Synthesis and Characterization of C, C -Type Palladacycles and Their Catalytic Application in Mizoroki-Heck Coupling Reaction

Article abstract of DOI:10.1021/acs.organomet.8b00054

Two series of ligand precursors, based on imidazo[1,2-a]pyridine and C2-phenyl substituted imidazole moieties, were developed and synthesized in high yields, featuring an N-CH₂(C=O)Ar substituent on the imidazole ring. Upon reacting with palladium acetate, both series of ligands underwent double C-H bond activations at the methylene and o-aryl carbon sites on the N-CH₂(C=O)Ar substituent, yielding C,C-type palladacycles bearing five-membered chelate rings. A dimeric palladium complex with bridging bromides was obtained from the ligand precursor with the bromide anion, whereas an ionic palladium complex with two "throw away" pyridine ligands was formed with the precursor of the tetrafluoroborate anion. All complexes are air-stable and were characterized by ¹H and ¹³C NMR spectroscopy and elemental analysis. The structures of three of the new complexes were further established by single-crystal X-ray diffraction studies. These complexes have been screened for catalyzing Mizoroki-Heck coupling reaction using ionic salt as solvent. The complex based on imidazo[1,2-a]pyridine, which has an electron-donating 4-methoxyphenyl ring on the ligand scaffold, was the most efficient catalyst, capable of using activated aryl chloride and sterically hindered aryl bromide as substrates. It was also successfully applied in the green process of one-pot Mizoroki-Heck coupling/trans-esterification reaction in molten ionic salt.

Full text of DOI:10.1021/acs.organomet.8b00054

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Synthesis and Characterization of C,C‑Type Palladacycles and Their
Catalytic Application in Mizoroki−Heck Coupling Reaction
Chi Hou Lo and Hon Man Lee*
Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan
*
S Supporting Information
ABSTRACT: Two series of ligand precursors, based on imidazo[1,2-
a]pyridine and C2-phenyl substituted imidazole moieties, were
developed and synthesized in high yields, featuring an N-CH (C
2
O)Ar substituent on the imidazole ring. Upon reacting with
palladium acetate, both series of ligands underwent double C−H
bond activations at the methylene and o-aryl carbon sites on the N-
CH (CO)Ar substituent, yielding C,C-type palladacycles bearing
2
five-membered chelate rings. A dimeric palladium complex with
bridging bromides was obtained from the ligand precursor with the
bromide anion, whereas an ionic palladium complex with two “throw
away” pyridine ligands was formed with the precursor of the
tetrafluoroborate anion. All complexes are air-stable and were
1
13
characterized by H and C NMR spectroscopy and elemental
analysis. The structures of three of the new complexes were further established by single-crystal X-ray diffraction studies. These
complexes have been screened for catalyzing Mizoroki−Heck coupling reaction using ionic salt as solvent. The complex based on
imidazo[1,2-a]pyridine, which has an electron-donating 4-methoxyphenyl ring on the ligand scaffold, was the most efficient
catalyst, capable of using activated aryl chloride and sterically hindered aryl bromide as substrates. It was also successfully applied
in the green process of one-pot Mizoroki−Heck coupling/trans-esterification reaction in molten ionic salt.
INTRODUCTION
ylides including a derivative of imidazole, affording several
orthometalated complexes via regioselective C−H bond
activation. Taking all of these into consideration, we intended
to further explore the possibility of obtaining novel palladium
complexes based on the ligand scaffold. We choose to append
an aryl group directly adjacent to the carbonyl carbon in the N-
■
Palladacycles or cyclopalladated compounds have attracted
much interest in the last two decades due to their wide
applicability in catalysis, and their bioactive, mesogenic, and
photoluminescent properties. Common palladacycles in the
literature are C,E-types which contain nitrogen, oxygen,
4b
1
2
CH (CO)R substituent (R = Ar). The target ligand
1
a−g
2
phosphorus, and sulfur donors, etc.
For C,C-palladacycles,
precursors also possess various potential sites for C−H
activation. These could possibly lead to the formation of a
variety of palladium complexes, including a C,C-type pallada-
cycle of five-membered chelate ring, aNHC complex,
zwitterionic palladium complex, or even a tridentate C,C,C-
type pincer complex. Herein, we report our results on the
synthesis and characterization of the new ligand precursors and
their successful palladation. The C,E-type palladacycles have
been generally applied in catalyzing Mizoroki−Heck coupling
the two Pd−C bonds can be used for the development of new3
catalytic reactions, such as the construction of cyclic structures,
hence are usually implicated as important intermediates in
catalytic cycles. Preformed C,C-type palladacycles are, however,
3
d,4
́
́
Lautens and Garcia-Lopez et al. recently
relatively rare.
reported several exemplary model intermediates including spiro
C,C-type palladacycles for the Pd-catalyzed cascade remote C−
H functionalization of N-(2-haloaryl)acrylamides. Previously,
we reported various palladium(II) complexes based on a ligand
3d
1a−g,6
reaction.
In contrast, the use of a C,C-type palladacycle in
scaffold bearing an imidazolyl moiety and an N-CH (CO)R
2
this reaction is very rare. Hence, another objective of this work
is to explore the potential catalytic applications of C,C-type
palladacycles in Mizoroki−Heck coupling reaction.
4a,5
substituent (R = NR′Ar, or Me) (Chart 1).
The ligand
scaffold contains various sites that can undergo C−H or N−H
cleavage, generating different palladium complexes. These
4a
include six-membered C,C-type palladacycle A, six-membered
C,C-type palladacycle B, palladalactam C, abnormal N-
heterocyclic carbene (aNHC) complex D, and monodentate
zwitterionic palladium complex E. We envision that further
RESULTS AND DISCUSSION
4a
4a
■
5a
Design and Synthesis of Ligand Precursors. Scheme 1
shows the synthetic pathways for the preparation of the two
5
b,c
modification of the N-CH (CO)R substituent in the ligand
2
scaffold could potentially lead to different palladation behavior.
In a previous work, Urriolabeitia et al. utilized a series of N-
Received: January 27, 2018
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00054
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Chart 1. A Range of Palladium(II) Complexes Based on a Ligand Scaffold with an Imidazolyl Moiety and an N-CH (CO)R
2
4a,5
Substituent (R = NR′Ar or Me)
Scheme 1. Synthesis of Ligand Precursors
series of ligand precursors. For the first series (Scheme 1a),
compounds 1a−c and 2a−c contain an imidazo[1,2-a]pyridine
ring, whereas, in the second series (Scheme 1b), the imidazole
rings in 3a−b and 4a−b contain a C2-phenyl group. The
reason for such design is that the C2-phenyl group from 3a−b
and 4a−b can potentially have an ortho carbon site for
palladation (see complex B in Chart 1). This is not possible for
compounds 1a−c and 2a−c. The key reaction for the
preparation of the imidazolium bromides is the quaternization
reaction between an imidazole derivative and organic bromide.
To enrich the electron density of the palladium center for the
oxidative addition of aryl halide substrates, the ligand scaffold
was appended with electron-donating methoxy groups on
phenyl rings, yielding isomers b and c. Compounds 1a−c and
Synthesis of Palladium Complexes. The palladation of
these new ligand precursors was investigated (Scheme 2).
