides. Further studies of other coupling reactions
catalysed by this system are currently in progress.
Entry
Substrate
Temperature
(ꢀC)
2
Time
(h)
Yieldb
(%)
(mol %)
1
2
3
4
5
6
7
8
1-Bromo-4-nitrobenzene
2-Bromo-anisole
4-Bromo-anisole
2-Bromo-toluene
4-Bromo-toluene
4-Bromo-phenol
Chlorobenzene
Chlorobenzene
Chlorobenzene
Chlorobenzene
Chlorobenzene
50
50
50
50
50
50
50
50
50
70
70
90
90
90
90
90
90
90
90
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.1
1
0.1
1
0.01
0.1
0.1
0.1
0.1
0.1
1
0.1
2
3
3
3
3
99
94
93
92
93
91
39
83
91
3
24
12
6
10
5
18
6
5
10
8
10
5
Acknowledgements
9
This work was supported by Brain Korea 21 program. We
gratefully acknowledge the support of the beamline 4A MXW of
Pohang Light Source, Korea, for the diffraction and computing
facilities.
10
11
12
13
14
15
16
17
18
19
93
96
87
Chlorobenzene
Chlorobenzene
95 (92)
96
1-Chloro-4-nitrobenzene
2-Chloro-anisol
4-Chloro-anisol
2-Chloro-toluene
2-Chloro-toluene
4-Chloro-toluene
80/7c
93
References and notes
75/8c
90
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91
Catalyst 2, H2O
+
B(OH)2
X
Na2CO3, TBAB
R
R
a
Molar ratio: aryl halide (1.0 mmol), phenylboronic acid (1.1 mmol), Pd complex
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