Efficient N-heterocyclic carbene palladium(II) catalysts for carbonylative Suzuki-Miyaura coupling reactions leading to aryl ketones and diketones

Article abstract of DOI:10.1016/j.jorganchem.2018.01.028

New N, N′-substituted imidazolium salts (L1 and L2) and their corresponding diiodopyridinepalladium(II) complexes (C1 and C2) were successfully synthesized and characterized. Reactions of palladium iodide with the newly synthesized N, N′-substituted imidazolium iodides in pyridine afforded the corresponding new palladium-N-heterocyclic carbene pyridine complexes in high yields. The new palladium(II) complex C1 was characterized by single crystal X-ray diffraction analysis. The Pd(II) ion is bonded to the nitrogen atom of the pyridine, the carbon atom of the NHC carbene ligand and two trans iodides resulting in distorted square planar geometry. The two Pd-NHC-Py complexes C1 and C2 displayed higher catalytic activity in the carbonylative Suzuki-Miyaura coupling reactions with much lower catalyst loading as compared to the catalytic systems reported in the literature.

Full text of DOI:10.1016/j.jorganchem.2018.01.028

Accepted Manuscript
Efficient N-heterocyclic carbene palladium(II) catalysts for carbonylative Suzuki-
Miyaura coupling reactions leading to aryl ketones and diketones
Mansur Ibrahim, Imran Malik, Waseem Mansour, Muhammad Sharif, Mohammed
Fettouhi, Bassam El Ali
PII:
S0022-328X(18)30034-2
10.1016/j.jorganchem.2018.01.028
JOM 20266
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 19 November 2017
Revised Date: 16 January 2018
Accepted Date: 19 January 2018
Please cite this article as: M. Ibrahim, I. Malik, W. Mansour, M. Sharif, M. Fettouhi, B. El Ali, Efficient
N-heterocyclic carbene palladium(II) catalysts for carbonylative Suzuki-Miyaura coupling reactions
leading to aryl ketones and diketones, Journal of Organometallic Chemistry (2018), doi: 10.1016/
j.jorganchem.2018.01.028.
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ACCEPTED MANUSCRIPT
Efficient N-heterocyclic carbene palladium(II) catalysts for carbonylative
Suzuki-Miyaura coupling reactions leading to aryl ketones and diketones
Mansur Ibrahim, Imran Malik, Waseem Mansour, Muhammad Sharif, Mohammed Fettouhi,
Bassam El Ali*
Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran 31261,
Saudi Arabia
ABSTRACT
New N, N'-substituted imidazolium salts (L1 and L2) and their corresponding
diiodopyridinepalladium(II) complexes (C1 and C2) were successfully synthesized and
characterized. Reactions of palladium iodide with the newly synthesized N, N'-substituted
imidazolium iodides in pyridine afforded the corresponding new palladium-N-heterocyclic
carbene pyridine complexes in high yields. The new palladium(II) complex C1 was
characterized by single crystal X-ray diffraction analysis. The Pd(II) ion is bonded to the
nitrogen atom of the pyridine, the carbon atom of the NHC carbene ligand and two trans
iodides resulting in distorted square planar geometry. The two Pd-NHC-Py complexes C1
and C2 displayed higher catalytic activity in the carbonylative Suzuki-Miyaura coupling
reactions with much lower catalyst loading as compared to the catalytic systems reported in
the literature.
Keywords: Pd-NHC-Py complex, carbonylative Suzuki, diiodides, diboronic acid,
diarylketone.
*
Corresponding author. Tel.: +966 13 860 4491; Fax: +966 13 860 4277
E-mail address: belali@kfupm.edu.sa (B. El Ali).
1

ACCEPTED MANUSCRIPT
1
. Introduction
Biaryl ketones are valuable structural moieties present in natural products, pharmaceuticals,
cosmetics and agrochemicals [1-3]. The carbonylative cross coupling reactions of various
organometallic reagents with aryl electrophiles [4-7] and the Friedel‐Crafts acylation of acyl
halides with aromatic compounds [1, 8] represent the common approaches for the synthesis
of biaryl ketones. Another attractive method for the synthesis of biaryl ketones is the
palladium catalyzed carbonylative Suzuki−Miyaura coupling reaction of aryl halides with
aryl boronic acids, utilizing carbon monoxide as the carbon source. Several palladium
catalysts have been tested in this regard. However, high catalyst loading, high CO pressure,
long reaction time or the need to handle air and moisture sensitive phosphines were some of
the drawbacks [9-16].
Recently, much attention has been paid to the development of N-heterocyclic carbene metal
complexes and remarkable advances have been made especially on their applications as
organometallic catalysts [17-23]. This was attributed to the ability of N-heterocyclic carbene
ligands to provide highly active and stable metal complexes for various catalytic applications.
The highly sigma donating property of NHC ligands prevents the formation of inactive
palladium black during the catalytic reactions [17, 20].
We have previously reported the synthesis and catalytic activities of new palladium(II)-
bis(oxazoline) complexes [24-26] and recently new triazole-derived NHC-palladium(II)
complexes [23]. In the present work, we report the synthesis and characterization of two new
mixed ligand diiodo-palladium-carbene pyridine (I -Pd-NHC-Py ) complexes (C1 and C2).
2
2
These palladium(II) complexes were found to be active catalysts in the carbonylative Suzuki-
Miyaura coupling reactions of aryl iodides and aryl diiodides with arylboronic acids and
diboronic acids. We also report the synthesis of the new compound, 4,4'-(benzene-1,4
diyldicarbonyl)dibenzonitrile (6ak), via the carbonylative Suzuki-Miyaura coupling reaction
of 1,4-diiodobenzene with 4-cyanophenylboronic acid using the new I -Pd-NHC-Py complex
2
C1 as a catalyst.
2
. Experimental
2
.1. General
Materials for the synthesis of the N-heterocyclic carbene ligand pre-cursors and palladium-
N-heterocyclic carbene complexes were purchased from Sigma Aldrich and used as received.
2

