Multidentate N-Heterocyclic Carbene Complexes of Nickel and Palladium: Structural Analysis and Catalytic Application in Mizoroki–Heck Coupling Reaction

Article abstract of DOI:10.1002/ejic.202000530

Two series of electron-rich metal (Ni and Pd) complexes, namely a pyridine-coordinated tridentate NHC/amidate/phenoxy metal complex and a tetradentate complex bearing an extra pyridyl group, were synthesized. Two carbene moieties, imidazole-based and benzimidazole-based NHCs, were also incorporated into the ligand backbones. Seven of the new complexes were structurally characterized and comparative structural analysis revealed that the tetradentate complex with a flanking pyridyl side-arm was less distorted, leading to chelation-assisted stronger NHC coordination and hence a shorter metal–carbene bond. The catalytic activities of the two sets of palladium complexes for the Mizoroki–Heck coupling reaction were investigated. The comparative data showed that despite the higher thermal stability and the presence of the flanking hemilabile pyridyl side-arm which provided unsaturation to the metal center, the catalytic performance was slightly inferior to that of the tridentate palladium complex with a “throw-away” pyridine ligand. The tridentate palladium complex with the benzimidazole-based NHC moiety was the most effective catalyst, allowing the utilization of a range of aryl chlorides including deactivated substrates with a low 0.2 mol-% Pd loading in molten n-tetrabutylammonium bromide.

Full text of DOI:10.1002/ejic.202000530

European Journal of Inorganic Chemistry
Accepted Article
Title: Multidentate N-Heterocyclic Carbene Complexes of Nickel
and Palladium: Structural Analysis and Catalytic Application in
Mizoroki-Heck Coupling Reaction
Authors: Li-Cheng Liu, Yan-Hsiang Tzeng, Cheng-Hau Hung, and Hon
Man Lee
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To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.202000530
Link to VoR: https://doi.org/10.1002/ejic.202000530
01/2020

10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Multidentate N-Heterocyclic Carbene Complexes of Nickel and Palladium: Structural Analysis
and Catalytic Application in Mizoroki-Heck Coupling Reaction
Li-Cheng Liu,a# Yan-Hsiang Tzeng,a† Cheng-Hau Hung,a Prof. Dr. Hon Man Leea*
a Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan.
# Equal Contribution
* Corresponding to Hon Man Lee (E-mail: leehm@cc.ncue.edu.tw), URL:
http://chem.ncue.edu.tw/front/Members/teacher/member.php?ID=JnRlYWNoZXI=&PID=4
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Abstract
Two series of electron-rich metal (Ni and Pd) complexes, namely a pyridine-coordinated tridentate
NHC/amidate/phenoxy metal complex and a tetradentate complex bearing an extra pyridyl group, were
synthesized. Two carbene moieties, imidazole-based and benzimidazole-based NHCs, were also
incorporated into the ligand backbones. Seven of the new complexes were structurally characterized
and comparative structural analysis revealed that the tetradentate complex with a flanking pyridyl side-
arm was less distorted, leading to chelation-assisted stronger NHC coordination and hence a shorter
metal—carbene bond. The catalytic activities of the two sets of palladium complexes for the Mizoroki-
Heck coupling reaction were investigated. The comparative data showed that despite the higher
thermal stability and the presence of the flanking hemilabile pyridyl side-arm which provided
unsaturation to the metal center, the catalytic performance was slightly inferior to that of the tridentate
palladium complex with a “throw away” pyridine ligand. The tridentate palladium complex with the
benzimidazole-based NHC moiety was the most effective catalyst, allowing the utilization of a range
of aryl chlorides including deactivated substrates with a low 0.2 mol% Pd loading in molten n-
tetrabutylammonium bromide.
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Introduction
The Mizoroki-Heck coupling reaction is a powerful cross-coupling reaction that is commonly
used in synthetic organic chemistry.[1] Aryl chlorides are attractive substrates for the reaction because
they are inexpensive, but are less reactive compared to aryl bromides and iodides. Therefore, the
reaction typically requires prolonged heating at high temperatures in a high polar solvent for the aryl
chloride activation. General phosphine-free palladium catalysts capable of using a broad range of aryl
chlorides, including deactivated substrates, under mild reaction conditions of low palladium loading
(<0.5 mol%), low reaction temperature (<150 °C), and a short reaction time (<12 h) remain an
important research topic. It is generally accepted that transition metal complexes with high denticity
ligands are thermally stable because of ligand chelation and therefore they are promising catalyst
precursors for reactions that require harsh conditions. Hence, robust palladium complexes with
tridentate pincer ligands have been extensively used for Mizoroki-Heck coupling reactions.[2] However,
studies of phosphine-free palladium pincer complexes that are efficient for catalyzing the Mizoroki-
Heck coupling reaction with deactivated aryl chloride substrates are rare.[3] In addition, only a few
examples of palladium complexes with tetradentate ligands for the Mizoroki-Heck coupling reaction
with aryl chlorides have been reported.[4] Kantam et al. reported that tetradentate
dicarboxyamidate/dipyridyl palladium complexes which were robust catalysts for the Mizoroki-Heck
reaction of deactivated aryl chlorides.[4a] Recently, Köhlera et al. reported a highly stable macrocyclic
palladium(II) which exhibited controlled release of active species and delivered high catalytic
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
performances in C—C coupling reactions with aryl bromides and chlorides.[4b] In these works a
relatively high Pd loading of 1 mol% or high reaction temperature of 160 °C was required for the
deactivated aryl chlorides reaction.