Different reaction conditions have been attempted previously,
and only reactions of the ligand precursors 1a−c and palladium
acetate in DMF at room temperature successfully yielded pure
products of dimeric C,C-type palladacycles 5a−c. The bidentate
ligand carries formally a net anionic charge, and a bromide
ligand is needed for the charge balance on the palladium(II)
center. To attain a stable palladium(II) structure, a dimeric
compound was formed by the bridging coordination of
bromide ligands. Notably, these complexes were zwitterionic
in nature with a positive charge on the nitrogen atom and a net
anion charge at the palladium center. The successful formation
of these dimeric, bromide-bridged complexes was confirmed by
+
the diagnostic peak of the [Pd L Br] ion at m/z = 914.8 in the
2
2
3a−b with bromide anions were obtained as white solids with
ESI-MS of 5a. Interestingly, an equally intense m/z peak at
6
8−85% yields. Salt metathesis reactions between these
+
1
412.5, attributable to a trimeric [Pd L Br ] ion, was also
3 3 2
bromide salts with NaBF in acetonitrile (ACN) allowed the
4
observed. The presence of this signal indicates that the μ-Br
coordination in the dimeric complex can dissociate facilely into
the neutral unsaturated mononuclear [PdLBr] species in
formation of imidazolium salts 2a−c and 4a−b with non-
coordinating tetrafluoroborate anions with 73−91% yields. The
characteristic signal for the methylene protons next to the
carbonyl group was observed at ca. 6.4 ppm in 1 and 2, 6.0 ppm
+
solution. This species reacts with the dimeric [Pd L Br] ion
2
2
+
1
13
to form the trimeric [Pd L Br ] ion. Diagnostic H and
C
3
3
2
1
3
in 3, and 5.6 ppm in 4. Their corresponding C NMR signals
were at ca. 53.2−55.9 ppm.
NMR signals were also measured. The methylene signal
corresponding to the two protons in 1a appeared at 6.49
B
DOI: 10.1021/acs.organomet.8b00054
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Scheme 2. Synthesis of C,C-Type Palladacycles
ppm. After complexation, the Pd−CH signal corresponding to
one proton was shifted downfield to 6.84 ppm. Consistently,
the coordinating methylene carbon signal appeared at 54.6
ppm. The signal was shifted downfield to 68.6 ppm upon
complexation. The coordinated phenyl carbon resonances in
complexes like the aforementioned 6a−c, bearing a five-
membered chelate ring, or C,C-type palladacycles like B in
Chart 1, bearing a six-membered chelate ring. The possibility of
forming a tridentate pincer C,C,C-type complex containing
both five- and six-membered chelate rings also exists. We
discovered that the reaction between precursors 4a−b with
palladium complexes yielded the C,C-type palladacycles 7a−b,
with 42% and 35% yields, respectively. The characteristic Pd−
CH signal appeared at 6.04 and 5.98 ppm in 7a−b, respectively,
which shifted significantly downfield relative to those of the
methylene signals at ca. 5.17 ppm in precursors 4a−b. The
much lower yields of these reactions were attributable to the
competitive reactions of the formation of the trans-
5
a−c were observed in the range of 153.8−156.8 ppm, which is
4b
typical for this type of carbon.
The bromide ions from the ligand precursors 1a−c
transformed into the bridging ligands in the dimeric complexes
5a−c. We then used ligand precursors 2a−c that contained
noncoordinating tetrafluoroborate anions, which were expected
to result in mononuclear complexes. As expected, the
complexation reaction between 2a−c and palladium acetate
in dry pyridine resulted in ionic C,C-type palladium complexes
7
PdCl (pyridine) side product.
2
2
6
a−c bearing two pyridine ligands and BF anions. A similar
4
It should be noted that the absence of C2 protons on the
imidazole/imidazo[1,2-a]pyridine rings in both series of ligand
precursors prevented the formation of palladium complexes
with normal NHC ligands. Conversely, the formation of
downfield shift in proton signal was observed upon complex-
ation. The Pd−CH proton signal in 6a appeared downfield at
6.72 ppm compared with that of the CH proton at 6.41 ppm in
2
the ligand precursor 2a. The mononuclear structure and ionic
nature of 6a−c was established by single-crystal X-ray
diffraction studies of 6a,b.
The ligand precursors 4a−b have a phenyl group attached to
the C2 carbon of the imidazolyl ring. As such, they can react
with palladium acetate to potentially form C,C-type palladium
5a,8
palladium abnormal NHC complexes
would be possible
upon the deprotonation of the C4/5 sites (see complex D in
Chart 1). Despite this, the formation of palladium abnormal
NHC complexes was not observed for both series of ligand
precursors. The formation of complex E is not observed either,
C
DOI: 10.1021/acs.organomet.8b00054
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Figure 1. (a) Molecular structure of cationic portion of 6a (left) at 50% probability level. Hydrogen atoms except that on C1 and C30 are omitted
for clarity. Selected bond distances (Å) and angles (deg): Pd1−C1, 2.050(5); Pd1−C17, 1.992(5); Pd1−N3, 2.150(4); Pd1−N4, 2.123(4); C1−
Pd1−C17, 80.37(19); C17−Pd1−N4, 96.25(19); N3−Pd1−N4, 90.26(16); C1−Pd1−N3, 93.66(17); C17−Pd1−N3, 172.17(18); C1−Pd1−N4,
172.50(17). (b) Molecular structure of cationic portion of 6b (right) at 50% probability level. Hydrogen atoms except that on C1 and C30 are
omitted for clarity. Selected bond distances (Å) and angles (deg): Pd1−C30, 2.022(7); Pd1−C20, 1.989(7); Pd1−N1, 2.122(6); Pd1−N4, 2.116(7);
C20−Pd1−C30, 79.6(3); C20−Pd1−N4, 94.7(3); N1−Pd1−N4, 90.0(3); C30−Pd1−N1, 95.7(3); C20−Pd1−N1, 175.0(3); C30−Pd1−N4,
173.7(3).
which is also attributable to the higher stability of bidenatate vs
monodentate coordination.
bromide (TBAB) as solvent, and a reaction time of 2 h at 140
°C, a benchmark reaction between 4-chloroacetophenone and
9
Structural Description. The structures of complexes 6a,
b, and 7b were confirmed by X-ray crystallographic studies
styrene was studied. TBAB is a solid at room temperature, but
becomes liquid at elevated temperatures. As shown from entries
1−6, among the new complexes tested, dimeric 5a and ionic 6b
and 7b were very active precatalysts, giving quantitative yields
of coupled product with high trans/gem ratios. The higher
activity of 6b vs 6a (entries 3 vs 2) and 7b vs 7a (entries 6 vs 5)
reflects the effectiveness of having the electron-donating 4-
methoxy group on the phenyl ring. Entries 3 and 4 indicate that
the position of the 4-methoxy group on the ligand scaffold is
also important in defining the performance of the catalyst. A
higher activity (100% vs 89%) was achieved if the electron-
donating group was installed on the phenyl ring next to the
carbonyl group. The dimeric complex 5a delivered somewhat
better activity than 6a, possessing two pyridine “throw away”
ligands (entries 1 vs 2). To determine the effectiveness of 5a,
6
(Figures 1 and 2). The crystallographic data are tabulated in
6a, and 7b in catalyzing the reaction, the palladium loading was
reduced from 0.5 to 0.2 mol %. In all three cases, quantitative
yields were still achieved (entries 7−9). Further reducing the
palladium loading to 0.1 mol % revealed that complex 6b was
the most active precatalyst with 88% yield (entry 11), whereas
complex 7b, with the phenyl ring attached at the C2 position,
gave only a 12% yield. The higher activity of 6b compared to 7b
can be attributed to the planar imidazo[1,2-a]pyridine moiety
in 6b, which is less sterically bulky than the nonplanar C2-
phenyl substituted imidazole ring in 7b (see Figure 2). Ligand-
free palladium acetate has been previously shown to exhibit
good Mizoroki−Heck coupling activity. To gauge the perform-
ance of 6b, the activity of palladium acetate was also
investigated. A comparison of entries 11 and 13 indicated
that 6b delivered a better yield than the ligand-free palladium
acetate. Overall, the optimized reaction conditions of 0.2−0.5
mol % 6b, NaOAc as base, TBAB as solvent, and a reaction
temperature of 140 °C were established.
