Monodentate palladium complexes bearing abnormal and normal carbene ligands with a formally identical steric environment

Article abstract of DOI:10.1021/om4004219

We report a series of novel isomeric Pd(II) complexes with monodentate abnormal and normal carbene ligands, possessing a formally identical steric environment around the metal center. The corresponding ligand precursors were prepared via the key steps based on Pd-catalyzed direct C-H arylation between imidazo[1,2-a]pyridine and aryl bromides and Cu-catalyzed C-N coupling reactions between benzoimidazole and aryl bromides. The new complexes were characterized by 1D and 2D NMR spectroscopy, X-ray crystallography, and elemental analysis. The isomeric pairs of ligands show minor differences among their steric properties, which were examined by calculating their buried volume. The abnormal carbene Pd(II) complexes were found to be more efficient in catalyzing Mizoroki-Heck coupling, direct C-H arylation, and decarboxylative coupling reactions, which can be clearly attributed to a stronger electronic donating effect of the abnormal carbene ligands.

Full text of DOI:10.1021/om4004219

Article
pubs.acs.org/Organometallics
Monodentate Palladium Complexes Bearing Abnormal and Normal
Carbene Ligands with a Formally Identical Steric Environment
Chun-Hung Ke, Bing-Chiuan Kuo, Debkumar Nandi, and Hon Man Lee*
Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan, Republic of China
S
* Supporting Information
ABSTRACT: We report a series of novel isomeric Pd(II)
complexes with monodentate abnormal and normal carbene ligands,
possessing a formally identical steric environment around the metal
center. The corresponding ligand precursors were prepared via the
key steps based on Pd-catalyzed direct C−H arylation between
imidazo[1,2-a]pyridine and aryl bromides and Cu-catalyzed C−N
coupling reactions between benzoimidazole and aryl bromides. The
new complexes were characterized by 1D and 2D NMR spectros-
copy, X-ray crystallography, and elemental analysis. The isomeric
pairs of ligands show minor differences among their steric properties,
which were examined by calculating their buried volume. The
abnormal carbene Pd(II) complexes were found to be more efficient in catalyzing Mizoroki−Heck coupling, direct C−H
arylation, and decarboxylative coupling reactions, which can be clearly attributed to a stronger electronic donating effect of the
abnormal carbene ligands.
in which the pair affords formally identical steric environment
around the metal center upon binding. In this regard, Albrecht
reported a unique example based on Pd complexes with
bidentate abnormal and normal carbene ligands.30 Since the use
of monodentate NHC ligand, such as IMes and IPr, is more
versatile in a variety of Pd-catalyzed cross-coupling reactions,6 it
is of great interest to obtain a formally and sterically identical
isomeric pair based on monodentate carbene ligands. However,
such isomeric pairs of Pd complexes have not yet been reported
in the literature.
In this study, we successfully addressed the aforementioned
problem by obtaining a series of novel Pd(II) dichloride
complexes bearing abnormal and normal carbene ligands. They
are isomeric pairs sharing formally the same steric environment
around the metal centers (Chart 2). The appropriate design of
INTRODUCTION
■
Following the isolation and structural characterization of free
carbene in a study by Arduengo,1 N-heterocyclic carbene
(NHC) ligands have been proven very effective in homoge-
neous catalysis.2−11 An experiment unexpectedly showed that
imidazole-based NHC ligands could have an alternative binding
mode via C(4/5) atom, instead of the common C(2) atom in
the imidazolium ring.12−14 This variant of NHC ligands, termed
“abnormal NHC ligands”, has been attracting attention15−20
because reports have shown that it is a stronger electron donor
than the normal carbene ligands;12,21−25 consequently, it
exhibits better catalytic activities in reactions involving the
activation of unreactive bonds as key steps.24−28 However,
metalation via C(4/5) atoms is typically accompanied by a
change in the steric environment around the metal center
(Chart 1), making it difficult to identify whether the enhanced
catalytic activity is because of steric hindrance or owing to the
intrinsic electronic property of the carbene ligand.29 In order to
obtain a rational design of precatalyst, it is desirable to develop
genuine isomeric pair of abnormal and normal carbene ligands,
Chart 2. Isomeric Normal and Abnormal Carbene Pd(II)
Complexes with a Formally Identical Steric Environment
a
around the Metal Center
Chart 1. Metal Binding of Abnormal and Normal Carbene
Ligands with Different Steric Environment around the Metal
a
Center
a
Numbering scheme is shown in red.
a
Received: May 14, 2013
Numbering scheme is shown in red.
© XXXX American Chemical Society
A
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Chart 3. Retrosynthetic Analysis of the Abnormal and Normal Carbene Ligand Precursors
Scheme 1. Preparation of Abnormal and Normal Carbene Ligand Precursors
Scheme 2. Preparation of Pd Complexes with Abnormal and Normal Carbene Ligands
the isomeric ligand precursors was crucial, and on the basis of
the easily available structural isomers of imidazo[1,2-a]pyridine
and benzoimidazole (Chart 3), we were able to obtain the
target ligand precursors via Pd-catalyzed direct C−H arylation
reactions and Cu-catalyzed C−N coupling reactions. Our
synthetic strategies also allowed a desirable, wide-ranging
tunability to access ligand precursors with different electronic
properties. The catalytic performances of these new abnormal
carbene Pd complexes in classical and nonclassical C−C
coupling reactions were compared with those of their normal
carbene Pd isomers. Our findings could be unambiguously
attributed to the electronic effect of the abnormal carbene
ligands.
RESULTS AND DISCUSSION
■
Preparation of Abnormal and Normal Carbene
Precursors. Carbene ligand precursors were prepared
according to Scheme 1. For the abnormal carbene ligand
precursors, the key intermediates 1a−c were prepared via the
Pd-catalyzed direct C−H arylation reactions of imidazo[1,2-
a]pyridine with aryl bromides.31 Arylation occurs regioselec-
tively at the C(3) position, affording reasonable yields of the
coupled products in the range of 60−67% yields. The abnormal
carbene precursors 2a−c were subsequently obtained by
quaternization reactions of 1a−c with 4-fluorobenzyl chloride,
with 60−67% yield. Unlike the previous procedures for
preparing an abnormal carbene ligand precursor with a C(2)
metalation site,32 the synthetic strategy based on Pd-catalyzed
direct C−H arylation is a facile method to access ligand
B
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Figure 1. Molecular structures of 3a (left) and 6a (right) with 50% probability ellipsoids for non-H atoms. Hydrogen atoms are omitted for clarity.
Figure 2. Molecular structures of 3b (left) and 6b (right) with 50% probability ellipsoids for non-H atoms. Hydrogen atoms are omitted for clarity.
precursors with different electronic property. Our method
allows for the preparation of ligand precursor 2a having a
phenyl ring in the C(3) position, whereas precursors with aryl
rings bearing electron-donating and -withdrawing groups (2b
and 2c respectively) can also be prepared straightforwardly.
Notably, a study by Ghosh also reported relevant Pd complexes
with abnormal carbene ligands based on imidazo[1,2-a]-
pyridines;33 however, in the complexes reported in that study,
metalation occurred at the C(3) position of the imidazo[1,2-
a]pyridine ring, whereas in our cases metalation took place at
the C(2) position. The CH protons on the heteroaromatic
rings in 2a−c that deprotonate resonate at ca. 8.8 ppm. To
unambiguously identify the NMR signal of the C(2) carbon, we
conducted the HMBC experiment (2c), thereby establishing
that the C(2) carbon and the quaternary NCN signals occurred
at 124.3 and 139.0 ppm, respectively (see the Supporting
Information).
In the corresponding normal carbene precursors, the N-
arylated imidazole intermediates 4a−c were prepared in good
yields via the Cu-catalyzed C−N coupling reactions between
benzoimidazole and aryl bromides in DMF at 120 °C.34
Following the quaternization reactions with 4-fluorobenzyl
chlorides, carbene precursors 5a−c were obtained with 58−
80% yields. The NCHN protons in 5a−c that deprotonate
upon metalation resonate at ca. 11.85 ppm, approximately 3
ppm more downfield compared to that of the corresponding
acidic C(2)H proton in the abnormal carbene precursors 2a−c.
The corresponding NCHN carbon signals were also observed
at more downfield positions compared to those of the C(2)H
carbons in the abnormal carbene precursors (143 vs 124 ppm).
