Novel (N-heterocyclic carbene)Pd(pyridine)Br2 complexes for carbonylative Sonogashira coupling reactions: Catalytic efficiency and scope for arylalkynes, alkylalkynes and dialkynes

Article abstract of DOI:10.1002/aoc.4280

New N,N′-substituted imidazolium salts and their corresponding dibromidopyridine–palladium(II) complexes were successfully synthesized and characterized. Reactions of palladium bromide with the newly synthesized N,N′-substituted imidazolium bromides (2a a

Full text of DOI:10.1002/aoc.4280

Received: 22 November 2017
DOI: 10.1002/aoc.4280
Revised: 26 December 2017
Accepted: 26 December 2017
F U L L P A P E R
Novel (N‐heterocyclic carbene)Pd(pyridine)Br2 complexes
for carbonylative Sonogashira coupling reactions: Catalytic
efficiency and scope for arylalkynes, alkylalkynes and
dialkynes
Mansur Ibrahim | Imran Malik | Waseem Mansour | Muhammad Sharif |
Mohammed Fettouhi | Bassam El Ali
Chemistry Department, King Fahd
New N,N′‐substituted imidazolium salts and their corresponding
University of Petroleum and Minerals,
Dhahran 31261, Saudi Arabia
dibromidopyridine–palladium(II) complexes were successfully synthesized
and characterized. Reactions of palladium bromide with the newly
Correspondence
synthesized N,N′‐substituted imidazolium bromides (2a and 2b) in pyridine
Bassam El Ali, Chemistry Department,
King Fahd University of Petroleum and
afforded the corresponding new N‐heterocyclic carbene pyridine palladium(II)
Minerals, Dhahran 31261, Saudi Arabia.
complexes (3a and 3b) in high yields. Their single‐crystal X‐ray structures show
Email: belali@kfupm.edu.sa
a distorted square planar geometry with the carbene and pyridine ligands in
Funding information
NUS/KFUPM collaboration; King
trans position. Both complexes show a high catalytic activity in carbonylative
Sonogashira coupling reactions of aryl iodides and aryl diiodides with
Abdulaziz City for Science and Technol-
ogy, Grant/Award Number: 14‐PET165‐04
arylalkynes, alkylalkynes and dialkynes.
KEYWORDS
alkynones, aryl diiodides, carbonylative Sonogashira coupling, dialkynes, Pd–NHC complex
1 | INTRODUCTION
industrial and organic chemistry. Palladium‐catalysed
carbonylation chemistry allows the direct synthesis of
Ynones (α,β‐acetylenic carbonyl compounds) are impor-
tant structural moieties found in natural products,
biologically active compounds and agrochemicals.[1]
They are also precursors for the synthesis of a variety of
organic compounds, especially aromatic heterocycles
such as pyrazoles,[2,3] quinolones,[4] furans[5] and pyrimi-
dines.[1,6–8]
Traditional methods for the synthesis of ynones often
involve multistep reactions and they are also associated
with side reactions.[9] Another way for their synthesis is
the catalytic carbonylative Sonogashira coupling reaction
of aryl halides with terminal alkynes in the presence of
palladium complexes.[10] This method offers access to a
variety of ynones via a single step and under mild reaction
conditions. Palladium‐catalysed carbonylation reactions
are now widely recognized as a very important tool in
carbonyl compounds using readily available feedstocks
such as carbon monoxide (CO).[10–13] Several palladium
complexes and supported palladium catalysts have been
considered and tested in catalytic carbonylative
Sonogashira coupling reactions.[14–36] However, the
use of phosphine, the low catalyst activity, the relatively
large loading of catalyst and the need for high CO
pressure were drawbacks.[37–42]
Recently, much attention has been paid to the devel-
opment of N‐heterocyclic carbene (NHC) metal com-
plexes, and notable advances have been made especially
for their applications as organometallic catalysts.[43–58]
This is attributed to the ability of NHC ligands to provide
highly active and stable transition metal catalysts for var-
ious organic transformations. The highly sigma‐donating
NHC ligands prevent the formation of inactive palladium
Appl Organometal Chem. 2018;e4280.
wileyonlinelibrary.com/journal/aoc
Copyright © 2018 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.4280

2 of 11
IBRAHIM ET AL.
black during catalysis.[43,46] In addition to the NHC
moieties, the presence of ancillary N‐ or P‐donating
ligands attached to the metal centre enhances the
catalytic activity of the metal carbene complexes.[46]
We have previously reported the synthesis and
catalytic activities of palladium(II) bis(oxazoline)
complexes,[50–53] and recently triazole‐derived NHC–
palladium(II) complexes.[49] In the present paper, we
report the synthesis and crystal structures of two new
mixed ligand palladium–carbene–pyridine (Pd–NHC–Py)
complexes. They were found to be active catalysts in the
carbonylative Sonogashira coupling reactions of aryl
iodides and aryl diiodides with arylalkynes, alkylalkynes
and dialkynes. We also report the synthesis of a new com-
pound, 1,1′‐benzene‐1,4‐diylbis(4,4‐dimethylpent‐2‐yn‐1‐
one), via the carbonylative Sonogashira coupling reaction
of 1,4‐diiodobenzene with 4,4‐dimethylpent‐2‐yne using
one of the new Pd–NHC–Py complexes as a catalyst.