Multidentate N-heterocyclic carbene (NHC) complexes of late transition metals have attracted
significant attention[5] due to the strong electron-donating properties of the carbene carbon. In addition,
ligand chelation can impart high thermal stability to electron-rich metal complexes, which is highly
desirable for the activation of inactive substrates in catalysis. Appropriate donor groups can also fine-
tune the reactivity of the metal centers. For example, nickel complexes with tetradentate pyridine-
functionalized NHC ligands are efficient catalysts for the Suzuki-Miyaura coupling reaction with aryl
chlorides.[6] Bidentate ligand scaffold combining a NHC (or an abnormal NHC) and amido functional
groups, both of which strongly donate electrons to the metal center upon coordination, are particularly
interesting. Their coordination with electron-rich metal centers facilitate the effective oxidative
addition of C－Cl bonds, leading to very effective palladium complexes for catalyzing the Mizoroki-
Heck coupling reaction with aryl chlorides.[7] Recently, the skeleton was further functionalized to form
palladium complexes with tridentate amidate- and phenoxy-functionalized NHC ligands, which were
effective in catalyzing the C─H arylation reaction between heterocyclic compounds and aryl halides.[8]
However, their catalytic performances for the Mizoroki-Heck coupling reaction has not yet been tested.
In this study, we prepared two series of metal complexes, namely a series of pyridine-coordinated
tridentate NHC metal complexes and another of electron-rich, robust metal complexes supported by a
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
tetradentate NHC ligand (Figure 1). The novel ligand is based on a tetradentate ligand scaffold with a
pyridyl functionality on one of the NHC flanking groups. This pyridyl side-arm was shown to be
hemilable for incoming substrates in nickel complexes containing pyridyl- and hydroxyl-
functionalized NHC ligand.[9] The anionic O and N coordination should render the ligand chelation
around the palladium(II) center highly stable. Since palladium[10] and nickel complexes[9, 10i, 11] with
benzimidazole-based NHC moieties are becoming increasingly common in the literature, a
benzimidazole-based NHC moiety was also incorporated into the ligand skeletons. A comparative
structural analysis of the two sets of metal complexes, the tridentate complex with a coordinating
pyridine ligand and the tetradentate complex bearing the pyridyl group, will provide insights into the
relationship between the ligand chelation and metal—NHC bond strength. The catalytic activities of
the palladium complexes for the Mizoroki-Heck coupling reaction with aryl chlorides were evaluated.
The comparative data allowed us to examine the importance of the monoligated pyridine ligand and
the hemilable pyridyl side-arm for defining the catalytic activity of these multidentate palladium
complexes. The results presented herein show that most of the robust palladium complexes are highly
effective, capable of using a range of aryl chlorides as substrates in the presence of a low Pd loading
in a molten salt solvent.
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Figure 1. Transition-metal complexes with multidentate NHC ligands
Results and Discussion
Synthesis of NHC Ligand Precursors. The preparation of ligand precursor 1 is shown in Scheme
1. Compounds 1b and 1b' without any substituent on the N-phenyl rings as well as 1d with a N-methyl
group were reported previously.[8] The palladium complexes derived from 1b and 1b' were sparingly
soluble in common organic solvents,[8] and we anticipated that substitution on the phenyl ring may
solubilize the complexes. Thus, ligand precursors 1a and 1a' were prepared with fluorine atoms
attached to the phenyl rings. Various imidazole and benzimidazole derivatives were refluxed with 2-
chloro-N-(2-hydroxyphenyl)acetamide in THF for 24 h, affording non-hygroscopic off-white solids of
precursor 1 with yields ranging from 66–84%. The prepared compounds were characterized by 1H and
1
13C{1H} NMR spectroscopy as well as high-resolution mass spectrometry. In the H NMR spectrum
of compound 1a, three downfield acidic signals were observed in 9.3–10.1 ppm. Based on a previous
study,[8] the most upfield reasonance could be attributable to the NCHN proton, followed by the NH
proton, while the most downfield signal corresponds to OH resonance. The remote electron-
withdrawing fluorine atom exerts a negligible effect on the chemical shifts of these acidic protons, as
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
the corresponding signals in 1b without fluorine were similarly observed at 9.4–10.1 ppm. The signals
were also similarly observed at 9.4–10.1 ppm after replacing the phenyl ring in 1b with a 2-pyridyl
ring in 1c. In sharp contrast, the extra fused aromatic rings in 1a', 1b'[8] and 1c' exert a significant
downfield effect such that these three signals were observed in a narrow range of 10.1–10.2 ppm.
Scheme 1. Synthesis of Ligand Precursors
Synthesis of Palladium(II) Complexes. The syntheses of complexes 2b, 2b', and 2d were
reported by us previously.[8] Following similar procedures, the new tridentate palladium complexes 2a
and 2a' were prepared by heating a mixture of the corresponding ligand precursor and PdCl2 with
K2CO3 as a base in neat pyridine at 50 °C, affording the air-stable, light-yellow solids in good yields
of 74 and 70%, respectively. The palladium complex 2c' supported by tetradentate pyridine-
functionalized NHC ligands was prepared using a similar protocol as the tridentate counterpart, but
with a slightly higher heating temperature of 80 °C to afford air-stable solids in 41% yield. In contrast,
preparation of tetradentate complex 2c was problematic, and the aforementioned conditions did not
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
provide a clean product. Instead, the complexation reaction was performed using of Pd(OAc)2 as the
o
metal precursor at 130 C for 12 h. Under these condition, pure 2c was cleanly obtained with a
satisfactory yield of 44%. As mentioned earlier, complexes 2b and 2b' are only soluble in highly polar
solvents such as DMSO, while all the other complexes are readily soluble in common polar organic
solvents.