On the basis of the explored conditions, the substrate scope
of the reaction was tested, beginning with a series of aryl
chlorides (Table 2). As shown in entries 1−3, activated aryl
chlorides can be effectively coupled with styrene in 2 h,
producing yields in the range of 82−97%. 4-Trifluoromethyl-
phenyl chloride can also be used as a substrate, albeit with a
slightly lower yield of 66% (entry 4). The catalyst system is,
however, less effective in utilizing electron-neutral and electron-
rich aryl chloride substrates (entries 5−7). For example, only a
13% yield was obtained with 4-chloroanisole, even with an
increase in palladium loading from 0.2 to 0.5 mol % (entry 7).
The reactivity trend of these aryl chloride substrates was similar
Figure 2. Molecular structure of cationic portion of 7b at 50%
probability level. Hydrogen atom except that on C17 is omitted for
clarity. Selected bond distances (Å) and angles (deg): Pd1−C17,
2
2
.044(3); Pd1−C24, 1.995(3); Pd1−N3, 2.140(3); Pd1−N4,
.116(2); C17−Pd1−C24, 80.60(11); C24−Pd1−N4, 95.64(9);
N3−Pd1−N4, 86.79(9); C17−Pd1−N3, 97.09(10); C24−Pd1−N3,
176.17(10); C17−Pd1−N4, 175.57(10).
Table S1 in the Supporting Information. In general, the
palladium center in each of the structures exhibits a distorted
square planar coordination geometry. The bite angles of these
ligands are all similar at ca. 80°. The Pd−CH distances are in
the range of 2.022(7)−2.050(5) Å, which are longer than those
of the Pd−C distances from the phenyl rings (1.989(7)−
10
1.995(3) Å). This reflects the stronger coordination of the
latter as a carbon donor. The Pd−CH distances are comparable
to that found in a related palladacycle reported by Urriolabeitia
et al. (1.964(2) Å), but the Pd−C distances from the phenyl
rings were significantly longer than that of 1.964(2) Å in the
4b
reported structure. In line with the expected trans influence,
the Pd−N bonds trans to the coordinated CH groups are
slightly shorter than those trans to the phenyl groups. This is
exemplified by the two Pd−N bond distances of 2.123(4) and
2
.150(4) Å in 6a.
Mizoroki−Heck Coupling Reaction. The potential
applications of the new palladium complexes as catalysts in
Mizoroki−Heck coupling reaction were investigated (Table 1).
With reference to our previously reported conditions of 0.5 mol
%
palladium loading, NaOAc as base, n-tetrabutylammonium
D
DOI: 10.1021/acs.organomet.8b00054
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a
Table 1. Catalyst Screening for Mizoroki−Heck Coupling Reaction
entry
cat.
Pd mol %
yield (%)
1
2
3
4
5
6
7
8
9
5a
6a
6b
6c
7a
7b
5a
6b
7b
5a
6b
7b
0.5
0.5
0.5
0.5
0.5
0.5
0.2
0.2
0.2
0.1
0.1
0.1
0.1
100 (92.8)
85 (95:5)
100 (96:4)
89 (94:6)
63 (94:6)
100 (96:4)
100 (96:4)
100 (94:6)
100 (96:4)
80 (96:4)
88 (96:4)
12 (92:8)
79 (95:5)
1
1
1
1
0
1
2
3
Pd(OAc)2
a
Reaction conditions: 1.4 mmol of styrene, 1 mmol of 4-chloroacetophenone, 1.1 mmol of NaOAc, 2 g of TBAB, 0.1−0.5 mol % of [Pd] cat., 140
1
°C. Yield determined by H NMR using 1,3,5-trimethoxybenzene as internal standard.
1
1
upon replacing styrene with n-butyl acrylate as the coupling
partner (entries 8−11). The catalyst system is, however,
ineffective with unactivated n-hexene as alkene substrate. Using
without the presence of palladium metal. Further, heating of
the methyl ester in TBAB for 12 h afforded the corresponding
n-butyl ester with 90% yield. To further confirm the reaction
profile of the Mizoroki−Heck coupling and trans-esterification,
the reaction between 4-chloronitrile and methyl acrylate was
allowed to react over 2 h. Only the methyl ester product was
obtained with 23% yield. Prolonging the reaction time to 12 h
led to the complete conversion to n-butyl ester. This indicates
that the trans-esterification reaction is slow compared with the
Mizoroki−Heck coupling reaction.
3,4-dimethoxystyrene, prolonged reaction time (12 h) was
needed to produce the same yield levels (entries 12−15). For
example, the reaction between the styrene derivative and 4-
nitrophenyl chloride produced a quantitative yield of product in
1
4
1
2 h. Similarly, prolonged heating permitted coupling between
-chlorobenzonitrile and phenyl acrylate with 60% yield (entry
6). Overall, complex 6b is effective in utilizing activated aryl
chlorides as substrates with good to excellent yielding coupled
products.
Finally, the one-pot Mizoroki−Heck coupling/trans-ester-
ification green reaction, using a range of activated chlorides
with methyl acrylate, was investigated (Table 4). In general, the
corresponding n-butyl ester coupled products were obtained in
excellent yields (entries 1−5). 3-Bromoanisole was also
successfully applied as a substrate, giving product with 92%
yield (entry 6).
It has been shown that cross-coupling reactions catalyzed by
soluble palladium precatalysts can proceed via heterogeneous
mechanistic pathways. To understand the possible involve-
ment of a heterogeneous pathway, a mercury drop test was
performed on the benchmark reaction between 4-chloroaceto-
phenone and styrene, catalyzed by 6b. In the presence of
mercury, the product yield was markedly reduced from
quantitative to 57%. This suggested that, beside homogeneous
pathways, a heterogeneous process is also likely to be involved.
To further confirm the involvement of heterogeneous species in
the reaction mixture, a drop of the reaction mixture was allowed
to evaporate and was examined under TEM. This revealed the
presence of palladium nanoparticles. The size of these particles
was ca. 2−3 nm (Figure S1 in the Supporting Information).
Since aryl bromides are more commonly used in organic
synthesis, the substrate scope of aryl bromides was also
investigated (Table 3). Because the activity of aryl bromide is
generally higher than that of aryl chloride, we focused on
challenging aryl bromide substrates with steric hindrance. As
shown in entries 1 and 2, 2- or 3-bromoanisoles could be
effectively coupled with styrene, giving good yields of coupled
products in 12 h. 3,4,5-Trimethoxyphenyl bromide reacted with
styrene with 42% yield (entry 3). Increasing the palladium
loading to 0.5 mol % improved the yield to 63%. The highly
bulky 2-bromomesitylene could couple with styrene, affording a
mediocre yield of 44% (entry 4). Similar yields were obtained
upon changing styrene to n-butyl acrylate and 3,4-dimethox-
ystyrene (entries 5−10). Overall, the complex 6b can utilize
sterically hindered aryl bromides as substrates with average to
good yielding coupled products.