90 °C for 24 h. After completion of the reaction, the mixture
was cooled and extracted three times with ethyl acetate. The
combined ethyl acetate extract was dried using anhydrous
MgSO4. The solvent was removed under vacuum 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.
1
White solid; isolated yield 78%. H NMR (500 MHz,
CDCl3, δ, ppm): 7.50 (s, 1H, C‐H arom), 7.41–7.38 (m,
2H, C‐H arom), 7.35–7.33 (m, 3H, C‐H arom), 7.07 (s,
1H, C‐H arom), 3.62 (s, 3H, CH3). 13C NMR (125 MHz,
CDCl3, δ, ppm): 32.45 (CH3), 127.31, 127.69, 127.85,
128.40, 128.64, 129.62, 133.39, 133.57, 138.85 (C‐ arom).
FT‐IR (ν, cm−1): 2353, 1718, 1489, 1444, 1115, 923, 824,
763, 701. GC‐MS: m/z 158 (M+1). Anal. Calcd for
C10H10N2 (158) (%): C, 75.92; H, 6.37; N, 17.71. Found
(%): C, 76.11; H, 6.43; N, 17.80.
2.3 | Synthesis of Precursors for NHC
Ligands (2a and 2b)
2 | EXPERIMENTAL
Compound 1 (0.50 mmol) and alkyl bromide (2.0 ml)
were added to a 10 ml round‐bottom flask. The mixture
was stirred at 120 °C for 48 h. The mixture was cooled
to room temperature. Diethyl ether (5 ml) was added
and stirred for 15 min. The ether was decanted and the
product was washed several times with ether. The pure
product was dried in a vacuum.
2.1 | Materials and Instrumentation
Materials for the synthesis of the carbene ligand precur-
sors and palladium carbene complexes were purchased
from Sigma Aldrich and were used as received. 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 60 F silica gel from Fluka Chemie AG,
Buchs, Switzerland) or by washing with the appropriate
solvent.
2.3.1 | 1‐Methyl‐3‐(2‐methylpropyl)‐5‐phe-
nyl‐1H‐imidazol‐3‐ium bromide (2a)
1H NMR and 13C NMR spectral data were obtained
using a 500 MHz NMR machine (Joel 1500). Chemical
shifts were recorded in ppm using tetramethylsilane as
reference and CDCl3 as solvent. Fourier transform infra-
red (FT‐IR) spectra were recorded using a PerkinElmer
16F FT‐IR spectrometer. Elemental analyses were per-
formed with a PerkinElmer Series 11 (CHNS/O) Analyzer
2400. Merck 60 F254 silica gel plates (250 μm layer thick-
ness) were used for TLC analyses. A Varian Saturn 2000
GC‐MS machine (30 m capillary column) was used to
analyse the products. An Agilent 6890 GC instrument
was used to monitor reactions and analyse products.
Yellow oil; isolated yield 71%. 1H NMR (500 MHz, CDCl3,
δ, ppm): 10.36 (s, 1H, C‐H arom), 7.54–7.51 (m, 6H, C‐H
arom), 4.14 (d, 2H, J = 7.3 Hz, CH2), 3.93 (s, 3H, CH3),
2.21 (m, 1H, CH), 0.95 (d, 6H, J = 6.7 Hz, 2 × CH3). 13C
NMR (125 MHz, CDCl3, δ, ppm): 19.51 (CH3), 19.45
(CH3), 29.28 (CH), 35.15 (CH3), 56.86 (CH2), 119.63,
124.33, 129.27, 130.55, 135.50, 137.29 (C‐ arom). FT‐IR
(ν, cm−1): 2962, 2353, 1669, 1527, 1459, 1376, 1236, 1160,
771, 697. GC‐MS: m/z 295 (M+1). Anal. Calcd for
C14H19BrN2 (295) (%): C, 56.96; H, 6.49; N, 9.49. Found
(%): C, 56.41; H, 6.72; N, 9.23.
