Zwitterionic palladium complexes: Room-temperature Suzuki-Miyaura cross-coupling of sterically hindered substrates in an aqueous medium

Article abstract of DOI:10.1021/om500834y

A series of new imidazolium chlorides were straightforwardly prepared from the reactions between chloroacetone and imidazole derivatives. Deprotonation of the methylene proton next to the ketone group in these salts by pyridine led to the formation of a monodentate ligand that coordinated to palladium, readily forming zwitterionic anionic palladium pyridine complexes bearing a formal positive charge on the ligand ancillary. The pyridine ligand in the zwitterionic complexes can be facilely replaced by phosphine ligands. Seven of these new complexes were successfully characterized by X-ray crystallography. The zwitterionic phosphine complexes were highly efficient in catalyzing room-temperature Suzuki-Miyaura reactions between sterically hindered aryl chlorides and arylboronic acids in an aqueous medium.

Full text of DOI:10.1021/om500834y

Article
pubs.acs.org/Organometallics
Zwitterionic Palladium Complexes: Room-Temperature Suzuki−
Miyaura Cross-Coupling of Sterically Hindered Substrates in an
Aqueous Medium
Jhen-Yi Lee, Dabalina Ghosh, Jing-Yi Lee, Shih-Sheng Wu, Ching-Han Hu, Shuang-De Liu,
and Hon Man Lee*
Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan, Republic of China
S
* Supporting Information
ABSTRACT: A series of new imidazolium chlorides were
straightforwardly prepared from the reactions between
chloroacetone and imidazole derivatives. Deprotonation of
the methylene proton next to the ketone group in these salts
by pyridine led to the formation of a monodentate ligand that
coordinated to palladium, readily forming zwitterionic anionic
palladium pyridine complexes bearing a formal positive charge
on the ligand ancillary. The pyridine ligand in the zwitterionic
complexes can be facilely replaced by phosphine ligands. Seven
of these new complexes were successfully characterized by X-
ray crystallography. The zwitterionic phosphine complexes
were highly efficient in catalyzing room-temperature Suzuki−
Miyaura reactions between sterically hindered aryl chlorides and arylboronic acids in an aqueous medium.
rings. Herein we found that a simple ketone group could be
employed and indeed monodentate zwitterionic anionic
palladium complexes could be achieved readily. Since the
metal centers of the new complexes may have significant
negative charge, which is a crucial factor for activation of
carbon−halide bonds in C−C coupling reactions, we
envisioned the possibility of utilizing the new complexes in
Suzuki−Miyaura cross-coupling of aryl chlorides. Although
catalyst systems have been developed for the use of readily
available and low cost aryl chlorides in the cross-coupling
reactions,19−22 the use of sterically hindered substrates at room
temperature remains one of the challenges in this field.23 To
our delight, a new complex reported herein could be employed
as a precatalyst to address this problem in an aqueous medium.
INTRODUCTION
■
Zwitterionic metal complexes that exhibit formal charge
separation within an overall neutral molecular framework are
currently attracting interest.1,2 Over the past few years, a wide
scope of zwitterionic cationic metal complexes, in particular
those of the platinum-group metals (PGM),1 have been
reported and some of them exhibited promising catalytic
properties.3−8 In contrast, zwitterionic complexes with reverse
polarity, that is complexes with formal negative charges on the
metal centers and positive charges on the ancillary ligands,2 are
less common and well-documented examples were mostly
derived from phosphonium ylides or conjugated equiva-
lents.9,10· Zwitterionic metalate derived from ammonium,11−13
iminium,14,15 and sulfonium16 ancillaries are also known.
Recently, we have reported a unique class of zwitterionic
anionic palladium complexes derived from imidazole derivatives
(Chart 1).17,18 These complexes, including palladalactams and
CC-type palladacycles, can be classified as “mesoionic” or “truly
zwitterionic”, since no nonzwitterionic connected Lewis
structure can be drawn by resonance of the π electrons.2
They were essentially formed by deprotonation of the
methylene protons between the imidazole ring and the CO
group of the ligands. Since in those complexes the ligand also
contained PhNCO functionalities, the formation of chelate
rings due to C−H or N−H activation occurred as well. To
further our exploration on the chemical properties of this type
of complexes, we hoped to understand if the amido
functionality was mandatory or if it could be replaced by
other functional groups, thus avoiding the formation of chelate
RESULTS AND DISCUSSION
■
Design and Synthesis of Ligand Precursors. Scheme 1
shows the target imidazolium salts 1a−f, which are the ligand
precursors for the preparation of zwitterionic palladium
complexes. Since an unsubstituted imidazolium salt at the C2
position of the imidazole ring contains an acidic NCHN proton
which can be deprotonated easily to form NHC com-
plexes,19,24−33 we chose to block the C2 position with methyl
(1a−c) and aryl groups (1d−f). In addition, in order to
understand the electronic effect of the ligands on the palladium
centers which could be important to their subsequent catalytic
Received: August 18, 2014
© XXXX American Chemical Society
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Chart 1. Zwitterionic Anionic Palladium Complexes Derived from Imidazole Derivatives
Scheme 1. Synthesis of Ligand Precursors 1a−f
Scheme 2. Synthesis of Zwitterionic Palladium Complexes 2a−g
performance, the two sets of ligand precursors consist of
electron-neutral benzyl, electron-withdrawing 4-fluorobenzyl,
and electron-donating 3-methoxybenzyl groups on the
imidazolium rings. These salts were straightforwardly prepared
by quaternization reactions between chloroacetone and the
appropriate imidazole derivatives in THF. They precipitated
out as white solids with 56−92% yields. Most of these salts are
hygroscopic. In general, the methyl and methylene proton
signals in 1a−c resonate at slightly lower field than those in
1d−f. For 1a−c, the proton signals for the ketone methyl
groups were observed at ca. 2.25 ppm, whereas those in 1d−f
appeared at ca. 2.14 ppm. The methyl protons on the
imidazolium rings in 1a−c were observed at ca. 2.51 ppm.
For 1a−c, the methylene group next to the ketone group
resonates at ca. 5.84 ppm, whereas that attached to the aryl ring
was observed at a higher field at ca. 5.37 ppm. For 1d−f, these
B
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Scheme 3. Synthesis of Zwitterionic Palladium Complexes 3a−g
Scheme 4. Resonance Structures in 2a−c
Scheme 5. Resonance Structures in 2d−f
1
two sets of signals appeared at more upfield positions of ca.
5.46 and 5.25 ppm, respectively. The assignment of these
signals was confirmed by the acquisition of an representative
HMBC spectrum of 1a (see the Supporting Information).
Synthesis of Zwitterionic Palladium Complexes. Since
palladium NHC complexes with 3-chloropyridine as ligand, the
so-called PEPPSI-type complexes, have been proven to be
versatile in various cross-coupling reactions,34−38 we targeted
the preparation of new zwitterionic palladium complexes
mimicking the PEPPSI skeleton. The new zwitterionic
palladium complexes 2a−g were successfully prepared by the
complexation reactions among the ligand precursors, pyridine
and 3-chloropyridine, and PdCl2 using K2CO3 as base in DMF
at ambient temperature (Scheme 2). The complexation
conditions afforded the new complexes in decent to good
yields (56−90%). Desirably, these new complexes have high
stability in air and on dissolution. The H and 13C NMR
spectra of all the complexes display characteristic signals for the
pyridine ligands. For 2a−c, the successful complexation was
confirmed by the presence of methine protons at ca. 6.20 ppm,
which were downfield from the original methylene signals at ca.