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All solvents (reagent grade) used in the synthesis were distilled and dried under molecular
sieves. The products were purified either using flash column chromatography (packed with
6
0 F Silica gel from Fluka Chemie AG, Buchs, Switzerland) or by washing with the
appropriate solvent.
1
13
H and C NMR spectral data were obtained using 500 MHz NMR machine (Joel 1500
-1
model). IR spectra were recorded in wave numbers (cm ) using FT-IR spectrometer (Perkin-
Elmer 16F model). Elemental analysis was performed on Perkin Elmer Series 11 (CHNS/O)
Analyzer 2400. Merck 60 F254 silica gel plates (250 µm layer thickness) were used for thin-
layer chromatography (TLC) analysis. A Varian Saturn 2000 GC-MS machine (30 m
capillary column) was used to analyze the products. Agilent 6890 gas chromatography (GC)
was used to monitor the reactions and analyze the products.
2
.2 Synthesis of 5-(4-methoxyphenyl)-1-methyl-1H-imidazole (1) and 4-(1-methyl-1H-
imidazol-5-yl)benzonitrile (2)
5
-Bromo-1-methyl-1H-imidazole (0.50 mmol), Pd(PPh ) Cl (0.025 mmol, 5.0 mol%),
3
2
2
K CO (1.0 mmol, 2.0 mol equivalent), DMF (2.0 mL), distilled water (2.0 mL) and the
2
3
corresponding phenylboronic acid (0.60 mmol), were added in a 10 mL round bottom flask.
o
The mixture was stirred at 90 C for 24 h. After completion of the reaction, the mixture was
cooled down to room temperature and extracted 3 times with ethyl acetate. The combined
ethyl acetate extract was dried using anhydrous MgSO . The solvent was removed under
4
reduced pressure and the product was purified by silica gel column chromatography using
hexane-ethyl acetate (1:1) followed by 7 % methanol in ethyl acetate as an eluent.
2
.2.1 5-(4-Methoxyphenyl)-1-methyl-1H-imidazole (1)
1
Yellow solid; isolated yield (83%); H NMR (500 MHz, CDCl ) δ (ppm): 7.48 (s, 1H, C-H-
3
arom), 7.30 (d, 2H, J=8.8 Hz, C-H arom), 7.03 (s, 1H, C-H-arom), 6.96 (d, 2H, J=8.5 Hz, C-
1
3
H arom), 3.84 (s, 3H, CH ), 3.62 (s, 3H, CH ). C NMR (125 MHz, CDCl ) δ (ppm): 32.20,
3
3
3
-
5
5.20, 114.03, 122.06, 127.39, 129.54, 129.78, 133.07, 138.47, 159.28 (C- arom); IR (v, cm
1
+1
)
: 3084, 2947, 1899, 1720, 1611, 1552,1491, 1234, 1116, 1023; GC-MS m/z: 188 (M ).
Anal. Calc. for C H N O (188): C, 70.19; H, 6.43; N, 14.88. Found: C, 70.35; H, 6.83; N,
1
1
12
2
1
4.80.
3

