Synthesis, structures, DFT calculations, and catalytic application in the direct arylation of five-membered heteroarenes with aryl bromides of novel palladium-N-heterocyclic carbene PEPPSI-type complexes

Article abstract of DOI:10.1039/d1nj03388c

A new series of Pd-catalysts based on an N-heterocyclic carbene PEPPSI-type ligand (PEPPSI = pyridine enhanced precatalyst preparation stabilization and initiation) with the general formula [Pd(ii)Br2(NHC)(pyridine)] was synthesized and fully characterize

Full text of DOI:10.1039/d1nj03388c

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DOI: 10.1039/D1NJ03388C
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Synthesis, structures, DFT calculations, and catalytic application in
the direct arylation of five-membered heteroarenes with aryl
bromides of novel Palladium-N-Heterocyclic carbene complexes
PEPPSI-Type
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Abd el-Krim Sandeli, Naima Khiri-Meribout, * Saida Benzerka, Houssem Boulebd,a,b Nevin
a,d
a,b
a,b
c,d
e
c,d
Gürbüz, Namık Özdemir, and İsmail Özdemir *
New series of Pd-catalysts based N-heterocyclic carbene ligand PEPPSI-Type, (PEPPSI = Pyridine Enhanced Precatalyst
Preparation Stabilization and Initiation) with the general formula [Pd(II)Br2(NHC)(pyridine)] were synthesized, and fully
characterized by spectroscopic analytical methods. Further, the structural characterization of 3a, 3b, and 3d was determined
by a single-crystal X-ray diffraction study, which supports the proposed structures and offered a more detailed structural
characterization. As well the result for representative molecule 3a has been confirmed on their electronic, vibrational,
thermodynamic, and optical properties utilizing Density Functional Theory (DFT) calculations. The experimental molecular
geometry of the ground state of complex 3a has been compared with the minimized structure obtained from DFT
calculations. B3LYP functional in conjunction with LANL2DZ basis set for Palladium atom and 6-311G(d,p) basis set for
hydrogen, carbon, nitrogen, and bromine atoms have been used for all calculations. Frontier molecular orbitals and
molecular electrostatic potential were also analyzed and discussed. Due to the big interest in halo substituted arylated
heteroarenes in organic chemistry. The capacity catalytic of these Pd(II)-NHC complexes PEPPSI – Type were evaluated by
the direct arylation process of five-membered heteroaromatics such as thiophene, furan, and thiazole derivatives with
various (hetero)aryl bromides in the presence of 1 mol% catalyst. The results showed that all new Pd-NHC complexes are
effective catalysts that exhibit very good catalytic activity and gave C-H activation selectively at the C(5)-position of 2-acetyl
furan and 2-acetyl thiophene.
transition metals such as Pd, Ru, Rh, etc, are effective for the
3
Introduction
direct arylation reactions. However, among them, the Pd‐
complexes are the most powerful. Today, palladium-catalyzed
N-Heterocyclic carbenes (NHC) are effective ligands that allow
the preparation of the most metal complexes, and chemically
acceptable catalysts by altering the substituents on the nitrogen
cross-coupling reactions are highly important synthetic tools in
4
organic chemistry. Due to these features, they have been
successfully employed in different applications of
organometallic chemistry as a key ligand for metal complexes.5
We can categorize the most used Pd-NHC complexes into four
main classes; bis-Pd-NHCs, allyl-type Pd-NHCs, incer-type Pd-
NHCs, and PEPPSI (Pyridine Enhanced Pre-catalyst Preparation
1
atom. They have become one of the most widely used ligand
classes in organometallic chemistry with new catalytic
applications. Due to the activity, stability, and selectivity of
metal complexes containing NHC ligand, they have been widely
used as highly reactive and rather selective catalysts for a lot of
reactions. Over the last few decades, considerable advances
have been achieved in direct arylation methods. Various
6
,7
Stabilization and Initiation) type Pd-NHCs Among the most
2
popular catalysts for such reactions are PEPPSI-type palladium-
NHC complexes of the type [PdX (NHC)(pyridine)] (X/halide)
2
which have gained real practical importance in various catalytic
processes.
a.
Research Laboratory of Synthesis of Molecules with Biological Interest, Mentouri
Constantine-1 University, CONSTANTINE, ALGERIA
b.
Faculty of Science, Department of Chemistry, Mentouri Constantine-1 University,
The direct arylation of heteroarenes is particularly attractive
since these moieties are present in many biologically active
compounds. In recent years, Pd‐catalyzed direct arylation of
(hetero)arenes with (pseudo)halides have received significant
attention as eco‐friendly and economic alternatives to
conventional methods. They consider as the most commonly
employed coupling partners for Pd‐catalyzed direct arylation
CONSTANTINE, ALGERIA
c.
Faculty of Science and Art, Department of Chemistry, İnönü University, MALATYA,
TURKEY
d.
Catalysis Research and Application Center, Inönü University, 44280 MALATYA,
TURKEY
e.
Department of Mathematics and Science Education, Faculty of Education,
Ondokuz Mayıs University, 55139 SAMSUN, TURKEY
Dedicated to Prof. Christian Bruneau for his outstanding contribution to
†
organometallic chemistryc atalysis
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
8
reactions. In 1985-1992, Ohta et al. first reported the direct
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arylation of heteroaromatics with aryl halides using a C-H Since they have such important biological activity, the discovery
View Article Online
DOI: 10.1039/D1NJ03388C
activation strategy through the cleavage of two C-H bonds, of
which Pd(PPh
dimethylacetamide (DMAc) as the solvent. After Organ et al
reported easily handled, air- and moisture-stable Pd–NHC chemistry. The use of such functional halo thiophenes for direct
complexes created by using the PEPPSI method, which featured arylation would be useful, as they would give simple access to a
Pd(II) species bearing an NHC ligand, two halides, and a labile wide variety of polyfunctionalized thiophenes useful for
ligand such as 3-chloropyridine. Following the discovery of material chemistry or pharmaceutical applications. In this
Organ's PEPPSI-type Pd‐complexes, which considers a new class context, recently in an attempt to provide a new vision of the
of Pd‐catalysts that are completely different from other Pd– topic, we report the successful synthesis of six new PEPPSI‐Type
NHC complexes and easier to synthesize and use. This type of Pd(II)-NHC complexes (3a–3e) of the general formula
complex has shown remarkable catalytic activities towards [PdX2(NHC)(pyridine)], (X=Br; NHC=1,3‐disubstituted 3,5-
various carbon-carbon and carbon-heteroatom coupling dimethylbenzimidazole‐2-ylidene). In the present study, we
reactions. In recent years some studies on the direct arylation have focused our attention on their applications in catalytic
reaction of PEPPSI type palladium-N-heterocyclic carbene (NHC) processes paying special investigation on the catalytic activity of
more
direct
and
selective
3
)
4
was used as the catalyst and procedures to synthesize arylated thiophene, thiazole, and
9
-11
3
furan derivatives is an important topic in synthetic organic
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complexes have been, published.
synthesized Pd-NHC complexes which contained different arylation reactions of a variety of five-membered heteroarenes
The researchers all these newly synthesized Pd(II)-NHC complexes in direct C5
1
5
16
imidazole, benzimidazole and benzotriazole. In the last two such as 2‐ acetylfuran, 2‐acetylthiophene, and furaldehyde with
decades, PEPPSI‐themed Pd‐complexes have been used as several aryl bromides in the presence of 1 mol% catalyst
effective catalysts in direct arylation and successful results have loading.
been obtained. Direct arylation reactions have received great
interest as possible alternatives to the most employed cross-
coupling reactions. Since then, palladium-catalyzed direct
arylation has been successfully applied for the arylation of
heteroaryl derivatives with aryl-halides has proved to be a
powerful method for the synthesis of a wide variety of arylated
1
7
Experimental
All manipulations were performed in Schlenk-type flasks under
an argon atmosphere. The melting point measurements were
determined in open capillary tubes with an Electrothermal-
9200 melting points apparatus. The IR spectra were recorded
on the Gladi ATR unit (Attenuated Total Reflection) in the range
1
8-22
heterocycles.
Very exciting results have been reported by
several groups using thiophenes, furans, pyrroles, thiazoles,
oxazoles, imidazoles, or triazoles.23,24 Azole-derived metal
complexes have found application in many fields.
particular, nucleophilic N-heterocyclic carbenes (NHCs) have
proven as useful ligands for transition metal catalysis.
another way both thiophene and thiazole derivatives have
attracted attention due to their important biological activity
such as Sulfathiazole is an antimicrobial drug, 2-arylthiophene
derivative Canagliflozin is a drug used in the treatment of type
2
5-27
In
-1
of 450-4000 cm with a Perkin Elmer Spectrum 100 Fourier-
1
13
transform infrared spectrometer. Routine H NMR and C NMR
2
8-30
In
spectra were recorded with a Bruker Ascend™ 400 Avance III HD
NMR spectrometer with sample solutions prepared in CDCl .
3
The chemical shifts (δ) were reported in parts per million (ppm)
relative to tetramethylsilane (TMS) as an internal standard.
Coupling constants (J values) were given in hertz (Hz). NMR
multiplicities were abbreviated as follows: s = singlet, d =
doublet, t = triplet, hept = heptet, dd = doublet of doublets, m
2
diabetes, Atliprofen is an anti-inflammatory drug, Motapizone
is used in the treatment against platelet aggregation diabetes,
and Tiemonium is antimuscarinics.