1
All the newly prepared palladium complexes were characterized by H and 13C{1H} NMR
spectroscopy and elemental analysis. For complexes 2a, 2c and 2c', their structures were further
established by single-crystal X-ray diffraction analyses. Successful coordination of the ligand around
the metal center was indicated by the disappearance of the three downfield signals arising from the
NCHN, NH and OH protons. The carbene carbon resonance in the tridentate complex 2a was observed
at 159.7 ppm, similar to that in tridentate complex 2b (157.8 ppm).[8] However, these signals in the
tridentate complex 2a' and 2b'[8] bearing benzimidazole moieties were downfield shifted to ca. 169.9
ppm. The overlapping signal at 164.5 ppm in the tetradentate complex 2c was attributable to the
carbene carbon. The corresponding signal in the tetradentate complex 2c' containing a benzimidazole-
based NHC moiety appeared slightly downfield at 166.3 ppm.
Scheme 2. Synthesis of Palladium NHC Complexes
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European Journal of Inorganic Chemistry
(a)
N
N
R
O
O
K2CO3, pyridine
N
N
+
PdCl2
N
Pd
O
N
R
N
H
50 °C, 12 h
OH
Cl
1
R =
Me
F
F
2d
2a
2b
2b'
2a'
(b)
N
N
O
O
K2CO3, pyridine
N
N
PdX2
+
NH
N
Pd
O
N
N
80-130 °C, 12 h
Cl
1c, 1c'
OH
2c (X = OAc)
2c'
(X = Cl)
(a prime symbol denotes a structure with a benzimidazole moiety)
Synthesis of Nickel(II) Complexes. The newly prepared tridentate nickel NHC complexes were
synthesized using procedures similar to those of their palladium counterparts (Scheme 3). By heating
a mixture of the corresponding ligand precursor and NiCl2 with K2CO3 as a base in neat pyridine at 80
°C for 12 h, air-stable, yellow solids of the tridentate complex 3a and tetradentate complexes 3c and
3c' were obtained with yields ranging from 44 to 69%. However, for the tridentate complexes 3a' and
3b, prolonged heating for 12–48 h at 130 °C was required to produce the air-stable products in 68 and
76% yields, respectively.
1
All new nickel complexes were characterized using H and 13C{1H} NMR spectroscopy and
elemental analysis. The structures of 3a, 3a', 3c and 3c' were further established by single-crystal X-
ray diffraction studies. Successful coordination of the ligand around the metal center was indicated by
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
the disappearance of the three downfield signals arising from the NCHN, NH and OH protons. The
carbene signals in tridentate complexes 3a and 3b were observed at 160.8 and 158.6 ppm, respectively.
The carbene resonance in the tetradentate complex 3c appeared more downfield at 166.7 ppm, and the
corresponding signal in tetradentate complex 3c' with a benzimidazol-2-ylidene moiety was slightly
downfield shifted to 168.0 ppm.
Scheme 3. Synthesis of Nickel NHC Complexes
Structural Description. The structures of palladium complex 2a, 2c, and 2c' were successfully
established by single-crystal X-ray crystallography (Figure 2–4). The structures of tridentate
complexes 2b and 2d were reported previously.[8] In the structure of the tetradentate complex 2c, two
independent molecules formed an asymmetric unit. Their structural parameters were similar and only
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
one of these two sets was used as part of the structural description. All newly prepared complexes
adopt a distorted coordination environment around the palladium center. A larger distortion was
observed for the tridentate complex 2a, as indicated by the larger deviation of the two linear bond
angles from the ideal 180°. The C—Pd—O and N—Pd—N bond angles in 2a were determined to be
168.9(3)° and 171.5(3)°, respectively, whereas the corresponding angles in the tetradentate complex
2c were 172.22(14)° and 176.70(13)°, respectively. The angles in the tetradentate complex 2c' were
closest to the ideal value (176.09(11)° and 176.96(12)°, respectively). The τ and τ'4 parameters which
describes the extent of distortion around a 4-coordinate complex (τ = 0 for a perfect square pyramidal
geometry and τ = 1 for a perfect tetrahedral geometry)[12] are 0.14 and 0.13 for 2a, 0.08 and 0.06 for
2c, and 0.05 and 0.05 for 2c', respectively. Twisting of the NHC moiety from the coordination plane
was also more pronounced in the tridentate complex 2a, as reflected by its larger interplanar angle of
38.4° between the NHC ring and the coordination plane, compared to 23.8° and 16.7° in the
tetradentate complexes 2c and 2c', respectively. The reduced twisting of the carbene moiety with
respect to the coordination plane in the latter complexes was attributed to the conformation rigidity
imposed by the coordination of the pyridine functionality in the tetradentate ligand.