5.84 ppm in the ligand precursors. For 2d−f, the methine
signals appeared at ca. 5.89 ppm, which were also slightly
downfield in comparison to the corresponding protons in the
ligand precursors (ca. 5.46 ppm). We also prepared 2g, in
which the pyridine ligand in 2e was replaced by 3-
chloropyridine. The NMR data of this pair were very similar.
Since a phosphine ligand can enhance the electron density on
the metal centers, allowing the activation of unreactive bonds
via oxidative addition,27,39 we also interested in replacing the
pyridine ligands in 2a−f with PPh3 or PCy3. The substitution
reactions were successfully carried out by stirring a dichloro-
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a
Scheme 6. Potential Palladium Complexes Formed from the Ligand Precursor 1a
a
Potential deprotonation sites are marked with asterisks. The relative free energies of complexes are listed (in units of kcal/mol).
Figure 1. Molecular structures of 2a (left) and 2d (right) with 50% probability ellipsoids for non-H atoms. H atoms, except for that on C1, are
omitted for clarity.
methane solution containing the respective compound and free
phosphine at room temperature. The new complexes 3a−f
were also stable in air (Scheme 3). However, as indicated by 1H
NMR spectroscopy, decomposition commenced when sol-
utions containing the compounds were exposed to air. For 3a−
c, the 31P NMR signals were observed at ca. 32.3 ppm and
those signals in 3d−c were slightly more upfield at ca. 30.6
ppm. The NMR signals for the methine carbons appeared as
singlets in 3a−f, reflecting the cis geometry of these complexes.
The methine proton signals in the phosphine complexes were
observed at positions much more upfield, in contrast with those
in the pyridine complexes 2a−f (∼4.15 ppm in 3a−c vs ∼6.20
ppm in 2a−c; ∼4.07 ppm in 3d−f vs ∼5.89 ppm in 2d−f). The
phosphine and the methine signals for the PCy3 complex 3g
were observed at 39.3 and 4.48 ppm, respectively, which were
downfield from those of the PPh3 analogue 3e at 30.6 and 4.06
ppm. The small JCP coupling constant of 25.6 Hz for the
doublet signal of the coordinated methine carbon also implies a
2
cis geometry of ligands in 3g.
The fact that the NMR signals in palladium complexes
derived from 1d−f were generally upfield in comparison with
those derived from 1a−c is attributable to the greater
delocalization of the positive charge in the latter set of
complexes, resulting in less reduced electron density on the
complexes (see Schemes 4 and 5).
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Figure 2. Molecular structures of 2f (left) and 2g (right) with 50% probability ellipsoids for non-H atoms. H atoms, except for that on C1, are
omitted for clarity.
Figure 3. Molecular structures of 3d (left), 3e (middle), and 3f (right) with 50% probability ellipsoids for non-H atoms. Hydrogen atoms, except for
that on C1, are omitted for clarity.
It should be noted that there are other protons in the ligand
precursor 1a which could undergo deprotonation. Complexes
A1 and A2 are abnormal NHC complexes formed from the
deprotonation of the CH protons on the heterocyclic ring
(Scheme 6). Relevant palladium abnormal carbene complexes
have reported by others and us.40−43 Complex B is a palladium
complex formed by the deprotonation of the methyl group on
the ligand precursor. Such kinds of complexes are also known
in the literature.44 Since the methylene proton in 1a is the most
acidic proton, it is obvious that 2a should be formed easily. In
fact, in the preparation of 2a, the zwittterion and the side
product trans-PdCl2(py)2 were formed exclusively even after
prolonged heating at 80 °C overnight, indicating that 2a is
either kinetically stable or is indeed the thermodynamic
product. To address this issue, a DFT calculation was
performed to understand the relative stabilities of the different
types of complexes. Our data shows that, in the gas phase, B is
slightly lower in energy than 2a, while in THF and in water 2a
is indeed the thermodynamically most stable species.
Molecular Structures. The pyridine complexes 2a,d,f,g
and the phosphine complexes 3d−f have been established by X-
ray diffraction studies (Figures 1−3). Selected bond distances
and angles are given in Tables 1 and 2. The crystallographic
studies confirmed the trans and cis geometries of the pyridine
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Table 1. Selected Bond Distances (Å) and Angles (deg) around Pd in 2
2a
2d
2f
2g
Pd1−C1
Pd1−N3
Pd1−Cl1
Pd1−Cl2
2.051(3)
2.038(4)
2.040(5)
2.049(5)
2.165(3)
2.108(4)
2.114(4)
2.095(4)
2.3034(11)
2.3145(11)
2.3082(12)
2.2968(12)
2.3167(14)
2.3120(14)
2.3055(17)
2.3305(16)
C1−Pd1−Cl1
C1−Pd1−Cl2
N3−Pd−Cl1
N3−Pd−Cl2
C1−Pd−N3
Cl1−Pd−Cl2
90.85(10)
86.08(10)
91.65(9)
87.74(12)
92.15(12)
90.45(10)
89.67(10)
177.83(14)
179.35(4)
86.83(15)
92.44(15)
90.24(12)
90.49(12)
176.48(17)
179.22(5)
93.94(17)
88.46(17)
89.66(14)
88.93(14)
176.2(2)
91.45(9)
174.47(13)
176.90(4)
178.58(6)
Table 2. Selected Bond Distances (Å) and Angles (deg)
around Pd in 3
Table 3. Catalyst Screening for Room-Temperature Suzuki−
a
Miyaura Coupling
3d
3e
3f
Pd1−C1
Pd1−P1
Pd1−Cl1
Pd1−Cl2
2.094(6)
2.103(5)
2.097(5)
2.2370(16)
2.3531(16)
2.3480(14)
2.2359(16)
2.3687(15)
2.3476(17)
2.2515(13)
2.3869(13)
2.3530(13)
entry
cat.
yield (%)
entry
cat.
yield (%)
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
13
5
8
3a
3b
3c
3d
3e
3f
39
40
9
C1−Pd1−Cl1
C1−Pd1−Cl2
P1−Pd1−Cl1
P1−Pd1−Cl2
C1−Pd1−P1
Cl2−Pd1−Cl1
89.60(16)
178.14(17)
176.51(5)
93.02(6)
91.77(16)
177.77(15)
178.46(6)
92.79(6)
89.86(13)
179.00(13)
179.45(5)
90.95(5)
6
10
11
12
13
14
56
6
68
16
5
78
66
87.51(16)
89.94(5)
87.19(16)
88.28(6)
89.90(13)
89.29(5)
2g
11
3g
>99
a
Reaction conditions: phenylboronic acid (0.6 mmol), bromoanisole
(0.5 mmol), 1,4-dixoxane/H2O (4/1, 2.0 mL), 2.5 mol % of Pd cat.,
GC yield.