3
1-33
Several thiophene
1
= multiplet. H NMR spectra were referenced to residual
derivatives containing a hydroxyalkyl group at C2 have also
been found to be bioactive. Duloxetine is employed against
major depressive disorder and penthienate is antimuscarinic;
also several 2-arylated furans display important biological
properties. For example, Dantrolene is a muscle relaxant and
lapatinib is employed against breast cancer (Figure 1).
13
protiated solvents (δ = 7.28 ppm for CDCl
3
), C NMR chemical
shifts were reported relative to deuterated solvents (δ = 77.16
ppm for CDCl ). The catalytic solutions were analyzed with a
Shimadzu GC 2025 equipped with a GC-FID sensor and RX-5ms
column of 30 m length, 0.25 mm diameter and 0.25 μm film
thickness. All the measurements were taken at room
temperature for freshly prepared solutions.
3
General procedure for the preparation of benzimidazolium
salts (2a-e)
A mixture of 1-benzhydryl-5,6-dimethyl-benzimidazole (1
mmol) and an equivalent amount of alkyl halide derivative (1
mmol), in degassed dimethylformamide. The reaction mixture
was heated and stirred at 80 °C for 48h under argon. The
obtained mixture was cooled at room temperature, After
completion of the reaction, 45 mL of ether were added, and
stirred for 1h, then the product filtered and washed with diethyl
ether to remove the impurities, and the product was left
Figure 1. Examples of bioactive thiazole, thiophene, and furan
derivatives.
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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precipitated with high purity. After, the crude products were
recrystallized in dichloromethane and dried under vacuum to
C
C
6
H
H
2
1
(CH
(CH
3
3
)
)
2
View Article Online
2
-N); 6.46 (s, 1H, Ph-CH-Ph); 6.17 (s, 2H, NCH -
DOI: 10.1039/D1NJ03388C
6
4
); 6.13 (s, 1H, C
); 2.00 (s, 3H, CH
, TMS, 25°C): δ(ppm) = 16.82 (2CH
stable white solids in high yields. For the H NMR, C NMR, and 20.28 (CH3, ); 20.60 (2CH ,C15,18); 51.19 (N-CH
FT-IR spectrums of the benzimidazolium salts. All CH-Ph,C21); 111.74 (CH,C ); 113.50 (CH,C
6 1 3 4 3
H (CH ) ); 2.29 (s, 6H, CH ); 2.28 (s,
provide pure products for experimental analysis. All 6H, CH
benzimidazolium salts (2a-e) were isolated as air- and moisture- CDCl
3
); 2.01 (s, 3H, CH
3
3
). 13C-NMR (400MHz,
);
,C10); 68,05 (Ph-
); 124.21 (CH,
3
3 5
,C13,20); 20.13 (CH3,C
1
13
C
7
3
2
8
3
3
4
benzimidazolium salts were published in our previous study.
NC
29.15 (4CH,C24,26,30,32); 130.84 (C11); 131.26 (C
General procedure for the preparation of the PEPPSI-type 132.35 (C ); 132.88 (C ); 134.23 (C12,19); 135.18(C14,17); 137.69
Pd(II)-NHC complexes (3a-e) (CH, NC ,C36); 137.85 (CH,C22,28); 152.56 (NC ,C34,38); 163.18
The palladium(II)-NHC complexes PEPPSI-type could be (Pd-Ccarb,C ). Elemental analysis calcd. (%) for C38 39Br
synthesized by the interaction of benzimidazolium salts with (M.w.= 803.98 g/mol): C 56.77, H 4.89, N 4.54; found (%): C
PdCl (1mmol) and pyridine in the presence of potassium 56.85, H 4.58, N 4.90.
carbonate K CO (5mmol). After the addition of KBr (10 mmol) Dibromo[1-benzhydryl-5,6-dimethyl-3-(2,4,6-
5 5
H ,C35,37); 127.91 (2CH,C25,31); 128.40 (4CH,C23,27,29,33);
1
9 2
); 131.50 (C );
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4
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H
5
5 5
H
1
H
2
N3Pd
2
2
3
solution was stirred and heated for 48 h at 80 °C. The reactions trimethylbenzyl)benzimedazole-2-ylidene]pyridinepalladium
were carried out in acetonitrile (15 mL) under an atmosphere of (II), 3c
nitrogen. The solvent was removed under vacuum to afford the Yield 81%; 130 mg; m.p: 153-154 °C; yellow-solid(crystal); FT-IR
-
1 1
product and eliminate pyridine then the mixture was washed ν(CN)=1400 cm . H-NMR (400MHz, CDCl
with hexane three times. The black solid formed was dissolved = 8.96 (d, J =5.2 Hz, 2H, NC ); 8.60 (s, 1H, N-C
in DCM (CH Cl ) and purified by a flash column chromatography 7.72 (t, J =7.7 Hz, 1H, NC ); 7.46 (d, J =6.6 Hz, 4H, CH-Ar); 7.36
on silica gel, eluting with DCM until the product was completely (m, 6H, CH-Ar); 7.30 (t, J =7.6 Hz, 2H, NC ); 6.95 (s, 2H,
); 6.46 (s, 1H, Ph-CH-Ph); 6.14 (s, 2H, NCH
); 6.13 (s, 1H, N-C (CH -N); 2.38 (s, 6H, CH ); 2.35
); 2.00 (s, 3H, CH ); 1.99 (s, 3H, CH
). 13C-NMR
hexane (1:6), to get pure complexes for analysis and catalysis. (400MHz, CDCl , TMS, 25°C): δ(ppm) = 20.13 (2C, CH ); 20.27
The palladium complexes, which are highly moisture- and air- (CH3, ); 20.28 (CH3, ); 21.16 (2CH3,
stable both in solution and solid-state against air, light and 50.79 (N-CH ,C10); 68,00 (Ph-CH-Ph,C20); 111.68 (CH,C
); 124.44 (CH, NC ,C34,36); 127.91(C11); 127.94
(2CH,C24,30); 128.40 (4CH,C22,26,28,32); 129.13 (4CH,C23,25,29,31);
3
, TMS, 25°C): δ(ppm)
5
H
5
6
H
2
(CH -N);
3 2
)
2
2
5 5
H
5 5
H
recovered. DCM was removed under reduced pressure and the
pure complex was obtained as a yellow powder solid. Further,
C
C
6
H
H
2
2
(CH
(CH
3
3
)
)
3
2
-
6
3
6
H
2
3
)
2
3
The crude product was recrystallized from dichloromethane: (s, 3H, CH
3
3
3
3
3
C
5
C
7
C13,19); 22.66 (CH3,C16);
2
8
); 113.53
moisture.
(CH,C
3
5 5
H
Dibromo[1-benzhydryl-5,6-dimethyl-3-(4-
methylbenzyl)benzimedazole-2-ylidene]pyridine palladium 129.45 (2CH,C14,17); 131.36 (C
II), 3a (C ); 137.74 (CH, NC ,C35); 137.82 (C21,27); 138.48(C15);
Yield 71%; 150 mg; m.p: 292-293°C; yellow-solid(crystal); FT-IR 138.92(C12,18); 152.61 (NC ,C33,37); 163.18 (Pd-Ccarb,C ).
, TMS, 25°C): δ(ppm) Elemental analysis calcd. (%) for C37 37Br Pd (M.w.= 789.95
); 8.58 (s, 1H, N-C (CH -N); g/mol): C 55.26, H 4.72, N 5.32; found (%): C 55.56, H 4.67, N
); 7.51 (d, J =8.1 Hz, 2H, N-C (CH )- 5.15.