ACCEPTED MANUSCRIPT
2
.2.2 4-(1-Methyl-1H-imidazol-5-yl)benzonitrile (2)
1
Light green solid; isolated yield (78%); H NMR (500 MHz, CDCl ) δ (ppm): 7.73 (d, 2H,
3
J=7.9 Hz, C-H arom), 7.57 (s, 1H, C-H- arom), 7.52 (d, 2H, J=8.2 Hz, C-H arom), 7.22 (s,
1
3
1
1
2
H, C-H-arom) 3.73 (s, 3H, CH ). C NMR (125 MHz, CDCl ) δ (ppm): 32.87, 111.28,
3
3
-1
18.49, 128.30, 129.78, 131.66, 132.58, 134.33, 140.47 (C- arom); IR (v, cm ): 3084, 2283,
+1
219, 1926, 1671,1606, 1491, 1230, 1118, GC-MS m/z: 183 (M ). Anal. Calc. for C H N
3
11
9
(183): C, 72.11; H, 4.95; N, 22.94. Found: C, 72.01; H, 4.76; N, 22.60.
2
.3 Synthesis of the precursors for N-Heterocyclic carbene ligands (L1 and L2)
-(4-Methoxyphenyl)-1-methyl-1H-imidazole (1) or 4-(1-methyl-1H-imidazol-5-yl)
5
benzonitrile (2) (0.50 mmol) and 1-iodo-2-methylpropane (2.0 mL) were added into a 10 mL
o
round bottom flask. The mixture was stirred at 100 C for 48 hours. The mixture was cooled
down to room temperature. Diethyl ether (5 mL) was added and stirred for 15 minutes. The
ether was decanted. The product was washed several times with ether. The pure product was
dried under vacuum.
2
.3.1 5-(4-Methoxyphenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-3-ium iodide (L1)
1
Brown gummy solid; isolated yield (84%); H NMR (500 MHz, CDCl ) δ (ppm): 9.97 (s, 1H,
3
C-H- arom), 7.40 (d, 2H, J=8.5 Hz, C-H arom), 7.24 (s, 1H, C-H arom), 7.04 (d, 2H, J=8.5
Hz, C-H arom), 4.17 (d, 2H, J=7.3 Hz, CH ), 3.90 (s, 3H, CH ), 3.87 (s, 3H, CH ), 2.30 (m,
2
3
3
13
1
H, CH), 1.04 (d, 6H, J=6.7 Hz, 2xCH ). C NMR (125 MHz, CDCl ) δ (ppm): 19.69
3 3
(
CH x2), 29.45 (CH), 35.28 (CH ), 55.53 (CH ), 57.03 (CH), 114.90, 119.06, 130.78, 130.97,
3
3
2
-
1
1
1
5
35.88, 137.07, 161.40 (C- arom); IR (v, cm ): 2951, 2354, 2041, 1610, 1510, 1448, 1365,
+
1
262, 1168, 1026; GC-MS m/z: 372 (M ) Anal. Calc. for C H IN O (372): C, 48.40; H,
15
21
2
.69; N, 7.53. Found: C, 48.45; H, 5.72; N, 7.66.
2
.3.2 5-(4-Cyanophenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-3-ium iodide (L2)
1
Brown gummy solid; isolated yield (78%); H NMR (500 MHz, CDCl ) δ (ppm): 9.86 (s,
3
1
H, C-H- arom), 7.87 (d, 2H, J=8.5 Hz, C-H- arom), 7.74 (d, 2H, J=8.5 Hz, C-H arom), 7.43
(
s, 1H, C-H arom), 4.22 (d, 2H, J=7.3 Hz, CH ), 4.06 (s, 3H, CH ), 2.33 (m, 1H, CH), 1.08
2
3
1
3
(
d, 2H, J=8.5 Hz, CH x2). C NMR (125 MHz, CDCl ) δ (ppm): 19.73 (CH x2), 29.45
3 3 3
(
CH ), 36.17 (CH ), 57.72 (CH), 114.68 (CN), 117.59, 120.89, 128.95, 130.47, 132.71,
2 3
-1
1
33.17, 138.16 (C-arom); IR (v, cm ) 2958, 2352, 2230, 1669, 1568, 1458,1384, 1154; GC-
4

ACCEPTED MANUSCRIPT
+1
MS m/z: 367 (M ); Anal. Calc. for C H IN (367): C 49.06; H, 4.94; N, 11.44. Found: C,
1
5
18
3
4
9.21; H, 4.46; N, 11.80.
2
.4 Synthesis of diiodo-palladium-N-heterocyclic carbene-pyridine complexes (C1 and
C2)
N-Heterocyclic carbene ligand precursor (L1 or L2) (0.5 mmol), palladium(II) iodide (0.50
mmol), potassium carbonate (2.0 mmol) and pyridine (5.0 mL) were added into a 15 mL
o
round bottom flask. The reaction mixture was stirred at 90 C for 24 h. The crude product was
cooled down to room temperature and diluted with 5 mL dichloromethane. The mixture was
then passed through a short silica column covered with a short pad of celite. The column was
eluted with methanol. The solvents were removed using rotary evaporator under reduced
pressure. The complexes were obtained as yellow crystals. The crystals were washed with
1
13
ether and dried in a vacuum. The complexes were characterized with H and C NMR, FT-
IR, ESI-MS, elemental analysis and the molecular structure of C1 was established using
single crystal X-ray diffraction analysis.
2
.4.1 Diiodido[5-(4-methoxyphenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-2-ylidene]
pyridinepalladium(II) (C1)
1
Yellow crystals; Yield (79%); H NMR (500 MHz, CDCl ) δ (ppm): 9.05 (d, 2H, J=4.88 Hz,
3
C-H- arom), 7.73 (t, 1H, J=7.6 Hz, C-H- arom), 7.34–7.26 (m, 4H, C-H arom), 6.97 (d, 2H,
J=8.54 Hz, C-H arom), 6.86 (s, 1H, C-H arom), 4.19 (d, 2H, J=7.6 Hz, CH ), 3.94 (s, 3H,
2
1
3
CH ), 3.85 (s, 3H, CH ), 2.79 (m, 1H, C-H), 1.08 (d, J=6.7 Hz, 6H, CH x2 ); C NMR (125
3
3
3
MHz, CDCl ) δ (ppm): 20.45, 28.21, 37.47, 55.37, 59.35, 114.20, 119.96, 120.06, 120.12,
3
-
1
1
1
24.40, 124.47, 130.59, 135.92, 137.50, 145.50, 153.36, 160.19 (C-arom). IR (vcm ): 2950,
+1
606, 1507, 1451, 1248, 1174, 1023; ESI-MS m/z: 684 (M ); Anal. Calc. for C H I N OPd
20
25 2
3
(684): C, 35.09; H, 3.83%; N, 6.14. Found: C, 35.69; H, 3.99; N, 6.53.
2
.4.2 Diiodo5-(4-cyanophenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-2-ylidene]
pyridinepalladium(II) (C2)
1
Yellow crystals; isolated yield (68%); H NMR (500 MHz, CDCl ) δ (ppm): 9.05 (s, 2H,
3
CH -arom), 7.77 (d, 3H, J= 8.54 Hz, C-H- arom), 7.52 (d, 2H, J= 8.2 Hz, C-H arom), 7.36–
2
7
.32 (m, 2H, C-H arom), 7.02 (s, 1H, C-H arom), 4.23 (d, 2H, J= 7.9 Hz, CH ), 4.03 (s, 3H,
2
5