2.3.2 | 3‐Benzyl‐1‐methyl‐5‐phenyl‐1H‐
imidazol‐3‐ium bromide (2b)
2.2 | Synthesis of 1‐Methyl‐5‐phenyl‐1H‐
imidazole (1)
Brown oil; isolated yield 68%. 1H NMR (500 MHz, CDCl3,
δ, ppm): 10.44 (s, 1H, C‐H arom), 7.60 (d, 2H, J = 7.0 Hz,
C‐H arom), 7.47 (d, 2H, J = 7.0 Hz, C‐H arom), 7.39–7.36
(m, 6H, C‐H arom), 5.67 (s, 2H, CH2), 3.93 (s, 3H, CH3).
13C NMR (125 MHz, CDCl3, δ, ppm): 34.92 (CH3), 53.19
(CH2), 118.84, 124.47, 128.32, 128.90, 129.13, 129.17,
5‐Bromo‐1‐methyl‐1H‐imidazole (0.50 mmol), Pd(PPh3)2Cl2
(0.025 mmol, 5.0 mol%), K2CO3 (1.0 mmol, 2.0 mol equiva-
lent), dimethylformamide (DMF; 2 ml), distilled water
(2 ml) and phenylboronic acid (0.6 mmol) were added to a
10 ml round‐bottom flask. The mixture was stirred at

IBRAHIM ET AL.
3 of 11
130.39, 133.00, 135.55, 137.54 (C‐ arom). FT‐IR (ν, cm−1):
2973, 2354, 1986, 1628, 1567, 1448, 1365, 1151. GC‐MS: m/
z 329 (M+1). Anal. Calcd for C17H17BrN2 (329) (%): C,
62.02; H, 5.20; N, 8.51. Found (%): C, 62.51; H, 5.33; N,
8.80.
127.70, 128.52, 128.77, 128.93, 129.08, 129.17, 129.25,
137.84, 152.59 (C arom). FT‐IR (ν, cm−1): 3043, 2932,
2300, 1958, 1605, 1446, 1213, 1160, 1065, 745, 693. ESI‐
MS: m/z 594 (M+1). Anal. Calcd for C22H21Br2N3Pd
(594) (%): C, 44.51; H, 3.57; N, 7.08. Found (%): C, 44.01;
H, 3.25; N, 7.00.
2.4 | Synthesis of Palladium NHC Pyridine
Complexes (3a and 3b)
2.5 | X‐ray Crystal Structure
NHC ligand precursor (2a or 2b; 0.50 mmol),
palladium(II) bromide (0.50 mmol), potassium carbonate
(2.0 mmol) and pyridine (5 ml) were added to a 15 ml
round‐bottom flask. The reaction mixture was stirred at
90 °C for 24 h. The crude product was cooled to room
temperature and diluted with 5 ml of 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 a rotary evaporator under reduced pressure. The
complex was obtained as yellow crystals. The crystals
were washed with ether and dried in vacuum. The
Single‐crystal data collection for 3a and 3b was performed
using a Bruker‐Axs Smart Apex system equipped with
graphite monochromatized Mo Ka radiation (k =
0.71073 Å). The data were collected using SMART and
the integration was performed using SAINT.[54] An
empirical absorption correction was carried out using
SADABS.[55] The structures were solved by direct
methods with SHELXS‐97 and refined by full‐matrix
least‐squares procedures on F2 using the program
SHELXL‐97.[56] Crystal data and details of the data
collection are summarized in Table 1.
1
complex was characterized with H NMR, 13C NMR and
2.6 | Procedure for Carbonylative
Sonogashira Coupling Reactions
FT‐IR spectroscopies, ESI‐MS, elemental analysis and
single‐crystal X‐ray diffraction analysis.
A 45 ml stainless steel autoclave equipped with a glass
liner, gas inlet valve and pressure gauge was used for
carbonylative Sonogashira coupling reactions. Palladium
complex (0.10 mol%), aryl iodide (1.0 mmol), alkyne
(1.2 mmol), base (2.0 mmol) and solvent (3 ml) were
added to the glass liner. Additional solvent (2 ml) was
added in the autoclave. The glass liner was then placed
in the autoclave. The autoclave was vented three times
with carbon monoxide and then pressurized to 200 psi
of CO. The mixture was heated to the required tempera-
ture and maintained under stirring for the required time.
After completion of reaction, the mixture was cooled to
room temperature and excess CO was vented under a
fume hood. The mixture was diluted with 5 ml of water
and extracted three times with 10 ml of ethyl acetate.