Preparation of Pd(II) Complexes with Abnormal and
Normal Carbene Ligands. The abnormal Pd complexes 3a−
c were prepared via the reactions between the ligand precursors
2a−c and PdCl2 in pyridine in the presence of K2CO3 as base
(Scheme 2). The reaction temperature was found to be crucial
because excess heating above 60 °C darkened the solution,
presumably because of the precipitation of Pd black. Successful
formation of 3 was indicated by the disappearance of a proton
signal at ca. 8.8 ppm in its NMR spectrum, with respect to that
of the ligand precursor. The HMBC experiment on 3c showed
that Pd−C resonances in 3 appear at ca. 138 ppm (see the
Supporting Information), which is downfield compared to the
relevant C(3)-coordinated abnormal complexes (ca. 130
ppm).33 These complexes were stable in solution, exhibiting
good solubility in common halogenated solvents. For instance,
1
the H NMR spectrum for 3a remained unchanged even when
the solution was allowed to stand in air for 3 d.
Similar complexation conditions for the abnormal carbene
complexes can also be applied to the preparation of the normal
carbene complexes 6a−c. Instead of heating at 60 °C, the
reactions for 6a and 6b were conducted at 40 °C. For complex
6c, it was necessary to conduct the reaction at 0 °C, because
otherwise an impure sample was obtained (according to the 1H
NMR spectrum). In fact, in an unsuccessful attempt of the
complexation reaction with the bromo analogue of 5c, the X-
ray structure of a decomposed product 6c′ was obtained from
C
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Figure 3. Molecular structures of 3c (left) and 6c (right) with 50% probability ellipsoids for non-H atoms. Hydrogen atoms are omitted for clarity.
Only one independent molecule in the structure of 6c was shown.
Table 1. Selected Bond Distances (Å) and Angles (°) around Pd in 3 and 6
3a
3b
3c
6a
6b
6c
Pd−C
Pd−N
Pd−Cl1
Pd−Cl2
C−Pd−Cl1
C−Pd−Cl2
N−Pd−Cl1
N−Pd−Cl2
C−Pd−N
Cl−Pd−Cl
1.960(8)
2.103(7)
2.298(2)
2.309(2)
89.0(2)
1.960(5)
1.971(4)
1.955(4)
1.950(5)
1.964(7)
2.095(6)
2.2868(19)
2.297(2)
89.20(19)
89.84(19)
90.98(17)
90.14(17)
175.9(3)
177.53(8)
2.094(4)
2.118(3)
2.124(3)
2.068(5)
2.3028(16)
2.2913(17)
90.84(15)
89.19(15)
89.93(13)
90.35(13)
174.72(19)
176.68(7)
2.3221(14)
2.3061(14)
89.53(11)
88.61(11)
89.59(10)
92.26(10)
178.91(13)
178.01(4)
2.2981(12)
2.3060(12)
90.50(12)
84.70(12)
92.99(10)
91.90(10)
176.13(14)
174.51(4)
2.2989(16)
2.3037(15)
88.87(14)
90.45(14)
90.25(13)
90.54(13)
176.61(19)
178.00(6)
89.9(2)
89.5(2)
91.8(2)
173.6(3)
177.96(9)
the impure sample (vide infra). In general, good yields (ca.
essentially the same (within standard derivations) to that in
6b (1.950(5) Å). The Pd−C bond lengths in the three
abnormal carbene complexes are in the range of 1.960(5) to
1.971(4) Å, and they are slightly shorter than the average bond
length of 1.99(3) Å (seen in 41 crystallographically determined
Pd complexes with abnormal carbene ligands).18
It has been shown that a more useful probe to gauge the
impact of an abnormal carbene ligand is to monitor its trans
influence. The Pd−N distances in the abnormal carbene
complexes 3a−c are in the range of 2.094(4) to 2.118(3) Å,
which is, however, essentially similar to that of 2.068(5) to
2.124(3) Å in the normal carbene complexes 6a−c.
Interestingly, the structure of 6a exhibits nonclassical intra-
molecular hydrogen bonds between the ortho protons of the
pyridine ligand and the coordinated chloride ions with C···Cl
contact distances of 3.289(5) and 3.226(5) Å. Their contact
angles are noticeably acute (ca. 117°).
Another interesting aspect of these structures is that the
interplanar angles between the heterocyclic ring and the
coordination plane of the metal center in the abnormal carbene
complexes 3a−c are 73.6(3)°, 77.4(1)°, and 74.9(1)°,
respectively, which are smaller than those in 6a−c (79.4(1)°,
79.9(1)°, and 82.9(2)°), indicating that the abnormal carbene
ligands are more appropriately oriented for Π-back bonding.
The structure of 6c′ features a Pd atom in square
coordination geometry with two trans bromide ligands and a
normal carbene ligand. Instead of pyridine ligand, the fourth
coordination site was occupied by an imidazole derivative that
was formed from the cleavage of the 4-fluorobenzyl wingtip
80%) of 6a−c were obtained. They were characterized by
1
elemental analysis, X-ray crystallographic studies, and H and
1
13C{1H} NMR spectroscopy. Their H NMR spectra in the
downfield region showed an absence of sharp signals owing to
NCHN protons at ca. 9.4 ppm, indicating the successful
formation of carbene complexes. Carbene signals (in their
13C{1H} NMR spectra) were observed at ca. 165 ppm, which is
significantly downfield (Δ ≈ 27 ppm) as compared to that of
the abnormal carbene complexes 3 and relevant trans-
Pd(L)(py)Cl2 with normal carbene ligands (Δ ≈ 13
ppm).35,36 All these carbene complexes showed good solubility
in halogenated solvents and appeared to be, except 6c, stable in
solution. As an example, the NMR spectrum in CDCl3 for 6a
remained unchanged even after the exposure of the solution in
the air for 3 d.
Structural Descriptions. In order to evaluate the differ-
ence in the structural parameters between the abnormal and
normal carbene complexes, crystals of 3 and 6 were grown. The
trans geometry of all the Pd complexes was unambiguously
established via X-ray diffraction studies (Figure 1−3). Selected
bond distances and angles are tabulated in Table 1. The Pd
atoms in these structures adopt distorted square planar
coordination geometry. Despite the fact that an abnormal
carbene ligand is more electron-donating than a normal one,
the structural analyses revealed that the Pd−C distances of
abnormal carbene complexes were comparable to those of
normal carbene complexes. For example, the Pd−C distance in
abnormal carbene complex 3b is 1.960(5) Å, which is
D
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group in 5c (Figure 4). The Pd−C bond length of 1.932(12) Å
is the shortest among all the new structures.
and aryl halides were investigated on the basis of our previously
established conditions that employ TBAB ionic liquid as
solvent (Table 2).42,43 In general, the abnormal carbene
Table 2. Mizoroki−Heck Cross-Coupling Reaction of Aryl
a
Halides
entry
Pd cat
R
X
product
time
yield (%)
b
1
3a
3b
3c
6a
6b
6c
3a
3b
3c
6a
6b
6c
3a
3b
3c
3a
3b
3c
4-COMe
4-COMe
4-COMe
4-COMe
4-COMe
4-COMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
3-OMe
3-OMe
3-OMe
2-OMe
2-OMe
2-OMe
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
7
2
82
b
2
7
2
95
b
3
7
2
85
b
4
7
2
67
b
5
7
2
79
b
6
7
2
34
7
8
24
24
24
24
24
24
24
24
24
24
24
24
54
54
52
32
16
24
77
85
70
69
70
59
8
8
9
8
Figure 4. Molecular structures of 6c′ with 50% probability ellipsoids
for non-H atoms. Hydrogen atoms are omitted for clarity. Selected
bond distances: Pd1−C14, 1.932(12); Pd1−N2, 2.085(9); Pd1−Br1,
2.3972(18); Pd1−Br2, 2.4049(18) Å. Selected bond angles: C14−
Pd1−N2, 175.8(4); Br1−Pd1−Br2, 174.85(7); C14−Pd1−Br1,
88.8(3); C14−Pd1−Br2, 86.9(3); N2−Pd1−Br1, 92.7(3); N2−
Pd1−Br2, 91.8(3) deg.