Notably, the Pd—C bond distances in the tetradentate complexes (2c': 1.909(3) Å; 2c: 1.911(4)
Å) were very short compared to those in the tridentate complexes (2a: 1.963(9) Å; 2b: 1.962(7) Å;[8]
2d: 1.973(7) Å[8]) (Figure 5). These short bond distances indicate formation of strong Pd─carbene
bonds due to the tetradentate chelation in which the NHC moiety was flanked by two donor groups
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European Journal of Inorganic Chemistry
and thus being part of two palladacyclic rings. In a relevant structure reported by Huynh et al., a longer
Pd—C bond distance [1.984 Å(3)] was observed if the NHC moiety was the terminal donor group of
a tetradentate ligand framework.[10j] From the large trans influence of carbene coordination, longer
trans Pd─O bond distances were observed in the tetradentate complexes (2.036(2) Å and 2.056(3) in
2c' and 2c, respectively) than in the tridentate complexes (2.015(6) Å and 2.020(4) Å in 2a and 2b,
respectively). However, all newly prepared complexes exhibited similar Pd─pyridine and Pd─amidate
bond lengths.
Figure 2. Molecular structure of complex 2a with 50% probability ellipsoids. Hydrogen atoms are
omitted for clarity. Selected bond distances (Å) and angles (deg): Pd1─C1, 1.963(9); Pd1─N1,
2.046(8); Pd1─O1, 2.015(6); Pd1─N2, 1.987(7); C1─Pd1─O1, 168.9(3); N1─Pd1─N2, 171.5(3);
C1─Ni1─N1, 97.9(3); C1─Ni1─N2, 89.5(3); O1─Ni1─N2, 82.9(3); O1─Ni1─N1, 90.3(3);
N3─C1─N4, 104.8(8).
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European Journal of Inorganic Chemistry
Figure 3. Molecular structure of complex 2c with 50% probability ellipsoids. Hydrogen atoms are
omitted for clarity. Only one of the independent molecules in an asymmetric unit was shown. Selected
bond distances (Å) and angles (deg): Pd1─C1, 1.911(4); Pd1─N4, 2.044(3); Pd1─O2, 2.056(3);
Pd1─N3, 1.997(3); C1─Pd1─O2, 172.22(14); N3─Pd1─N4, 176.7(13); C1─Pd1─N4, 89.27(15);
C1─Pd1─N3, 91.25(15); O2─Pd1─N3, 83.43(12); O2─Pd1─N4, 96.36(11); N1─C1─N2, 105.9(3);
Figure 4. Molecular structure of complex 2c' with 50% probability ellipsoids. Hydrogen atoms are
omitted for clarity. Selected bond distances (Å) and angles (deg): Pd1─C1, 1.909(3); Pd1─N3,
2.044(3); Pd1─O1, 2.036(2); Pd1─N4, 2.003(2); C1─Pd1─O1, 176.09(11); N3─Pd1─N4, 176.96(12);
C1─Pd1─N3, 90.09(12); C1─Pd1─N4, 92.88(12); O1─Pd1─N4, 83.71(10); O1─Pd1─N3, 93.34(10);
N1─C1─N2, 106.8(3).
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Figure 5. The bond distances around the metal centers in palladium complex 2 and nickel complex 3.
There are two sets of data for 2c because of two independent molecules in an asymmetric unit.
The structures of nickel complexes 3a, 3a', 3c and 3c' were successfully established by X-ray
crystallography (Figure 6-9). Because of the geometry of the multidentate ligand and the strong-field
nature of the NHC donor, the new nickel(II) complexes were expected to be low spin, diamagnetic,
and adopt a square-planar coordination geometry. Indeed, the structural studies confirmed a distorted
square planar coordination geometry of the nickel centers. Similar to the cases in the palladium
counterpart, the distortion in the tridentate complexes 3a and 3a' was larger than in the tetradentate
complexes 3c and 3c' as reflected by the extent of deviation of the C─Ni─O and N─Ni─N bond angles
from linearity (3a: 166.42(17)° and 167.82(16)°; 3a': 168.49(7)° and 168.27(6)° vs 3c: 171.09(16)°
and 172.49(14)°; 3c':174.45(10)° and 175.23(9)°). The τ and τ'4 parameters are 0.18 and 0.18 for 3a,
0.16 and 0.16 for 3a', 0.12 and 0.11 for 3c, and 0.07 and 0.07 for 3c', respectively. The tridentate
complexes 3a and 3a' were more twisted from planarity due to the large interplanar angles between
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
their coordination planes and NHC rings (3a: 39.7° and 3a': 43.7°). The corresponding angles in
tetradentate complex 3c and 3c' were significantly smaller (24.3° and 24.8°, respectively). Similar to
the palladium complexes, the tetradentate complexes 3c and 3c' exhibited much shorter Ni—carbene
distances (1.812(4) and 1.819(3) Å) compared to the 1.869(5) and 1.8666(16) Å of tridentate
complexes 3a and 3a', respectively. The trans Ni─O bond distances were similar in these complexes
along with their Ni─amidate distances. Notably, the Ni─pyridine bond distances in the tetradentate
complexes 3c and 3c' (1.913(4) and 1.926(2) Å) were longer than those in the tridentate complexes 3a
and 3a' (1.892(4) and 1.8947(15) Å, respectively).
Figure 6. Molecular structure of complex 3a with 50% probability ellipsoids. Hydrogen atoms and the
CH2Cl2 solvent molecule are omitted for clarity. Selected bond distances (Å) and angles (deg): Ni1─C1,
1.869(5); Ni1─N4, 1.881(4); Ni1─O2, 1.864(3); Ni1─N3, 1.892(4); C1─Ni1─O2, 166.42(17);
N3─Ni1─N4, 167.82(16); C1─Ni1─N3, 95.31(18); C1─Ni1─N4, 92.55(18); O2─Ni1─N4,
86.64(15); O2─Ni1─N3, 87.88(15); N1—C1—N2, 103.7(4).