ACCEPTED MANUSCRIPT
13
CH ), 2.81 (m, 1H, C-H), 1.09 (d, J=6.4 Hz, 6H, CH x 2 ), C NMR (125 MHz, CDCl ) δ
3
3
3
(
ppm): 20.34 (CH X 2), 28.14 (CH), 37.97 (CH ), 59.60 (CH ), 121.10, 124.49, 128.18,
3 3 2
-
1
1
1
8
29.31,132.66, 153.83 (C-arom); IR (v, cm ) 2931, 2353, 2224, 1717, 1598, 1453, 1386,
+
1
073; ESI-MS m/z 679 (M ) Anal. Calc. for C H I N Pd, (679): C, 35.34; H, 3.41; N,
20
23 2
4
.24. Found: C, 35.21; H, 3.35; N, 8.20.
2
.5 X-Ray crystal structure
Single-crystal data collections were performed at 150 K on a Bruker APEX-II CCD
diffractometer using a graphite mono-chromated MoKα radiation (λ = 0.71073 Å). The data
were collected using APEX2 [27], integrated and reduced using SAINT [28]. An empirical
absorption correction was carried out using SADABS [29]. The structure was solved with
direct methods using SHELXS-97 and refined by full matrix least square methods based on
2
F , using SHELXL [30]. Graphics were generated using ORTEP3 [31]. All non-hydrogen
atoms were refined with anisotropic displacement parameters. All H atoms were included at
calculated positions using a riding model. Crystal data and details of the data collection are
summarized in Table 1.
Table 1
Crystal data and structure refinement for C1.
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
C H I N O Pd
20 25 2 3
683.63
150(2) K
0.71073 Å
Monoclinic
P 21/c
Unit cell dimensions
a = 9.0779(5) Å
b = 27.5230(17) Å
c = 9.2686(6) Å
α= 90°
β= 99.8203(10)°
γ = 90°
3
Volume
Z
2281.8(2) Å
4
3
Density (calculated)
1.990 g/cm
-1
Absorption coefficient
F(000)
3.533 mm
1304
3
Crystal size
Theta range for data collection
Index ranges
Reflections collected
Independent reflections
Absorption correction
0.257 x 0.125 x 0.066 mm
1.480 to 26.999°.
-11≤ h ≤11, -35≤ k ≤35, -11≤ l ≤11
33812
4972 [R(int) = 0.0323]
Semi-empirical from equivalents
6