and phosphine complexes, respectively. The palladium centers
in all of the structures adopt a slightly distorted coordination
geometry. The most important features are the shorter Pd−C
distances in the pyridine complexes in comparison with those
in the phosphine complexes. The Pd−C distance in the
pyridine complexes varies in the range 2.03−2.06 Å, whereas
that in the phosphine complex is in the range 2.09−2.11 Å. All
of these Pd−C distances are long in comparison with the usual
bond lengths in palladium complexes with normal and
abnormal NHC ligands, which are typically below 2.0 Å.40,45
Also notably, the Pd−N distance of 2.165(3) Å in 2a, which
contains a methyl group on the imidazole ring, is significantly
longer than those in the other pyridine complexes featuring
phenyl groups on the heterocyclic rings (2.09−2.12 Å),
reflecting a greater trans influence exerted by the ligand
derived from 1d−f. The Pd−N distance of 2.095(4) Å in 2g,
featuring 3-chloropyridine as ligand, is comparable to those in
palladium NHC complexes with the same pyridine li-
gand.35,37,46,47
Catalysis. Most of the Suzuki−Miyaura cross-coupling were
conducted in organic solvents. Recently, efforts have been made
to perform the reaction in green solvents under mild
conditions.48−52 Because of the zwitterionic nature of the
new palladium complexes, we envisioned that the new
zwitterionic palladium complexes may catalyze the cross-
coupling in an aqueous medium. Initially, the coupling between
4-bromoanisole and phenylboronic acid was chosen as the
benchmark reaction (Table 3). The reaction was carried out at
room temperature in a 1,4-dioxane/water mixture (4/1) for 12
h, employing 2.5 mol % of palladium precatalyst. Pleasingly, the
new complexes can deliver coupling activities and the
phosphine complexes prevail over the pyridine complexes in
catalyzing the reaction. Among the phosphine complexes
screened, 3g afforded the best yield of quantitative formation
of 4-methyoxylbiphenyl (entry 14). The optimal ligand
structure is derived from ligand precursor 1e, bearing a phenyl
group attached to the imidazolyl ring and an electron-releasing
N-3-methoxybenzyl group.
Having the most active precatalyst 3g in hand, the solvent
and base were then optimized, employing the coupling between
phenylboronic acid and 4-chloroacetophenone as the bench-
mark reaction (Table 4). Entries 1−3 show that the reaction
did not proceed well when the reaction was conducted in
toluene, 1,4-dioxane, or water. Toluene/water and THF/water
solvent mixtures also did not work. Surprisingly, the reaction
went smoothly, delivering a quantitative yield of product, when
1,4-dioxane/H2O (4/1) was used as the solvent (entry 6). The
use of KOH as base was preferred to NaOH, KOtBu, and
K3PO4, producing the optimal yield (entry 6 vs entries 7−9).
On application of the commonly used combinations of bases
and solvents in the literature, Cs2CO3/1,4-dioxane53,54 (entry
10) and K3PO4/toluene55−57 (entry 11) produced inferior
yields.
Then the substrate scope was investigated (Table 5).
Complex 3g allows a wide range of aryl chlorides and
arylboronic acids with different electronic and steric properties
to be employed as substrates. It was highly effective in
catalyzing the coupling reaction with electron-poor substrates,
such as 4-chloroacetophenone, 4-chlorobenzonitrile, and 4-
chlorobenzaldehyde, affording yields of over 90% in 2−7 h
(entries 1, 2, and 5). The electron-rich substrate 4-
chloroanisole was also successfully utilized, affording an 80%
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a
Table 4. Optimization of Reaction Conditions
Table 5. Substrate Scope of Room-Temperature Suzuki−
a
Miyaura Coupling Reactions
entry
base
solvent
yield (%)
1
KOH
toluene
6
15
11
5
2
KOH
1,4-dioxane
3
KOH
H2O
4
KOH
toluene/H2O (4/1)
THF/H2O (4/1)
1,4-dioxane/H2O (4/1)
1,4-dioxane/H2O (4/1)
1,4-dioxane/H2O (4/1)
1,4-dioxane/H2O (4/1)
1,4-dioxane
5
KOH
4
6
KOH
>99
90
17
57
12
21
7
NaOH
KOt-Bu
K3PO4
Cs2CO3
K3PO4
8
9
10
11
toluene
a
Reaction conditions: phenylboronic acid (0.6 mmol), 4-chloroaceto-
pheone (0.5 mmol), base (2.0 equiv), solvent (2.0 mL), 3g (2.0 mol
%), GC yield.
yield of product (entry 3). The coupling reaction between
phenylboronic acid and chlorobenzene, however, gave a
somewhat low 33% yield (entry 6). Arylboronic acids featuring
different functional groups were tolerated (entries 7−20). The
catalyst system allowed the use of both ortho-substituted aryl
chlorides (entries 7, 8, 13, and 16−18) and arylboronic acids
(entries 7, 8, 12, and 19) as coupling partners. Markedly,
diortho-substituted compounds could also be successfully
utilized (entries 9−12). For example, the di-ortho-substituted
2-chloro-m-xylene could react with the ortho-substituted 2-
methoxylphenylboronic acid, affording a 69% yield of product
(entry 12). Since the coupling reaction takes place in an
aqueous medium, the use of unprotected 4-hydroxyphenylbor-
onic acid was well tolerated, leading to the formation of
coupled product with 2,6-dimethylchlorobenzene in a decent
65% yield (entry 10). The catalyst system is also applicable for
coupling partners featuring heterocyclic aromatic (entries 4, 14,
and 16) or anthracenyl rings (entries 14 and 15). Double
arylation of the challenging substrate 1,4-dichlorobenzene also
occurred readily, affording good yields of triaryl products
(entries 19 and 20).
Finally the catalytic performance of 3g was compared with
that of the well-known PdCl2(IPr)(3-chloropyridine)37 (4)
(Table 6). In Table 4, entry 3 (vide supra), we showed that a
poor 11% yield of coupled product was produced using 3g as
catalyst in the coupling reaction between phenylboronic acid
and 4-chloroacetophenone in water. In contrast, a good yield of
76% was formed when the bromo analogue was employed
(entry 1). The yield was much superior to that obtained by 4
(entry 2). The activity of 3g was slightly inferior to that of 4 in
the coupling reaction between 4-chloroanisole and phenyl-
boronic acid (entry 3 vs entry 4). In contrast, 3g gave a better
yield in the reaction with sterically hindered substrates (entry 5
vs entry 6).
Electrospray Mass Spectrometry (ES-MS). To under-
stand the properties of the new complexes in solvent, ES-MS
was performed, taking 2e and 3g as representative examples.
ES-MS is based on a soft ionization technique which allows the
smooth transfer of ions from solution to the gas phase with
little fragmentation, and therefore it is ideal for the observation
of short-lived molecular ions.58 For the pyridine complex 2e,
the major metal-containing positive ion was observed at m/z
a
Reaction conditions: phenyl- or arylboronic acid (0.6 mmol), aryl
chloride (0.5 mmol), KOH (2.0 equiv), 1,4-dixoxane/H2O (4/1, 2.0
b
c
mL), 3g (2.0 mol %), isolated yield. GC yield. Reaction conditions:
phenyl- or arylboronic acid (1.2 mmol), KOH (4.0 equiv), 1,4-
dixoxane/H2O (4/1, 3.0 mL).