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European Journal of Inorganic Chemistry
Figure 7. Molecular structure of complex 3a' with 50% probability ellipsoids. Hydrogen atoms and
the CH2Cl2 solvent molecule are omitted for clarity. Selected bond distances (Å) and angles (deg):
Ni1─C1, 1.8666(16); Ni1─N3, 1.8667(15); Ni1─O2, 1.8616(12); Ni1─N4, 1.8947(15); C1─Ni1─O2,
168.49(7); N3─Ni1─N4, 168.27(6); C1─Ni1─N4, 95.74(7); C1─Ni1─N3, 91.65(7); O2─Ni1─N3,
86.82(6); O2─Ni1─N4, 87.71(6); N1—C1—N2, 105.80(14).
Figure 8. Molecular structure of complex 3c with 50% probability ellipsoids. Hydrogen atoms are
omitted for clarity. Selected bond distances (Å) and angles (deg): Ni1─C3, 1.812(4); Ni1─N4,
1.867(4); Ni1─O2, 1.856(3); Ni1─N1, 1.913(4); C3─Ni1─O2, 171.09(16); N1─Ni1─N4, 172.49(14);
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European Journal of Inorganic Chemistry
C3─Ni1─N1, 90.95(18); C3─Ni1─N4, 92.75(18); O2─Ni1─N4, 87.26(14); O2─Ni1─N1, 90.09(14);
N2—C1—N3, 104.8(4).
Figure 9. Molecular structure of complex 3c' with 50% probability ellipsoids. Hydrogen atoms are
omitted for clarity. Selected bond distances (Å) and angles (deg): Ni1─C7, 1.819(3); Ni1─N4,
1.8775(19); Ni1─O2, 1.8676(17); Ni1─N1, 1.926(2); C7─Ni1─O2, 174.45(10); N1─Ni1─N4,
175.23(9); C7─Ni1─N1, 91.64(10); C7─Ni1─N4, 91.91(10); O2─Ni1─N4, 86.93(8); O2─Ni1─N1,
89.84(8); N2—C7—N3, 106.4(2).
For metal complexes containing benzimidazole-based NHC moieties, their N—C—N bond
angles are typically larger than those with imidazole-based NHC counterparts. The tetradentate
palladium complex 2c' with benzimidazole-based NHC moiety showed a large N—C—N bond angle
of 106.8(3)°, compared to 105.9(3)° in 2c with an imidazole-based NHC counterpart. Similarly, the
N—C—N bond angles in nickel complexes 3c' and 3a' were determined to be 106.4(2)° and
105.80(14)°, respectively, whereas those in 3c and 3a were 104.8(4)° and 103.7(4)°, respectively.
Structural Analysis. It has been shown that the strong σ-effect of NHC causes the widening of
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European Journal of Inorganic Chemistry
the N—C—N bond angle in the carbene moiety.[13] In addition, strong σ-donation leads to a higher
demand for electron density on the carbene carbon, resulting in a higher degree of NÆC lone pair
donation and reduction in the average Ccarbene─N bond distance.[14] As a result, a linear regression line
can be plotted such that the N─Ccarbene─N bond angle increases with decreasing average Ccarbene─N
bond distance. Deviation from this linear correlation should occur with π-back bonding because
electron population in the carbene p orbital would lead to elongation of the average Ccarbene─N bond
distance.[15] Figure 10 shows a plot of the N─C─N bond angles and average Ccarbene─N bond distances
obtained from the X-ray structures of the metal complexes with imidazole-based NHC ligands. A good
linear correlation (R2 = 0.9279) was obtained from the geometrical parameters of metal complexes
with imidazole-based NHC ligands, indicating that the imidazole-based NHC moieties in tridentate
palladium complexes 2a-d and the tridentate nickel complex 3a were predominately σ-donors. Notably,
the geometrical data for the tetranuclear nickel complex 3c with an imidazole-based NHC moiety
slightly deviated from the linear regression. When this data is excluded, the correlation can be
improved to R2 = 0.9771, implying that the imidazole-based NHC ligand in 3c could be a weak π-
acceptor. In contrast, the ligand in the palladium counterpart 2c is predominately a σ-donor, consistent
with a previous report that π-interaction is more significant in nickel than in palladium complexes.[13a]
It has been shown that an incorporation of a pyridine functionality into an imidazole-based NHC ligand
scaffold can influence the electronic properties of the NHC ligand,[16] resulting in significant π-back
bonding from the metal center. But it should be noted that the deviation of bond parameters in 3c could
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European Journal of Inorganic Chemistry
also be due to other factors such as packing in the crystal structure. More vigorous studies such as the
measurement of 77Se NMR parameters of NHC-selenium adduct and the DFT calculation of HOMO-
LUMO energies are needed to confirm the π-accepting property of the ligand in 3c.[17]
Figure 10 also shows that the tetradentate complexes contained stronger NHC donation resulting
in wide N—C—N angles and short C—N bonds in the carbene moieties (see 2c vs 2d, 2b, 2a; 3c vs
3a). These results are consistent with the resultant short Pd—C bond distances observed (vide supra),
confirming the chelation-assisted formation of strong NHC donation due to the extra pyridine
functionality.
Figure 10. A plot of N—C—N bond angles and C—N bond distances in the carbene moieties of the
metal complexes with imidazole-based NHC ligands. Two sets of data for 2c because of two
independent molecules in an asymmetric unit.