10
11
12
13
14
15
16
17
18
8
8
8
9
9
9
10
10
10
Buried Volume of the Abnormal and Normal Carbene
Ligands. Although theoretically the abnormal and normal
carbene ligands should offer an identical steric environment
around the metal centers, minor differences in steric properties
between the isomeric pairs can still exist. In order to
understand the steric properties of the new abnormal and
normal carbene ligands, percent buried volumes (%Vbur) were
calculated from the corresponding X-ray structures of Pd
complexes (radius of the sphere, R = 3.5 Å; M−NHC length =
2.00 Å; Bondi radii scaled by 1.17).37−39 As expected, the %Vbur
values of the abnormal carbene ligands in 3a,b (32.0 and
30.6%) were similar to those of their normal carbene
counterparts in 6a,b (31.1 and 30.9%), but surprisingly, the
steric properties of the abnormal carbene ligand in 3c and the
normal carbene ligand in 6c and 6c′ were significantly different,
as indicated by the large difference in their %Vbur values [33.2%
in 3c vs 30.0 and 31.8% in 6c (two independent molecules) and
31.0% in 6c′]. The large %Vbur value (33.2%) implied that the
abnormal carbene ligand featuring 4-fluorophenyl and 4-
fluorobenzyl as wingtip groups was bulkier than expected.
Notably, the large variation in the %Vbur values of the abnormal
carbene ligands (30.6−33.2%) is in sharp contrast to the
narrower range (30.9−31.1%) observed for their normal
counterparts, indicating the greater sensitivity of the abnormal
carbene ligands toward substituents at the para position of the
phenyl wingtip groups. For comparison, the %Vbur values of IPr
and 1,3-dibenzylimidazol-2-ylidene were calculated from the
reported structures of Pd(NHC)(py)Cl240,41 and were found to
be 34.5 and 31.5%, respectively.
a
Reaction conditions: aryl halide (1.0 mmol), styrene (1.4 mmol),
NaOAc (2.0 mmol), Pd catalyst (0.5 mol %), TBAB (2.0 g), 140 °C, 2
or 24 h, isolated yield. NMR yield.
b
complexes delivered greater yields than the normal ones. For
example, in the reaction between styrene and 4-chloroanisole,
reasonable yields of coupled product were obtained (52−54%)
(entries 7−9), whereas the normal carbene complexes only
afforded 16−32% yields (entries 10−12). Among the abnormal
carbene complexes, the more electronic rich 3b bearing an N-4-
methoxyphenyl group produced the best yields (entries 2 and
14). Sterically bulky aryl bromides could also be utilized to
produce coupled products in good yields (entries 16−18).
Recently, C−H arylation44−47 has emerged as an appealing
approach for the synthesis of biaryls. These nonclassical C−C
coupling reactions do not require stoichiometric organometallic
substrates, which can help in avoiding problems related to
availability and metal waste, as well as the requirement for
additional synthetic steps. The new abnormal and normal
carbene complexes were tested in the direct C−H arylation
reactions between imidazo[1,2-a]pyridine and aryl halides
(Table 3). In general, the abnormal carbene complexes
outperformed the corresponding normal carbenes complexes,
delivering greater yields (entries 1−3 vs 4−6 and 7−9 vs 10−
12). Entries 1−3 show that the abnormal carbene complex 3b
bearing the N-4-methoxyphenyl group exhibited better
coupling activities in the direct C−H arylations, as in the
case of Mizoroki−Heck cross-coupling reactions. In Scheme 1,
we employed the simple Pd(OAc)2 as catalyst for the direct C−
H arylation to generate intermediates 1a and 1b with 60 and
64% yields, respectively. By employing 3b as catalyst, these
products could be obtained in improved yields of 99 and 74%
Catalytic Studies. The catalytic performance of the
abnormal carbene Pd complexes 3a−c in C−C coupling
reactions was compared to their normal counterparts 6a−c.
The Mizoroki−Heck cross-coupling reactions between styrene
E
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a
were dried with standard procedures. Starting chemicals were
purchased from a commercial source and used as received. H and
Table 3. Direct C−H Arylation Reaction
1
13C{1H} NMR spectra were recorded at 300.13 and 75.48 MHz,
respectively, on a Bruker AV-300 spectrometer. Elemental analyses
were performed on a Thermo Flash 2000 CHN-O elemental analyzer.
High-resolution mass spectroscopy (HRMS) was measured on a
Finnigan/Thermo Quest MAT mass spectrometer at the National
Chung Hsing University (Taiwan). Imidazo[1,2-a]pyridine was
prepared according to the literature procedure.53
entry
Pd cat
R
X
product
yield (%)
1
3a
3b
3c
6a
6b
6c
3b
3b
3b
6b
6b
6b
OMe
OMe
OMe
OMe
OMe
OMe
COMe
H
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Br
Br
Cl
1b
1b
1b
1b
1b
1b
11
1a
11
11
1a
11
68
74
56
53
66
32
100
99
38
86
85
15
2
General Procedure of the Synthesis of 1a−c. To a 50 mL
Schlenk flask was added imidazo[1,2-a]pyridine (3.0 g, 0.025 mol),
KOAc (5.0 g, 0.050 mol) and Pd(OAc)2 (0.14 g, 0.64 mmol).
Degassed DMA (10 mL) and aryl bromide (0.02 mol) were also
added. The mixture was allowed to heat at 140 °C for 18 h. After
cooling, the solvent was removed under a vacuum. The residue was
extracted with DCM. The extract was washed with water, dried over
anhydrous MgSO4, and filtered through a pad of Celite. The filtrate
was purified by column chromatography on silica gel, using 30:70 ethyl
acetate/hexane as eluent. A viscous brown liquid was obtained.
3
4
5
6
7
8
9
COMe
COMe
H
10
11
12
Synthesis of 1a.52 Yield: 2.48 g, 60.3%, mp = 111.5 °C. H NMR
1
COMe
(300 MHz, CDCl3): δ 6.67 (t, J = 6.0 Hz, 1H, Ar H), 7.08 (t, J = 9.0
Hz, 1H, Ar H), 7.30−7.60 (m, 7H, imi H, Ar H), 8.20 (d, J = 9.0 Hz,
1H, Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 112.3 (CH), 117.7
(CH), 123.0 (CH), 124.0 (CH), 125.3 (quatenary C), 127.6 (CH),
127.9 (CH), 128.8 (quatenary C), 128.9 (CH), 131.9 (CH), 145.6
(quatenary C).
a
Reaction conditions: imidazo[1,2-a]pyridine (1.5 mmol), aryl halide
(1.0 mmol), KOAc (2.0 mmol), DMA (5 mL), Pd catalyst (2.5 mol
%), 140 °C, 18 h, isolated yield.
(entries 8 and 2). Notably, these findings are in contrast with
those reported by Fagnou, who showed that intramolecular
direct C−H arylation with aryl chloride proceeded better with a
normal carbene Pd complex than when a mixed normal/
abnormal Pd complex was used.48
Decarboxylative coupling is an equally interesting approach
for preparing heteroaromatic biaryls, because the carboxyl
group can direct regioselectivity and the only waste product
from the reaction is CO2.49−51 Decarboxylative coupling
reactions between 3-(4-fluorophenyl)-5-methylisoxazole-4-car-
boxylic acid and aryl halides were also investigated (Table 4),
on the basis of our previous established procedure.52 Again,
abnormal carbene complexes showed better yields. For
example, employing 3b as catalyst, a good yield of 72% could
be obtained from 4-bromocyanobenzene (entry 3), but only a
50% yield could be obtained from 6b (entry 7).
Synthesis of 1b.54 Yield: 2.97 g, 64.2%, mp = 126.5 °C. H NMR
1
(300 MHz, CDCl3): δ 3.62 (s, 3H, OCH3), 6.53 (t, J = 9.0 Hz, 1H, Ar
H), 6.81 (d, J = 9.0 Hz, 2H, Ar H), 6.93 (t, J = 9.0 Hz, 1H, Ar H), 7.20
(d, J = 6.0 Hz, 2H, Ar H), 7.41−7.74 (m, 2H, imi H, Ar H), 8.00 (d, J
= 6.0 Hz, 1H, Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 54.7 (CH3),
111.9 (CH), 114.0 (CH), 117.2 (CH), 120.6 (quatenary C), 122.6
(CH), 123.5 (CH), 124.9 (quatenary C), 128.9 (CH), 130.9 (CH),
144.9 (quatenary C), 159.0 (quatenary C).
Synthesis of 1c.55 Yield: 3.29 g, 66.7%, mp = 92.5 °C. H NMR
1
(CDCl3): δ 6.74 (t, J = 6.0 Hz, 1H, Ar H), 7.11−7.19 (m, 3H, Ar H),
7.42−7.47 (m, 2H, Ar H), 7.59 (s, 1H, C2H), 7.62 (d, J = 9.0 Hz, 2H,
Ar H), 8.12 (d, J = 9.0 Hz, 1H, Ar H). 13C{1H} NMR (CDCl3): δ
112.8 (CH), 116.3 (d, JCF = 21.9 Hz, CH), 118.2 (CH), 123.1 (CH),
124.4 (CH), 124.6 (quatenary C), 125.2 (d, JCF = 3.0 Hz, quatenary
C), 130.1 (d, JCF = 7.5 Hz, CH), 132.2 (CH), 145.9 (quatenary C),
162.6 (d, JCF = 248.3 Hz, CF).