9 2 4
); 131.60 (C ); 132.95 (C ); 134.05
(
6
5 5
H
5
H
5
1
-
1 1
ν(CN)=1400cm . H-NMR (400MHz, CDCl
3
H
2 3
N
=
7
8.98 (d, J =5.0 Hz, 2H, NC
.72 (t, J =7.6 Hz, 1H, C
5
H
5
6
H
2
3 2
)
5
H
5
6
H
4
3
N); 7.48 (d, J =8.6 Hz, 4H, CH-Ar); 7.32-7.27 (m, 6H, CH-Ar); 7.18 Dibromo[1-benzhydryl-5,6-dimethyl-3-(3,4,5-
d, J =8.1 Hz, 2H, N-C (CH )-N); 6.82 (s, 1H, N-C (CH -N); trimethoxybenzyl)benzimedazol-2-ylidene]pyridinepalladium
.45 (s, 1H, Ph-CH-Ph); 6.14 (s, 2H, NCH -C (CH )); 2.34 (s, 3H, (II), 3d
CH ); 2.14 (s, 3H, CH ); 2.02 (s, 3H, CH ). C-NMR (400MHz, Yield 69%; 220 mg; m.p: 264-265 °C; yellow-solid(crystal); FT-IR
CDCl , TMS, 25°C): δ(ppm) = 20.13 (CH3,
1.22 (CH3, 15); 53.42 (N-CH ,C10); 67,97 (Ph-CH-Ph,C18); 111.75 = 8.99 (d, J =5.2 Hz, 2H, NC
CH,C ); 113.73 (CH,C ); 124.46 (CH, NC ,C32,34); 127.94 7.72 (t, J =7.6 Hz, 1H, NC ); 7.47 (d, J =5.3 Hz, 4H, CH-Ar); 7.35-
2CH,C22,28); 128.01 (2CH,C13,16); 128.44 (4CH,C20,24,26,30); 129.18 7.37 (m, 6H, CH-Ar); 7.30 (t, J =7.6 Hz, 2H, NC ); 6.90 (s, 2H,
4CH,C21,23,27,29); 129.47 (2CH, C12,17); 131.84 (C11); 131.97 (C ); -(OCH ); 6.88 (s, 1H, s, 1H, N-C (CH -N); 6.46 (s, 1H,
,C33); Ph-CH-Ph); 6.09 (s, 2H, NCH -C (OCH ); 3.87 (s, 6H, OCH );
,C31,35); 163.38 (Pd- 3.84 (s, 3H, OCH ); 2.17 (s, 3H, CH ); 2.04 (s, 3H, CH
). 13C-NMR
). Elemental analysis calcd. (%) for C35 Pd (400MHz, CDCl , TMS, 25°C): δ(ppm) = 20.20 (CH ,C ); 20.27
M.w.= 761.90 g/mol): C 55.18, H 4.37, N 5.52; found (%): C (CH ,C ); 53.79 (N-CH ,C10); 56.69 (2OCH
4.98, H 4.43, N 5.37. (OCH ,C16); 67,94 (Ph-CH-Ph,C20); 111.70 (CH,C
(CH,C ); 124.58 (CH, NC ,C34,36); 125.37 (2CH,C12,19); 128.07
(2CH,C24,30); 128.44 (4CH,C22,26,28,32); 129.14 (4CH,C23,25,29,31);
(
6
6
H
4
3
6
H
2
3 2
)
2
6
H
4
3
1
3
3
3
3
-1 1
3
C
5
); 20.25 (CH3,
C
7
); ν(CN)=1404 cm . H-NMR (400MHz, CDCl
3
, TMS, 25°C): δ(ppm)
(CH -N);
2
C
2
5
H
5
); 8.58 (s, 1H, N-C
6
H
2
3 2
)
(
(
(
8
3
5
H
5
5 5
H
5 5
H
)
3 2
9
C
6
H
2
3
)
3
6
H
3
2
1
32.05 (C
2
); 133.15 (C
6
); 133.57 (C
4
); 137.68 (CH, NC
5
H
5
2
6
H
2
)
3
3
137.74 (C19,25); 137.78 (C14); 152.65 (NC
5
H
5
3
3
3
3
Ccarb,C
1
H
33Br
2
N
3
3
5
(
5
3
7
2
3
,C14,18); 60.85
3
8
); 113.78
Dibromo[1-benzhydryl-5,6-dimethyl-3-(2,3,5,6-
tetramethylbenzyl)-benzimedazole-2-
ylidene]pyridinepalladium (II), 3b
3
5 5
H
131.83 (C11); 131.94 (C
9
); 132.05 (C
2
); 133.15 (C
4
); 133.58 (C
,C35); 150.89
,C33,37); 163.29 (Pd-Ccarb,C ). Elemental
-N); analysis calcd. (%) for C37 37Br Pd (M.w.= 837.95 g/mol): C
5 5
H ); 7.46 (d, J =6.7 Hz , 4H, CH-Ar); 7.35 53.04, H 4.45, N 5.01; found (%): C 52.81, H 4.27, N 5.04.
6
);
5 5
Yield 85%; 215 mg; m.p: 244-245 °C; yellow-solid(crystal); FT-IR 137.62 (C15); 137.68(C21,27); 137.85(CH, NC H
ν(CN)=1400 cm . H-NMR (400MHz, CDCl
-
1 1
3
, TMS, 25°C): δ(ppm) (C13,17); 152.65 (NC
5
H
5
1
=
7
8.91 (d, J =5.0 Hz, 2H, NC
.70 (t, J =7.6 Hz, 1H, NC
5
H
5
); 8.60 (s, 1H, N-C (CH
6
H
2
3
)
2
H
2 3 3
N O
(m, 6H, CH-Ar); 7.29 (t, J =7.6 Hz, 2H, NC
5
H
5
); 7.10 (s, 1H, N-
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
also offers a nice balance between cost and preciVsiieownA.r 4t i 4c -l 4e 6OTnlhinee
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Dibromo[1-benzhydryl-5,6-dimethyl-3-(4-tert-
butylbenzyl)benzimedazole-2-ylidene]pyridinepalladium (II), ground state was validated by the aDbOseI:n10ce.103o9f/Di1mNJa0g3in38a8rCy
3e
frequencies (no imaginary frequency).
Yield 98%; 100 mg; 3.p: 276-277 °C; yellow-solid(crystal); FT-IR
ν(CN)=1399cm . H-NMR (400MHz, CDCl
-
1 1
3
, TMS, 25°C): δ(ppm) Catalytic study of Pd(II)-NHC complexes PEPPSI-type
H ); 8.59 (s, 1H, N-C H (CH ) -N); General Procedure for the direct arylation reaction
5 5 6 2 3 2
=
7
7
7
C
C
8.98 (d, J =5.1 Hz, 2H, NC
.71 (t, J =7.7 Hz, 1H, NC ); 7.57 (d, J =8.2 Hz, 2H, C
.49 (d, J =6.7 Hz, 4H, CH-Ar); 7.40 (d, J =8.2 Hz, 2H, C
.35 (m, 6H, CH-Ar); 7.29 (t, J =7.6 Hz, 2H, NC
5
H
5
6
H
H
4
-(tBu)); In 1990, the first examples of Pd‐catalyzed direct arylation of
-(tBu)); furans and thiophenes were reported by Ohta.10 In this
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
4
5
H
5
)6.82 (s, 2H, N- pioneering work, the direct C(5)‐arylation of furan, thiophene,
-N); 6.45 (s, 1H, Ph-CH-Ph); 6.15 (s, 2H, NCH and furaldehyde was carried out with electron‐rich or electron‐
(tBu)); 2.14 (s, 3H, CH ); 2.03 (s, 3H, CH ); 1.31 (s, 9H, poor aryl bromides using [Pd(II)Br (NHC)(pyridine)] as the
, TMS, 25°C): δ(ppm) = catalyst. In the last two decades, Pd‐catalyzed direct arylation
6
H
H
2
(CH
3
)
2
2
-
6
4
3
3
2
CH
0.08 (CH
CH 15); 53.37 (N-CH
CH,C ); 113.72 (CH,C ); 124.45 (CH, NC
3
/(tBu)). 13C-NMR (400MHz, CDCl
,C ); 20.25 (CH ,C ); 31.33 (3CH
,C10); 67,95 (Ph-CH-Ph,C21); 111.83 study, we selected DMA as the solvent, and KOAc as the base
,C35,37); 125.73 according to the methods described in the literature.49 In a
3
4
7-48
2
3
5
3
7
3
,C16,17,18); 34.58 (C- was successfully performed.
Therefore, in this catalysis
(
(
(
(
(
(
3
)
3,
C
2
8
3
5
H
5
2CH,C23,19); 125.72 (2CH,C24,30); 128.01 (2CH,C12,20); 128.44 typical experiment an oven-dried 10 mL Schlenk tube was
4CH,C23,27,29,33); 129.17 (4CH,C24,26,30,32); 131.83 (C11); 131.94 charged with 1 mol% of Pd(II)-NHC complexes (0.01 mmol) as
C
9
); 132.05 (C
CH, NC ,C36); 150.89(C14); 152.65 (NC
). Elemental analysis calcd. (%) for C38
2
); 133.15 (C
4
); 133.58 (C
6
); 137.75 (C22,28); 137.77 catalyst, five-membered heteroaromatic compound derivative
5
H
5
5 5
H
,C34,38); 163.39 (Pd- (2.0 mmol), (hetero)aryl halide (1.0 mmol), KOAc (2.0 mmol) as
Ccarb,C
1
H
39Br
2
N
3
Pd a base, and DMAc (dimethylacetamide, 2 mL) as solvent under
(M.w.= 803.98 g/mol): C 56.77, H 4.89, N 5.23; found (%): C an argon atmosphere. The Schlenk tube was placed in a
56.43, H 4.71, N 5.16.
preheated oil bath at 120 °C, and the reaction mixture was
stirred for 1h. After completion of the reaction, the solvent was
X-Ray crystallographic analysis study
The structure of Pd(II)-NHC complexes 3a, 3b and 3d was (2 mL) and charged directly onto
removed under vacuum and the residue was solved with CH
2 2
Cl
a
micro-silica gel
determined by the X-ray diffraction technique, the obtained chromatography column. The products were eluted by using n-
results confirmed all the spectroscopic data. A single Suitable hexane/diethyl ether mixture (5:1, v/v) as eluent to afford the
crystal of complex 3a, 3b and 4d for X-ray diffraction analysis pure product. The chemical characterizations of the products
was grown by slow diffusion of diethyl ether in a saturated were checked by gas chromatography GC spectrometry. GC
chloroform solution at room temperature. Crystallographic yields and Conversions were calculated by taking into account
data of 3a, 3b and 3d were collected with an STOE IPDS II the conversion of aryl bromides to products from the results of
diffractometer at room temperature using graphite- GC spectrometry with dodecane as an internal standard.
monochromated Mo Kα radiation by applying the
method. Data collection and cell refinement were carried out
using X-AREA while data reduction was applied using X-RED32
The structures were solved by direct methods with SIR2019
-scan
3
5
Results and discussion
3
6
Preparation of PEPPSI-type palladium–NHC complexes 3a-e
The PEPPSI‐themed Pd(II)-NHC complexes (3a–e) were
synthesized according to procedures reported by Organ for
other Pd–NHC–PEPPSI complexes.[21] All reactions for the
preparation of the Palladium complexes were carried out under
argon using standard Schlenk techniques. A solution of
and refined through the full-matrix least-squares calculations
2
37
on F using SHELXL-2018 inserted in idealized positions and
treated using a riding model, fixing the bond lengths at 0.93,
0
.98, 0.97, and 0.96 Å for aromatic CH, methine CH, CH2, and CH
atoms, respectively. The displacement parameters of the H
atoms were fixed at Uiso(H) = 1.2Ueq (1.5Ueq for CH ) of their
3
3
benzimidazolium salts (1eq), PdCl
2
(1,5 eq.), in pyridine (2 eq.),
parent atoms. The crystallographic data and refinement
parameters are summarized in Table 1. Molecular graphics were
generated by using OLEX2.