ACCEPTED MANUSCRIPT
Max. and min. transmission
0.76 and 0.61
2
Refinement method
Full-matrix least-squares on F
Data / restraints / parameters
4972 / 1 / 248
2
Goodness-of-fit on F
1.197
Final R indices [I>2sigma(I)]
R indices (all data)
R1 = 0.0364, wR2 = 0.0801
R1 = 0.0441, wR2 = 0.0835
-3
Largest diff. peak and hole
1.396 and -1.019 e.Å
2
.6 Procedure for the carbonylative Suzuki-Miyaura coupling reaction
A 45 mL stainless steel autoclave equipped with a glass liner, gas inlet valve and pressure
gauge was used for the carbonylative Suzuki coupling reaction. Palladium complex (0.010
mol%), aryl iodide (1.0 mmol), arylboronic acid (1.2 mmol), base (2.0 mmol) and solvent
(3.0 mL) were added into the glass liner. The autoclave was vented three times with carbon
monoxide and then pressurized to 200 psi of CO. The mixture was heated to the required
temperature and maintained under stirring for the required time. After complete reaction, the
mixture was cooled down to room temperature and CO excess was released under fume hood.
The mixture was diluted with 5 mL of water and extracted three times with 10 mL ethyl
acetate. The combined ethyl acetate extract was concentrated under reduced pressure in a
rotavapor. The product was analyzed with GC and GC-MS. The spectral data of the
diarylketones prepared in this study were in full agreement with those reported in literature
[
1, 2, 32-37].
Analytical
and
Spectroscopic
data
of
new
compound:
4,4'-(benzene-1,4
1
diyldicarbonyl)dibenzonitrile (6ak),: White solid; yield 69%; H NMR (500 MHz, DMSO): δ
(ppm): 8.45 (s, 4H, C-H arom), 7.90 (d, J=7.32 Hz, 4H, C-H arom), 7.78 (d, J=7.32 Hz ,4H,
1
3
C-H arom), C NMR (125 MHz, DMSO): δ (ppm): 194.50, 142.78, 134.87, 132.80, 130.17,
-1
1
29.19, 119.11, 112.49; IR (v cm ): 2249, 2128, 1734, 1651, 1591, 1546; GC–MS: m/z 336
(
M+1); Anal. Calcd for C H N O (336): C, 78.56; H, 3.60; N, 8.33. Found: C, 78.71; H,
22
12
2
2
3
.85; N, 8.46.
7

ACCEPTED MANUSCRIPT
3
. Results and Discussion
3
.1 Synthesis of 5-(4-methoxyphenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-3-ium
iodide (L1) and 5-(4-cyanophenyl)-1-methyl-3-(2-methylpropyl)-1H-imidazol-3-ium
iodide (L2)
The ligands L1 and L2 were prepared as shown on Scheme 1. The formation of the
imidazolium iodides were confirmed by the presence of downfield singlet peaks at 9.97 ppm
(
L1) and 9.86 ppm (L2) in their proton NMR spectra, which are assigned to C-2 protons of
the imidazole rings.
3
.2 Synthesis of the Pd-NHC-Py complexes (C1 and C2)
The diiodo-palladium(II)-N-heterocyclic carbene-pyridine complexes (C1 and C2) were
prepared by reacting palladium iodide with 1 equivalent of the appropriate ligand precursor in
pyridine.The formation of the new complexes was confirmed by the disappearance of the
acidic C-2 protons of the imidazole rings, initially present in the N-substituted imidazolium
salts due to palladation of the NHC ligand precursors. Furthermore, there is appearance of
13
new signal at 153 ppm in the C spectra of both complexes assignable to the Pd-C=N bond.
The ESI mass spectra of the two complexes, base peaks were observed at 684 (C1) and 679
(C2) confirming the formation of the Pd-carbene complexes.
N
Pd(PPh ) Cl
2
3
2
N
B(OH)2
K CO
2
3
N
+
DMF-H O
CH
3
N
2
Br
R
R
CH3
1
2
: R: OCH3
: R: CN
N
N
I
o
1
20 C
N
N
+
I
2 days
CH3
CH3
R
R
L1: R = OCH3
L2: R = CN
1
/ 2
Scheme 1. Synthesis of NHC Ligand (L1 and L2) Precursors
8

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I
N
N I
Pd N
I
N
N
+
PdI2
N
9
0oC, 24 h
CH3
CH3
R
R
C1: R = OCH3
C2: R = CN
L1 / L2
Scheme 2. Synthesis of Palladium(II)-NHC-Pyridine Complexes (C1and C2)
3
.3 Molecular structure of the palladium complex C1
The palladium complex C1 crystallizes in the P 2 /c space group. The Pd(II) ion is bonded to
1
two trans iodides, the nitrogen atom of the pyridine, in addition to the carbon atom of the
NHC carbene ligand. The geometry around the metal ion is distorted square planar. The cis-
bond angles are in the range 85.32(13) - 93.78(12)°. The Pd-C, Pd-N and Pd-Iaverage bond
lengths are 1.959(5) Å, 2.136(4) Å and 2.5806(5) Å respectively. These data are similar to
those reported for other diiodidopyridine(imidazol-2-ylidene)palladium(II) complexes [38,
3
9]. In the Pd(II) coordination sphere, the trans imidazol-2-ylidene and pyridine ligands are
not coplanar. The dihedral angle between the two corresponding mean planes is 48.8(2)°. In
the case of the NHC ligand, the imidazol-2-ylidene and the phenyl group are also not
coplanar likely due to the steric effect of the methyl substituent. The corresponding torsion
angle N1-C3-C8-C13 is 41.7(7)°.
Figure 1. ORTEP diagram of the molecular structure of C1 showing the atomic labeling
scheme. Thermal ellipsoids have been drawn at 50% probability level.
9