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a
Table 6. Suzuki−Miyaura Coupling Reaction Catalyzed by 3g and 4
a
Reaction conditions: phenyl- or arylboronic acid (0.6 mmol), aryl halide (0.5 mmol), KOH (2.0 equiv), 1,4-dixoxane/H2O (4/1, (2.0 mL), 3g or 4
b
c
(2.0 mol %). GC yield. Isolated yield.
Figure 4. Major metal-containing positive ions observed in (a) 2e and (b) 3g by ES-MS.
462.8, corresponding to a two-coordinate [PdLCl]+ species
(Figure 4). The observed isotopic pattern matched well with
that of theoretical calculations. In contrast, for the phosphine
complex 3g, where there may not be sufficient energy for PCy3
to dissociate, a three-coordinate [PdL(PCy3)Cl]+ was detected
at m/z 741.1 as the base peak. Thus, the ES-MS data were in
accord with a proposition that, at room temperature, 3 could
generate a L(PR3)Pd0 active species that was electron-rich for
the activation of C−Cl bonds. In contrast, in the case of 2, an
electron-poor LPd0 species was likely involved, leading to its
poor coupling activities. It should be noted that the base peak
observed in the spectra of 2e was due to L+. In contrast, the
base peak in the spectrum of 3g corresponds to the three-
coordinate species. The high stability of this unsaturated species
could also be attributed to the high effectiveness of 3g in
Suzuki−Miyaura cross-coupling among all the precatalysts
tested.
X-ray Photoelectron Spectroscopy (XPS). We also
probed the electron-donating properties of ligands in 3g by
XPS. The binding energies of Pd electrons in the core 3d3/2 and
the 3d5/2 orbitals were found to be 341.8 and 336.4 eV,
respectively. For comparison, the corresponding binding
energies in a Pd(II) complex with a bidentate carbene with
abnormal binding are much higher at ca. 348.0 and 342.6 eV.59
We also reported a series of robust and electron-rich cis-Pd(II)
complexes having phosphine and carbene ligands with higher
binding energies of ca. 343 and 337 eV.53 In fact, the binding
energies in 3g are close to those of 340.5 and 335.1 eV in
Pd(0).60 These exceptionally low binding energies indicate that
the Pd(II) center in the 3g is highly electron rich due to the
electron-donating nature of the ligands.
CONCLUSIONS
■
We have successfully prepared a series of new imidazole
derivatives which could be employed to prepare zwitterionic
anionic palladium complexes. The zwitterion with PCy3 was
robust and highly electron rich, thus delivering efficient
activities in room-temperature Suzuki−Miyaura cross-coupling
conducted in a 1,4-dioxane/water mixture as solvent. Sterically
hindered aryl chlorides and arylboronic acids were effectively
utilized as substrates. Since the ligand precursors can be
obtained readily by an nucleophilic substitution reaction
between chloroacetone and imidazole derivatives, it can be
expected that the replacement of the organic halide with
appropriate hydrophilic compounds can yield water-soluble
ligands. Currently, we are working along this direction to
synthesize water-soluble zwitterionic palladium complexes and
H
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3.0 Hz, imi H), 8.27 (d, 1H, J = 3.0 Hz, imi H). 13C{1H} NMR
(CDCl3): δ 27.2 (CH3CO), 52.1 (CH2), 55.1 (OCH3), 57.5
(CH2CO), 113.0, 114.3, 119.5, 120.3, 122.1, 124.2, 129.6, 129.9,
130.0, 132.7 (quaternary C), 134.5 (quaternary C), 145.0 (NCN),
159.7 (quaternary C), 199.3 (CO). HRMS (ESI): m/z calcd for
C20H21N2O2 [M−Cl]+ 321.1602, found 321.1595.
investigate their catalytic potentials on cross-coupling reactions
in water.
EXPERIMENTAL SECTION
■
General Considerations. All manipulations were performed
under a dry nitrogen atmosphere using standard Schlenk techniques.
Solvents were dried by standard procedures. Starting chemicals were
purchased from commercial sources and used as received. 1H,
13C{1H}, and 31P{1H} NMR spectra were recorded at 300.13, 75.48,
and 121.49 MHz, respectively. Elemental analyses were performed on
a CHN-O elemental analyzer. ESI-MS was carried out on a sector field
mass spectrometer. X-ray photoelectron spectroscopy was performed
using Mg Kα radiation (hν = 1253.6 eV).
Synthesis of 1f. The compound was prepared by a procedure
similar to that for 1a. A mixture of 1-(4-fluorobenzyl)-2-phenyl-1H-
imidazole (2.9 g, 11.6 mmol) and chloroacetone (0.92 mL, 11.6
1
mmol) was used. Yield: 2.3 g (56%). Mp: 126.3−126.9 °C. H NMR
(CDCl3): δ 2.17 (s, 3H, CH3), 5.29 (s, 2H, CH2), 5.44 (s, 2H,
CH2CO), 6.91 (t, 2H, J = 9.0 Hz, Ar H), 7.04−7.09 (m, 2H, Ar H),
7.38−7.40 (m, 2H, Ar H), 7.51 (t, 2H, J = 6.0 Hz, Ar H), 7.61 (t, 1H, J
= 6.0 Hz, Ar H), 7.98 (d, 1H, J = 3.0 Hz, imi H), 8.24 (d, 1H, J = 3.0
Hz, imi H). 13C{1H} NMR (CDCl3): δ 27.3 (CH3), 51.6 (CH2), 57.6
(CH2CO), 116.0 (d, J = 21.8 Hz, Ar C), 120.5, 122.2, 124.3, 129.2
(quaternary C), 129.7, 129.9 (d, J = 9.0 Hz, Ar C), 130.1, 132.8
(quaternary C), 145.0 (NCN), 162.7 (d, J = 249.0 Hz, CF), 199.6
(CO). HRMS (ESI): m/z calcd for C19H18FN2O [M−Cl]+
309.1403, found 309.1395.
Synthesis of 1a. A mixture of 1-benzyl-2-methyl-1H-imidazole
(2.1 g, 12.2 mmol) and chloroacetone (0.97 mL, 12.2 mmol) in THF
(30 mL) was placed in a Schlenk flask. The mixture was heated under
reflux for 48 h. After the mixture was cooled, the white solid was
collected on a frit, washed with THF, and dried under vacuum. Yield:
1
2.9 g (90%). H NMR (CDCl3): δ 2.24 (s, 3H, CH3CO), 2.49 (s,
Synthesis of 2a. In a 20 mL Schlenk flask, PdCl2 (0.052 g, 0.29
mmol), 1a (0.078 g, 0.29 mmol), pyridine (23.8 μL, 0.29 mmol), and
K2CO3 (0.16 g, 1.2 mmol) were dissolved in dry DMF (10 mL) under
a nitrogen atmosphere. The solution was stirred at room temperature
for 12 h. The residue was washed with water and extracted twice with
DCM. The extract was dried over anhydrous MgSO4 and evaporated
to dryness under vacuum to give a solid. Diethyl ether was added, and
the yellowish solid that formed was collected on a frit and dried under
vacuum. Yield: 0.082 g (56%). Mp: 160.8−161.3 °C. Anal. Calcd for
C19H21Cl2N3OPd: C, 47.07; H, 4.36; N, 8.66. Found: C, 47.15; H,
4.60; N, 8.26. 1H NMR (CDCl3): δ 2.50 (s, 3H, CH3CO), 2.66 (s,
3H, CH3), 5.10 (s, 2H, CH2), 6.20 (s, 1H, Pd−CH), 6.87 (d, 1H, J =
3.0 Hz, imi H), 7.15−7.18 (m, 2H, Ar H), 7.21−7.26 (m, 2H, Py H),
7.40−7.42 (m, 3H, Ar H), 7.65 (t, 1H, J = 9.0 Hz, Py H), 8.20 (d, 1H,
J = 3.0 Hz, imi H), 8.88 (d, 2H, J = 3.0 Hz, Py H). 13C{1H} NMR
(CDCl3): δ 10.9 (CH3), 28.7 (CH3CO), 40.9 (Pd-CH), 51.7
(CH2), 118.2, 124.0 (Py C), 126.2, 127.4, 129.3, 129.5, 132.0
(quaternary C), 137.2 (Py C), 140.7 (NCN), 151.5 (Py C), 204.8
(CO).