K
2
CO (5 eq.) and a large excess of KBr(10 eq.), were dissolved
3
in 15 mL of acetonitrile (15 mL) under an atmosphere of
nitrogen. The reaction was stirred and heated for 02 days at 80
°C until the mixture becomes black. After the reaction was
finished, the solvent was removed under vacuum to afford the
product and eliminate pyridine then the mixture was washed
with hexane three times. After removal of the hexane solvent,
3
8
Density Functional Theory (DFT) calculations
Computational details
All DFT (Density Functional Theory) calculations of this work
have been performed using Gaussian09 software.39 The B3LYP
the residue was re-dissolved in CH
covered with Celite, to remove unreacted PdCl
product was obtained after evaporating the CH Cl
2 2
Cl , filtered on a pad of silica
2
. The crude
2
solvent. The
(Becke-Lee-Parr hybrid exchange-correlation three-parameter
2
4
0,41
42
functional) functional
in conjunction with LANL2DZ basis
crude product was recrystallized from dichloromethane:
hexane (1:4). After chromatography on silica gel, the pure
complex was obtained as a yellow Pd(II)-NHC complexes (3a-e)
were obtained. All Pd(II)-NHC complexes were prepared in good
yields through a simple procedure in a three-steps (Scheme 1)
4
3
set for Palladium atom and 6-311G(d,p) basis set for
hydrogen, carbon, nitrogen, and bromine atoms have been
used for all calculations. The B3LYP method is efficient for the
prediction of molecular geometry and electronic properties and
4
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DOI: 10.1039/D1NJ03388C
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from 5,6-dimethylbenzimidazole and benzhydryl reagents for obtain
the preparation of product 1 as a starting material, then the benzimidazolium salts (2a-e) were used as a precursor for the
starting material reacts with various ligands of chlorobenzyl to synthesis of Pd(II)-NHC complexes.
5,6-dimethylbenzimidazoluim
salts.
These
Table 1. Crystal data and structure refinement parameters for 3a, 3b, and 3d.
Pd(II)-NHC complexes PEPPSI-Type
Parameters
3a
3b
3d
CCDC depository
Color/shape
2073777
Yellow/prism
2073779
Yellow/prism
2073780
Yellow/prism
Chemical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
[PdBr
761.86
296(2)
0.71073 Mo Kα
Monoclinic
2
(C30
H
28
N
2
)(C
5
H
5
N)]
[PdBr
803.94
296(2)
0.71073 Mo Kα
Triclinic
P−1 (No. 2)
2
(C33
H
34
N
2
)(C
5
H
5
N)]
2 32 2 3 5 5
[PdBr (C32H N O )(C H N)]
837.91
296(2)
0.71073 Mo Kα
Monoclinic
1
P-2 /n (No. 14)
P2
1
/n (No. 14)
Unit cell parameters
a, b, c (Å)
14.9802(13),
0.2398(15)
11.0510(7), 9.3043(7),
17.5332(14)
11.1447(9), 11.9557(9),
18.4136(13)
104.973(6), 90, 106.908(6), 90
16.6440(8),
2
α, β, γ (°)
90, 106.685(6), 90
91.190(6),
03.026(6)
1705.1(2)
2
1.566
2.918
1
Volume (Å3)
3209.6(4)
4
1.577
3505.7(4)
4
1.588
Z
D
3
calc. (g/cm )
−
1
μ (mm )
3.096
2.848
Absorption correction
Integration
0.5504, 0.8967
1520
Integration
0.1567, 0.3154
808
0.73 × 0.55 × 0.53
STOE IPDS II/ω scan
Integration
0.2890, 0.7055
1680
0.48 × 0.45 × 0.11
STOE IPDS II/ω scan
T
F
min., Tmax.
000
3
Crystal size (mm )
0.35 × 0.08 × 0.04
Diffractometer/measur STOE IPDS II/ω scan
ement method
Index ranges
−19 ≤ h ≤ 19, −14 ≤ k ≤ 14, −12 ≤ h ≤ 12, −14 ≤ k ≤ 14, −22 −15 ≤ h ≤ 15, −21 ≤ k ≤ 19, −24
−
26 ≤ l ≤ 26
≤ l ≤ 22
≤ l ≤ 24
1.683 ≤ θ ≤ 27.737
θ
range for data 1.993 ≤ θ ≤ 27.956
1.882 ≤ θ ≤ 27.802
collection (°)
Reflections collected
36397
21039
54952
8206/6602
Independent/observed 7650/3046
reflections
7945/4779
R
int.
0.2489
0.1482
0.0762
Refinement method
Full-matrix least-squares on Full-matrix least-squares on Full-matrix least-squares on
2
2
2
F
F
F
Data/restraints/param
eters
7650/0/373
7945/0/403
8206/0/420
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Δρmax., Δρmin. (e/Å3)
0.972
1.036
1.165
R
R
1
1
= 0.0927, wR
= 0.2310, wR
2
2
= 0.1253
= 0.1641
R
R
1
1
= 0.0771, wR
= 0.1301, wR
2
2
= 0.1750
= 0.2089
R
R
1
1
= 0.0534, wR
= 0.0727, wR
2
= 0.0962
= 0.1022
2
1.06, −0.69
1.17, −1.56
0.70, −0.56
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Scheme 1. Synthetic route and structure of Pd(II)-NHC complexes PEPPSI-type (3a-e).
1
pyridine ring were observed as downfield resonances in the H NMR
spectra in the d range of δ = 7.71-8.99 ppm. These signals suggest
that the pyridine ring coordinated to the palladium centre to form a
All new five Pd(II)-NHC complexes 3a–e were showed good solubility
in most organic solvents, such as chloroform, dichloromethane,
ethanol, acetonitrile, and dimethylsulfoxide except non‐polar ones,
as pentane and hexane. They are highly moisture‐ and air‐stable both
in solution and in the solid-state against air, light, and moisture,
which could be stored at room temperature for months without an
obvious decline in catalytic efficiency. The new compounds were
successfully characterized by spectroscopic techniques such as NMR,
FT‐IR, and elementary analysis to confirm the formation of the
complexes. The physical and some spectroscopic data of Pd(II)-NHC
complexes PEPPSI-type are summarized in Table 2. Firstly, the FT-IR
spectroscopy data indicated that the PEPPSI-type Pd(II)-NHC
complexes 3a-e exhibit a characteristic ν(CN) band typically at 1400,
1
3
PEPPSI-type palladium complex. While in C NMR the signals of the
aromatic carbons of pyridine ring were detected at δ =152.65,
52.56, 152.61, 152.64, 152.65 ppm for the first two carbons CHNCH.
While the second 2 carbons CH-CNC-CH were detected at δ =124.46,
24.21, 124.44, 124.58, 124.45 ppm, and δ =137.68, 137.69, 137.74,
37.85, 137.77 ppm for the carbon CHCHCH. All these data support
the formation of the PEPPSI-type palladium complex. The PEPPSI Pd-
NHC complexes were identified compared to benzimidazolium salts
by a characteristic proton peak at the 2-position which not appeared
1
1
1
1
as a signal of an acidic proton (NCHN) in the H NMR and carbon peak
in C NMR (NCHN) spectra, the characteristic signals of the acidic
proton and the benzimidazolium salts were not observed, which
13
1
400, 1400, 1404 and 1399 cm-1 respectively. The formation of
confirm the formation of Pd-carbene bond. The characteristic Pd–C
2
-
carbenes is correlated by a shift of the (CN) vibration. The FT-IR
spectra of these five Pd (II)-NHC complexes show similar absorption
bands. Due to the flow of electrons from the carbene ligand to the
palladium center, the C=N bond is weakened, and as a result, a
decrease in the v(CN) stretching frequency is observed. Secondly, in
carbene signals of 3a-e complexes appear as a singlet at δ = 163.38,
1
3
1
63.18, 163.18, 163.29 and 163.39 ppm, respectively in C NMR
spectra. The elemental analysis results of these complexes are in
agreement with the proposed molecular formula. These five new
complexes show typical spectroscopic signatures, values are in
1
the H NMR the characteristic signals of aromatic hydrogens of
6
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agreement with reported data for similar PEPPSI type Pd(II)-NHC
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DOI: 10.1039/D1NJ03388C
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4,49
complexes.