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Table 2
Selected Bond lengths [Å] and angles [°] for C1.
I1-Pd1
I2-Pd1
N3-Pd1
C1-Pd1
C1-N2
C1-N1
C3-N1
C2-N2
C2-C3
2.5791(5)
2.5820(5)
2.136(4)
1.959(5)
1.339(6)
1.348(6)
1.398(6)
1.374(6)
1.345(7)
C1-Pd1-I1
N3-Pd1-I1
C1-Pd1-I2
N3-Pd1-I2
N2-C1-N1
C1-N2-C2
N2-C1-Pd1
N1-C1-Pd
C1-N1-C3
87.66(13)
93.28(12)
85.32(13)
93.78(12)
106.0(4)
110.1(4)
127.7(3)
126.1(3)
110.3(4)
3
.4 Carbonylative Suzuki-Miyaura coupling reactions of aryl iodide with arylboronic acid
by Pd-NHC-Py complexes. Optimization of the reaction conditions
The Pd(II)-NHC complexes have proven to be efficient and active catalysts for a wide range
of cross coupling reactions, especially the C-C bond coupling [23, 30-31, 38-43]. On the
other hand, the application of Pd(II)-NHC complexes in carbonylative cross coupling
reactions is still limited. Therefore, we have examined in detail the applications of the newly
synthesized I -Pd-(II)-NHC-Pyridine complexes (C1 and C2) in the carbonylative Suzuki
2
coupling reaction of aryl iodides with aryl boronic acids.
The carbonylative Suzuki coupling reaction of iodobenzene with phenylboronic acid in the
presence of a catalytic amount of the Pd-NHC-Py (C1) was adopted as a model reaction (Eq.
1
). The results of the optimization reactions are summarized in Table 3. A complete
conversion of the iodobenzene was observed and 98% isolated yield of the aryl ketone were
o
achieved at 120 C (Table 3, entry 3). A more careful optimization of the reaction time
reveals that the reaction essentially completed within 6 h (Table 3, entry 6-9). No product
was observed when the reaction was carried out in the absence of a base (Table 3, entry 10).
While KOH gave similar activity with K CO (Table 3, entry 12), only traces of product were
2
3
observed with Et N (Table 3, entry 11). Based on the above results, the subsequent reactions
3
10

ACCEPTED MANUSCRIPT
o
were carried out using C1 (0.01 mol%), toluene, K CO at 120 C for 6 h. These optimized
2
3
o
conditions (Toluene / K CO / 120 C / 6 h) were used with the palladium catalysts C2;
2
3
similarly, excellent isolated yield (92%) was also obtained with the same aryl ketone (Table
, entry 12). No Suzuki-Miyaura coupling product and no homocoupling products were
3
detected in the reaction mixtures. A comparison of the catalytic carbonylative Suzuki-
Miyaura coupling reactions under the optimized conditions using commercially available
palladium catalysts (Table 3, entries 13-16) showed clearly the high efficiency of the
palladium(II)-NHC-Pyridine catalysts C1 and C2.
Table 3
Carbonylative Suzuki-Miyaura coupling reaction of iodobenzene with phenylboronic
a
acid.
O
I
B(OH)2
CO
[
Pd]
+
+
Base, Toluene
2
00 psi
4
a
6aa
5
a
Eq. 1
T
C
Catalyst
(mol %)
Time
(h)
Yield
(%)
Entry
o
Base
b
C1
0.01)
C1
0.01)
C1
0.01)
C1
0.02)
C1
0.01)
C1
0.01)
C1
0.01)
C1
0.01)
C1
0.01)
C1
0.01)
C1
1
2
3
4
5
6
7
8
9
80
K CO
16
16
16
16
16
6
80
90
2
3
3
3
3
3
3
3
3
3
(
(
(
100
120
100
100
120
120
120
120
120
120
120
120
K CO
2
K CO
2
98
K CO
2
79
(
K CO
2
80
(
K CO
2
91
(
(
(
(
(
(
(
(
K CO
2
4
86
K CO
2
3
79
K CO
2
1
54
10
11
12
13
-
6
Traces
7
Et N
3
6
0.01)
C1
0.01)
C2
0.01)
KOH
6
88
K CO
6
92
2
3
11

ACCEPTED MANUSCRIPT
PdI2
14
15
16
120
120
120
K CO
6
70
72
69
2
3
3
3
(
0.01)
Pd(PPh ) Cl
2
3
3
K CO
2
6
6
(
0.01)
Pd(OAc)2
0.01)
K CO
2
(
a. Iodobenzene (1.0 mmol), phenylboronic acid (1.2 mmol), base (2.0 mmol),
toluene (5.0 mL), CO (200 psi).
b. Isolated yield.
3
.5 Carbonylative Suzuki Coupling Reactions catalyzed by the complex C1.
Scope of Substrates
We have adopted the optimized experimental conditions (0.010 mol% of C1, 2.0 equivalent
o
of K CO , 5 ml of toluene, 200 psi CO, 120 C, 6 h) to study the substrate scope. Various aryl
2
3
iodides with a range of functionalized aryl boronic acids were considered (Eq. 2, Table 4).
The carbonylative Suzuki-Miyaura coupling reaction of phenylboronic acid with un-activated
aryl iodide (Table 4, entry 1), deactivated aryl iodides (Table 4, entries 2 and 3) and activated
aryl iodides (Table 4, entries 4 and 5) afforded the corresponding diaryl ketones in excellent
yields (94-98%). The carbonylative Suzuki-Miyaura coupling reactions of aryl iodide with
activated aryl boronic acids (Table 4, entries 5-6) were also very successful. Deactivated aryl
boronic acids were relatively less reactive when toluene was used as solvent. However,
moderate to excellent isolated yields (71-94%) of the functionalized biaryl ketones were
achieved using acetonitrile as solvent (Table 4, entries 7-10). This can be attributed probably
to the relatively higher solubility of the aryl boronic acid in acetonitrile.
Table 4
Carbonylative Suzuki-Miyaura coupling reaction of different aryl iodides with various
a
aryl boronic acids.
O
I
B(OH)
2
C1
K CO , Toluene
+
CO
+
R2
2
3
R1
R1
R2
o
200 psi, 120 C
5a-g
6aa-ah
4a-e
6 h
Eq. 2
Carbonylation
Product
aa-ah
Aryl iodide
a-e
Aryl boronic acid
5a-g
Yield
(%)
Entry
c
4
6
O
I
B(OH)2
1
97
5a
4a
6aa
12