3H, CH3), 5.36 (s, 2H, CH2), 5.85 (s, 2H, CH2CO), 7.10−7.25 (m,
5H, Ar H), 7.44 (d, 1H, J = 3.0 Hz, imi H), 7.81 (d, 1H, J = 3.0 Hz, imi
H). 13C{1H} NMR (CDCl3): δ 10.5 (CH3), 27.4 (CH3CO), 51.8
(CH2), 57.6 (CH2CO), 121.1, 122.9, 127.4, 128.8, 129.1, 132.6
(quaternary C), 145.1 (NCN), 199.5 (CO). HRMS (ESI): m/z
calcd for C14H17N2O [M − Cl]+ 229.1340, found 229.1333.
Synthesis of 1b. The compound was prepared by a procedure
similar to that for 1a. A mixture of 1-(3-methoxybenzyl)-2-methyl-1H-
imidazole (2.5 g, 12.2 mmol) and chloroacetone (0.97 mL, 12.2
mmol) was used. Yield: 2.9 g (81%). 1H NMR (CDCl3): δ 2.28 (s, 3H,
CH3CO), 2.52 (s, 3H, CH3), 3.66 (s, 3H, OCH3), 5.34 (s, 2H,
CH2), 5.88 (s, 2H, CH2CO), 6.67−6.76 (m, 3H, Ar H), 7.17 (t, 1H,
J = 9.0 Hz, Ar H), 7.44 (d, 1H, J = 3.0 Hz, imi H), 7.83 (d, 1H, J = 3.0
Hz, imi H). 13C{1H} NMR (CDCl3): δ 10.5 (CH3), 27.4 (CH3CO),
51.7 (CH2), 55.2 (OCH3), 57.7 (CH2CO), 112.9, 114.2, 119.3,
121.1, 122.9, 130.3, 134.1 (quaternary C), 145.3 (NCN), 160.0
(quaternary C), 199.5 (CO). HRMS (ESI): m/z calcd for
C15H19N2O2 [M − Cl]+ 259.1446, found 259.1439.
Synthesis of 1c. The compound was prepared by a procedure
similar to that for 1a. A mixture of 1-(4-fluorobenzyl)-2-methyl-1H-
imidazole (3.8 g, 20.2 mmol) and chloroacetone (1.6 mL, 20.2 mmol)
was used. Yield: 5.2 g (92%). 1H NMR (CDCl3): δ 2.24 (s, 3H,
CH3CO), 2.51 (s, 3H, CH3), 5.40 (s, 2H, CH2), 5.80 (s, 2H,
CH2CO), 6.91 (t, 2H, J = 9.0 Hz, Ar H), 7.17−7.21 (m, 2H, Ar H),
7.53 (d, 1H, J = 3.0 Hz, imi H), 7.78 (d, 1H, J = 3.0 Hz, imi H).
13C{1H} NMR (CDCl3): δ 10.5 (CH3), 27.4 (CH3CO), 51.0
(CH2), 57.6 (CH2CO), 116.1 (d, J = 21.9 Hz, Ar C), 121.1, 122.9,
128.6 (quaternary C), 129.7 (d, J = 8.3 Hz, Ar C), 145.1 (NCN), 162.6
(d, J = 249.8 Hz, CF), 199.4 (CO). HRMS (ESI): m/z calcd for
C14H16FN2O [M − Cl]+ 247.1246, found 247.1237.
Synthesis of 2b. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.060 g, 0.34 mmol), 1b
(0.10 g, 0.34 mmol), pyridine (27.6 μL, 0.34 mmol), and K2CO3 (0.19
g, 1.4 mmol) was used. Yield: 0.11 g (63%). Mp: 175.6−176.3 °C.
Anal. Calcd for C20H23Cl2N3O2Pd: C, 46.6; H, 4.50; N, 8.16. Found:
C, 46.38; H, 4.25; N, 7.75. 1H NMR (CDCl3): δ 2.50 (s, 3H, CH3C
O), 2.66 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 5.06 (s, 2H, CH2), 6.19 (s,
1H, Pd−CH), 6.67−6.73 (m, 2H, Ar H), 6.87−6.92 (m, 2H, Ar H, imi
H), 7.21−7.26 (m, 2H, Py H), 7.32 (t, 1H, J = 9.0 Hz, Ar H), 7.65 (t,
1H, J = 9.0 Hz, Py H), 8.19 (d, 1H, J = 3.0 Hz, imi H), 8.87 (d, 2H, J =
6.0 Hz, Py H). 13C{1H} NMR (CDCl3): δ 10.0 (CH3), 28.8 (CH3C
O), 41.1 (Pd-CH), 51.8 (CH2), 55.4 (OCH3), 113.3, 114.5, 118.3,
119.5, 124.2 (Py C), 126.3, 130.8, 133.5 (quaternary C), 137.4 (Py C),
140.9 (NCN), 151.6 (Py C), 160.4 (quaternary C), 204.9 (CO).
Synthesis of 2c. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.038 g, 0.21 mmol), 1c
(0.090 g, 0.32 mmol), pyridine (17.2 μL, 0.34 mmol), and K2CO3
(0.12 g, 0.84 mmol) was used. Yield: 0.054 g (51%). Mp: 145.4−146.7
°C. Anal. Calcd for C19H20Cl2FN3OPd: C, 45.39; H, 4.01; N, 8.35.
Synthesis of 1d. The compound was prepared by a procedure
similar to that for 1a. A mixture of 1-benzyl-2-phenyl-1H-imidazole
(1.6 g, 6.8 mmol) and chloroacetone (0.54 mL, 6.8 mmol) was used.
1
Yield: 1.9 g (86%). Mp: 198.5−199.1 °C. H NMR (CDCl3): δ 2.14
(s, 3H, CH3), 5.26 (s, 2H, CH2), 5.49 (s, 2H, CH2CO), 6.97−7.00
(m, 2H, Ar H), 7.17−7.22 (m, 3H, Ar H), 7.29−7.32 (m, 2H, Ar H),
7.46 (t, 2H, J = 6.0 Hz, Ar H), 7.57 (t, 1H, J = 6.0 Hz, Ar H), 7.85 (d,
1H, J = 3.0 Hz, imi H), 8.31 (d, 1H, J = 3.0 Hz, imi H). 13C{1H} NMR
(CDCl3): δ 27.2 (CH3), 52.3 (CH2), 57.5 (COCH2), 120.3, 122.0,
124.3, 127.6, 128.8 (quaternary C), 129.0, 129.7, 129.9, 132.8, 133.1
(quaternary C), 145.1 (NCN), 199.4 (CO). HRMS (ESI): m/z
calcd for C19H19N2O [M − Cl]+ 291.1497, found 291.1490.