Table 2. Physical and some spectroscopic data of Pd(II)-NHC complexes PEPPSI-type
Code
Chemical Formula
Molecular
Weight
Melting point
13C NMR
(C ) ppm
IR
°C
2
ν
(CN)
(
g/mol)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
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1
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1
2
3
4
5
6
7
8
9
0
3
a
b
C
35
C
38
C
37
C
37
C
38
H34Br
H40Br
H38Br
H38Br
H40Br
2
N
3
Pd
Pd
Pd
Pd
Pd
761,90
803,98
789,95
837,95
803,98
292-293
244-245
153-154
264-265
276-277
163,38
163,18
163,18
163,29
163,39
1400
1400
1400
1404
1399
3
2 3
N
3c
2 3
N
3
d
e
2
N
3
O
3
3
2 3
N
X-ray crystal structures
The solid-state structures of 3a, 3b, and 3d with the adopted atom-
labeling scheme are shown in Figs. 2-4, while important bond
distances and angles are listed in Table 3. The palladium complexes
are four-coordinated in a square-planar geometry and surrounded
by the carbene carbon atom of the NHC ligand, the nitrogen atom of
the pyridine ring, and two bromide atoms. The complexes have a
slightly distorted square-planar geometry, in which the anion atoms
are trans to each other. The cis angles varying from 85.32(19) to
9
3.23(17)° and the trans angles changing from 173.05(4) to
179.17(14)° deviate from their ideal values of 90 and 180°,
respectively. For quantitative evaluation of the extent of distortion
5
0
′
51
around the metal center, the structural indexes 흉
and 흉
were
ퟒ
ퟒ
ퟑퟔퟎ°−(휶+휷)
ퟑퟔퟎ°−ퟐ휽
휷−휶
ퟏퟖퟎ°−휷
ꢀ ퟏퟖퟎ°−휽
′
employed; 흉 =
흉 =
ퟒ
ퟑퟔퟎ°−휽
ퟒ
where 휶 and 휷 (휷 > 휶) are the two greatest valence angles and 휽 is
′
ퟒ
the ideal tetrahedral angle (109.5°). The 흉 and 흉 values for ideal
ퟒ
square-planar and tetrahedral coordination spheres are 0 and 1,
′
ퟒ
respectively. The calculated 흉 and 흉 geometry indices are 0.07,
ퟒ
0
.06 for 3a, both 0.04 for 3c, and 0.03, 0.02 for 3d, respectively,
Figure 3. Molecular structure of 3b drawn at 20% probability level.
pointing out a slightly distorted square-planar geometry.
H atoms have been omitted for clarity.
Figure 4. Molecular structure of 3d drawn at 20% probability level.
Figure 2. Molecular structure of 3a drawn at 20% probability level.
H atoms have been omitted for clarity.
H atoms have been omitted for clarity.
This journal is © The Royal Society of Chemistry 20xx
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4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 3. Selected distances (Å) and angles (°) for 3a, 3c and 3e
The deviations between calculated and experimental angles for
View Article Online
DOI: 10.1039/D1NJ03388C
Br1-Pd-Br2 and Br1-Pd-N9 are only -0.02° and -0.01°
Pd(II)-NHC complexes PEPPSI-Type
respectively. The maximal discrepancies are found for the bond
N8-Pd with a deviation of ‐0.249 Å, and the angles N8-Pd-C1 and
Br1-Pd-C1 with deviations of 0.380° and 0.259°, respectively.
These findings indicate that the DFT approach used is
sufficiently accurate to predict the molecular geometry of
complex 3a.
Parameters
3a
3c
3e
Pd1─Br1
Pd1─Br2
2.4281(9) 2.4182(16) 2.4339(5)
2.4102(10) 2.4352(15) 2.4052(5)
Bond
distances Pd1─N3
Pd1─C1
2.127(6)
1.965(8)
1.353(9)
1.341(9)
2.078(8)
1.949(9)
1.350(11)
1.365(10)
2.111(3)
1.964(3)
1.349(4)
1.346(5)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N1─C1
N2─C1
Br1─Pd1─Br2 173.05(4)
175.95(6)
91.7(2)
91.1(2)
90.1(2)
87.0(2)
178.1(4)
107.1(7)
Br1─Pd1─N3
Br2─Pd1─N3
Br1─Pd1─C1
Br2─Pd1─C1
N3─Pd1─C1
N1─C1─N2
93.23(17)
91.57(17)
89.92(19)
85.32(19)
176.8(2)
108.5(6)
176.09(2)
91.91(10)
91.83(9)
87.27(10)
88.99(10)
179.17(14)
Bond
angles
(
°)
The average Pd─CNHC bond distance (1.96 Å) is smaller than the
sum of the individual covalent radii of the palladium and carbon
atoms (2.12 Å), while the average Pd─Npyridine bond distance
(2.10 Å) is equal to the sum of the individual covalent radii of
5
2
the palladium and nitrogen atoms (2.10 Å). The Pd─Br
distances are in the usual range, and the internal N─C─N ring
angles at the carbene centers vary from 107.1(7) to 108.5(6)° in
the complexes. In sum, these parameters are comparable with
those observed for Pd-NHC-pyridine-Br
carbene ring is almost perpendicular to the coordination plane
Figure 5. (a) The optimized molecular structure, and (b) atom-by-
atom superimposition of the crystal structure (cyan) and the
optimized molecular structure (yellow) of complex 3a.
5
3-59
2
complexes.
The
Table 4. Selected experimental and theoretical geometric
parameters of complex 3a.
with a dihedral angle of 76.3(3)° in 3a, 89.3(2)° in 3b and
76.07(11)° in 3d, which is typical for NHC complexes to reduce
Complex 3a
Calculated
Experimental
Discrepancy
steric congestion. On the other hand, the dihedral angle
between the pyridine ring and the coordination plane is 68.7(5)°
in 3a, 40.7(4)° in 3b, and 51.8(2)° in 3d.
Bond Distance
(
ꢀ)
N8-Pd
Br1-Pb
Br2-Pb
C1-Pb
C1-N1
1.850
2.441
2.434
1.838
1.346
1.349
2.099
2.448
2.438
1.959
1.364
1.368
-0.249
-0.007
-0.004
-0.121
-0.018
-0.019
Theoretical investigations
To gain further insights into the molecular structure and
electronic properties of the synthesized complexes, DFT
calculations at B3LYP/6-311G(d,p)/LANL2DZ level have been
performed for complex 3a as an example molecule. The
obtained molecular geometry by DFT calculations was C1-N2
compared to that of X-ray analysis and the obtained results are
shown in Figure 5. Some selected experimental and theoretical
geometric parameters of complex 3a are also reported in Table
Bond Angle (°)
N8-Pd-C1
178.31
175.42
87.491
90.836
177.93
175.44
87.231
90.840
0.380
-0.020
0.259
-0.010
Br1-Pd-Br2
4
. As can be seen, the predicted molecular geometry of complex
3
a is strongly in agreement with the experimental results. The Br1-Pd-C1
calculated Br1-Pb and Br2-Pb bond lengths were found to be
.441 and 2.434 Å, respectively, which are in very good
agreement with the experimental values (2.448 and 2.438 Å).
Br1-Pd-N9
2
8
| J. Name., 2012, 00, 1-3
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0
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 6. Frontier molecular orbitals of complex 3a computed at B3LYP/6-311G(d,p)/ LANL2DZ level of theory.
are mainly concentred on the metal center and the benzene ring for
LUMO+1. The HOMO+2 is located on the pyridine ring, while
LUMO+3 is distributed on the benzene rings and slightly on the Pd
atom. These distributions of the electron density of HOMOs and
LUMOs clearly show the transfer of the electron density from the
benzimidazole and pyridine nucleus to the metal center and other
regions of the molecule.
Frontier molecular orbitals (FMOs), i.e. HOMO (Highest occupied
molecular orbital) and LUMO (lowest unoccupied molecular orbital),
are important parameters that could be used to characterize the
6
0,61
stability and chemical reactivity of molecules.
The energy of
HOMO is related to the electron donation ability, whereas that of
LUMO represents the ability to accept electrons. The shape of FMOs
could also give insights into the sites of electrophilic and nucleophilic
attacks. The energy and distribution of FMOs, ranging from HOMO-3
to LUMO+3, of complex 3a, have been calculated at B3LYP/6-
311G(d,p)/LANL2DZ level and are reported in Figure 5 and Table 5,
respectively. As illustrated in Table 5, the calculated FMOs energies
are in the range of –0.43 to –5.91 eV. The difference between HOMO
and LUMO energy (energy Gap) is only 2.26 eV, suggesting a high
Molecular electrostatic potential (MEP) is another useful tool that
can be used to describe the electronic properties and chemical
64,65
reactivity of molecules.
MEP represents a 3D view of charge
distributions within a molecule, color codes ranging from deep red
for electron-rich sites to deep blue for electron-deficient sites are
used. Figure 7 shows the MEP of complex 3a calculated at B3LYP/6-
311G(d,p)/ LANL2DZ level in the gas phase. The analysis of the
obtained MEP reveals that the most electron-deficient sites of
complex 3a are located on the aromatic rings, in particular on the
benzimidazole and pyridine. This suggests that these sites are the
most suitable for nucleophilic attacks. On the other hand, the
positive charges were found distributed on several aromatic
hydrogen atoms and the metal center, indicating that these sites are
the most electron-deficient and could be considered electrophilic
sites.
6
2,63
chemical reactivity of complex 3a.
We can see also from Figure 6
that the HOMO and HOMO-1 are mainly distributed on the
benzimidazole and the pyridine moieties with very small
contributions of the Pd atom. HOMO-2 is located on the
benzimidazole, while HOMO-3 is distributed on the benzimidazole,
pyridine and Pd atom. These results indicate that the pyridine and
the benzimidazole moieties are the most active sites for electron
donation. Different from HOMOs which have relatively similar
distributions, LUMOs of complex 3a is different. LUMO and LUMO+1
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2
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DOI: 10.1039/D1NJ03388C
ARTICLE
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0
work and no desired product was formed. While in the same
condition with the presence of 1 mol% Pd-catalyst complex, the
reaction was working.
Table 5. Energies in eV of the frontier molecular orbitals of complex
a.
To optimize and determine the best reaction conditions of the direct
arylation, we studied the reaction on changing (solvent, base,
temperature, and time). Complex 3b was selected as a model test
catalyst, 2-acetylfurane as heteroaromatic substrates, and the p-
bromobenzene as model coupling partner. As commonly used for the
3
Complex 3a
LUMO+3
LUMO+2
LUMO+1
LUMO
Energy in eV
–0.43
6
6,68
direct arylation of hetero-arenes, based on previous studies.