Interestingly, when methyl acrylate was employed as a
coupling partner, the expected methyl ester product was not
formed. Instead, trans-esterification occurred, producing n-butyl
ester and n-pentyl ester when TBAB and tetrapentyl
ammonium bromide (TPeAB) were used as solvents,
respectively (Scheme 3). It is apparent that the n-butyl and
n-pentyl groups are from TBAB and TPeAB, respectively. To
prove this, a simple reaction between 4-chlorobenzonitrile and
methyl acrylate, catalyzed by 6b, was conducted in organic
solvent. As expected, only the methyl ester, (E)-methyl 3-(4-
cyanophenyl)acrylate, was obtained, albeit with low yield. It was
reported that the trans-esterification involving TBAB can occur
12
13
CONCLUSION
■
Continuing our interest in the ligand scaffold based on an
imidazolyl moiety and an N-CH (CO)R substituent, we fine-
2
tuned our ligand scaffold by the installation of an aryl group on
the carbonyl carbon (R = Ar). Two different series of ligand
precursors based on imidazo[1,2-a]pyridine and C2-phenyl
substituted imidazole moieties were developed. These ligand
E
DOI: 10.1021/acs.organomet.8b00054
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a
a
Table 2. Substrate Scope of Aryl Chlorides
Table 3. Substrate Scope of Hindered Aryl Bromides
a
Reaction conditions: 1.4 mmol of alkene, 1 mmol of aryl bromide, 1.1
mmol of NaOAc, 2 g of TBAB, 0.2 mol % of 6b, 140 °C, 12 h, isolated
b
yield. 0.5 mol % of 6b.
a
Reaction conditions: 1.4 mmol of alkene, 1 mmol of aryl chloride, 1.1
mmol of NaOAc, 2 g of TBAB, 0.2 mol % of 6b, 140 °C, isolated yield.
b
EXPERIMENTAL SECTION
General Information. All manipulations were performed under a
dry nitrogen atmosphere using standard Schlenk techniques. Solvents
were dried with standard procedures. Starting chemicals were
0.5 mol % of 6b.
■
1
purchased from a commercial source and used as received. H and
precursors possess multiple sites for C−H activation that can
give rise to a range of different palladium complexes. Both sets
of ligands reacted regioselectively with palladium acetate,
forming a series of C,C-type palladacycles featuring five-
membered chelate rings via double C−H bond activation at
the methylene and o-aryl carbons. This result highlights the
strong directing effect of the carbonyl group. Among the new
complexes, the mononuclear complex with the ligand scaffold
bearing an imidazo[1,2-a]pyridine moiety and an electron-
donating methoxy group, was found to be the most effective in
catalyzing the Mizoroki−Heck coupling reaction. Subsequently,
the screened complex was successfully applied in the one-pot
Mizoroki−Heck coupling/trans-esterification green reaction,
with activated aryl chloride substrates in ionic salt as solvent.
Further investigation on the reactivity of these complexes with
compounds of unsaturated bonds is ongoing in our lab in the
hope of devising new catalytic transformations.
13
1
C{ H} NMR spectra were recorded at 300.13 and 75.47 MHz,
respectively, on a Bruker AV-300 spectrometer. Elemental analyses
were performed on a Thermo Flash 2000 CHN-O elemental analyzer.
ESI-MS was carried out on a Finnigan/Thermo Quest MAT 95XL
mass spectrometer at National Chung Hsing University (Taiwan).
Synthesis of 1a. A mixture of 3-phenylimidazo[1,2-a]pyridine
(
1.60 g, 8.24 mmol) and 2-bromo-1-phenylethanone (1.65 g, 8.24
mmol) in THF (30 mL) was placed in a Schlenk flask. The mixture
was heated to 80 °C for 2 days. After cooling, the white solid was
collected on a frit, washed with THF three times, and dried under
vacuum. Yield: 2.22 g (68%). Mp = 206.4−207.1 °C. ESI-HRMS m/z:
+
1
[M − Br] Calcd for C H N O 313.1340; Found 313.1334. H
21
17
2
NMR (300 MHz, DMSO-d ): δ 6.49 (s, 2H, CH ), 7.62−7.79 (m, 9H,
Ar H), 8.15 (d, 3H, J = 6.0 Hz, 8.41 (d, 1H, J = 9.0 Hz, Ar H),
.51 (s, 1H, imi H), 8.90 (d, 1H, J = 6.0 Hz, Ar H). C{ H} NMR
6
2
3
3
HH
HH
3
13
1
8
(
(
1
HH
75.4 MHz, DMSO-d ): δ 54.6 (CH ), 112.5, 118.6, 124.8, 125.0
6 2
quaternary C), 126.7 (quaternary C), 127.6, 129.0, 129.5, 129.7,
30.1, 130.9, 134.3 (quaternary C), 134.7, 135.0, 140.7 (quaternary C),
192.0 (CO).
F
DOI: 10.1021/acs.organomet.8b00054
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 3. Mizoroki−Heck Coupling Reaction and Trans-esterification in Ionic Salt: (a) One-Pot and (b) Stepwise Procedures
Table 4. One-Pot Mizoroki−Heck Coupling Reaction and
Synthesis of 1c. The compound was prepared with a similar
procedure to that of 1a. A mixture of 3-(4-methoxyphenyl)imidazo-
a
Trans-esterification of Aryl Halides and Methyl Acrylate
[
1,2-a]pyridine (1.87 g, 8.33 mmol) and 2-bromo-1-phenylethanone
1.66 g, 8.33 mmol) was used. A white solid was obtained. Yield: 2.99
(
+
g (85%). Mp = 253.3−253.9 °C. ESI-HRMS m/z: [M − Br] Calcd
for C H N O 343.1446; Found 343.1443. H NMR (300 MHz,
1
22
19
2
2
3
DMSO-d ): δ 3.88 (s, 3H, CH ), 6.42 (s, 2H, CH ), 7.24 (d, 2H, J
=
6
3
2
HH
3
9.0 Hz, Ar H), 7.59 (t, 1H, J = 9.0 Hz, Ar H), 7.65−7.73 (m, 4H,
HH
3
Ar H), 7.81 (t, 1H, J = 6.0 Hz, Ar H), 8.08−8.16 (m, 3H, Ar H),
HH
3
8
.34−8.36 (m, 2H, imi H, Ar H), 8.82 (d, 1H, J = 6.0 Hz, Ar H).
C{ H} NMR (75.4 MHz, DMSO-d ): δ 54.4 (CH ), 56.0 (CH ),
HH
13
1
6
2
3
1
1
12.4, 115.6, 116.9 (quaternary C), 118.4, 124.3, 126.7 (quaternary C),
27.5, 128.9, 129.5, 131.5, 134.3 (quaternary C), 134.5, 135.0, 140.5
(quaternary C), 161.2 (quaternary C), 192.0 (CO).
Synthesis of 2a. A mixture of 1a (2.0 g, 8.92 mmol) and NaBF (5
4
g, 46 mmol) in acetonitrile (30 mL) was placed in a Schlenk flask. The
mixture was heated to 80 °C for 48 h. After, the reaction was cooled,
extracted with DCM (3 × 10 mL), and dried with anhydrous MgSO4.