ACCEPTED MANUSCRIPT
O
I
B(OH)2
2
95
O
O
5
a
4b
6ab
O
I
B(OH)2
3
4
5
6
94
98
96
98
NC
CN
4
c
5a
6ac
O
I
B(OH)2
3
CH O
3
CH O
4d
5a
6
ad
O
I
B(OH)
2
O
O
O
O
CH
3
5b
6ae
O
4e
I
B(OH)2
CH O
3
OCH
3
5c
4a
6ad
O
B(OH)
2
I
HO
b
OH
7
78
O
O
4a
4a
4a
5
d
6
af
O
I
I
B(OH)2
b
b
8
9
71
94
NC
CN
5e
5f
6ac
O
B(OH)
2
F
F
6
ag
O
I
B(OH)
2
b
10
80
O N
2
NO
2
4a
5g
6ah
a. C1 (0.010 mol %), aryl iodide (1.0 mmol), aryl boronic acid (1.2 mmol),
o
K CO (2.0 mmol), toluene (5.0 mL), CO (200psi), 120 C, 6 h.
2
3
b. CH CN was used as solvent, 20 h
3
c. Isolated yield
3
.6 Carbonylative Suzuki-Miyaura coupling reaction of aryl iodides or aryl diiodides with
aryl boronic acids or aryl diboronic acids catalyzed by the complex C1
Considering the high catalytic performance of the I -Pd-NHC-Py complexes C1 and C2, we
2
have investigated the carbonylative Suzuki-Miyaura coupling reactions of aryl diiodides with
aryl boronic acids and aryl iodides with aryl diboronic acids. For instance, we have
considered the carbonylative Suzuki-Miyaura coupling of 1,4-diiodobenzene with phenyl
13

ACCEPTED MANUSCRIPT
boronic acid. The reaction successfully proceeded to give a symmetrical diaryl ketone in very
good yield (78%) (Table 5, entry 1). Similarly, the carbonylative Suzuki coupling of 1,4-
diiodobenzene with 4-methoxy phenylboronic acid was also successful (82%) (Table 5, entry
2
). Additionally, the new Pd-NHC-complex C1 showed high catalytic performance in the
carbonylative Suzuki coupling of 1,4-diidobenzene with 4-cyanophenyl boronic acid to yield
,4'-(benzene-1,4-diyldicarbonyl) dibenzonitrile in good yield (69%) (Table 5, entry 3) The
4
.
carbonylative coupling reaction of 1,4-benzene diboronic acid with iodobenzene and with 4-
iodo anisole were also successful and yielded the corresponding symmetrical diarylketones in
good yields (70-76%) (Table 5, entries 4 and 5).
Table 5
Carbonylative Suzuki-Miyaura coupling reaction of aryl iodides or aryl diiodides with aryl
a
boronic acids or aryl diboronic acids by the palladium complex C1.
O
O
I
B(OH)
2
C1
+
R2
+
CO
R1
K CO , Solvent
2
3
o
2
00 psi, 120 C
6ai-ak
1
2
2
1
4
a-f
5a-h
(
R )R
R (R )
Eq. 3
Carbonylation product
6ai - ak
Isolated
Aryl iodide
a-f
Arylboronic acid
5a-h
Entry
Yield
4
c
(
%)
O
I
B(OH)2
a
1
78
I
O
5a
5c
5e
4
f
6
ai
O
I
I
B(OH)
2
CH O
3
2
82
79
CH
3
O
OCH
3
I
I
O
4
f
f
6aj
O
B(OH)
2
NC
b
3
NC
CN
O
4
6ak
O
I
B(OH2)
b
4
70
B(OH)
2
O
5h
4a
6ai
14