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Mizoroki-Heck Coupling Reaction. The multidentate palladium complexes were used to
catalyze the Mizorok-Heck coupling reaction (Table 1). To gauge the efficiency of the newly prepared
complexes, the reaction between 4-chloroacetophenone and styrene was used as a benchmark. Based
on previous works,[7, 18] the initial conditions of 0.2–0.5 mol% of precatalyst, NaOAc as a base, and a
reaction time of 2 h at 140 °C in molten n-tetrabutylammonium bromide (TBAB) as a solvent were
employed. Using a low 0.5 mol% of Pd loading, tridentate complexes 2a, 2a' and 2b (entries 1–3) and
the tetradentate complex 2c' (entry 5) were equally effective, affording the product in 97% yields with
an excellent trans/gem ratio. However, the tetradentate complex 2c was less effective, affording the
product in an inferior 64% yield. To differentiate the effectiveness of the four complexes, Pd loading
was reduced to 0.2 mol% (entries 6–9). At this very low Pd loading, the tridentate complex 2a afforded
a 85% yield (entry 6), whereas its analogous complex 2a' bearing a benzimidazole moiety was the
most effective catalyst, providing the product in 94% (entry 7). The higher activity of palladium
complexes with benzimidazole-based NHC ligands was also observed previously for the direct C—H
arylation between heteroaromatics and aryl halides.[8] Complex 2b afforded a comparable yield of 91%
(entry 8), while the tetradentate complex 2c' produced an inferior 79% yield (entry 9). Attempts were
made to further reduce Pd loading, but unsatisfactory yields were obtained. Thus, a 0.2 mol% of
tridentate complex 2a' is the optimum conditions to catalyze the reaction. Compared to the tetradentate
complexes, the higher activity of the tridentate complexes indicated that coordinative unsaturation of
the palladium centers by fast pyridine dissociation was more important for efficient catalytic activity.
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
This is despite the higher stability of the tetradentate complexes. In fact, the presence of “throw away”
3-chloropyridine ligand was very important for PEPPSI-themed palladium NHC precatalysts which
are highly efficient for various cross-coupling reactions.[19] Under the same catalytic conditions, the
newly prepared nickel complexes did not exhibit activity. In general, the reaction conditions required
for nickel-catalyzed Heck-type reactions are quite different from those suitable for the palladium-
catalyzed reactions;[20] for example, a much higher catalyst loading was required in the nickel-
catalyzed reaction.
Table 1. Catalyst Screening in Mizoroki-Heck Reactiona
Entry
Cat.
2a
mol%
0.5
0.5
0.5
0.5
0.5
0.2
0.2
0.2
0.2
Yield (%)
97 (98:2)
97 (97:3)
97 (97:3)
64 (97:3)
97 (98:2)
85 (98:2)
94 (97:3)
91 (97:3)
79 (98:2)
1
2
3
4
5
6
7
8
9
2a'
2b
2c
2c'
2a
2a'
2b
2c'
a
Reaction conditions: 1.4 mmol of styrene, 1 mmol of 4-
chloroacetophenone, 1.1 mmol of NaOAc, 2 g of TBAB, 0.2 or
0.5 mol % of cat., 140 °C. Yield determined by using 1,3,5-
trimethoxybenzene as internal standard (trans/gem ratio in
parenthesis).
After identifying the best precatalyst, the substrate scope was investigated (Table 2). Generally,
the catalyst system was active with a range of aryl chlorides. Entries 1–3 show that activated aryl
chlorides, including 4-chloroacetophenone, 4-nitrochlorobenzene, and 4-chlorobenzonitrile, reacted
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
smoothly with styrene to afford the coupled products in 2 h with excellent yields (91–99%). For 4-
chlorobenzotrifluoride and 4-chlorobenzaldehyde, a 6 h reaction time was required to achieve the
coupled products in good yield (86%). For deactivating substrates, a prolonged reaction time of 12 h
was required. A reasonable 59% product yield was obtained even with electron-neutral chlorobenzene
(entry 6). The product yields were reduced to 45 and 40% when the deactivating 4-chlorotoluene and
4-chloroanisole substrates were used (entries 7-8, respectively). When the 3-chloroacetophenone
substrate was used instead of its para isomer, the product yield was slightly reduced from 99 to 85%
due to the steric hindrance around the palladium species (entries 9 vs 1). Similarly, the product yields
were reduced to 87 and 33% when 3- and 2-chlorobenzonitrile substrates were used instead of its para
isomer (entries 10-11 vs 3). A mediocre 62% yield was obtained when 1,4-dichlorobenzene was used
as substrate (entry 12). Next, different substituted styrene substrates were tested and entries 13-19
show that 4-chlorostyrene, 4-methylstyrene, and 4-methoxystyrene reacted smoothly with a range of
activated aryl chlorides, affording good yields of the coupled products (76-99%). n-Butylacrylate was
also a viable substrate to couple with 1-chloro-4-nitrobenzene, affording a quantitative product yield
(entry 20).