The solvent was removed completely under high vacuum, and the
white solid was collected on a frit, washed with ether, and dried under
vacuum. Yield: 1.36 g (89%). Mp = 196.8−197.5 °C, ESI-HRMS m/z:
+
1
[
M − BF ] Calcd for C H N O 313.1340; Found 313.1333. H
4
21 17
2
NMR (300 MHz, DMSO-d ): δ 6.41 (s, 2H CH ), 7.59−7.72 (m, 6H,
6
2
Ar H), 7.79−7.81 (m, 3H, Ar H), 8.11−8.17 (m, 3H, Ar H), 8.38 (d,
3
3
1
H, J = 9.0 Hz, Ar H), 8.42 (s, 1H, imi H), 8.9 (d, 1H, J = 9.0
H
H
H
H
1
3
1
Hz, Ar H). C{ H} NMR (75.4 MHz, DMSO-d ): δ 54.2 (CH ),
6
2
1
12.3, 118.5, 124.8, 125.0 (quaternary C), 126.8 (quaternary C), 127.7,
a
Reaction conditions: 1.4 mmol of methyl acrylate, 1 mmol of aryl
128.9, 129.5, 129.7, 130.2, 131.0, 134.3 (quaternary C), 134.7, 135.1,
140.7 (quaternary C), 192.0 (CO).
halide, 1.1 mmol of NaOAc, 2 g of TBAB, 0.2 mol % of 6b, 140 °C, 12
h, isolated yield. TPeAB instead of TBAB.
b
Synthesis of 2b. The compound was prepared with a similar
procedure to that of 2a. A mixture of 1b (2.0 g, 8.9 mmol) and NaBF4
Synthesis of 1b. The compound was prepared with a similar
procedure to that of 1a. A mixture of 3-phenylimidazo[1,2-a]pyridine
(5 g, 46 mmol) was used. A white solid was obtained. Yield: 1.1 g
+
(73%). Mp = 163.1−163.7 °C. ESI-HRMS m/z: [M − BF
] Calcd for
4
1
1.60 g, 8.24 mmol) and 2-bromo-1-(4-methoxyphenyl)ethanone
C
22
H
19
N
2
O
2
343.1446; Found 343.1437. H NMR (300 MHz,
): δ 3.91 (s, 3H, CH ), 6.33 (s, 2H, CH ), 7.21 (d, 2H,
HH = 9.0 Hz, Ar H), 7.60 (t, 1H, JHH = 6.0 Hz, Ar H), 7.67−7.71 (m,
3H, Ar H), 7.78−7.81 (m, 2H, Ar H), 8.09−8.13 (m, 3H, Ar H), 8.33
1.64 g, 8.24 mmol) was used. A white solid was obtained. Yield: 2.96
DMSO-d
J
6
3
2
+
3
3
1
22
19
2
2
3
3
3
=
(d, 1H, J = 9.0 Hz, Ar H), 8.41 (s, 1H, imi H), 8.89 (d, 1H, J
=
6
3
2
HH
HH
HH
13
1
9
.0 Hz, Ar H), 7.60−7.78 (m, 6H, Ar H), 8.12 (br s, 3H, Ar H), 8.35
6.0 Hz, Ar H). C{ H} NMR (75.4 MHz, CDCl ): δ 53.2 (CH ), 55.6
3 2
3
3
(
3
5
d, 1H, J = 6.0 Hz, Ar H), 8.47 (s, 1H, imi H), 8.90 (d, 1H, J
.0 Hz, Ar H). C{ H} NMR (75.4 MHz, DMSO-d ): δ 54.1 (CH ),
=
(CH ), 112.2, 114.4, 118.1, 123.9 (quaternary C), 124.5, 125.7, 126.3
HH
HH
3
13
1
(quaternary C), 127.0 (quaternary C), 129.2, 129.9, 130.9, 131.1,
134.0, 140.3 (quaternary C), 164.8 (quaternary C), 189.0 (CO).
Synthesis of 2c. The compound was prepared with a similar
procedure to that of 2a. A mixture of 1c (2.0 g, 8.9 mmol) and NaBF4
(5.0 g, 46.0 mmol) was used. A white solid was obtained. Yield: 1.38 g
6
2
6.3 (CH ), 112.5, 114.7, 118.5, 124.9, 125.1 (quaternary C), 126.7
3
(
quaternary C), 127.1 (quaternary C), 127.6, 129.7, 130.1, 130.9,
31.4, 134.6, 140.7 (quaternary C), 164.6 (quaternary C), 190.1 (C
O).
1
G
DOI: 10.1021/acs.organomet.8b00054
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
+
(
91%). Mp = 159.7−160.2 °C. ESI-HRMS m/z: [M − BF ] Calcd for
129.1, 129.4, 130.0, 130.8, 132.9, 133.2 (quaternary C), 146.2
(quaternary C), 164.8 (quaternary C), 188.9 (CO).
Synthesis of 5a. To a 20 mL Schlenk flask containing Pd(OAc)
2
4
1
C H N O 343.1446; Found 343.1437. H NMR (300 MHz,
DMSO-d ): δ 3.88 (s, 3H, CH ), 6.38 (s, 2H, CH ), 7.24 (d, 2H,
22
19
2
2
6
3
2
3
3
JHH = 9.0 Hz, Ar H), 7.59 (t, 1H, J = 9.0 Hz, Ar H), 7.66−7.73 (m,
(0.047 g, 0.21 mmol), 1a (0.1 g, 0.25 mmol) was added dry DMF (8
mL). The mixture was allowed to stir at room temperature for
overnight. The solvent was completely removed under vacuum. The
residue was dissolved in dichloromethane. The organic layer was then
washed twice with water. After drying with anhydrous magnesium
sulfate, the solvent was completely removed under vacuum. The
residue was washed with diethyl ether and filtered on a frit and dried
under vacuum. An air-stable, yellow solid was obtained. Yield: 0.15 g
HH
3
4
H, Ar H), 7.81 (t, 1H, J = 9.0 Hz, Ar H), 8.08−8.16 (m, 3H, Ar
HH
3
H), 8.32−8.36 (m, 2H, Ar H, imi H), 8.82 (d, 1H, J = 6.0 Hz, Ar
HH
H). 1 C{ H} NMR (75.4 MHz, DMSO-d ): δ 54.1 (CH ), 56.0
3
1
6
2
(
(
1
CH ), 112.2, 115.6, 116.9 (quaternary C), 118.4, 124.3, 126.8
quaternary C), 127.6, 128.9, 129.5, 131.5, 134.3 (quaternary C),
34.5, 135.0, 140.5 (quaternary C), 161.3 (quaternary C), 191.8 (C
O).