1
Found: C, 45.04; H, 4.30; N, 8.04. H NMR (CDCl3): δ 2.50 (s, 3H,
CH3CO), 2.67 (s, 3H, CH3), 5.08 (s, 2H, CH2), 6.19 (s, 1H, Pd−
CH), 6.86 (d, 1H, J = 3.0 Hz, imi H), 6.99−7.26 (m, 6H, Ar H, Py H),
7.66 (t, 1H, J = 9.0 Hz, Py H), 8.19 (d, 1H, J = 3.0 Hz, imi H), 8.87 (d,
2H, J = 3.0 Hz, Py H). 13C{1H} NMR (CDCl3): δ 11.1 (CH3), 28.8
(COCH3), 41.2 (Pd-CH), 51.1 (CH2), 116.8 (d, J = 21.8 Hz, Ar C),
118.1, 124.2 (Py C), 126.4, 128.0 (d, J = 3.7 Hz, Ar C), 129.6 (d, J =
9.0 Hz, Ar C), 137.4 (Py C), 140.8 (NCN), 151.6 (Py C), 163.1 (d, J =
250.5 Hz, CF), 205.0 (CO).
Synthesis of 1e. The compound was prepared by a procedure
similar to that for 1a. A mixture of 1-(3-methoxybenzyl)-2-phenyl-1H-
imidazole (3.3 g, 12.4 mmol) and chloroacetone (0.99 mL, 12.4
mmol) was used. Yield: 3.6 g (82%). 1H NMR (CDCl3): δ 2.11 (s, 3H,
CH3CO), 3.61 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 5.46 (s, 2H,
CH2CO), 6.50−6.52 (m, 2H, Ar H), 6.70 (d, 1H, J = 9.0 Hz, Ar H),
7.07 (t, 1H, J = 9.0 Hz, Ar H), 7.30 (d, 2H, J = 9.0 Hz, Ar H), 7.45 (t,
2H, J = 9.0 Hz, Ar H), 7.55 (t, 1H, J = 6.0 Hz, Ar H), 7.86 (d, 1H, J =
Synthesis of 2d. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.054 g, 0.31 mmol), 1d
(0.10 g, 0.31 mmol), pyridine (24.7 μL, 0.31 mmol), and K2CO3 (0.17
I
dx.doi.org/10.1021/om500834y | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
g, 1.2 mmol) was used. Yield: 0.12 g (72%). Mp: 156.2−156.8 °C.
Synthesis of 3b. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2b (0.18 g, 0.34 mmol)
and PPh3 (0.092 g, 0.34 mmol) was used. Yield: 0.17 g (71%). Mp:
179.1−181.2 °C. Anal. Calcd for C33H33Cl2N2O21PPd: C, 56.79; H,
4.76; N, 4.01. Found: C, 56.90; H, 4.90; N, 3.90. H NMR (DMSO-
d6): δ 1.39 (s, 3H, CH3CO), 2.17 (s, 3H, CH3), 3.73 (s, 3H,
OCH3), 4.15 (d, 1H, J = 6.0 Hz, Pd−CH), 5.21 (m, 2H, CH2), 6.77
(d, 1H, J = 6.0 Hz, Ar H), 6.96 (d, 1H, J = 9.0 Hz, Ar H), 7.31−7.66
(m, 18H, Ar H, imi H), 8.30 (s, 1H, imi H). 13C{1H} NMR (DMSO-
d6): δ 8.7 (CH3), 28.8 (CH3CO), 50.7 (CH2), 53.7 (Pd−CH), 55.6
(OCH3), 113.9, 114.1, 120.1, 126.8, 128.9 (d, J = 11.3 Hz, Ar C), 130.6
(d, J = 10.6 Hz, Ar C), 131.2, 134.6 (d, J = 10.6 Hz, Ar C), 134.9, 136.6
(quaternary C), 143.9 (NCN), 160.1 (quaternary C), 202.4 (CO).
31P{1H} NMR (DMSO-d6): δ 32.2.
Synthesis of 3c. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2c (0.12 g, 0.24 mmol)
and PPh3 (0.064 g, 0.24 mmol) was used. Yield: 0.077 g (48%). Mp:
171.9−172..6 °C. Anal. Calcd for C32H30Cl2FN2OPPd: C, 56.03; H,
4.40; N, 4.08. Found: C, 56.36; H, 4.66; N, 4.23. 1H NMR (CDCl3): δ
1.28 (s, 3H, CH3CO), 2.36 (s, 3H, CH3), 4.25 (d, 1H, J = 6.0 Hz,
Pd−CH), 4.96−5.26 (m, 2H, CH2), 6.98 (t, 2H, J = 9.0 Hz, Ar H),
7.18−7.67 (m, 17H, Ar H), 7.98 (s, 1H, imi H), 8.51 (s, 1H, imi H).
13C{1H} NMR (DMSO-d6): δ 8.8 (CH3), 28.8 (CH3CO), 50.1
(CH2), 53.7 (Pd−CH), 116.4 (d, J = 21.8 Hz, Ar C), 119.8, 126.9,
128.9 (d, J = 9.8 Hz, Ar C), 130.5, 130.8 (d, J = 9.8 Hz, Ar C), 131.2
(d, J = 9.8 Hz, Ar C), 131.3, 134.6 (d, J = 11.3 Hz, Ar C), 143.8
(NCN), 162.5 (d, J = 245.2 Hz, CF), 202.4 (CO). 31P{1H} NMR
(CDCl3): δ 32.5.
Anal. Calcd for C24H23Cl2N3O2Pd: C, 52.71; H, 4.23; N, 7.68. Found:
1
C, 52.93; H, 4.59; N, 7.26. H NMR (CDCl3): δ 2.28 (s, 3H, CH3),
4.96 (s, 2H, CH2), 5.89 (s, 1H, Pd−CH), 7.03−7.07 (m, 4H, imi H, Ar
H), 7.21−7.26 (m, 3H, Ar H, Py H), 7.35 (t, 4H, J = 3.0 Hz, Ar H),
7.60−7.67 (m, 3H, Ar H, Py H), 8.61 (d, 1H, J = 3.0 Hz, imi H), 8.89
(d, 2H, J = 3.0 Hz, Py H). 13C{1H} NMR (CDCl3): δ 28.3 (CH3),
42.3 (Pd−CH), 52.0 (CH2), 118.8, 121.5, 124.1 (Py C), 127.6, 128.0
(quaternary C), 129.2, 129.4, 132.4, 132.8 (quaternary C), 137.3 (Py
C), 142.6 (NCN), 151.6 (Py C), 206.4 (CO).
Synthesis of 2e. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.050 g, 0.28 mmol), 1e
(0.10 g, 0.28 mmol), pyridine (22.7 μL, 0.28 mmol), and K2CO3 (0.16
g, 11.2 mmol) was used. Yield: 0.15 g (90%). Mp: 90.1−90.8 °C. Anal.