In
–0.73
this part, we start selected dimethylacetamide DMAc as a solvent,
and potassium acetate KOAc as a base. Then we tried changing the
time (1h, 2h, 4h) and temperature (80, 100, 120, 150°C) of the
reaction. However, several attempts were made also with many
solvents and bases for this study. The reactions were performed
under argon. The results are summarized in Table 6.
–0.87
–1.22
HOMO
–3.48
HOMO-1
HOMO-2
HOMO-3
–4.21
–5.79
–5.91
Scheme 2. Influence of the reaction conditions on the Pd-catalyzed
direct arylation of five-membered heteroaromatics with p-
bromobenzene
As shown in Table 6, The preliminary data demonstrated that the
reaction displayed the best performance at 120°C temperature, and
in a short time (1h) in presence of KOAc. When the reaction time was
increased to 2 or 4 h, we observed full conversion, but no significant
difference in yield. (Table 6, entries 7 and 10). When the temperature
was increased from 120 °C, no noticeable effect on the yield was
observed (Table 6, entry 4). When the temperature was reduced
from 120 °C, low yields were observed (Table 6, entries 1 and 2). It
was found also that DMAc was the best solvent among other solvents
under the conditions tested. The evaluation of the effect of reaction
temperature on yield at 150,120,100 and 80°C, gives the best yield
at 120 °C. After fixing the first conditions of the reaction (time and
Figure 7. Molecular electrostatic potential (MEP) of complex 3a
computed at B3LYP/6-311G(d,p)/LANL2DZ level of theory.
Catalytic evaluation study
Optimization of the reaction conditions for the direct arylation of
heteroaromatics with aryl bromides
The catalytic capacity of new Pd(II)-NHC complexes 3a-e in temperature) with the successful results achieved in the optimization
intermolecular direct arylation reactions between aryl bromides and step. The evaluation of the reaction using various solvents and bases
substituted furan, and thiophene derivatives were performed. As an was carried out to confirm our coupling solvent/base choice. The test
°
attempt the first test was carried out at 120 C for 24 h without Pd- with different solvents as H O, EtOH, THF, Toluene, DMF, DMSO and
2
catalyst, to examine the effect of catalyst, the reaction of 2- dioxane was performed firstly in the presence of only 1 mol% 3b
acetylfurane with bromobenzene was done in presence of KOAc as a catalyst, the reaction conversion was low with all solvent used, and
base and dimethylacetamide (DMAc) as a solvent. The reaction didn’t
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2
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
the yield was dropped to less than 10% (Table 6, entries 12-18). As a conclusion of these preliminary studies, it was obsVeierwveAdrtitchleaOtntlhinee
When the test was done with various bases such as K CO , KOH, TEA, best condition for direct arylation reactionDOusI:in10g.1o0u39r/PDd1N-cJa0t3a3l8y8stCs
and t-BuOK in the presence of only 1 mol% 3b catalyst. The reaction complexes is 1h time, 120 °C temperature, and the couple
was working, but with low conversion and the final product was DMAc/KOAc solvent/base.
formed at lowest yields 5,7,6,9 % respectively (Table 6, entries 19-
2
3
2
2). Therefore, DMAc and KOAc proved to be the best couple
solvent/base in this reaction.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 6. Optimization of the best conditions for direct arylation reaction
Entry
Solvent
Time (h)
Base
Temperature °C
Conversion (%)
Yield (%)
0
0
0
0
0
0
07
08
16
09
1
1
1
1
1
1
1
1
1
1
2
2
2
1
2
3
4
5
6
80
04
63
95
95
04
70
94
96
95
80
99
97
06
08
02
10
09
03
04
10
14
13
11
04
23
86
75
04
45
80
81
82
65
70
82
05
05
01
09
06
02
03
05
09
07
06
1
KOAc
100
120
150
80
100
120
150
80
2
4
KOAc
KOAc
DMAc
100
120
150
0
1
2
3
4
5
6
7
8
9
0
1
2
2
H O
EtOH
THF
Toluene
DMF
DMSO
dioxane
1
1
KOAc
120
2 3
K CO
KOH
TEA
DMAc
120
t-BuOK
bromoacetophenone, p- bromoanisole. The preliminary studies
showed that all Pd(II)-NHC complexes were active. The results of our
experiments are summarized in Table 7. As shown in Table 7, an
excellent conversion was observed with all Pd-catalysts, depending
on the Pd(II) catalysts and the aryl bromides high‐yield C(5)‐ arylated
products were obtained for almost reactions. When 2-acetylfurane
was arylated with bromobenzene, the products 5-phenyl-2-
acetylfurane were obtained at 44-78% yields using Pd-complexes
The direct arylation of 2‐acetylfuran, 2-acetylthiophene and
furaldehyde with aryl bromides
Firstly, under the optimal condition, an investigation of the reactivity
of 2-acetylfuran in Pd-catalyzed direct arylation with various
(
hetero)aryl bromides were carried out, a C(5)-arylated furane
(
3a-e) as a catalyst (Table 7, entries 1-5), the lowest yield was
derivatives were obtained easily. The substate was coupling with
eight p-substituted aryl bromides, (bromobenzene, p-bromotoluene,
p-bromobenzaldehyde, p-bromoacetophenone, p- bromoanisole, 1-
bromo-4-fluorobenzene, 1-bromo-4-(trifluoromethyl)benzene, and
observed with Pd catalyst 3c, the reaction was working in 95-99%
conversion. The same reaction of 2- acetylfurane with p-
bromotoluene gave the desired product at 67-85% yield (Table 7,
entries 6-10), and the conversion of the reaction was 89-99%. The
reaction of 2- acetylfurane with p-bromobenzaldehyde gave the
expected product with 64-91 yields (Table 7, entries 11-15), and with
3-bromoquinoline). Due to the Pd-catalyst, the reaction was
perfectly working and the desired products were obtained with
moderate to high yield, by using only 1 mol% Pd-complexes (3a-e) as
a catalyst. The best yield was detected for the arylation with
(hetero)aryl bromides which are poor of the electron as
bromobenzene, p-bromotoluene, While the lowest yield was
observed for electron-rich (hetero)aryl bromides as p-
9
9% conversion with all Pd-catalysts. The coupling with electron‐
poor p-bromoacetophenone was also given the expected product
with a high yield at 71-82% and with 99 % conversion (Table 7,
entries 16-20).
This journal is © The Royal Society of Chemistry 20xx
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Table 7. Direct C5-arylation of 2-acetylfuran with aryl bromides by using the new Pd-catalyst.
Journal Name
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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DOI: 10.1039/D1NJ03388C
Entry
Aryl Bromide
[Pd]
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
Product
Conversion (%)
Yield (%)
78
67
44
72
64
85
73
74
67
78
75
64
88
85
91
80
71
82
72
73
80
70
80
82
78
76
74
85
76
75
77
62
69
43
39
82
80
86
84
75
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
98
95
99
99
99
94
98
98
89
99
99
99
99
99
99
93
99
99
99
99
99
99
99
99
99
98
99
97
99
95
98
77
86
81
57
95
97
99
93
88
10
11
12
13
14
15
16
17
18
19
20
21
22
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
3
4
9
0
3d
3e
The reaction conditions: Pd catalyst (0.01 mmol), 2-acetylfuran (1.0 mmol), aryl bromide (1.0 mmol), KOAc (2 mmol), DMAc (2 mL), 120 °C
and 1 h. GC yields were calculated concerning aryl bromide from the results of GC.
1
2 | J. Name., 2012, 00, 1-3
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1
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2
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6
The
trifluoromethyl)benzene generated the 5-(4-trifluoromethyl)-2-
acetylfurane at 70-86% yield and 99% conversion (Table 7, entries
1-25). The coubling with 1-bromo-4-fluorobenzene was given also a
reaction
of
2-acetylfurane
with
1-bromo-4- perfectly working and the desired product was oVbietwaAinrteicdle Ownliitnhe
(
DOI: 10.1039/D1NJ03388C
moderate to high yield, the lowest yield was detected for the
arylation with p- bromoanisole which is electron-rich. The results of
this test showed that all Pd(II)-NHC complexes PEPPSI-type were
catalytic active. The results of these experiments are summarized in
Table 9.
2
high yield at 74-85 (Table 7, entries 26-30) with 99% conversion.
When the reaction was done with the p-bromoanisole, the obtained
product formed with a moderate yield at 39-77%, and conversion
between 57-99% (Table 7, entries 31-35). When the coupling was
done with 3-bromoquinoline, the reaction gave a lower C5-arylated
As shown in Table 9, good results were observed with all Pd-catalysts,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
product with the lowest yield comparing with other reaction, the and high‐to moderate yield C(5)‐ arylated products were obtainedfor
yield was observed between 8 % and 42% (Table 7, entries 36-40).
almost all reactions. When 2-furaldehyde was arylated with
bromobenzene, the products 5-phenyl-2-carbaldehyde were
obtained at 46-86% yields using Pd-complexes (3a-d) as a catalyst,
while the lowest yield (22%) was observed with Pd-catalyst 3e (Table
Using the same reaction conditions, The second test was performed,
for the direct arylation of 2- acetylthiofene with the (hetero)aryl
bromides used in the first test, C(5)-arylated thiophene derivatives 9, entries 1-5), the reaction was working in 26-99% conversion. The
were obtained. The arylation of 2-acetylthiophene was tested with a same reaction of furaldehyde with p-bromotoluene gave the desired
range of para-substituted aryl bromides wich were used in the first
test, under the optimized conditions using all the Pd-catalysts. Due
to these Pd-catalysts (3a-e), the reaction was perfectly working in 98-
product at 51-82% yield (Table 9, entries 6-10), and the conversion
of the reaction was 99%. The reaction of furaldehyde with p-
bromobenzaldehyde gave the expected product with moderate
yields at 53-65 (Table 9, entries 11-15), and with 78-99% conversion.