The combined ethyl acetate extract was concentrated
under reduced pressure in a rotary evaporator. The
products were purified using column chromatography
with hexane–ethyl acetate (9:1) as eluent. The products
were analysed using GC‐MS, 1H NMR and 13C NMR
analyses. The spectral data of the alkynones prepared in
this study were in full agreement with those reported
in the literature and they are provided in the
supporting information.[22,29,37,41,44,59–61]
2.4.1 | Dibromide(1‐methyl‐3‐(2‐
methylpropyl)‐5‐phenyl‐1H‐imidazol‐2‐yli-
dene)pyridine palladium(II) (3a)
1
Yellow crystals; isolated yield 77%. H NMR (500 MHz,
CDCl3, δ, ppm): 9.04 (s, 2H, C‐H arom), 7.75 (s, 1H, C‐H
arom), 7.43–7.34 (m, 7H, C‐H arom), 6.89 (s, 1H, C‐H
arom), 4.31 (d, 2H, J = 7.6 Hz, CH2), 4.09 (s, 3H, CH3),
2.80–2.74 (m, 1H, C‐H), 1.09 (d, J = 6.7 Hz, 6H, CH3 ×
2). 13C NMR (125 MHz, CDCl3, δ, ppm): 20.15 (CH3 ×
2), 28.74 (CH), 36.61 (CH3), 58.54 (CH2), 120.08, 124.30,
127.54, 128.63, 128.84, 128.92, 135.74, 137.38, 148.06,
149.54, 152.29, 153.99 (C‐ arom). FT‐IR (ν, cm−1): 3039,
2933, 2296, 1599, 1437, 1386, 1008, 748, 690. ESI‐MS: m/
z 560 (M+1). Anal. Calcd for C19H23Br2N3Pd (559) (%):
C, 40.78; H, 4.14; N, 7.51. Found (%): C, 40.89; H, 4.52;
N, 7.63.
2.4.2 | Dibromide(3‐benzyl‐1‐methyl‐5‐
phenyl‐1H‐imidazol‐2‐ylidene)pyridine
palladium(II) (3b)
1
Yellow crystals; isolated yield 82%. H NMR (500 MHz,
CDCl3, δ, ppm): 9.08 (d, 2H, J = 6.41 Hz, CH2 arom),
7.77 (t, 1H, J = 7.6 Hz, C‐H arom), 7.56 (d, 2H, J =
6.7 Hz, C‐H arom), 7.41–7.26 (m, 11H, C‐H arom), 5.82
(s, 2H, CH2), 4.12 (s, 3H, CH3). 13C NMR (125 MHz,
CDCl3, δ, ppm): 36.74 (CH3), 55.13 (CH2), 119.10, 124.50,
Analytical and spectroscopic data of the new com-
pound: 1,1′‐benzene‐1,4‐diylbis(4,4‐dimethylpent‐2‐yn‐1‐
1
one) (6fi). White solid; yield 71%. H NMR (500 MHz,
CDCl3, δ, ppm): 8.20 (s, 4H, C‐H arom), 1.40 (s, 18H, 6
× CH3). 13C NMR (125 MHz, CDCl3, δ, ppm): 177.42,

4 of 11
IBRAHIM ET AL.
TABLE 1 Crystallographic data for compounds 3a and 3b
3a
3b
Chemical formula
CCDC no.
C19H23Br2N3Pd
C22H21Br2N3Pd
1554542
559.62
Monoclinic
P21/c
1554544
593.64
Monoclinic
P21/c
Formula weight
Crystal system
Space group
Temperature (K)
Radiation
299
296
Mo Kα (λ = 0.71073 Å)
ρcalc (g cm−3
a (Å)
b (Å)
)
1.739
1.720
9.3722(5)
24.1786(14)
9.4781(5)
95.4890(10)
2138.0(2)
4
8.9016(7)
24.764(2)
10.4222(9)
93.681(2)
2292.8(3)
4
SCHEME 1 Synthesis of NHC ligand precursors
3.2 | Synthesis of Complexes 3a and 3b
c (Å)
β (°)
V (Å3)
The Pd–NHC–Py complexes 3a and 3b were prepared in
good yields by reacting palladium bromide with 1.0 eq.
of the appropriate ligand precursor (2a or 2b) in pyridine
(Scheme 2). Complexes 3a and 3b were purified by pass-
ing through a column of silica gel layered with a short
pad of celite. Complexes 3a and 3b were isolated as yellow
solids. The formation of the complexes was confirmed by
the disappearance of the acidic C‐2 protons of the
imidazole rings, initially present in the N‐substituted
imidazolium salts, following palladation of the NHC
ligand precursors. Furthermore, there is the appearance
of a new signal at 152 ppm in the 13C NMR spectra of both
complexes assignable to the palladated carbon Pd―C. In
the ESI‐MS of the two complexes, base peaks were
observed at 560 (3a) and 594 (3b) which confirmed the
formation of the two Pd–carbene complexes.
Z
Refl. collect. / uniq.
29000 / 5308
4653
31073 / 5685
4835
Refl. obser.