Calcd for C25H25Cl2N3O2Pd: C, 52.05; H, 4.36; N, 7.28. Found: C,
1
52.10; H, 4.77; N, 6.81. H NMR (CDCl3): δ 2.29 (s, 3H, CH3C
O), 3.76 (s, 3H, OCH3), 4.92 (s, 2H, CH2), 5.89 (s, 1H, Pd−CH),
6.55 (t, 1H, J = 3.0 Hz, Ar H), 6.63 (d, 1H, J = 9.0 Hz, Ar H), 6.87
(dd, 1H, J = 9.0 Hz, 3.0 Hz, Ar H), 7.08 (d, 1H, J = 3.0 Hz, imi H),
7.21−7.29 (m, 5H, Ar H, Py H), 7.50−7.68 (m, 4H, Ar H, Py H), 8.62
(d, 1H, J = 3.0 Hz, imi H), 8.89 (d, 2H, J = 3.0 Hz, Py H). 13C{1H}
NMR (CDCl3): δ 28.2 (COCH3), 42.3 (Pd-CH), 51.9 (CH2), 55.3
(OCH3), 113.3, 114.4, 118.8, 119.6, 121.4, 124.1 (Py C), 127.9, 129.4,
130.5, 132.3 (quaternary C), 134.2 (quaternary C), 137.3 (Py C),
142.5 (NCN), 151.6 (Py C), 160.1 (quaternary C), 206.4 (CO).
Synthesis of 2f. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.050 mg, 0.29 mmol), 1f
(0.10 g, 0.29 mmol), pyridine (23.5 μL, 0.29 mmol), and K2CO3 (0.16
g, 11.6 mmol) was used. Yield: 0.14 g (87%). Mp: 150.8−151.4 °C.
Anal. Calcd for C24H22Cl2FN3OPd: C, 51.03; H, 3.92; N, 7.44. Found:
Synthesis of 3d. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2d (0.12 g, 0.22 mmol)
and PPh3 (0.058 g, 0.22 mmol) was used. Yield: 0.15 g (90%). Mp:
180.5−181.1 °C. Anal. Calcd for C37H33Cl2N2OPPd: C, 60.87; H,
1
C, 50.60; H, 3.90; N, 7.20. H NMR (CDCl3): δ 2.29 (s, 3H, CH3),
4.94 (s, 2H, CH2), 5.88 (s, 1H, Pd−CH), 7.02−7.07 (m, 5H, Ar H, imi
H), 7.21−7.26 (m, 4H, Ar H, Py H), 7.49−7.78 (m, 4H, Ar H, Py H),
8.63 (d, 1H, J = 3.0 Hz, imi H), 8.89 (d, 2H, J = 3.0 Hz, Py H).
13C{1H} NMR (CDCl3): δ 28.2 (CH3), 42.3 (Pd-CH), 51.3 (CH2),
116.4 (d, J = 21.8 Hz, Ar C), 118.6, 121.3, 124.1 (Py C), 124.9, 128.0,
128.6 (quaternary C), 129.6 (d, J = 8.3 Hz, Ar C), 132.4, 137.3 (Py C),
142.5 (NCN), 151.6 (Py C), 162.9 (d, J = 249.8 Hz, CF), 206.4 (C
O).
1
4.55; N, 3.83. Found: C, 60.48; H, 4.06; N, 3.59. H NMR (DMSO-
d6): δ 1.52 (s, 3H, CH3), 4.07 (d, 1H, Pd−CH), 5.05−5.20 (m, 2H,
CH2), 6.18 (s, 1H, Ar H), 6.96 (s, 2H, Ar H), 7.31−7.62 (m, 22H, Ar
H), 8.03 (s, 1H, imi H), 8.72 (s, 1H, imi H). 13C{1H} NMR (DMSO-
d6): δ 27.4 (CH3), 51.7 (CH2), 53.3 (Pd-CH), 121.5, 127.3, 127.8,
128.1, 128.9 (d, J = 9.8 Hz, Ar C), 129.3, 129.6 (d, J = 5.3 Hz, Ar C),
130.1, 130.8, 131.2, 131.8 (quaternary C), 132.6, 133.9 (d, J = 10.6 Hz,
Ar C), 134.9 (quaternary C), 143.4 (NCN), 202.3 (CO). 31P{1H}
NMR (DMSO-d6): δ 30.6.
Synthesis of 2g. The compound was prepared by a procedure
similar to that for 2a. A mixture of PdCl2 (0.056 g, 0.31 mmol), 1g
(0.11 g, 0.31 mmol), 3-chloropyridine (29.8 μL, 0.31 mmol), and
K2CO3 (0.17 g, 12.4 mmol) was used. Yield: 0.13 g (69%). Mp:
133.3−134.1 °C. Anal. Calcd for C25H24Cl3N3O2Pd: C, 49.12; H, 3.95;
N, 6.87. Found: C, 49.28; H, 3.99; N, 6.66. 1H NMR (CDCl3): δ 2.29
(s, 3H, CH3CO), 3.76 (s, 3H, OCH3), 4.92 (s, 2H, CH2), 5.92 (s,
1H, Pd−CH), 6.55 (t, 1H, J = 3.0 Hz, Ar H), 6.63 (d, 1H, J = 9.0 Hz,
Ar H), 6.88 (dd, 1H, J = 9.0 Hz, 3.0 Hz, Ar H), 7.08 (d, 1H, J = 3.0 Hz,
imi H), 7.18−7.30 (m, 4H, Ar H, Py H), 7.61−7.67 (m, 4H, Ar H, Py
H), 8.58 (d, 1H, J = 3.0 Hz, imi H), 8.84 (dd, 1H, J = 6.0 Hz, 3.0 Hz,
Py H), 8.94 (d, 1H, J = 3.0 Hz, Py H). 13C{1H} NMR (CDCl3): δ 28.3
(CH3CO), 41.7 (Pd−CH), 52.0 (CH2), 55.3 (OCH3), 113.4, 114.5,
118.9, 119.7, 121.4, 124.6 (Py C), 128.0, 129.5, 130.6, 132.2
(quaternary C), 132.5 (Py C), 134.1 (quaternary C), 137.3 (Py C),
142.7 (NCN), 149.6 (Py C), 150.6 (Py C), 160.2 (quaternary C),
206.2 (CO).
Synthesis of 3e. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2e (0.15 g, 0.26 mmol)
and PPh3 (0.069 g, 0.26 mmol) was used. Yield: 0.17 g (85%). Mp:
191.4−192.1 °C dec. Anal. Calcd for C38H35Cl2N2O2PPd: C, 60.05; H,
4.64; N, 3.68. Found: C, 59.99; H, 4.80; N, 3.24. 1H NMR (DMSO-
d6): δ 1.53 (s, 3H, CH3), 3.68 (s, 3H, OCH3), 4.07 (d, 1H, J = 9.0 Hz,
Pd−CH), 5.07−5.09 (m, 2H, CH2), 6.20 (s, 1H, Ar H), 6.49−6.54 (m,
2H, Ar H), 6.92 (d, 1H, J = 9.0 Hz, Ar H), 7.24−7.65 (m, 20H, Ar H),
8.04 (s, 1H, imi H), 8.72 (s, 1H, imi H). 13C{1H} NMR (DMSO-d6):
δ 27.5 (CH3), 51.6 (CH2), 53.3 (Pd-CH), 55.5 (OCH3), 113.7, 114.3,
120.0, 121.6, 127.3, 128.9 (d, J = 9.8 Hz, Ar C), 129.6 (d, J = 6.0 Hz,
Ar C), 130.1, 130.5, 130.8, 131.2, 132.6, 133.9 (d, J = 10.5 Hz, Ar C),
134.9 (quaternary C), 136.3 (quaternary C), 143.4 (NCN), 159.8
(quaternary C), 202.3 (CO). 31P{1H} NMR (DMSO-d6): δ 30.6.