Synthesis of 3a. A mixture of 1-benzyl-2-phenyl-1H-imidazole
2.71 g, 11.6 mmol) and 2-bromo-1-phenylethanone (2.3 g, 11.6
3
(
5
71%); Mp = 214.3-215.2 °C. Anal. Calcd for C H Br N O Pd : C,
42 30 2 4 2 2
1
0.81; H, 3.04; N, 5.64. Found: C, 50.73; H, 3.07; N, 5.33%. H NMR
(
(
300 MHz, DMSO-d ): δ 6.84 (s, 2H, Pd−CH), 7.15 (br s, 4H, Ar H),
6
mmol) in THF (30 mL) was placed in a Schlenk flask. The mixture
was heated to 80 °C for 2 days. After cooling, the white solid was
collected on a frit, washed with THF for three times, and dried under
vacuum. Yield: 3.65 g (74%). Mp = 204.7−205.2 °C. ESI-HRMS m/z:
7
4
.42−7.47 (m, 4H, Ar H), 7.61−7.68 (m, 6H, Ar H), 7.72−7.74 (m,
3
H, Ar H), 7.93 (t, 2H, Ar H, J = 9.0 Hz), 8.17−8.27 (m, 4H, Ar
HH
3
13
1
H), 8.41 (s, 2H, imi H), 8.78 (d, 2H, J = 6.0 Hz, Ar H). C{ H}
HH
+
1
NMR (75.4 MHz, DMSO-d
1
1
6
): δ 68.6 (Pd−CH), 112.8, 114.3, 117.5,
24.5 (quaternary C), 125.1, 125.7, 126.6, 128.9 (quaternary C), 129.4,
29.8, 130.1, 130.5, 132.3, 134.5, 139.7 (quaternary C), 141.4
[
M − Br] Calcd for C H N O 353.1653; Found 353.1651. H
24
21
2
NMR (300 MHz, CDCl ): δ 5.24 (s, 2H, NCH ), 5.99 (s, 2H, O
3
2
3
CCH ), 7.01 (t, 2H, J = 3.0 Hz, Ar H), 7.15−7.17 (m, 3H, Ar H),
2
HH
(
quaternary C), 153.8 (Pd−C), 199.1 (CO).
3
7
.27 (t, 2H, J = 6.0 Hz, Ar H), 7.33−7.47 (m, 6H, Ar H), 7.78 (s,
HH
Synthesis of 5b. The compound was prepared with a similar
3
1
H, imi H), 7.83 (d, 2H, J = 9.0 Hz, Ar H), 8.0 (s, 1H, imi H).
HH
procedure to that of 5a. A mixture of Pd(OAc) (0.044 g, 0.20 mmol),
1
3
1
2
C{ H} NMR (75.4 MHz, CDCl ): δ 52.6 (NCH ), 55.9 (O
3
2
1
b (0.1 g, 0.24 mmol), was added in dry DMF (8 mL). An air-stable,
CCH ), 125.0 (quaternary C), 122.4, 124.3, 127.9, 128.5, 128.9, 129.0,
2
yellow solid was obtained. Yield: 0.14 g (68%). Mp = 228.6−229.4 °C.
Anal. Calcd for C H Br N O Pd : C, 50.19; H, 3.25; N, 5.32. Found:
C, 50.16; H, 3.12; N, 5.48%. H NMR (300 MHz, DMSO-d ): δ 3.76
1
1
29.2, 129.8, 130.3, 132.9, 133.1 (quaternary C), 133.4 (quaternary C),
34.6, 145.8 (quaternary C), 191.0 (CO).
44
34
2
4
4
2
1
6
Synthesis of 3b. The compound was prepared with a similar
(
s, 6H, CH ), 6.71−6.79 (m, 3H, Pd−CH, Ar H), 7.37−7.46 (m, 4H,
3
procedure to that of 3a. A mixture of 1-benzyl-2-phenyl-1H-imidazole
2.7 g, 11.8 mmol) and 2-bromo-1-(4-methoxyphenyl)ethanone (2.65
g, 11.8 mmol) was used. A white solid was obtained. Yield: 4.43 g
Ar H), 7.60−7.67 (m, 6H, Ar H), 7.71−7.73 (m, 4H, Ar H), 7.89−
(
7.94 (m, 4H, Ar H), 8.08−8.17 (m, 3H, Ar H), 8.40 (s, 2H, imi H),
3
13
1
8.78 (d, 2H, J = 6.0 Hz, Ar H). C{ H} NMR (75.4 MHz, DMSO-
HH
+
(
85%). Mp = 208.1−208.4 °C. ESI-HRMS m/z: [M − Br] Calcd for
d ): δ 55.5 (CH ), 68.0 (Pd−CH), 112.3, 117.4, 125.0 (quaternary C),
6
3
1
C H N O 383.1759; Found 383.1752. H NMR (300 MHz,
125.7, 125.9, 126.3 (quaternary C), 126.6, 129.3, 129.7, 130.1, 130.2
(quaternary C), 130.5, 132.3, 134.5, 139.6 (quaternary C), 156.8 (Pd−
C), 160.1 (quaternary C), 199.3 (CO).
25
23
2
2
CDCl ): δ 3.77 (s, 3H, CH ), 5.30 (s, 2H, NCH ), 6.07 (s, 2H,
3
3
2
3
OCCH ), 6.86 (d, 2H, J = 9.0 Hz, Ar H), 7.09−7.12 (m, 2H, Ar
2
HH
H), 7.26−7.29 (m, 3H, Ar H), 7.44−7.56 (m, 5H, Ar H), 7.77 (d, 1H,
Synthesis of 5c. The compound was prepared with a similar
3
3
J
= 3.0 Hz, imi H), 7.93 (d, 2H, J = 12.0 Hz, Ar H), 8.09 (d, 1H,
procedure to that of 5a. A mixture of Pd(OAc)
2
(0.044 g, 0.20 mmol),
HH
HH
3J = 3.0 Hz, imi H). C{ H} NMR (75.4 MHz, CDCl ): δ 52.7
13
1
1
c (0.1 g, 0.24 mmol), was added in dry DMF (8 mL). An air-stable,
HH
3
yellow solid was obtained. Yield: 0.13 g (65%). Mp = 203.3−203.5 °C.
Anal. Calcd for C H Br N O Pd : C, 50.19; H, 3.25; N, 5.32. Found:
C, 49.71; H, 3.34; N, 5.39%. H NMR (300 MHz, DMSO-d ): δ 3.86
(
1
1
NCH ), 55.6 (CH ), 55.7 (OCCH ), 114.3, 120.7 (quaternary C),
2
3
2
22.0, 124.6, 126.2 (quaternary C), 127.9, 129.1, 129.3, 129.8, 130.5,
31.2, 132.9, 133.1 (quaternary C), 146.1 (quaternary C), 164.8
44 34
2
4
4
2
1
6
(
s, 6H, CH ), 6.82 (s, 2H, Pd−CH), 7.15−7.25 (m 7H, Ar H), 7.40−
3
(
quaternary C), 189.1 (CO).
3
7
.44 (m, 4H, Ar H), 7.62−7.74 (m, 5H, Ar H), 7.91 (t, 2H, J = 9.0
HH
Synthesis of 4a. A mixture 3a (2.0 g, 4.32 mmol) and NaBF4
2.48 g, 22.6 mmol) in acetonitrile (30 mL) was placed in a Schlenk
flask. The mixture was heated to 80 °C for 48 h. After, the reaction was
cooled, extracted with DCM (3 × 10 mL), and dried with anhydrous
MgSO . The solvent was removed completely under high vacuum, and
3
Hz, Ar H), 8.14−8.30 (m, 6H, imi H, Ar H), 8.69 (d, 2H, J = 6.0
HH
(
Hz, Ar H). 13C{ H} NMR (75.4 MHz, DMSO-d ): δ 55.9 (CH ), 68.5
1
6
3
(
1
Pd−CH), 115.5, 117.3, 117.6, 124.5 (quaternary C), 125.0, 125.2,
26.5, 128.9 (quaternary C), 129.5, 129.8, 131.1, 131.9, 134.6, 139.4
4
(
quaternary C), 141.5 (quaternary C), 153.8 (Pd−C), 160.9
the white solid was collected on a frit, washed with ether, and dried
(quaternary C), 199.2 (CO).
under vacuum. Yield: 1.7 g (84%). Mp = 204.0−204.6 °C. ESI-HRMS
Synthesis of 6a. To a 20 mL Schlenk flask containing Pd(OAc)
+
2
m/z: [M − BF ] Calcd for C H N O 353.1653; Found 353.1651.