[I > 2σ(I)]
R(int)
0.0267
0.0329
Data / restr. /
parameter
5308 / 0 / 229
5685 / 0 / 254
Goodness‐of‐fit
on F2
1.073
1.017
R indices
[I > 2σ(I)]
R1 = 0.0614;
wR2 = 0.2243
R1 = 0.0305;
wR2 = 0.0740
R indices
(all data)
R1 = 0.0671;
wR2 = 0.2320
R1 = 0.0384;
wR2 = 0.0782
Largest diff.
peak, hole (e Å–3
2.927, −2.097
1.320, −1.211
)
3.3 | Molecular Structures of Palladium
Complexes 3a and 3b
140.39, 137.79, 129.64, 105.33, 78.02, 30.07, 29.05. GC‐MS:
m/z 294 (M + 1). Anal. Calcd for C20H22O2 (294) (%): C,
81.60; H, 7.53. Found (%): C, 81.91; H, 7.88.
X‐ray‐quality single crystals were grown by slow
evaporation of a solution of the compounds in a mixture
of dichloromethane and diethyl ether. Both complexes
crystallize in the monoclinic P21/c space group with one
molecule in the asymmetric unit. Selected bond distances
and bond angles are listed in Tables 2 and 3. The molecu-
lar structures are depicted in Figures 1 and 2. In both
3 | RESULTS AND DISCUSSION
3.1 | Synthesis of Ligands 2a and 2b
Compound 1 was prepared in good yield from the
Suzuki–Miyaura cross‐coupling reaction of 5‐bromo‐1‐
methyl‐1H‐imidazole with phenylboronic acid (Scheme 1).
Ligands 2a and 2b were prepared in good yields by
the direct alkylation of 1 with either isobutyl bromide
or benzyl bromide (Scheme 1). Formation of the
imidazolium bromides was confirmed by the presence of
downfield singlet peaks at 10.21 ppm (2a) and
10.44 ppm (2b) in the 1H NMR spectra, which are
assigned to C‐2 protons of the imidazole rings.
SCHEME 2 Synthesis of complexes 3a and 3b

IBRAHIM ET AL.
5 of 11
TABLE 2 Selected bond distances and bond angles for 3a
Bond distance (Å)
Bond angle (°)
Pd1–C1
Pd1–N3
Pd1–Br2
Pd1–Br1
N1–C1
N1–C3
N1–C4
N2–C1
N2–C2
N2–C5
1.954(6)
C1–Pd1–N3
178.1(2)
86.83(19)
91.55(18)
88.74(19)
92.87(18)
175.53(3)
110.8(5)
122.2(6)
126.9(6)
2.124(6)
2.5123(8)
2.5565(8)
1.370(8)
1.377(8)
1.478(8)
1.342(8)
1.382(9)
1.473(8)
C1–Pd1–Br2
N3–Pd1–Br2
C1–Pd1–Br1
N3–Pd1–Br1
Br2–Pd1–Br1
C1–N1–C3
C1–N1–C4
C3–N1–C4
C1–N2–C2
C1–N2–C5
C2–N2–C5
110.6(6)
126.3(6)
123.0(6)
FIGURE 1 ORTEP diagram of 3a showing the atomic labelling
scheme. Thermal ellipsoids are drawn at 30% probability level
palladium(II) complexes 3a and 3b, the NHC carbene and
pyridine ligands are in trans positions and the geometry is
distorted square planar. The Pd―C, Pd―Br and Pd―N
bond distances are in the same range as those reported
for analogous palladium complexes.[57,58] The dihedral
angles between the NHC and [PdBr2CN] mean planes
are 89.6(2)° and 86.68(9)° for 3a and 3b, respectively,
while those between the pyridine and [PdBr2CN] mean
planes are 42.9(2)° and 53.4(1)°, respectively. This signifi-
cant difference is likely due to van der Walls packing con-
tacts with the ligands of neighbouring complex molecules.
reactions, especially C―C bond coupling. A plethora of
articles have been published on this topic.[43,45–49]
However, the application of Pd(II)–NHC complexes
in carbonylative cross‐coupling reactions is limited. In
previously reported works, higher catalyst loading[37]
and long reaction time[44] limited the scope of these
reactions.
However, we have examined in detail the applications
of the newly synthesized complexes 3a and 3b in the
carbonylative Sonogashira coupling reactions of aryl
iodides with arylalkynes and alkylalkynes.