Synthesis of 3f. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2f (0.094 g, 0.16 mmol)
and PPh3 (0.043 g, 0.16 mmol) was used. Yield: 0.063 g (51%). Mp:
177.7−178.6 °C. Anal. Calcd for C37H32Cl2FN2OPPd: C, 59.41; H,
Synthesis of 3a. A mixture of 2a (0.040 g, 0.083 mmol) and PPh3
(0.022 g, 0.083 mmol) in dichloromethane (10 mL) was stirred in a 20
mL Schlenk flask at ambient temperature overnight. The solvent was
removed completely under vacuum. The residue was washed
thoroughly with THF to afford a yellowish solid. Yield: 0.040 g
(73%). Mp: 136.2−136.5 °C. Anal. Calcd for C32H31Cl2N2OPPd: C,
1
4.31; N, 3.74. Found: C, 59.40; H, 4.21; N, 3.80. H NMR (DMSO-
d6): δ 1.51 (s, 3H, CH3), 4.06 (d, 1H, J = 9.0 Hz, Pd−CH), 5.10 (s,
2H, CH2), 6.18 (s, 1H, Ar H), 7.01−7.62 (m, 23H, Ar H), 8.02 (s, 1H,
imi H), 8.72 (s, 1H, imi H). 13C{1H} NMR (DMSO-d6): δ 27.4
(CH3), 51.0 (CH2), 53.3 (Pd-CH), 116.2 (d, J = 21.8 Hz, Ar C), 121.5,
127.2 (quaternary C), 128.5 (d, J = 9.0 Hz, Ar C), 128.9 (d, J = 10.5
Hz, Ar C), 129.6 (d, J = 9.8 Hz, Ar C), 130.1, 130.6 (d, J = 7.5 Hz, Ar
C), 131.2, 131.9 (d, J = 9.0 Hz, Ar C), 132.6, 133.9 (d, J = 10.5 Hz, Ar
C), 134.9 (quaternary C), 143.3 (NCN), 162.4 (d, J = 245.2 Hz, CF),
202.3 (CO). 31P{1H} NMR (DMSO-d6): δ 30.7.
1
57.54; H, 4.67; N, 4.19. Found: C, 57.26; H, 5.14; N, 4.25. H NMR
(DMSO-d6): δ 1.39 (s, 3H, CH3CO), 2.17 (s, 3H, CH3), 4.15 (d,
1H, J = 6.0 Hz, Pd-CH), 5.25−5.47 (m, 2H, CH2), 7.24−7.66 (m,
21H, imi H, Ar H), 8.29 (s, 1H, imi H). 13C{1H} NMR (DMSO-d6): δ
8.8 (CH3), 28.8 (CH3CO), 50.8 (CH2), 53.7 (Pd-CH), 120.0, 126.8,
128.0, 128.2, 128.9 (d, J = 9.8 Hz, Ar C), 129.5, 130.4, 131.2 (d, J = 9.8
Hz, Ar C), 134.6 (d, J = 10.6 Hz, Ar C), 135.1 (quaternary C), 143.8
(NCN), 202.4 (CO). 31P{1H} NMR (DMSO-d6): δ 32.1.
J
dx.doi.org/10.1021/om500834y | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Synthesis of 3g. The compound was prepared by a procedure
similar to that for 3a. A mixture of complex 2e (0.17 g, 0.29 mmol)
and PCy3 (0.081 g, 0.29 mmol) was used. Yield: 0.19 g (84%). Mp:
151.2−151.9 °C dec. Anal. Calcd for C38H53Cl2N2O2PPd: C, 58.65; H,
6.86; N, 3.60. Found: C, 58.80; H, 6.44; N, 3.33. 1H NMR (CDCl3): δ
1.10−1.28 (m, 9H, Cy H), 1.51−2.10 (m, 21H, Cy H), 2.41 (s, 3H,
CH3), 3.82 (s, 3H, OCH3), 4.48 (d, 1H, J = 6.0 Hz, Pd-CH), 4.84 (d,
1H, J = 15.0 Hz, CHaHb), 5.58 (d, 1H, J = 15.0 Hz, CHaHb), 6.66 (d,
1H, J = 6.0 Hz, Ar H), 6.80 (s, 1H, Ar H), 6.88 (d, 1H, J = 6.0 Hz, Ar
H), 7.24−7.28 (m, 2H, Ar H), 7.55−7.80 (m, 5H, Ar H, imi H), 9.08
(s, 1H, imi H). 13C{1H} NMR (CDCl3): δ 26.2 (d, J = 11.3 Hz, Cy
CH2), 26.5 (d, J = 18.1 Hz, Cy CH2), 26.8 (d, J = 15.0 Hz, Cy CH2),
27.0 (d, J = 8.3 Hz, Cy CH2), 27.2, 27.7 (d, J = 11.3 Hz, Cy CH2),
28.8, 29.7 (CH3CO), 31.9 (d, J = 18.8 Hz, Cy C), 33.9 (d, J = 24.9
Hz, Cy C), 51.4 (CH2), 52.3 (d, J = 25.6 Hz, Pd−CH), 55.5 (OCH3),
113.2, 114.3, 114.7, 118.9, 119.7, 121.0, 122.2, 129.0, 129.9, 130.3,
130.5 (quatenary C), 132.6 (quatenary C), 142.4 (NCN), 160.1
(quatenary C), 205.5 (CO). 31P{1H} NMR (CDCl3): δ 39.3.
Room-Temperature Suzuki−Miyaura Cross-Coupling Reac-
tions. In a typical reaction, a mixture of aryl halide (0.5 mmol),
phenyl- or arylboronic acid (0.6 mmol), base (2.0 equiv), and
palladium catalyst (2.0−2.5 mol %) in solvent (2.0 mL) was stirred at
room temperature for an appropriate period of time (2−12 h) under
nitrogen. GC yields were calculated by using benzophenone as an
internal standard. In the standard workup, the solvent was removed
completely under vacuum. A 1/1 ethyl acetate/water mixture (20 mL)
was added. The organic layer was washed, separated, further washed
with another 10 mL of ethyl acetate, and dried with anhydrous
MgSO4. The solvent was removed completely under high vacuum.
Crude products were purified through flash column chromatography
on 230−400 mesh silica gel using hexane or hexane/ethyl acetate as
eluent in a suitable ratio according to the TLC experiments.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the Ministry of Science and Technology of
Taiwan for financial support of this work. We also thank the
National Center for High-performance Computing of Taiwan
for computing time and financial support of the Conquest
software.
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*H.M.L.: tel, +886 4 7232105 ext. 3523; fax, +886 4 7211190;
e-mail, leehm@cc.ncue.edu.tw; web, http://chem.ncue.edu.tw/
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K
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