4
24 21
2
(
(
0.047 g, 0.21 mmol), 2a (0.1 g, 0.25 mmol) was added dry pyridine
8 mL). The mixture was allowed to stir at room temperature for
1
H NMR (300 MHz, CDCl ): δ 5.17 (s, 2H, NCH ), 5.65 (s, 2H, O
3
2
3
CCH ), 7.09 (t, 2H, J = 3.0 Hz, Ar H), 7.30−7.31 (m, 3H, imi H,
2
HH
overnight. The solvent was completely removed under vacuum. The
residue was dissolved in dichloromethane. The organic layer was then
washed twice with water. After drying with anhydrous magnesium
sulfate, the solvent was completely removed under vacuum. Diethyl
ether and THF was added and the solid formed was filtered on a frit
and dried under vacuum. An air-stable yellow solid was obtained.
Yield: 0.11 g (88%); Mp = 212.3-213.1 °C. Anal. Calcd for
C H BF N OPd: C, 56.18; H, 3.80; N, 8.45. Found: C, 56.03; H,
3
Ar H), 7.40 (t, 2H, J = 9.0 Hz, Ar H), 7.45−7.49 (m, 5H, imi H, Ar
HH
3
H), 7.52−7.58 (m, 3H, imi H, Ar H), 7.85 (d, 2H, J = 6.0 Hz, Ar
HH
H). 13C{ H} NMR (75.4 MHz, CDCl ): δ 52.5 (NCH ), 55.1 (O
1
3
2
CCH ), 120.5 (quaternary C), 122.1, 124.1, 127.8, 128.3, 129.1, 129.3,
2
1
1
29.8, 130.3, 132.9 (quaternary C), 133.0 (quaternary C), 133.1, 134.8,
46.1 (quaternary C), 190.8 (CO).
Synthesis of 4b. The compound was prepared with a similar
3
1
25
4
4
1
3
procedure to that of 4a. A mixture of 3b (2.05 g, 4.32 mmol) and
NaBF (2.5 g, 22.6 mmol) was used. A white, moisture-sensitive solid
was obtained. Yield: 1.79 g (88%). ESI-HRMS m/z: [M − BF ] Calcd
for C H N O 383.1759; Found 383.1748. H NMR (300 MHz,
3.81; N, 8.37%. H NMR (300 MHz, CDCl ): δ 6.62 (d, 1H, J
=
3
HH
4
3.0 Hz, Ar H), 6.72 (s, 1H, Pd−CH), 6.96−7.02 (m, 2H, Ar H), 7.09
+
4
(t, 1H, J = 9.0 Hz, Ar H), 7.38−7.58 (m, 10H, Py H, Ar H), 7.77−7.88
1
3
25
23
2
2
(m, 3H, imi H, Py H), 8.17 (d, 2H, J = 6.0 Hz, Ar H), 8.25 (d, 2H,
HH
3
3
13
1
CDCl ): δ 3.79 (s, 3H, CH ), 5.16 (s, 2H, NCH ), 5.58 (s, 2H, O
JHH = 3.0 Hz, Py H), 8.75 (d, 2H, J = 6.0 Hz, Py H). C{ H}
3
3
2
HH
3
CCH ), 6.85 (d, 2H, J = 9.0 Hz, Ar H), 7.06−7.09 (m, 2H, Ar H),
NMR (75.4 MHz, CDCl ): δ 35.2 (Pd−CH), 113.4, 117.6, 124.1
2
HH
3
7
.27−7.32 (m, 3H, imi H, Ar H), 7.44−7.51 (m, 6H, Ar H), 7.54−7.58
(quaternary C), 125.0, 125.8, 127.6, 128.5, 128.7, 128.9 (Py C), 129.2,
129.4, 130.0 (Py C), 130.6, 130.7, 132.9, 134.3, 138.0 (quaternary C),
138.3 (Py C), 138.4 (Py C), 142.3 (quaternary C), 150.0 (Py C), 151.3
(Pd−C), 151.7 (Py C), 200.4 (CO).
3
13
1
(
(
1
m, 1H, Ar H), 7.83 (d, 2H, J = 9.0 Hz, Ar H). C{ H} NMR
HH
75.4 MHz, CDCl ): δ 52.5 (NCH ), 54.8 (OCCH ), 55.6 (CH ),
3
2
2
3
14.3, 120.6 (quaternary C), 122.0, 124.1, 126.0 (quaternary C), 127.8,
H
DOI: 10.1021/acs.organomet.8b00054
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Synthesis of 6b. The compound was prepared with a similar
126.3, 127.3, 127.8 (Py C), 128.9, 129.2 (Py C), 130.4, 132.6, 133.5
(quaternary C), 135.9 (quaternary C), 138.5 (Py C), 139.3 (Py C),
143.6 (quaternary C), 149.9 (Py C), 151.5 (Py C), 156.1 (Pd−C),
160.9 (quaternary C), 202.0 (CO).
procedure to that of 6a. A mixture of Pd(OAc) (0.044 g, 0.20 mmol),
2
2
b (0.1 g, 0.25 mmol), was added in dry pyridine (8 mL). An air-
stable, yellow solid was obtained. Yield: 0.10 g (72%). Mp = 263.1−
2
8
63.4 °C. Anal. Calcd for C H BF N O Pd: C, 55.48; H, 3.93; N,
General Procedure for Mizoroki−Heck Reaction. In a typical
reaction, a mixture of aryl halide (1 mmol), styrene (1.4 mmol), base
(1.1 equiv), and palladium catalyst (0.2 mol %) in TBAB (2 g) was
stirred at 140 °C for an appropriate period of time (2−12 h). After, the
reaction was cooled, extracted with ethyl ether (3 × 10 mL), and dried
3
2
27
4
4
2
1
.09. Found: C, 55.49; H, 3.94; N, 8.19%. H NMR (300 MHz,
CDCl ): δ 3.58 (s, 3H, CH ), 6.64−6.67 (m, 2H, Ar H, Pd−CH), 6.99
3
3
3
(
5
t, 2H, J = 6.0 Hz, Ar H), 7.21−7.25 (m, 1H, Ar H), 7.37−7.42 (m,
HH
H, Py H, Ar H), 7.47−7.56 (m, 4H, Py H, Ar H), 7.76−7.91 (m, 3H,
3
imi H, Py H), 8.06−8.09 (m, 3H, Ar H), 8.24 (d, 2H, J = 6.0 Hz,
with anhydrous MgSO . The solvent was removed completely under
HH
4
3
13
1
Py H), 8.77 (d, 2H, J = 6.0 Hz, Py H). C{ H} NMR (75.4 MHz,
high vacuum. Crude products were purified through flash column
chromatography on 230−400 mesh silica gel using hexane or hexane/
ethyl acetate as eluent with a suitable ratio according to the TLC
experiments. Yield was determined by using 1,3,5-trimethoxybenzene
as internal standard.