The carbonylative Sonogashira coupling reaction of
iodobenzene with phenylacetylene in the presence of a
catalytic amount of 3a was adopted as a model reaction
(equation (1)). The results of the optimization reactions
are summarized in Table 4. When the reaction was
run with triethylamine as base, at 60 °C for 6 h, only
20% of 1,3‐diphenylprop‐2‐yn‐1‐one (Table 4, entry 1)
3.4 | Carbonylative Sonogashira Coupling
of Iodobenzene and Phenylacetylene
Catalysed by Complexes 3a and 3b:
Optimization of Reaction Conditions
Pd(II)–NHC complexes have proven to be efficient and
active catalysts for a wide range of cross‐coupling
TABLE 3 Selected bond distances and bond angles for 3b
Bond distance (Å)
Bond angle (°)
Pd1–C1
Pd1–N3
Pd1–Br2
Pd1–Br1
N1–C1
N1–C9
N1–C2
N2–C1
N2–C1
N2 C17
1.967(2)
C1–Pd1–N3
176.85(10)
87.00(7)
90.60(7)
91.50(7)
90.87(7)
178.067(17)
110.4(2)
125.5(2)
124.0(2)
2.103(2)
2.4148(4)
2.4226(4)
1.339(3)
1.384(3)
1.467(3)
1.349(3)
1.396(3)
1.459(3)
C1–Pd1–Br2
N3–Pd1–Br2
C1–Pd1–Br1
N3–Pd1–Br1
Br2–Pd1–Br1
C1–N1–C9
C1–N1–C2
C9–N1–C2
C1–N2–C10
C1–N2–C17
C10–N2–C17
110.6(2)
122.9(2)
126.5(2)
FIGURE 2 ORTEP diagram of 3b showing the atomic labelling
scheme. Thermal ellipsoids are drawn at 30% probability level

6 of 11
IBRAHIM ET AL.
TABLE 4 Optimization of carbonylative Sonogashira coupling reactions of iodobenzene (4a) and phenylacetylene (5a)a
(1)
Entry
Solvent
Temp. (°C)
Base
Catalyst
3a
Time (h)
Yield of 6aa (%)b
1
Toluene
60
Et3N
6
20
2
Toluene
Toluene
Toluene
Toluene
DMF
80
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
—
3a
6
6
6
6
6
6
6
6
6
6
1
2
3
4
6
6
6
6
51
3
100
110
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
3a
70
4
3a
83
5
3a
95
6
3a
67
7
CH3CN
Dioxane
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
3a
81
8
3a
43
9
3a
0
10
11
12
13
14
15
16
17
18
19
K2CO3
KOH
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
3a
Trace
Trace
38
3a
3a
3a
65
3a
82
3a
97
3b
95
Pd(PPh3)2Cl2
Pd(PhCN)2Cl2
PdBr2
78
48
40
aReaction conditions: [Pd] (0.10 mol%), iodobenzene (1.0 mmol), phenylacetylene (1.5 mmol), base (2.0 mmol), solvent (5 ml), CO (200 psi).
bIsolated yield.
as a product was obtained. The yield of the product
gradually increased with an increase in temperature
3.5 | Carbonylative Sonogashira Coupling
Reactions of Aryl Iodides with Arylalkynes
(Table 4, entries 1–4). Complete conversion of
iodobenzene and 95% isolated yield of alkynone were
achieved at 120 °C (Table 4, entry 5). A substantial
decrease in the isolated yield was noted when DMF
(Table 4, entry 6), acetonitrile (Table 4, entry 7) or diox-
ane (Table 4, entry 8) was used in place of toluene as a
solvent. No product was observed when the reaction
was carried out in the absence of a base (Table 4, entry
9). Moreover, only traces of product were observed with
K2CO3 (Table 4, entry 10) and KOH (Table 4, entry 11)
as bases. Based on the above results, the subsequent
reactions were carried out using toluene as a solvent,
Et3N as a base and at 120 °C for 6 h. These optimized
conditions were adopted, under which the other catalyst
(3b) gave similar results (Table 4, entry 16). For compar-
ison, commercially available palladium catalysts were
also investigated (Table 4, entries 17–19).
Catalysed by 3a
Since the optimized conditions showed excellent results
for the newly synthesized Pd complexes in carbonylative
Sonogashira coupling reactions, the scope of substrates
was considered using catalyst 3a. Using optimized condi-
tions (0.10 mol% of 3a, 2.0 eq. of Et3N, 5 ml of toluene,
200 psi CO, 120 °C), various aryl iodides were reacted
with a range of functionalized arylalkynes (equation (2),
Table 5).
A variety of electron‐withdrawing and
electron‐donating substituted aryl iodides were reacted
efficiently with arylalkynes and CO to produce the corre-
sponding alkynones in excellent yields. The carbonylative
Sonogashira coupling reaction of phenylacetylene with
unactivated aryl iodide (Table 5, entry 1), deactivated aryl
iodides (Table 5, entries 2 and 3) and activated aryl iodides
(Table 5, entries 4 and 5) afforded the corresponding

IBRAHIM ET AL.