9
9% conversion with almost reaction tested, and the desired
product was obtained at high yield in the average of 80%, the best
yield was detected for the arylation with (hetero)aryl bromides
The coupling with electron‐poor p-bromoacetophenone was also
which are poor of the electron as bromobenzene, p-bromotoluene. given the expected product with a lower yield at 23-48% and with 27-
The results of this evaluation showed that all Pd(II)-NHC complexes 71% conversion (Table 9, entries 16-20). The reaction of furaldehyde
PEPPSI-type were active catalysts. The results of these experiments
are summarized in Table 8. As presented in Table 8, direct C5
arylation reactions resulted in moderate to high yields of desired
coupling products. The excellent conversion was observed with all
Pd-catalysts. When 2-acetylthiophene was arylated with
bromobenzene, desired products were obtained at 78-93% yields
with 1-bromo-4-(trifluoromethyl)benzene generated the 5-(4-
trifluoromethyl)-2-furaldehyde at 47-75% yield and 64-98%
conversion (Table 9, entries 21-24), while the lowest yield was
observed with the Pd-catalyst 3e at 26%. The coupling with 1-bromo-
4
-fluorobenzene was given also a high yield at 55-85 (Table 9, entries
using Pd-complexes (3a-e) as a catalyst (Table 8, entries 1-5), the 26-30) with 77-99% conversion. Relatively low yields were obtained
reaction was working in 98% conversion. The same reaction of 2- for the coupling of furaldehyde with 4-bromoanisole, which an
acetylthiophene with p-bromotoluene gave the desired product at
electron-rich aryl bromide, the obtained product formed at 09-16%
(Table 9, entries 31-40). When the coupling was done with 3-
bromoquinoline, the reaction gave a good C5-arylated product
8
4-92% yield (Table 8, entries 6-10), the conversion of the reaction
was 92-98%. The reaction of 2- acetylthiophene with p-
bromobenzaldehyde gave the expected product with 70-81 yields
(
Table 9, entries 36-40). Because pyridine derivatives such as
(
Table 8, entries 11-15), with 99% conversion with almost Pd-
catalysts. The coupling with electron‐poor p-bromoacetophenone quinolines are known π-electrondeficient heterocycles. Therefore,
was also given the expected product with a high yield at 73-84% and reactivity of these type compounds is quite similar to electron-
with 93-99 % conversion (Table 8, entries 16-20). The reaction of 2-
acetylthiophenene with 1-bromo-4-(trifluoromethyl)benzene
generated the desired product at 60-94% yield and 65-98%
conversion (Table 8, entries 21-55). Furthermore, 1-bromo-4-
fluorobenzene was also successfully coupled with 2-acetylthiophene
to give C5 arylated products in high yields at 86-95% (Table 8, entries
deficient aryl bromides such as 4-bromoacetophenone [69]. Also as
a result of this study, it was observed that the less active catalyst was
3e
complex at 22,28,26,16,55,37% yield (Table 9, entries
5,10,15,20,25,40)
2
6-30) with 95-99% conversion. When the reaction was done with
the p-bromoanisole, the obtained product formed with moderate to
high yield at 56-82%, and conversion between 60-90% (Table 8,
entries 31-35). When the coupling was done with 3-bromoquinoline,
the reaction gave a good C5-arylated product with the same yield
(
(
80%) with all Pd-catalysts, the conversion o the reaction was 99 %
Table 8, entries 36-40).
The last evaluation of the new Pd-catalysts was performed, under the
same condition, the direct arylation of 2- furaldehyde with the
(
hetero)aryl bromides which used in the first and second test, C(5)-
arylated furaldehyde derivatives were obtained. The arylation of 2-
furaldehyde was carried out using different p-substituted aryl
bromides,
bromobenzaldehyde, p-bromoacetophenone, p-bromoanisole, and
-bromoquinoline). Due to the Pd-catalyst (3a-e), the reaction was
(bromobenzene,
p-bromotoluene,
p-
3
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Journal Name
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
DOI: 10.1039/D1NJ03388C
Table 8. Direct C5-arylation of 2-acetylthiophene with aryl bromides by using the new Pd-catalyst.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Entry
Aryl Bromide
[Pd]
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
Product
Conversion (%)
Yield (%)
78
93
93
92
93
86
92
84
89
89
70
75
81
80
81
77
84
75
82
73
75
94
60
85
85
95
93
94
90
86
80
56
74
60
82
80
80
80
80
79
1
2
3
4
5
6
7
8
9
98
98
99
98
98
92
96
98
95
95
99
98
99
99
99
99
96
94
98
93
77
98
65
90
90
99
97
97
96
95
90
60
82
67
90
99
99
99
99
99
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
3d
3e
The reaction conditions: Pd catalyst (0.01 mmol), 2-acetylthiophene (1.0 mmol), aryl bromide (1.0 mmol), KOAc (2 mmol), DMAc (2 mL), 120
C and 1 h. GC yields were calculated concerning aryl bromide from the results of GC.
°
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ARTICLE
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
DOI: 10.1039/D1NJ03388C
Table 9. Direct C5-arylation of 2-furaldeyde with aryl bromides by using the new Pd-catalyst.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Entry
Aryl Bromide
[Pd]
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
Product
Conversion (%)
Yield (%)
86
90
76
46
22
76
79
82
51
82
65
63
65
53
63
27
23
46
47
28
75
59
50
47
26
82
85
72
70
55
09
09
10
10
16
74
48
77
47
37
1
2
3
4
5
6
7
8
9
99
99
98
50
26
99
98
99
98
99
99
93
99
78
94
35
27
71
66
41
98
79
65
64
29
99
99
99
99
74
13
11
13
11
19
99
75
93
69
55
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
3d
3e
The reaction conditions: Pd catalyst (0.01 mmol), 2-furaldeyde (1.0 mmol), aryl bromide (1.0 mmol), KOAc (2 mmol), DMAc (2 mL), 120 °C
and 1 h. GC yields were calculated concerning aryl bromide from the results of GC.
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2
3
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6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
DOI: 10.1039/D1NJ03388C
CCDC 2073777, 2073779, 2073780 contains the supplementary
crystallographic data for the compounds reported in this article.
These data can be obtained free of charge on application to CCDC, 12
Conclusions
In summary, a new series of PEPPSI-type palladium-NHC
complexes (3a-e) based benzimidazole group were prepared Union Road, Cambridge CB2 1EZ, UK [Fax: +44 1223 336 033, e-mail:
using 5,6-dimethylbenzimidazolium salts with PdCl in pyridine deposit@ccdc.cam.ac.uk, https://www.ccdc.cam.ac.uk/structures/].
to give a new Pd-catalysts. All Pd(II)-NHC complexes were All the supplementary data ( H, C-NMR, and Crystallographic data)
successfully characterized by spectroscopic analytical methods.
Further, the crystal structures of 3a, 3b, and 3d Pd-NHC
complexes were also reported. Theoretical calculations using
DFT/B3LYP approach have been performed to gain further
insights into the molecular structure and electronic properties
of complex 3a. The catalytic activities of these Pd(II)-NHC
complexes were investigated in the direct C(5)‐arylation of C(2)‐
blocked as 2-acetylfuran, 2-acetylthiophene, and 2-
furaldehyde. In most cases, high yields were observed using
only 1 mol% catalyst of Pd-catalyst with all complexes in a very
short time (1h). All of these Pd(II)-NHC complexes were found
to be suitable for the arylation reaction of aryl bromide with
heteroaromatics. Moreover, thiophene and furan derivatives
can be efficiently and selectively arylated at the C(5)‐position.
Satisfactory results were obtained as compared with previously
reported similar studies. All new PEPPSI-type palladium-NHC
complexes (3a-e) proved to be active in the direct arylation
reaction. In addition, it was seen that the reaction conditions
were more moderate in terms of reaction temperature, time,
and quantity of catalyst amount.
2
1
13
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
are given in supplementary information
Notes and references
1
2
3
4
A. J. Arduengo III, R. L. Harlow, and M. Kline, J. Am. Chem. Soc.
1
991, 113, 361-363.
F. Glorius, N-heterocyclic carbenes in transition metal
catalysis, vol. 21. Springer, 2007.
M. G. Organ, G. A. Chass, D.-C. Fang, A. C. Hopkinson, and C.
Valente, Synthesis, 2008, 17, 2776-2797.
C. C. C. Johansson Seechurn, M. O. Kitching, T. J. Colacot, and
V. Snieckus, Angew. Chem. Int. Ed., 2012, 51, 5062–5085.
W. A. Herrmann, Angew. Chem. Int. Ed., 2002, 41, 1290–1309.
N. Gürbüz, E. Ö. Karaca, İ. Özdemir, B. Cetinkaya, Turkish J.
Chem., 2015, 39, 1115–1157.
E. A. B. Kantchev, C. J. O’Brien, and M. G. Organ, Angew.
Chem. Int. Ed., 2007, 46, 2768–2813.
5
6
7
8
9
F. Bellina and R. Rossi, Chem. Rev., 2010, 110, 1082–1146.
Y. Akita, A. Inoue, K. Yamamoto, A. Ohta, and T. Kurihara,
Heterocycles, 1985, 23, 2327–2333.
1
0 A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, and R. Fukunaga,
Heterocycles, 1990, 31, 1951–1958.
11 Y. Aoyagi, A. Inoue, R. Honma, Y. Akita, and A. Ohta,
Heterocycles, 1992, 33, 257–272.
1
2 N. Marion and S. P. Nolan, Acc. Chem. Res., 2008, 41, 1440–
1449.