HH
7
1
(
5.4 MHz, CDCl ): δ 31.0 (Pd−CH), 55.0 (CH ), 111.6, 113.3, 114.4,
3
3
17.6, 118.7, 124.1, 125.0, 125.5 (quaternary C), 125.8, 127.0
quaternary C), 128.9 (Py C), 129.9 (Py C), 130.6, 131.2 (quaternary
C), 132.8, 135.6, 138.0 (Py C), 138.4 (Py C), 138.5 (quaternary C),
1
50.0 (Py C), 151.6 (Py C), 154.9 (Pd−C), 160.7, 200.3 (CO).
Single-Crystal X-ray Diffraction. 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
Synthesis of 6c. The compound was prepared with a similar
procedure to that of 6a. A mixture of Pd(OAc) (0.044 g, 0.20 mmol),
2
stable, yellow solid was obtained. Yield: 0.12 g (87%). Mp = 218.6−
2
2
c (0.1 g, 0.25 mmol), was added in dry pyridine (8 mL). An air-
1
4
19.6 °C. Anal. Calcd for C H BF N O Pd: C, 55.48; H, 3.93; N,
Bruker APEX2 and SAINT software. Absorption corrections were
3
2
27
4
4
2
1
15
8
.09. Found: C, 55.32; H, 3.78; N, 8.27%. H NMR (300 MHz,
performed using the SADABS program. All the structures were
3
CDCl ): δ 3.83 (s, 3H, CH ), 6.63 (d, 1H, J = 9.0 Hz, Ar H), 6.69
solved by direct methods and refined by full-matrix least-squares
3
3
HH
2
16
(
s, 1H, Pd−CH), 6.92−7.13 (m, 7H, Py H, Ar H), 7.19−7.24 (m, 1H,
methods against F with the SHELXTL software package. All non-H
atoms were refined anisotropically. All H atoms were fixed at
calculated positions and refined with the use of a riding model. A
disordered DMF solvent molecule in 7b was refined using a rigid +
model. CCDC files 1816353 (6a), 1816354 (6b), and 1816355 (7b)
contain supplementary crystallographic data for this paper.
Ar H), 7.30−7.33 (m, 1H, Ar H), 7.38−7.46 (m, 3H, Py H, Ar H),
7
2
3
.57 (d, 1H, J = 6.0 Hz, Ar H), 7.69 (s, 1H, imi H), 7.78−7.85 (m,
HH
3
H, Py H), 8.12−8.15 (m, 2H, Ar H), 8.22 (d, 2H, J = 6.0 Hz, Py
HH
3
13
1
H), 8.75 (d, 2H, J = 3.0 Hz, Py H). C{ H} NMR (75.4 MHz,
DMSO-d ): δ 39.1−40.8 (Pd−CH, overlapping with residual DMSO
signals), 56.0 (CH ), 115.6, 116.9, 117.6, 124.3 (quaternary C), 124.7,
HH
6
3
1
1
1
25.0, 126.5, 129.6 (quaternary C), 130.3, 130.5 (Py C), 131.1, 132.8,
34.5, 138.4 (Py C), 139.3 (quaternary C), 142.8 (quaternary C),
50.3 (Py C), 152.0 (Pd−C), 161.1 (quaternary C), 199.6 (CO).
Synthesis of 7a. To a 20 mL Schlenk flask containing Pd(OAc)2
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00054.
■
*
S
(0.05 g, 0.23 mmol), 4a (0.1 g, 0.23 mmol), NaOAc (0.018 g, 0.23
mmol) was added in dry pyridine (8 mL). The mixture was allowed to
stir at room temperature for overnight. The solvent was completely
removed under vacuum. The residue was dissolved in dichloro-
methane. The organic layer was then washed twice with water. After
drying with anhydrous magnesium sulfate, the solvent was completely
removed under vacuum. Diethyl ether and THF were added, and the
solid formed was filtered on a frit and dried under vacuum. An air-
stable yellow solid was obtained. Yield: 0.06 g (42%); Mp = 231.2−
Additional drawings, crystallographic data, 1H NMR
assignment of coupled products, NMR spectra of ligand
precursors, palladium complexes and coupled products,
ESI-MS spectra of ligand precursors (PDF)
Accession Codes
CCDC 1816353−1816355 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
2
7
31.4 °C. Anal. Calcd for C H BF N OPd: C, 58.10; H, 4.16; N,
34 29 4 4
1
.97. Found: C, 58.52; H, 4.41; N, 7.72%. H NMR (300 MHz,
CDCl ): δ 5.03 (AB q, 2H, Δ = 18.7 Hz, JAB = 15.0 Hz, CH ), 6.04
3
AB
2
3
(
s, 1H, Pd−CH), 6.51 (d, 1H, J = 9.0 Hz, Ar H), 6.88−7.03 (m,
HH
3
4
2
7
=
H, imi H, Ar H), 7.10 (t, 1H, J = 9.0 Hz, Ar H), 7.25−7.26 (m,
HH
H, Ar H), 7.29 (m, 1H, Ar H), 7.36−7.43 (m, 7H, Py H, Ar H),
.54−7.60 (m, 4H, Ar H), 7.78−7.87 (m, 2H, Py H), 8.24 (d, 2H, J
3
HH
3
13
1
6.0 Hz, Py H), 8.63 (d, 2H, J = 6.0 Hz, Py H). C{ H} NMR
HH
AUTHOR INFORMATION
Corresponding Author
E-mail: leehm@cc.ncue.edu.tw.
■
*
(
(
1
75.4 MHz, CDCl ): δ 30.5 (Pd−CH), 52.3 (CH ), 121.5, 121.7
3
2
quaternary C), 125.0, 125.3, 125.5, 126.1, 126.5, 128.0 (Py C), 129.1,
29.3 (Py C), 130.2, 130.5, 130.9, 132.8 (quaternary C), 133.7, 134.4,
38.7 (Py C), 139.4 (Py C), 142.8 (quaternary C), 143.5 (quaternary
1
ORCID
C), 150.1 (Py C), 151.7 (Py C), 152.9 (Pd−C), 202.5 (CO).
Hon Man Lee: 0000-0002-9557-3914
Notes
The authors declare no competing financial interest.
Synthesis of 7b. The compound was prepared with a similar
procedure to that of 7a. A mixture of Pd(OAc) (0.04 g, 0.23 mmol),
4
2
b (0.1 g, 0.23 mmol), was added in dry pyridine (8 mL). An air-
stable, yellow solid was obtained. Yield: 0.04 g (35%). Mp = 235.8−
2
36.4 °C. Anal. Calcd for C H BF N O Pd: C, 57.36; H, 4.26; N,
ACKNOWLEDGMENTS
3
5
31
4
4
2
■
1
7
.65. Found: C, 57.34; H, 4.26; N, 7.59%. H NMR (300 MHz,
We are grateful to the Ministry of Science and Technology of
Taiwan (MOST 106-2113-M-018-001) for financial support of
this work.
2
CDCl ): δ 3.57 (s, 3H, CH ), 5.03 (AB q, 2H, Δ = 19.5 Hz, J
=
3
3
AB
AB
3
1
6.5 Hz, CH ), 5.98 (s, 1H, Pd−CH), 6.66 (dd, 1H, J = 9.0 Hz,
2
HH
4
3
J
= 3.0 Hz, Ar H), 6.88−6.91 (m, 2H, Ar H), 7.05 (d, 1H, J
=
HH
HH
3
.0 Hz, imi H), 7.25−7.26 (m, 2H, Ar H), 7.32−7.43 (m, 8H, imi H,
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DOI: 10.1021/acs.organomet.8b00054
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