Molten TBAB is a promising green solvent for enhancing the reactivity of chlorobenzene.[1c, 21]
Therefore, the Mizoroki-Heck reaction was successfully conducted using various types of palladium
complexes for aryl chloride substrate activation in TBAB.[7, 18, 22] The present system based on 2a'
provided a 40% product yield in the reaction between styrene and 4-chloroanisole with 0.2 mol% Pd
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
loading (vide supra), outperforming previously reported systems based on palladium(0) complexes
with NHCs,[18b, 22b] zwitterionic complexes,[22a] and C,C-type palladacycles.[22c] The obtained activity
is comparable to those of other palladium(II) NHC complexes.[7a, 7b, 18a, 23] Nevertheless, its activity is
inferior to those based on tetranuclear palladium complexes of abnormal NHC ligands.[7c] It should be
noted that palladium nanoparticles in TBAB have also been successfully used for the activation of aryl
chloride in Mizoroki-Heck coupling.[24] For the catalytic system based on 2a', beside homogeneous
catalytic centers, the plausible involvement of heterogeneous species cannot be excluded.[21d, 25] In fact,
a mercury drop test[26] was performed on the benchmark reaction between 4-chloroacetophenone and
styrene, catalyzed by 2a'. In the presence of mercury, the product yield was markedly reduced from
99 to 28%.
Table 2. Substrate Scope
Entry
Ar–X
Alkene
Product
Time Yield
(h) (%)
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European Journal of Inorganic Chemistry
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
Reaction conditions: a1.4 mmol of styrene, 1 mmol of aryl chlorides, 1.1 mmol
of NaOAc, 2 g of TBAB, 0.2 mol % of cat., 140 °C. Isolated yield.
Conclusions
Two series of metal complexes with multidentate NHC ligands were prepared in this study. The
first series consisted of tridentate NHC-amidate-phenoxy ligands, whereas the second contained
tetradentate ligands bearing an additional pyridyl functionality. Two types of carbene moieties,
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
benzimidazole-based and imidazole-based NHCs, were also incorporated into the ligand backbones.
Comparative structural studies showed that the tetradentate complexes with flanking pyridine
functionalities were less distorted, leading to chelation-assisted stronger NHC coordination and a
shorter metal—carbene bond. The two sets of palladium complexes with multidentate ligands were
tested for the Mizoroki-Heck coupling reaction between aryl chlorides and alkenes. The newly
prepared palladium complex with the tetradentate NHC ligand was effective for catalyzing the reaction
with aryl chlorides. However, despite the improved thermal stability and the presence of the hemilable
flanking pyridyl side-arm for unsaturation, its catalytic performance was slightly inferior to that of the
tridentate palladium complex that contained a “throw away” pyridine ligand. The tridentate palladium
complex 2a' containing a benzimidazole-based NHC moiety was the most effective catalyst compared
to its imidazole-based NHC counterpart. This high activity allowed a range of aryl chloride substrates
to react in molten TBAB. This study demonstrates the promising applicability of electron-rich
palladium complexes with multidentate functionalized benzimidazole-based NHC ligands for
catalyzing the Mizoroki-Heck coupling reaction of aryl chlorides in TBAB.
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
purchased from commercial source and used as received. 1H and 13C{1H} were recorded at 300.13 and
75.47 MHz, respectively, on a Bruker AV-300 spectrometer. Elemental analyses were performed on a
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
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). Ligand precursors 1b,
1b' and 1d and palladium complexes 2b, 2b', and 2d were prepared according to the literature
procedure.[8]
Synthesis of 1-(4-Fluorobenzyl)-3-(2-((2-hydroxyphenyl)amino)-2-oxoethyl)-1H-imidazol-
3-ium Chloride (1a). 1-(4-Fluorobenzyl)-1H-imidazole (1.0 g, 6.92 mmol) and 2-chloro-N-(2-
hydroxyphenyl)acetamide (1.28 g, 6.92 mmol) were added to a 50 mL Schlenk flask equipped with a
stirring bar, and sealed with a septum. The flask was evacuated and backfilled with nitrogen three
times. Dried THF (20 mL) was then added via syringe, and the reaction mixture was stirred at 80 oC
for 24 h. It was then allowed to cool down to ambient temperature. The solvent was completely
evaporated under vacuum. THF was added, and the off-white solid formed was collected on a frit,
further washed with THF, and dried under vacuum. Yield: 1.98 g (84%). 1H NMR (DMSO-d6): δ 5.28
(s, 2H, CH2), 5.50 (s, 2H, CH2), 6.76 (t, 1H, J = 6.0 Hz, Ar H), 6.94–6.96 (m, 2H, imi H, Ar H), 7.43
(br s, 5H, imi H, Ar H), 7.82 (d, 2H, J = 12.0 Hz, Ar H), 9.35 (s, 1H, NCHN), 9.90 (s, 1H, NH), 10.10
(s, 1H, OH). 13C{1H} NMR (DMSO-d6): δ 51.5 (CH2), 52.0 (CH2), 116.1, 116.4 (d, J = 20.4 Hz, Ar
C), 119.2, 122.3, 122.6, 124.8, 125.4, 125.9 (quaternary C ), 131.3 (d, J = 8.3 Hz, Ar C), 131.7 (d, J =
3.8 Hz, quaternary C), 138.0, 148.6 (quaternary C), 161.1 (d, J = 246.0 Hz, C—F), 164.3 (C=O).
HRMS (ESI) m/z calcd for C18H17FN3O2 [M – Cl]+ 326.1299, found 326.1303.
Synthesis
of
1-(4-Fluorobenzyl)-3-(2-((2-hydroxyphenyl)amino)-2-oxoethyl)-1H-
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
benzo[d]imidazol-3-ium Chloride (1a'). Compound 1a' was prepared by a similar procedure of 1a.