ACCEPTED MANUSCRIPT
O
I
B(OH2)
3
CH O
5
76
OCH
3
CH O
B(OH)
2
3
O
4d
5h
6aj
a. C1 (0.010 mol%), aryl diiodide (0.50 mmol), aryl boronic acid (1.2 mmol), K CO (2.0 mmol),
2
3
o
toluene (5.0 mL), CO (200 psi), 120 C, 20 h.
b. Acetonitrile was used as solvent.
c. Isolated yield.
The high yield and selectivity obtained in the catalytic carbonylative coupling of aryl iodides
and aryl diiodides with aryl boronic acids and aryl diboronic acids showed the high catalytic
efficiency of the new palladium complexes C1 and C2. These complexes exhibited higher
catalytic activity with much lower catalyst loading as compared to different catalytic systems
reported in the literature (Table 6).
Table 6
Comparison of the activity of the new catalytic system including Pd-NHC-Py (C1) in the
carbonylative Suzuki-Miyaura coupling reactions of aryl iodides and aryl boronic acids
with previously published data.
Catalyst loading
mol
Time
(h)
Yield
(%)
Catalyst
Pd-NHC
Base
Ref.
10
2
%
1.0 mol %
2.0 mol %
2.0 mol %
1.0 mol %
1.0 mol %
3.0 mol %
K CO
2
5
6
76 - 90
70 - 96
60 - 93
67 - 98
72 - 99
63 - 89
3
3
3
3
3
3
Pd(tmdh)2*
K CO
2
10% Pd/C
K CO
2
8
12
13
15
32
Pd(dba)2
K CO
2
20
4-12
5
Fe O @SiO -SH-Pd
K CO
2
3
4
2
PdCl (PPh )
K CO
2
2
3 2
[
PdCl (o‐PPh )
2
2
C H CH=NCH(CH)
0.02 mol %
K CO
2
6
< 40
44
6
4
2
3
C H (p‐NO )]
6
4
2
Present
work
Pd-NHC-Py
0.01 mol %
K CO
70 - 98
2
3
*
tmdh: 2,2,4,6-tetramethyl-3,5-heptanedionate
15

ACCEPTED MANUSCRIPT
3
.7 Proposed mechanism for the carbonylative Suzuki-Miyaura coupling reaction
The proposed mechanism is illustrated in scheme 3. The activation of the palladium(II) pre-
catalyst (I) proceeds first by transmetallation with aryl boronic acid in the presence of
potassium carbonate, followed by a trans-cis isomerization step and a reductive elimination
of the diaryl compound to generate the Pd(0) active catalyst (IV). The aryl iodide is then
added to the Pd(0) in the oxidative addition step to form the palladium(II) intermediate (V).
This addition is strongly favored by the carbene and the pyridine ligands [45]. This step is
followed by CO insertion into the Ar-Pd bond to form the acyl Pd intermediate (VI).
Transmetallation with aryl boronic acid in the presence of potassium carbonate, produces the
intermediate VII followed by trans-cis isomerization and reductive elimination to yield the
diaryl ketone as the product of the carbonylative Suzuki-Miyaura reactions accompanied with
the regeneration of the Pd(0) active catalyst IV [46].
Ar2
Ar2
L Pd Ar2
L
II
Pd
I
2
Ar B(OH)
2
L Pd Py
I
K CO
Py
2
3
Ar2
Py
I
II
III
O
Ar -Ar2
2
A1
Ar2
L Pd0 Py
Ar1I
IV
Ar2
L
I
L
Pd
Pd
Ar1
O
V Py
Py
Ar1
VIII
trans-cis
isomerization
CO
Ar2
Py
L
L
I
2
Ar B(OH)2
Pd
Pd
O
O
K CO3
2
Py
Ar1
VII
Ar1
VI
Scheme 3. A plausible mechanism for the carbonylative Suzuki-Miyaura coupling reaction
catalyzed by I -Pd-NHC-pyridine complexes.
2
16

ACCEPTED MANUSCRIPT
4
. Conclusion
Two new diiodo palladium N-heterocyclic carbene pyridine complexes C1 and C2 have been
successfully synthesized and characterized using various analytical and spectroscopic
techniques. The molecular structure of C1 was established based on a single crystal X-ray
diffraction. The catalytic activities of the new complexes C1 and C2 were investigated in the
carbonylative Suzuki-Miyaura coupling reactions of various aryl iodides and aryl diiodides
with aryl boronic acids and aryl diboronic acids. Excellent yields of the expected aryl ketones
were obtained. Similarly, very good yields were observed for the aryl diiodides and the aryl
diboronic acids substrates.
Acknowledgement
This project was funded by the National Plan for Science, Technology and Innovation
(MARIFAH)-King Abdulaziz City for Science and Technology-through the Science &
Technology Unit at King Fahd University of Petroleum & Minerals (KFUPM), the Kingdom
of Saudi Arabia, award number (14-PET165-04) and also by the KFUPM/NUS collaboration.
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19

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Highlights:
•
•
New N, N'-substituted imidazolium salts was synthesized and characterized.
New diiodopyridinepalladium(II) complexes were successfully synthesized and
characterized.
•
•
Single crystal x-ray structure reveals a distorted square planar geometry.
The two palladium complexes were found to be highly active catalyst for carbonylative
Suzuki-Miyaura coupling reactions.
•
The catalyst functions effectively at lower loading.