General Procedure for the Synthesis of 2a−c. A mixture of 1
(12.8 mmol) and 4-fluorobenzyl chloride (1.53 mL, 12.8 mmol) in
degassed THF (25 mL) was heated at 80 °C for 24 h. After cooling,
white solid was formed. The solvent was removed under a vacuum.
The residual solid was thoroughly washed with ether and then dried
under a vacuum. A white solid was obtained.
CONCLUSIONS
■
We prepared a series of abnormal carbene Pd complexes and
their normal analogues, the first examples of isomeric pairs
based on monodentate carbene systems sharing a formally
identical steric environment around the Pd centers. The key
steps in the preparation of the abnormal carbene ligand
precursors was based on the Pd-catalyzed direct C−H arylation
between imidazo[1,2-a]pyridine and aryl bromides, which
allows ligand accessibility with wide-ranging electronic
property. Minor differences exist in the steric property between
abnormal and normal carbene ligands in 3c and 6c. Because of
the minimal steric difference between the isomeric pairs as
shown by the buried volume calculation, the enhanced catalytic
activities exhibited by the abnormal carbene complexes in
Mizoroki−Heck coupling, direct C−H coupling, and decarbox-
ylative coupling reactions can be concluded with the stronger
electron donating property of the abnormal carbene ligands.
Thus the more electron-rich abnormal carbene complex 3b
excelled in all these coupling reactions.
Synthesis of 2a. Yield: 2.85 g, 66%, mp = 186 °C. HRMS (ESI; m/
1
z): calcd for C20H16ClFN2 303.1292 [M − Cl]+, found 303.1297. H
NMR (CDCl3): δ 6.21 (s, 2H, CH2), 6.89 (t, J = 9.0 Hz, 2H, Ar H),
7.37 (t, J = 6.0 Hz, 1H, Ar H), 7.47−7.53 (m, 5H, Ar H), 7.69−7.74
(m, 2H, Ar H), 7.91 (t, J = 9.0 Hz, 1H, Ar H), 8.39 (d, J = 6.0 Hz, 1H,
Ar H), 8.80−8.83 (m, 2H, Ar H, C2H). 13C{1H} NMR (CDCl3): δ
50.6 (CH2), 113.4 (CH), 116.0 (d, J = 21.9 Hz, CH), 118.1 (CH),
123.7 (CH), 124.0 (quatenary C), 125.4 (CH), 127.0 (quatenary C),
129.3 (CH), 129.8 (CH), 129.9 (quatenary C), 130.9 (CH), 131.2 (d,
J = 8.3 Hz, CH), 133.9 (CH), 139.0 (quatenary C), 162.8 (d, J = 248.3
Hz, CF).
Synthesis of 2b. Yield: 4.61 g, 73%, mp = 184.3 °C. HRMS (ESI;
m/z): calcd for C21H18ClFN2O 333.1398 [M − Cl]+, found 333.1405.
1H NMR (CDCl3): δ 3.81 (s, 3H, OCH3), 6.17 (s, 2H, CH2), 6.90 (t, J
= 6.0 Hz, 2H, Ar H), 7.00 (d, J = 6.0 Hz, 2H, Ar H), 7.37 (t, J = 6.0
Hz, 1H, Ar H), 7.46 (d, J = 9.0 Hz, 2H, Ar H), 7.68−7.73 (m, 2H, Ar
H), 7.90 (t, J = 9.0 Hz, 1H, Ar H), 8.36 (d, J = 6.0 Hz, 1H, Ar H), 8.70
(s, 1H, C2H), 8.76 (d, J = 9.0 Hz, 1H, Ar H). 13C{1H} NMR (CDCl3):
δ 50.4 (CH2), 55.4 (CH3), 133.2 (CH), 115.2 (CH), 115.6 (quatenary
C), 115.9 (d, J = 21.1 Hz, CH), 117.9 (CH), 123.4, (CH), 125.4 (CH),
126.8 (CH), 129.9 (d, J = 3.8 Hz, quatenary C), 130.8 (CH), 131.1 (d,
EXPERIMENTAL SECTION
General Information. All manipulations were performed under a
dry nitrogen atmosphere using standard Schlenk techniques. Solvents
■
F
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a
Table 4. Pd-Catalyzed Decarboxylative Coupling Reaction
a
Reaction conditions: 3-(4-fluorophenyl)-5-methylisoxazole-4-carboxylic acid (0.5 mmol), aryl halide (0.5 mmol), KOAc (1.0 mmol), dry DMA (3
mL), Pd cat. (2.5 mol %), 160 °C, 24 h, isolated yield.
J = 8.3 Hz, CH), 133.5 (quatenary C), 138.7 (quatenary C), 161.3
(quatenary C), 162.7 (d, J = 248.3 Hz, CF).
(d, J = 9.1 Hz, CH), 133.9 (CH), 139.0 (NCN), 162.8 (d, J = 248.3
Hz, CF), 164.0 (d, J = 252.8 Hz, CF).
Synthesis of 2c. Yield: 2.46 g, 60%, mp = 232.1−232.7 °C. HRMS
(ESI; m/z): calcd for C20H15ClF2N2 321.1198 [M − Cl]+, found
321.1204. 1H NMR (CDCl3): δ 6.16 (s, 2H, CH2), 6.91 (t, J = 9.0 Hz,
2H, Ar H), 7.21 (t, J = 9.0 Hz, 2H, Ar H), 7.40 (t, J = 9.0 Hz, 1H, Ar
H), 7.58−7.73 (m, 4H, Ar H), 7.92 (t, J = 9.0 Hz, 1H, Ar H), 8.36 (d, J
= 6.0 Hz, 1H, Ar H), 8.73 (d, J = 9.0 Hz, 1H, Ar H), 8.85 (s, 1H,
C2H). 13C{1H} NMR (CDCl3): δ 50.6 (CH2), 113.4 (CH), 116.1 (d, J
= 21.9 Hz, CH), 117.2 (d, J = 22.6 Hz, CH), 118.2 (CH), 120.0 (d, J =
3.7 Hz, quatenary C), 124.3 (C2H), 125.5 (CH), 125.9 (quatenary C),
129.9 (d, J = 3.0 Hz, quatenary C), 131.3 (d, J = 9.8 Hz, CH), 131.8
General Procedure for the Synthesis of 3a−c. Degassed
pryidine (5 mL) was added to a mixture of 2 (0.59 mmol), PdCl2
(0.11 g, 0.59 mmol) and K2CO3 (0.32 g, 2.36 mmol) in a 50 mL
Schlenk flask. The solution was allowed to heat at 60 °C for 12 h. After
cooling, the solvent was removed completely under a vacuum. The
residual was washed with water and extracted with DCM twice. The
extract was washed with water and dried over anhydrous MgSO4. The
solvent was then removed under a vacuum. The solid was then washed
thoroughly with ether and dried under a vacuum. A brown solid was
obtained.
G
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Synthesis of 3a. Yield: 0.26 g, 79%, mp = 220.3−222.4 °C. Anal.
Calcd for C25H20Cl2FN3Pd: C, 53.73; H, 3.61; N, 7.52. Found: C,
53.49; H, 3.61; N, 7.29. 1H NMR (CDCl3): δ 6.29 (s, 2H, NCH2Ph),
6.92−7.03 (m, 4H, Ar H), 7.19−7.26 (m, 2H, Ar H), 7.42 (t, J = 6.0
Hz, 2H, Ar H), 7.54 (t, J = 9.0 Hz, 2H, Ar H), 7.60−7.66 (m, 3H, Ar
H), 8.09 (d, J = 6.0 Hz, 2H, py H), 8.28 (d, J = 6.0 Hz, 1H, py H), 8.88
(d, J = 6.0 Hz, 2H, py H). 13C{1H} NMR (CDCl3): δ 53.8 (CH2),
109.7 (CH), 115.0 (CH), 115.9 (d, JCF = 21.9 Hz, CH), 123.1 (CH),
124.2 (py C), 126.2 (quatenary C), 127.5 (CH), 128.7 (quatenary C),
129.0 (CH), 129.1 (CH), 129.9 (d, JCF = 8.3 Hz, CH), 130.5 (CH),
130.9 (d, JCF = 3.0 Hz, quatenary C), 137.6 (py C), 138.0 (PdC), 139.8
(quatenary C), 151.2 (py C), 162.5 (d, JCF = 246.8 Hz, CF).