7 of 11
TABLE 5 Carbonylative Sonogashira coupling reactions of aryl iodides (4a–e) with arylalkynes (5a–e) catalysed by 3aa
(2)
Entry
Aryl iodide (4)
Arylalkyne (5)
Product (6)
Yield (%)b
1
96
2
5a
92
3
4
5
6
5a
5a
5a
94
93
94
96
4a
7
8
4a
4a
95
93
9
4a
92
aReaction conditions: 3a (0.10 mol%), aryl iodide (1.0 mmol), alkyne (1.5 mmol), Et3N (2.0 mmol), toluene (5 ml), CO (200 psi), 120 °C, 6 h.
bIsolated yield.
alkynones in excellent yields (92–96%). The carbonylative
various arylalkynes (Table 5, entries 6–9) were also very
Sonogashira coupling reactions of iodobenzene with
successful.

8 of 11
IBRAHIM ET AL.
iodobenzene with 3,3‐dimethyl‐1‐butyne yielded 94% of
the expected alkynone (Table 6, entry 4). The reactivity
of phenyl‐substituted alkylalkynes with iodobenzene is
also comparable with that of other alkylalkynes
(Table 6, entries 5 and 6).
3.6 | Carbonylative Sonogashira Coupling
Reactions of Aryl Iodides with Alkylalkynes
The phosphine‐free carbonylative Sonogashira cross‐cou-
pling reactions of aryl iodides with alkylalkynes have
been rarely investigated. Interestingly, complexes 3a and
3b were found to be highly active in the carbonylative
coupling reactions of aryl iodides with alkylalkynes with
a catalyst loading as low as 0.10 mol% (equation (3),
Table 6). For instance, the carbonylative coupling reac-
tions of iodobenzene with 1‐pentyne (Table 6, entry 1),
1‐hexyne (Table 6, entry 2) and 1‐decyne (Table 6, entry
3) were successful to afford the expected alkynones in
very good to excellent yields (80–91%). The yields of the
reactions were found to vary slightly with the alkyl chain
lengths. Alkylalkynes having fewer carbon atoms, such as
1‐pentyne (Table 6, entry 1), were found to be more
reactive as compared to alkylalkynes with higher num-
bers of carbon atoms such as 1‐decyne (Table 6, entry 3)
under the same experimental conditions. Similarly,
the carbonylative Sonogashira coupling reaction of
3.7 | Carbonylative Sonogashira Coupling
Reactions of Aryl Iodides with Dialkynes
and Aryl Diiodides with Alkynes Catalysed
by 3a
Considering the high catalytic performance of the newly
synthesized Pd–NHC–Py complexes 3a and 3b, we inves-
tigated the carbonylative Sonogashira coupling reactions
of aryl iodides with dialkynes and of aryl diiodides with
alkynes. Notably, the reactions successfully proceeded to
give symmetrical dialkynones in good to very good iso-
lated yields. For instance, the coupling reaction of 1,4‐
diethynylbenzene and 1,3‐diethynylbenzene with 2 eq.
of iodobenzene proceeded smoothly to afford the
TABLE 6 Carbonylative Sonogashira coupling reactions of iodobenzene (4a) with alkylalkynes (5f–l) catalysed by 3aa
(3)
Entry
Aryl iodide
Alkylalkyne
Product
Yield (%)b
1
91
2
3
4
4a
4a
4a
87
80
94
5
6
4a
4a
81
77
aReaction conditions: 3a (0.10 mol%), aryl iodide (1.0 mmol), alkyne (1.5 mmol), Et3N (2.0 mmol), toluene (5 ml), CO (200 psi), 120 °C, 18 h.
bIsolated yield.

IBRAHIM ET AL.
9 of 11
TABLE 7 Comparison of activity of new catalytic system 3a in carbonylative Sonogashira coupling reactions of aryl iodides and alkynes
with previously published data
Ref.
[30]
Catalyst
Co‐catalyst/ligand/additive
Base
Time (h)
Yield (%)
PdCl2 (5 mol%)
PPh3 (10 mol%)
Et3N
24
46–95
[16]
[21]
[64]
Pd(OAc)2 (3 mol%)
Pd(OAc)2 (3 mol%)
Pd(OAc)2 (5 mol%)
Pd–NHC–Py (0.1 mol%)
PPh3 (6 mol%), diisopropylcarbodiimide (2 eq.)
Et3N
Et3N
Et3N
Et3N
20
63–99
43–88
45–84
88–94
PPh3 (6 mol%)
TBAAc (1.5 eq.)