1
3 X.-X. He, Y. Li, B.-B. Ma, Z. Ke, and F.-S. Liu, Organometallics,
2016, 35, 2655–2663.
14 M. Kaloğlu, İ. Özdemir, V. Dorcet, C. Bruneau, and H. Doucet,
Eur. J. Inorg. Chem., 2017, 2017, 1382–1391.
5 H. Lv, L. Zhu, Y. Tang, and J. Lu, Appl. Organomet. Chem., 2014,
Author Contributions
Abd el-Krim Sandeli: Investigation; Naima Khiri-Meribout:
Supervision, Writing –Review and Editing; Saida Benzerka: Formal
analysis; Houssem Boulebd: Formal analysis; Nevin Gürbüz:
Investigation, Visualization; Namık Özdemir: Formal analysis; İsmail 16 W. Sikorski, W. Zawartka, and A. M. Trzeciak, J. Organomet.
Özdemir: Resources, Funding acquisition, Writing-Review and
Editing.
1
28, 27–31.
Chem., 2018, 867, 323–332.
17 S. Karthik and T. Gandhi, Org. Lett., 2017, 19, 5486–5489.
8 M. Ionita, J. Roger, and H. Doucet, ChemSusChem, 2010, 3,
1
367–376.
1
9 A. L. Gottumukkala and H. Doucet, Eur. J. Inorg. Chem. 2007,
Conflicts of interest
There are no conflicts to declare.
3629–3632.
20 P. Xi, F.Yang, S. Qin, D. Zhao, J. Lan, G. Gao, C. Hu and J. You,
J. Am. Chem. Soc., 2010, 132,1822–1824.
2
2
1 T. Satoh and M. Miura, Chem. Lett., 2007, 36, 200–205.
2 S. Yang, C. Sun, Z. Fang, B. Li, Y. Li, and Z. Shi, Angew. Chem.,
Acknowledgements
The authors greatly acknowledge financial support from the
İnönü University Research Fund (İÜ‐BAP: FBG-2019-1594) of
this work. X-ray study was supported by the Scientific Research
Projects Unit of Ondokuz Mayıs University (Project No: 25 E. Üstün, Ş. Koç, S. Demir, and İ. Özdemir, J. Organomet.
PYO.FEN.1906.19.001).
2008, 120, 1495–1498.
2
3 L. Chen, J. Roger, C. Bruneau, P. H. Dixneuf, and H. Doucet,
Chem. Commun., 2011, 47, 1872–1874.
24 M. Nakano, H. Tsurugi, T. Satoh, and M. Miura, Org. Lett.,
2008, 10, 1851–1854.
Chem. 2016, 815, 16–22.
2
6 E. Üstün, A. Özgür, K. A. Coşkun, S. D. Düşünceli, İ. Özdemir,
and Y. Tutar, Transit. Met. Chem., 2017, 42, 331–337.
27 G. Onar, C. Gürses. M. O. Karataş, S. Balcıoğlu, N. Akbay, N.
Özdemir, B. Ateş and B. Alıcı, J. Organomet. Chem., 2019, 886,
48–56.
Appendix A. Supplementary data
2
8 E. Peris and R. H. Crabtree, Coord. Chem. Rev., 2004, 248,
2239–2246.
1
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 17 of 17
Pl eNa es we dJ oo u nr no at l ao df j Cu hs te mm i as tr rgy ins
Journal Name
ARTICLE
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
9 S. P. Nolan, N-Heterocyclic carbenes in synthesis. John Wiley 62 M. Kumar, M. Kariem, H. N. Sheikh, A. Frontera, SVi.eKw.ASrteictlehO, anlninde
Sons, 2006. A. K. Jassal, Dalton Trans., 2018, 47, 12318–12336.
0 Y. Borguet, G. Zaragoza, A. Demonceau, and L. Delaude, 63 Y.-Y. Cai, L.-Y. Xu, L.-Q. Chai, and Y.-X. Li, J. Mol. Struct., 2020,
Dalton Trans., 2013, 42, 7287–7296. 1204, 127552-127561.
&
DOI: 10.1039/D1NJ03388C
3
31 A. Beladhria, A. L.Gottumukkala, C. Youssef, C. B. Bheeter, H. 64 H. Boulebd, Free Radic. Res., 2020, 54, 221–230.
Ben Ammar, R. Ben Salem and H. Doucet Cat. Commun., 2013, 65 H. Boulebd, Phytochemistry, 2021, 184, 112670-112677.
41, 119–122.
66 E. David, C. Rangheard, S. Pellet-Rostaing, and M. Lemaire,
Synlett, 2006, 2006, 2016–2020.
67 E. O. Karaca, N. Gürbüz, İ. Özdemir, H. Doucet, O. Şahin, O.
Büyükgüngör and B. Çetinkaya, Organometallics, 2015, vol.
34, no. 11, pp. 2487–2493.
3
2 I. Smari, C. Youssef, H. Ben Ammar, B. Ben Hassine, J.-F. Soulu,
and H. Doucet, Tetrahedron, 2015, 71, 6586–6593.
3 E. C. Chao, Drugs Future, 2011, 36, 351–357.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
34 A.-K. Sandeli, N. Khiri-Meribout, S. Benzerka, N. Gürbüz, M.
Dündar, H. Karcı, C. Bensouici, El H. Mokrani, İ. Özdemir, A. 68 E. David, S. Pellet-Rostaing, and M. Lemaire, Tetrahedron,
Koç, N. Özdemir, A. Debache and İ.Özdemir, Inorg. Chim. Acta,
2007, 63, 8999–9006.
2021, 525, 120486-120499.
69 Y. Fall, C. Reynaud, H. Doucet and M. Santelli, Eur. J. Org.
Chem. 2009, 24, 4041–4050.
35 S. Cie, “X-area (version 1.18) and X-red32 (version 1.04),”
Darmstadt, Germany, 2002.
36 L. Palatinus and G. Chapuis, J. Appl. Crystallogr., 2007, 40,
786–790.
3
3
7 D. Kratzert, J. J. Holstein, and I. Krossing, J. Appl. Crystallogr.,
2015, 48, 933–938.
8 O. V Dolomanov, L. J. Bourhis, and R. J. Gildea, J. Appl.
Crystallogr., 2009, 42, 339–341.
39 R. A. Gaussian09, Inc., Wallingford CT, 2009, 121, 150–166.
40 P. C. Hariharan and J. A. Pople, Theor. Chim. Acta, 1973, 28,
213–222.
4
1 A. D. Becke, Phys. Rev. A,1988, 38, 3098.
4
2 P. J. Hay and W. R. Wadt, Int. J. Chem. Phys., 1985, 82, 270–
283.
43 A. D. McLean and G. S. Chandler, Int. J. Chem. Phys., 1980, 72,
639–5648.
4 J. Tirado-Rives and W. L. Jorgensen, J. Chem. Theory Comput.,
5
4
4
2
008, 4, 297–306.
5 I. A. Khodja, H. Boulebd, C. Bensouici, and A. Belfaitah, J. Mol.
Struct., 2020, 1218, 128527.
46 I. A. Khodja and H. Boulebd, Mol. Divers., 2020, 1–12.
4
7 M. Kaloğlu and İ. Özdemir, Appl. Organomet. Chem., 2018, 32,
e4399.
4
8 H. A. Chiong and O. Daugulis, Org. Lett., 2007, 9, 1449–1451.
9 İ. Özdemir, Y. Gök, Ö. Özeroğlu, M. Kaloğlu, H. Doucet and C.
Bruneau, Eur. J. Inorg. Chem., 2010, 1798-1805.
4
50 L. Yang, D. R. Powell, and R. P. Houser, Dalton Trans. 2007, 9,
55–964.68
9
5
1 A. Okuniewski, D. Rosiak, J. Chojnacki, and B. Becker,
Polyhedron, 2015, 90, 47–57.
5
2 B. Cordero, V. Gómez, Ana E. Platero-Prats, M. Revés, J.
Echeverría, E. Cremades, F. Barragána and S. Alvarez, Dalton
Trans. 2008, 2832–2838.
53 Y. Han, H. V. Huynh, and G. K. Tan, Organometallics, 2007, 26,
6447–6452.
54 H. V. Huynh, W. Sim, and C. F. Chin, Dalton Trans., 2011, 40,
11690–11692.
55 Y.-C. Lin, H.-H. Hsueh, S. Kanne, L.-K. Chang, F.-C. Liu, I. J. B.
Lin, G.-H. Lee and S.-M. Peng, Organometallics, 2013, 32,
3859–3869.
5
6 L. Barbu, M. M. Popa, S. Shova, M. Ferbinteanu, C. Draghici,
and F. Dumitrascu, Inorg. Chim. Acta, 2017, 463, 97–101.
7 N. Kaloğlu, M. Kaloğlu, M.N. Tahir, C. Arıcı, C. Bruneau, H.
Doucet, P. H. Dixneuf, B. Cetinkaya and İ. Özdemir, J.
Organomet. Chem., 2018, 867, 404–412.
5
5
8 M. Kaloğlu, N. Kaloğlu, İ. Yıldırım, N. Özdemir, and İ. Özdemir,
J. Mol. Struct., 2020, 1206, 127668-127679.
59 M. Kaloğlu, N. Gürbüz, İ. Yıldırım, N. Özdemir, and İ. Özdemir,
Appl. Organomet. Chem., 2020, 34, p. e5387.
60 H. Boulebd, Y. D. Lahneche, I. A. Khodja, M. Benslimane, and
A. Belfaitah, J. Mol. Struct., 2019, 1196, 58–65.
61 A. Nataraj, V. Balachandran, and T. Karthick, J. Mol. Struct.,
2013, 1038, 134–144.
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