The residual solid was thoroughly washed with ether and then dried
under a vacuum. A white solid was obtained.
Synthesis of 5a. Yield: 3.65 g, 58%, mp = 204.2 °C. HRMS (ESI;
m/z): calcd for C20H16ClFN2 303.1292 [M − Cl]+, found 303.1298.
1H NMR (CDCl3): δ 6.14 (s, 2H, CH2), 7.01 (t, J = 6.0 Hz, 2H, Ar
H), 7.60−7.77 (m, 11H, Ar H), 11.95 (s, 1H, NCHN). 13C{1H} NMR
(CDCl3): δ 50.5 (CH2), 113.5 (CH), 114.0 (CH), 116.1 (d, JCF = 21.9
Hz, CH), 124.6 (CH), 127.6 (d, JCF = 7.5 Hz, CH), 128.9 (d, J = 3.0
Hz, quatenary C), 130.6 (CH), 130.9 (CH), 131.0 (CH), 131.1
(quatenary C), 131.1 (quatenary C), 132.8 (quatenary C), 142.6
(NCHN), 162.8 (d, J = 282.3 Hz, CF).
Synthesis of 5b. Yield: 4.92 g, 73%, mp = 241.2 °C. HRMS (ESI;
m/z): calcd for C21H18ClFN2O 333.1398 [M − Cl]+, found 333.1403.
1H NMR (CDCl3): δ 3.83 (s, 3H, CH3), 6.11 (s, 2H, CH2), 6.96−7.08
(m, 4H, Ar H), 7.54−7.76 (m, 8H, Ar H), 11.85 (s, 1H, NCHN).
13C{1H} NMR (CDCl3): δ 50.6 (CH2), 55.8 (CH3), 113.6 (CH),
113.9 (CH), 115.7 (CH), 116.2 (d, J = 21.9 Hz, CH), 125.4 (CH),
126.2 (CH), 127.5 (d, J = 6.8 Hz, CH), 129.0 (d, J = 3.7 Hz, quatenary
C), 130.9 (quatenary C), 131.0 (quatenary C), 131.7 (quatenary C),
142.8 (NCHN), 161.0 (quatenary C), 162.9 (d, J = 249.1 Hz, CF).
Synthesis of 5c. Yield: 3.25 g, 80%, mp = 220.1 °C. HRMS (ESI;
m/z): calcd for C20H15ClF2N2 321.1198 [M − Cl]+, found 321.1204.
1H NMR (CDCl3): δ 6.05 (s, 2H, CH2), 6.97 (t, J = 6.0 Hz, 2H, Ar
H), 7.25 (t, J = 9.0 Hz, 2H, Ar H), 7.53−7.58 (m, 3H, Ar H), 7.65−
7.71 (m, 3H, Ar H), 7.80−7.85 (m, 2H, Ar H), 11.79 (s, 1H, NCHN).
13C{1H} NMR (CDCl3): δ 50.8 (CH2), 113.3 (CH), 114.1 (CH),
116.2 (d, J = 21.9 Hz, CH), 117.8 (d, J = 21.9 Hz, CH), 127.0 (d, J =
9.0 Hz, CH), 127.6 (d, J = 12.8 Hz, CH), 128.9 (d, J = 3.8 Hz,
quatenary C), 128.9 (d, J = 3.1 Hz, quatenary C), 130.9 (CH), 131.0
(CH), 131.1 (quatenary C), 131.5 (quatenary C), 143.2 (NCHN),
161.9 (d, J = 86.0 Hz, CF), 163.2 (d, J = 221.9 Hz, CF).
General Procedure for the Synthesis of 6a and b. Degassed
pyridine (5 mL) was added to a mixture of 5 (0.59 mmol),
PdCl2(COD) (0.168 g, 0.59 mmol) and K2CO3 (0.32 g, 2.36 mmol)
in a 50 mL Schlenk flask. The solution was allowed to heat at 40 °C for
12 h. After cooling, the solvent was removed completely under a
vacuum. The residual was washed with water and extracted with DCM
twice. The extract was washed with water and dried over anhydrous
MgSO4. The solvent was then removed under a vacuum. The brown
solid was then washed thoroughly with ether and dried under a
vacuum.
Synthesis of 6a. Yield: 0.27 g, 82%, mp = 221.0−213.4 °C. Anal.
Calcd for C25H20Cl2FN3Pd: C, 53.85; H, 3.61; N, 7.54. Found: C,
53.74; H, 3.77; N, 7.56. 1H NMR (CDCl3): δ 6.21 (s, 2H, CH2), 7.00
(t, J = 9.0 Hz, 2H, Ar H), 7.08−7.23 (m, 6H, Ar H), 7.50−7.67 (m,
6H, Ar H), 7.97 (d, J = 6.0 Hz, 2H, Ar H), 8.72 (d, J = 6.0 Hz, 2H, py
H). 13C{1H} NMR (CDCl3): δ 52.6 (CH2), 111.2 (CH), 111.4 (CH),
115.9 (d, JCF = 21.9 Hz, CH), 123.7 (CH), 124.4 (py C), 127.9 (CH),
Synthesis of 3b. Yield: 0.26 g, 81%, mp = 208.6−214.3 °C. Anal.
Calcd for C26H22Cl2FN3OPd: C, 53.04; H, 3.76; N, 7.13. Found: C,
1
53.32; H, 3.67; N, 7.00. H NMR (CDCl3): δ 3.83 (s, 3H, OCH3),
6.28 (s, 2H, NCH2Ph), 6.91−7.08 (m, 6H, Ar H), 7.18−7.24 (m, 3H,
Ar H), 7.60−7.66 (m, 3H, Ar H), 7.97 (d, J = 9.0 Hz, 2H, imipy H),
8.22 (d, J = 6.0 Hz, 1H, imipy H), 8.89 (d, J = 3.0 Hz, 2H, py H).
13C{1H} NMR (CDCl3): δ 53.8 (CH2), 55.3 (CH3), 109.6 (CH),
114.6 (CH), 114.9 (CH), 115.9 (d, JCF = 28.7 Hz, CH), 120.8
(quatenary C), 123.0 (CH), 124.1 (py C), 126.0 (quatenary C), 127.2
(CH), 129.9 (d, JCF = 8.3 Hz, CH), 130.9 (d, JCF = 3.7 Hz, quatenary
C), 132.0 (CH), 137.1 (PdC), 137.5 (py C), 139.5 (quatenary C),
151.2 (py C), 160.0 (quatenary C), 162.6 (d, JCF = 246.8 Hz, CF).
Synthesis of 3c. Yield: 0.26 g, 81%, mp = 213.0−217.4 °C. Anal.
Calcd for C25H19Cl2F2N3Pd: C, 52.06; H, 3.32; N, 7.28. Found: C,
1
51.82; H, 3.47; N, 7.00. H NMR (CDCl3): δ 6.33 (s, 2H, CH2),
7.00−7.08 (m, 3H, Ar H), 7.27−7.34 (m, 6H, Ar H), 7.69 (t, J = 9.0
Hz, 3H, Ar H), 8.10 (m, 2H, imipy H, py H), 8.25 (d, J = 6.0 Hz, 1H,
imipy H), 8.92 (d, J = 3.0 Hz, 2H, py H). 13C{1H} NMR (CDCl3): δ
53.8 (CH2), 109.8, 115.2, 116.0 (d, JCF = 24.2 Hz), 116.3 (d, JCF = 21.9
Hz), 122.9, 124.2 (py C), 124.7, 125.0, 127.7, 130.0 (d, JCF = 8.3 Hz),
130.9, 132.6 (d, JCF = 8.3 Hz), 137.6 (py C), 138.1 (PdC), 139.7, 151.1
(py C), 162.6 (d, JCF = 248.3 Hz), 163.0 (d, JCF = 248.3 Hz).
General Procedure of the Synthesis of 4a−c. Degassed DMF
(10 mL) was added to a mixture of benzoimidazole (1.0 g, 8.47
mmol), Cs2CO3 (4.2 g, 12.74 mmol), CuI (0.24 g, 1.47 mmol), and
aryl halide (6.37 mmol). The solution was allowed to heat at 120 °C
for 40 h. After cooling, the solvent was removed completely under a
vacuum. The residual was washed with water and extracted with DCM
twice. The extract was washed with water and dried over anhydrous
MgSO4. The solvent was then removed under a vacuum. The solid was
then washed thoroughly with ether and dried under a vacuum. The
filtrate was purified by column chromatography on silica gel, using
30:70 ethyl acetate/hexane as eluent. A viscous brown liquid was
obtained.