1-(4-Fluorobenzyl)-1H-benzo[d]imidazole (1.0 g, 4.42 mmol) and 2-chloro-N-(2-
hydroxyphenyl)acetamide (0.818 g, 4.42 mmol) were used as starting materials. An off-white solid
was obtained. Yield: 1.25 g (69%). 1H NMR (DMSO-d6): δ 5.67 (s, 2H, CH2), 5.87 (s, 2H, CH2), 6.73
(t, J = 6.0 Hz, 1H, Ar H), 6.97 (br s, 2H, Ar H), 7.28 (t, J = 9.0 Hz, 2H, Ar H), 7.62–7.67 (m, 4H, Ar
H), 7.80 (d, 1H, J = 9.0 Hz, Ar H), 8.01–8.06 (m, 2H, Ar H), 10.08 (s, 1H, NCHN), 10.12 (s,1H,NH),
13
10.21 (s, 1H, OH). C{1H} NMR (DMSO-d6): δ 49.6 (CH2), 49.7 (CH2), 114.3, 116.0, 116.4 (d, J
= 21.9 Hz, Ar C), 119.3, 122.7, 125.6, 125.8 (quaternary C ), 127.2, 127.4, 130.5, 130.6 (d, J = 2.3 Hz,
quaternary C ), 130.8 (quaternary C ), 131.3 (d, J = 8.3 Hz, Ar C), 132.4 (quaternary C ), 144.2, 148.7
(quaternary C ), 162.7 (d, J = 264.0 Hz, C–F), 164.3 (C=O). HRMS (ESI) m/z calcd for C22H19O2N3F
[M – Cl]+ 376.1456, found 376.1461.
Synthesis
of
1-(2-((2-Hydroxyphenyl)amino)-2-oxoethyl)-3-(pyridin-2-ylmethyl)-1H-
imidazol-3-ium Chloride (1c). Compound 1c was prepared by a similar procedure of 1a. 2-((1H-
Imidazol-1-yl)methyl)pyridine (1.0 g, 6.29 mmol) and 2-chloro-N-(2-hydroxyphenyl)acetamide
(1.163 g, 6.29 mmol) were used as starting materials. An off-white solid was formed. Yield: 1.28 g
(66%). 1H NMR (DMSO-d6): δ 5.53 (s, 2H, CH2), 5.65 (s, 2H, CH2), 6.72–6.78 (m, 1H, Ar H), 6.92–
6.96 (m, 2H, imi H, Ar H), 7.41 (t, 1H, J = 6.0 Hz, py H), 7.49 (d, 1H, J = 6.0 Hz, py H), 7.81–7.92
(m, 4H, imi H, py H, Ar H), 8.57 (d, 1H, J = 3.0 Hz, py H), 9.37 (s, 1H, NCHN), 9.94 (s, 1H, NH),
10.13 (s, 1H, OH). 13C{1H} NMR (DMSO-d6): δ 52.0 (CH2), 53.5 (CH2), 116.1, 119.2, 122.5, 123.0,
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10.1002/ejic.202000530
European Journal of Inorganic Chemistry
123.1, 124.2, 124.5, 125.4, 125.9 (quaternary C), 138.1, 138.6, 148.6 (quaternary C), 150.1, 154.1
(quaternary C), 164.3 (C=O). HRMS (ESI) m/z calcd for C17H17O2N4 [M – Cl]+ 309.1346, found
309.1347.
Synthesis
of
1-(2-((2-Hydroxyphenyl)amino)-2-oxoethyl)-3-(pyridin-2-ylmethyl)-1H-
benzo[d]imidazol-3-ium Chloride (1c'). Compound 1c' was prepared by a similar procedure of 1a.
1-(Pyridin-2-ylmethyl)-1H-benzo[d]imidazole (2.0 g, 9.56 mmol) and 2-chloro-N-(2-
hydroxyphenyl)acetamide (1.77g, 9.56 mmol) were used as starting materials. An off-white solid was
formed. Yield: 2.88 g (80%). 1H NMR (DMSO-d6): δ 5.72 (s, 2H, CH2), 6.03 (s, 2H, CH2), 6.74–6.98
(m, 2H, Ar H), 7.38 (d, J = 3.0 Hz, 1H, py H), 7.67–8.05 (m, 8H, py H, Ar H), 8.50 (s, 1H, py H),
10.11–10.22 (m, 3H, NCHN, NH, OH). 13C{1H} NMR (DMSO-d6): δ 49.7 (CH2), 51.4 (CH2), 114.3,
114.4, 116.0, 119.3, 122.5, 123.3, 124.2, 125.5, 125.9 (quaternary C), 127.2, 127.3, 131.4 (quaternary
C), 132.2 (quaternary C), 138.1, 144.7, 148.5 (quaternary C), 150.1, 153.4 (quaternary C), 164.0 (C=O).
HRMS (ESI) m/z calcd for C21H19O2N4 [M – Cl]+ 359.1503, found 359.1507.
Synthesis of Palladium Complex 2a. Ligand precursor 1a (0.1 g, 0.275 mmol), PdCl2 (0.0488
g, 0.275 mmol), and K2CO3 (0.152 g, 1.10 mmol) were added to a Schlenk flask equipped with a
stirring bar. The flask was evacuated and backfilled with nitrogen three times. Pyridine (5 mL) was
then added via syringe and the reaction mixture was stirred at 50 oC for 12 h. It was then allowed to
cool down to ambient temperature. The solvent was then completely removed under vacuum. The solid
residue was taken up in CH2Cl2. The organic phase was washed with water several times and dried
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