Synthesis of 4a.56 Yield: 2.89 g, 88%, mp = 94.3 °C. H NMR
1
(CDCl3): δ 7.18−7.29 (m, 2H, Ar H), 7.36−7.52 (m, 6H, Ar H),
7.79−7.82 (m, 1H, Ar H), 8.03 (s, 1H, NCHN). 13C{1H} NMR
(CDCl3): δ 110.4 (CH), 120.5 (CH), 122.7 (CH), 123.6 (CH), 124.0
(CH), 127.9 (CH), 130.0 (CH), 133.6 (quatenary C), 136.3
(quatenary C), 142.2 (NCHN), 144.0 (quatenary C).
129.5 (d, JCF = 15.8 Hz, CH), 129.9 (CH), 130.1 (CH), 130.5 (d, JCF
=
3.8 Hz, quatenary C), 133.7 (quatenary C), 135.9 (quatenary C), 136.9
(quatenary C), 138.0 (py C), 151.1 (py C), 162.6 (d, JCF = 246.8 Hz,
CF), 164.7 (PdC).
Synthesis of 4b.57 Yield: 3.12 g, 82%, mp = 98.5 °C. H NMR
1
Synthesis of 6b. Yield: 0.22 g, 79%, mp = 212.7−214.7 °C. Anal.
Calcd for C26H22Cl2FN3OPd: C, 53.04; H, 3.76; N, 7.13. Found: C,
52.58; H, 3.79; N, 7.16. 1H NMR (CDCl3): δ 3.86 (s, 3H, CH3), 6.20
(s, 2H, CH2), 6.97−7.30 (m, 10H, Ar H), 7.60−7.66 (m, 3H, Ar H),
7.84 (d, J = 9.0 Hz, 2H, Ar H), 8.74−8.79 (m, 2H, Ar H). 13C{1H}
NMR (CDCl3): δ 52.5 (CH2), 55.5 (CH3), 111.1 (CH), 111.2 (CH),
114.6 (CH), 115.8 (d, JCF = 21.9 Hz, CH), 123.6 (CH), 123.7 (CH),
124.4 (py C), 129.1 (CH), 129.5 (quatenary C), 130.0 (d, JCF = 8.3
Hz, CH), 130.5 (quatenary C), 133.6 (quatenary C), 136.2 (quatenary
(CDCl3): δ 3.91 (s, 3H, OCH3), 7.10 (d, J = 9.0 Hz, 2H, Ar H), 7.28−
7.37 (m, 2H, Ar H), 7.42−7.49 (m, 3H, Ar H), 7.87−7.91 (m, 1H, Ar
H), 8.07 (s, 1H, NCHN). 13C{1H} NMR (CDCl3): δ 55.6 (CH3),
110.2 (CH), 115.1 (CH), 120.4 (CH), 122.5 (CH), 123.4 (CH), 125.7
(CH), 129.1 (quatenary C), 134.2 (quatenary C), 142.5 (NCHN),
143.8 (quatenary C), 159.3 (quatenary C).
Synthesis of 4c.58 Yield: 2.54 g, 85%, mp = 91.3 °C. H NMR
1
(CDCl3): δ 7.16−7.27 (m, 4H, Ar H), 7.37−7.43 (m, 3H, Ar H),
7.79−7.82 (m, 1H, Ar H), 7.99 (s, 1H, NCHN). 13C{1H} NMR
(CDCl3): δ 110.1 (CH), 116.9 (d, JCF = 23.3 Hz, CH), 120.6 (CH),
122.8 (CH), 123.7 (CH), 126.0 (d, JCF = 7.5 Hz, CH), 132.3
(quatenary C), 133.8 (quatenary C), 142.2 (NCHN), 143.8 (quatenary
C), 161.9 (d, JCF = 248.2 Hz, CF).
General Procedure for the Synthesis of 5a−c. A mixture of 4
(19.21 mmol) and 4-fluorobenzyl chloride (2.25 mL, 19.21 mmol) in
degassed DMF (25 mL) was allowed to heat at 100 °C for 24 h. After
cooling, solid was formed. The solvent was removed under a vacuum.
C), 138.0 (py C), 151.1 (py C), 159.9 (quatenary C), 162.3 (d, JCF
=
246.8 Hz, CF), 164.6 (PdC).
Synthesis of 6c. It was prepared following a procedure similar to
that of 6a and b, except that the reaction was conducted at 0 °C for 6
h. Yield: 0.26 g, 81%, mp = 183.2−187.1 °C. Anal. Calcd for
C25H19Cl2F2N3Pd: C, 52.06; H, 3.32; N, 7.28. Found: C, 51.98; H,
3.21; N, 6.88. 1H NMR (CDCl3): δ 6.25 (s, 2H, CH2), 7.06 (t, J = 9.0
Hz, 2H, Ar H), 7.14−7.37 (m, 8H, Ar H), 7.65−7.74 (m, 3H, Ar H),
H
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7.96−8.00 (m, 2H, Ar H), 8.79 (d, J = 6.0 Hz, 2H, Ar H). 13C{1H}
NMR (CDCl3): δ 52.7 (CH2), 111.0 (CH), 111.5 (CH), 115.9 (d, JCF
= 21.9 Hz, CH), 116.7 (d, JCF = 23.4 Hz, CH), 123.9 (d, JCF = 4.5 Hz,
quatenary C), 124.6 (py C), 130.0 (d, JCF = 7.5 Hz, CH), 130.1 (d, JCF
= 8.3 Hz, CH), 130.5 (quatenary C), 132.9 (CH), 133.7 (quatenary
(CH), 128.5 (CH), 128.6 (CH), 129.0 (CH), 137.8 (quatenary C),
156.8 (quatenary C).
4-Imidazo[1,2-a]pyridin-3-ylacetophenone (11).52 Yellow solid.
1H NMR (300 MHz, CDCl3): δ 2.60 (s, 3H, CH3), 6.82 (t, J = 6.0 Hz,
1H, Ar H), 7.20 (t, J = 9.0 Hz, 1H, Ar H), 7.61−7.74 (m, 4H, Ar H,
imi H), 8.04 (d, J = 6.0 Hz, 2H, Ar H), 8.35 (d, J = 6.0 Hz, 1H, Ar H).
13C{1H} NMR (75 MHz, CDCl3): δ 26.5 (CH3), 113.0 (CH), 118.3
(CH), 123.2 (CH), 124.6 (quatenary C), 124.8 (CH), 127.1 (CH),
129.2 (CH), 133.6 (CH), 133.8 (quatenary C), 136.0 (quatenary C),
146.7 (quatenary C), 197.1 (CO).
C), 136.1 (quatenary C), 138.2 (py C), 151.1 (py C), 163.1 (d, JCF
=
247.5 Hz, CF), 162.9 (d, JCF = 249.8 Hz, CF), 165.2 (PdC).
Mizoroki−Heck Cross-Coupling Reactions. In a typical run, a
Schlenk tube was charged with aryl halide (1.0 mmol), styrene (1.4
mmol), NaOAc (2.0 mmol), and Pd precatalyst (0.5 mol %). The flask
was thoroughly degassed, added with TBAB (2.0 g), and then placed
in a preheated oil bath at 140 °C. After the mixture was cooled, the
mixture was diluted with water (10 mL) and extracted with ether (3 ×
10 mL). The combined organic portions were dried over anhydrous
MgSO4. After filtration, the solvent was removed completely under a
vacuum. Products were identified by comparison of NMR data with
those in the literature; yields and regioselectivity were determined by
integration ratio using 1,3,5-trimethoxylbenzene as internal standard or
after purification with column chromatography on silica gel.
Direct C−H Arylation Reactions. Typically, a mixture of aryl
halide (1.0 mmol), imidazo[1,2-a]pyridine (1.5 mmol), KOAc (2.0
mmol), and Pd precatalyst (2.5 mol %) was dissolved in DMA (5 mL)
under a nitrogen atmosphere. The reaction mixture was stirred at 140
°C in a preheated oil bath for 18 h. After the mixture was cooled, ethyl
acetate (10 mL) was added. The solution was poured into water (50
mL) and extracted with ethyl acetate (3 × 25 mL). The combined
extract was washed with brine, dried over anhydrous MgSO4, and
evaporated to dryness under a vacuum to give the crude product,
which was purified by column chromatography. Compounds were
identified by comparison of NMR data with those in the literature.
Decarboxylative Coupling Reactions. To a 50 mL flask fitted
with magnetic stirrer, 3-(4-fluorophenyl)-5-methylisoxazole-4-carbox-
ylic (0.50 mmol), aryl halide (0.50 mmol), KOAc (1.0 mmol), and Pd
precatalyst (2.5 mol %) were added under nitrogen. Dry DMA (3 mL)
was added to it. The reaction mixture was stirred at 160 °C for 24 h
and then was allowed to cool at room temperature. After dilution with
distilled water (15 mL), the solution was extracted with ethyl acetate
(3 × 15 mL). The organic layer was separated and dried over
anhydrous MgSO4. Removal of the solvent resulted in a brownish
gummy mass, which was subjected to column chromatography over
silica gel using n-hexane and an increasing proportion of ethyl acetate
as eluent. Compounds were identified by comparison of NMR data
with those in the literature.
1-(4-(3-(4-Fluorophenyl)-5-methyl-isoxazol-4-yl)phenyl)-
ethanone (12).52 Yellow solid. H NMR (300 MHz, CDCl3): δ 2.44
1
(s, 3H, CH3), 2.59 (s, 3H, CH3), 6.98 (t, J = 8.7 Hz, 2H, Ar H), 7.25
(d, J = 1.8 Hz, 2H, Ar H), 7.33−7.38 (m, 2H, Ar H), 7.94 (d, J = 6.6
Hz, 2H, Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 11.8 (CH3), 26.7
(COCH3), 114.9 (CH), 115.8 (d, JCF = 21.9 Hz, CH), 124.8
(quatenary C), 127.5 (quatenary C), 128.8 (CH), 129.9 (CH), 130.5
(d, JCF = 7.5 Hz, CH), 135.2 (quatenary C), 136.3 (quatenary C),
160.2 (quatenary C), 163.5 (d, JCF = 249.1 Hz, CF), 167.3 (quatenary
C), 197.6 (CO).
4-(3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)benzonitrile (13).52
Orange red solid. 1H NMR (300 MHz, CDCl3): δ 2.43 (s, 3H,
CH3), 6.98 (t, J = 8.7 Hz, 2H, Ar H), 7.23−7.33 (m, 4H, Ar H), 7.63
(d, J = 8.1 Hz, 2H, Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 11.8
(CH3), 111.7 (CH), 114.4 (CH), 116.0 (d, JCF = 22.6 Hz, CH), 118.4
(quatenary C), 124.5 (d, JCF = 3.0 Hz, quatenary C), 128.0 (quatenary
C), 130.4 (d, JCF = 12.0 Hz, CH), 132.9 (quatenary C), 135.2
(quatenary C), 160.5 (quatenary C), 163.6 (d, JCF = 249.1 Hz, CF),
167.5 (CN).
3-(4-Fluorophenyl)-4-(4-methoxyphenyl)-5-methylisoxazole
(14).52 Yellow solid. H NMR (300 MHz, CDCl3): δ 2.40 (s, 3H,
1
CH3), 3.81 (s, 3H, OCH3), 6.89 (d, J = 6.0 Hz, 2H, Ar H), 6.98 (t, J =
9.0 Hz, 2H, Ar H), 7.06 (d, J = 9.0 Hz, 2H, Ar H), 7.39−7.44 (m, 2H,
Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 11.4 (CH3), 55.1
(OCH3), 114.1 (CH), 115.1 (quatenary C), 115.5 (d, JCF = 21.8 Hz,
CH), 122.1 (quatenary C), 125.3 (d, JCF = 3.0 Hz, quatenary C), 130.2
(d, JCF = 7.5 Hz, CH), 130.8 (CH), 159.0 (quatenary C), 160.1
(quatenary C), (d, JCF = 249.0 Hz, CF), 166.4 (quatenary C).
3-(4-Fluorophenyl)-5-methyl-4-(4-nitrophenyl)isoxazole (15). Yel-
low solid, mp = 118.9−119.7 °C. HRMS (EI; m/z): calcd for
C16H11FN2O3 298.0753, found 298.0744. 1H NMR (300 MHz,
CDCl3): δ 2.49 (s, 3H, CH3), 7.02 (t, J = 9.0 Hz, 1H, Ar H), 7.15 (d, J
= 12.0 Hz, 1H, Ar H), 7.31−7.36 (m, 2H, Ar H), 7.78 (d, J = 9.0 Hz,
1H, Ar H), 8.20−8.34 (m, 3H, Ar H). 13C{1H} NMR (75 MHz,
CDCl3): δ 11.8 (CH3), 116.0 (d, J = 21.8 Hz, CH), 124.1 (CH), 124.3
(CH), 126.2 (CH), 128.3 (CH), 130.4 (d, J = 8.3 Hz, CH), 137.2
(quatenary C), 145.0 (quatenary C), 147.2 (quatenary C), 148.0
(quatenary C), 160.1 (quatenary C), 163.6 (d, J = 249.0 Hz, CF),
167.6 (quatenary C).
X-ray Diffraction Studies. Samples were collected at 150(2) K on
a Bruker APEX II equipped with a CCD area detector and a graphite
monochromator utilizing Mo Kα radiation (λ = 0.71073 Å). The unit
cell parameters were obtained by least-squares refinement. Data
collection and reduction were performed using the Bruker APEX2 and
SAINT software.36 Absorption corrections were performed using the
SADABS program.62 All the structures were solved by direct methods
and refined by full-matrix least-squares methods against F2 with the
SHELXTL software package.63 All non-H atoms were refined
anisotropically. All H atoms were fixed at calculated positions and
refined with the use of a riding model. Crystallographic data are given
in Table S1 of the Supporting Information. CCDC files 917931 (3a),
917933 (3b), 917932 (3c), 917935 (6a), 917934 (6b), 917936 (6c),
and 918254 (6c′) contain supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
(E)-1-Acetyl-4-styrylbenzene (7).59 Yellow solid. 1H NMR (300
MHz, CDCl3): δ 2.59 (s, 3H, CH3), 7.08−7.19 (m, 2H, Ar H), 7.30
(d, J = 9.0 Hz, 1H, CH), 7.37 (t, J = 9.0 Hz, 2H, Ar H), 7.51−7.58 (m,
4H, Ar H), 7.94 (d, J = 9.0 Hz, 2H, Ar H). 13C{1H} NMR (75 MHz,
CDCl3): δ 26.5 (CH3), 126.4 (CH), 126.7 (CH), 127.3 (CH), 128.2
(CH), 128.7 (CH), 128.8 (CH), 131.3 (CH), 135.8 (quatenary C),
136.6 (quatenary C), 141.9 (quatenary C), 197.5 (CO).
(E)-1-Methoxy-4-styrylbenzene (8).59 Yellow solid. H NMR (300
1
MHz, CDCl3): δ 3.81 (s, 3H, OCH3), 6.87−6.92 (m, 2H, Ar H, CH),
6.98−7.08 (m, 2H, Ar H, CH), 7.19−7.21 (m, 1H, Ar H) 7.32 (t, J =
6.0 Hz, 2H, Ar H), 7.45 (t, J = 9.0 Hz, 4H, Ar H). 13C{1H} NMR (75
MHz, CDCl3): δ 55.3 (CH3), 114.1(CH), 126.2 (CH), 126.6 (CH),
127.2 (CH), 127.7 (CH), 128.2 (CH), 128.6 (CH), 130.1 (quatenary
C), 137.6 (quatenary C), 159.2 (quatenary C).
(E)-1-Methoxy-3-styrylbenzene (9).60 Yellow liquid. 1H NMR (300
MHz, CDCl3): δ 3.84 (s, 3H, OCH3), 6.81 (d, J = 9.0 Hz, 1H, CH),
7.04−7.12 (m, 4H, Ar H), 7.25−7.37 (m, 4H, Ar H), 7.49 (d, J = 9.0
Hz, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 55.1 (OCH3), 111.6
(CH), 113.2 (CH), 119.1 (CH), 126.4 (CH), 127.6 (CH), 128.4
(CH), 128.6 (CH), 128.9 (CH), 129.5 (CH), 137.1 (quatenary C),
138.6 (quatenary C), 159.7 (quatenary C).
(E)-1-Methoxy-2-styrylbenzene (10).61 Yellow solid. 1H NMR (300
MHz, CDCl3): δ 3.91 (s, 3H, OCH3), 6.93 (d, J = 9.0 Hz, 1H, CH),
7.02 (t, J = 6.0 Hz, 1H, Ar H), 7.17 (d, J = 18 Hz, 1H, CH), 7.29 (t, J =
9.0 Hz, 2H, Ar H), 7.40 (t, J = 9.0 Hz, 2H, Ar H, 7.54−7.67 (m, 4H,
Ar H). 13C{1H} NMR (75 MHz, CDCl3): δ 55.4 (CH3), 110.8 (CH),
120.6 (CH), 123.3 (CH), 126.3 (CH), 126.5 (CH, quatenary C), 127.2
I
dx.doi.org/10.1021/om4004219 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(27) Yang, L.; Kruger, A.; Neels, A.; Albrecht, M. Organometallics
2008, 27, 3161.
(28) Xu, X.; Xu, B.; Li, Y.; Hong, S. H. Organometallics 2010, 29,
6343.
(29) Kruger, A.; Haller, L. J. L.; Muller-Bunz, H.; Serada, O.; Neels,
A.; Macgregor, S. A.; Albrecht, M. Dalton Trans. 2011, 40, 9911.
(30) Heckenroth, M.; Neels, A.; Garnier, M. G.; Aebi, P.; Ehlers, A.
W.; Albrecht, M. Chem.Eur. J. 2009, 15, 9375.
(31) Kumar, P. V.; Lin, W.-S.; Shen, J.-S.; Nandi, D.; Lee, H. M.
Organometallics 2011, 30, 5160.
(32) Song, G.; Zhang, Y.; Li, X. Organometallics 2008, 27, 1936.
(33) John, A.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2009, 0,
10581.
̈
ASSOCIATED CONTENT
■
S
* Supporting Information
NMR spectra for products and crystal data (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Tel: +886 4 7232105 ext. 3523. Fax: +886 4 7211190. E-mail:
leehm@cc.ncue.edu.tw.
Notes
The authors declare no competing financial interest.
(34) Zhu, L.; Guo, P.; Li, G.; Lan, J.; Xie, R.; You, J. J. Org. Chem.
2007, 72, 8535.
ACKNOWLEDGMENTS
(35) Liao, C.-Y.; Chan, K.-T.; Zeng, J.-Y.; Hu, C.-H.; Tu, C.-Y.; Lee,
H. M. Organometallics 2007, 26, 1692.
■
We are grateful to the National Science Council 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.
(36) Ray, L.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2007, 0, 4546.
(37) Poater, A.; Cosenza, B.; Correa, A.; Giudice, S.; Ragone, F.;
Scarano, V.; Cavallo, L. Eur. J. Inorg. Chem. 2009, 2009, 1759.
(38) Huynh, H. V.; Yeo, C. H.; Tan, G. K. Chem. Commun. 2006,
3833.
(39) Clavier, H.; Nolan, S. P. Chem. Commun. 2010, 46, 841.
(40) Shi, Y.; Cai, Z.; Peng, Y.; Shi, Z.; Pang, G. J. Chem. Res. 2011, 35,
161.
REFERENCES
■
(1) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
113, 361.
(2) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(3) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.;
Nolan, S. P. J. Organomet. Chem. 2002, 653, 69.
(4) Herrmann, W. A.; Ofele, K.; von Preysing, D.; Schneider, S. K. J.
Organomet. Chem. 2003, 687, 229.
(5) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. Rev. 2004,
248, 2283.
(6) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.
(7) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int.
Ed. 2007, 46, 2768.
(41) Chan, K.-T.; Tsai, Y.-H.; Lin, W.-S.; Wu, J.-R.; Chen, S.-J.; Liao,
F.-X.; Hu, C.-H.; Lee, H. M. Organometallics 2010, 29, 463.
(42) Lee, J.-Y.; Cheng, P.-Y.; Tsai, Y.-H.; Lin, G.-R.; Liu, S.-P.; Sie,
M.-H.; Lee, H. M. Organometallics 2010, 29, 3901.
(43) Sie, M.-H.; Hsieh, Y.-H.; Tsai, Y.-H.; Wu, J.-R.; Chen, S.-J.;
Kumar, P. V.; Lii, J.-H.; Lee, H. M. Organometallics 2010, 29, 6473.
(44) Godula, K.; Sames, D. Science 2006, 312, 67.
(45) Campeau, L.-C.; Fagnou, K. Chem. Commun. 2006, 1253.
(46) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107,
174.
̈
(47) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38,
2447.
(48) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7,
1857.
(8) Wurtz, S.; Glorius, F. Acc. Chem. Res. 2008, 41, 1523.
̈
(9) Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440.
(10) Organ, M. G.; C
Angew. Chem., Int. Ed. 2009, 48, 2383.
(11) de Fremont, P.; Marion, N.; Nolan, S. P. Coord. Chem. Rev.
2009, 253, 862.
̧alimsiz, S.; Sayah, M.; Hoi, K. H.; Lough, A. J.
(49) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373.
(50) Rodriguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030.
(51) Cornella, J.; Larrosa, I. Synthesis 2012, 2012, 653.
(52) Nandi, D.; Jhou, Y.-M.; Lee, J.-Y.; Kuo, B.-C.; Liu, C.-Y.; Huang,
P.-W.; Lee, H. M. J. Org. Chem. 2012, 77, 9384.
(53) Adams, R.; Pachter, I. J. J. Am. Chem. Soc. 1954, 76, 1845.
(54) Wu, Z.; Pan, Y.; Zhou, X. Synthesis 2011, 2011, 2255.
(55) Fu, H. Y.; Chen, L.; Doucet, H. J. Org. Chem. 2012, 77, 4473.
(56) Suresh, P.; Pitchumani, K. J. Org. Chem. 2008, 73, 9121.
(57) Maheswaran, H.; Krishna, G. G.; Prasanth, K. L.; Srinivas, V.;
Chaitanya, G. K.; Bhanuprakash, K. Tetrahedron 2008, 64, 2471.
(58) Altman, R. A.; Koval, E. D.; Buchwald, S. L. J. Org. Chem. 2007,
72, 6190.
́
(12) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J. W.;
̈
Crabtree, R. H. J. Am. Chem. Soc. 2002, 124, 10473.
(13) Appelhans, L. N.; Zuccaccia, D.; Kovacevic, A.; Chianese, A. R.;
Miecznikowski, J. R.; Macchioni, A.; Clot, E.; Eisenstein, O.; Crabtree,
R. H. J. Am. Chem. Soc. 2005, 127, 16299.
(14) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller Robert, J.
W.; Crabtree, H. Chem. Commun. 2001, 0, 2274.
(15) Arnold, P. L.; Pearson, S. Coord. Chem. Rev. 2007, 251, 596.
(16) Albrecht, M. Chem. Commun. 2008, 0, 3601.
(17) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M.
Chem. Rev. 2009, 109, 3445.
(18) Poulain, A.; Iglesias, M.; Albrecht, M. Curr. Org. Chem. 2011, 15,
3325.
(19) Crabtree, R. H. Pure Appl. Chem. 2003, 75, 435.
(20) Guisado-Barrios, G.; Bouffard, J.; Donnadieu, B.; Bertrand, G.
Angew. Chem., Int. Ed. 2010, 49, 4759.
(59) Kong, G.-Q.; Ou, S.; Zou, C.; Wu, C.-D. J. Am. Chem. Soc. 2012,
134, 19851.
(60) Xu, H.-J.; Zhao, Y.-Q.; Zhou, X.-F. J. Org. Chem. 2011, 76, 8036.
(61) McNulty, J.; Das, P. Eur. J. Org. Chem. 2009, 2009, 4031.
(62) Sheldrick, G. M. SADABS; University of Gottingen: Gottingen,
̈
̈
Germany, 1996.
(63) Sheldrick, G. Acta Crystallogr. 2008, A64, 112.
(21) Bacciu, D.; Cavell, K. J.; Fallis, I. A.; Ooi, L.-l. Angew. Chem., Int.
Ed. 2005, 44, 5282.
(22) Chianese, A. R.; Kovacevic, A.; Zeglis, B. M.; Faller, J. W.;
Crabtree, R. H. Organometallics 2004, 23, 2461.
(23) Schutz, J.; Herdtweck, E.; Herrmann, W. A. Organometallics
̈
2004, 23, 6084.
(24) Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. J. Am.
Chem. Soc. 2004, 126, 5046.
(25) Iglesias, M.; Albrecht, M. Dalton Trans. 2010, 39, 5213.
(26) Heckenroth, M.; Kluser, E.; Neels, A.; Albrecht, M. Angew.
Chem., Int. Ed. 2007, 46, 6293.
J
dx.doi.org/10.1021/om4004219 | Organometallics XXXX, XXX, XXX−XXX