—
17–24
12
Present work
6
corresponding para‐dialkynone (6 am; equation (4)) and
meta‐dialkynone (6an; equation (5)) in yields of 77 and
70%, respectively. Additionally, the new Pd–NHC–Py
complexes show high catalytic performance in the
carbonylative Sonogashira coupling of 1,4‐diiodobenzene
with alkylalkynes to yield the corresponding dialkynones
6fi (equation (6)) and 6fo (equation (7)), respectively.
alkynes and dialkynes showed the high efficacy of the
new complexes 3a and 3b in catalysis. Complex 3a
exhibited superior catalytic activity with much lower
loading as compared to other catalytic systems reported
in the literature (Table 7).
+B: 2.8 Plausible Mechanism for Carbonylative
Sonogashira Coupling Reaction
The palladium(II) pre‐catalyst undergoes first a substi-
tution of bromides by acetylides, formed by deprotonation
of alkynes in the presence of triethylamine, followed by a
trans–cis isomerization step and a reductive elimination
of the dialkyne to generate the Pd(0) active catalyst
(Scheme 3). NHCs are known to be stronger s donors than
phosphine ligands and their transition metal complexes
are more stable than the phosphine‐based analogues, this
despite the fact that they are less prone to p back‐bonding
from transition metal ions.[62,63] In light of these facts, the
higher catalytic activity of 3a, relative to the literature‐
reported palladium/phosphine systems, may be rational-
ized in several ways. On the one hand, in terms of the
higher stability of both the pre‐catalyst (NHC)Pd(II)(Py)
Br2 and the proposed active species (NHC)Pd(0)(Py), in
(4)
(5)
(6)
(7)
The high yields and selectivities obtained with the
catalytic coupling of aryl iodides and diiodides with
SCHEME 3 Plausible mechanism for carbonylative Sonogashira
coupling reaction catalysed by Pd–NHC–Py complex

10 of 11
IBRAHIM ET AL.
comparison with their phosphine‐based counterparts.
On the other hand, both the oxidative addition and
substitution steps are likely to be enhanced by the more
electron‐rich species (NHC)Pd(0)(Py) and (NHC)Pd(II)
(Py)(RCO)(I), respectively, compared to their phosphine‐
based analogues in the case of Pd(PPh3)2Cl2‐catalysed
reactions. Accordingly, the inductive effect of 2‐
methylpropyl substituent in 3a, leading to a more elec-
tron‐rich palladium centre relative to the benzyl
group in 3b, is likely at the origin of the higher activity
of the former. Aryl iodide is then added to Pd(0) in the
oxidative addition step to form the palladium(II) interme-
diate ArPdLPyI (V). This step is followed by CO insertion
into the Ar―Pd bond to form the acyl Pd intermediate
(VI). Substitution of the iodide by the acetylide (VII),
trans–cis isomerization (VIII) followed by reductive elim-
ination yield the carbonylative Sonogashira product with
the subsequent regeneration of the Pd(0) catalyst.[40,42]
REFERENCES
[1] A. S. Karpov, E. Merkul, F. Rominger, T. J. Müller, Angew.
Chem. Int. Ed. 2005, 44, 6951.
[2] J. D. Kirkham, S. J. Edeson, S. Stokes, J. P. Harrity, Org. Lett.
2012, 14, 5354.
[3] M. S. Mohamed Ahmed, K. Kobayashi, A. Mori, Org. Lett. 2005,
7, 4487.
[4] A. Arcadi, M. Aschi, F. Marinelli, M. Verdecchia, Tetrahedron
2008, 64, 5354.
[5] C. G. Lee, K. Y. Lee, S. Lee, J. N. Kim, Tetrahedron 2005, 61,
493.
[6] P. Bannwarth, A. Valleix, D. Grée, R. Grée, J. Org. Chem. 2009,
74, 4646.
[7] E. Awuah, A. Capretta, Org. Lett. 2009, 11, 3210.
[8] Z. She, D. Niu, L. Chen, M. A. Gunawan, X. Shanja, W. H.
Hersh, Y. Chen, J. Org. Chem. 2012, 77, 3627.
[9] C. L. Taylor, Y. Bolshan, J. Vis. Exp. 2015, 9, 52401.
[10] A. Zapf, M. Beller, Topics Catal. 2002, 19, 101.
[11] X. F. Wu, H. Neumann, M. Beller, Chem. Soc. Rev. 2011, 40,
4 | CONCLUSIONS
4986.
[12] J. B. Peng, X. Qi, X. F. Wu, Synlett 2017, 28, 175.
[13] C. Shen, X. F. Wu, Chem. A Eur. J. 2017, 23, 2973.
[14] X. F. Wu, H. Neumann, M. Beller, Chem. Rev. 2013, 113, 1.
New NHC–Py ligands and new Pd–NHC–Py complexes
(3a and 3b) have been successfully synthesized and
characterized using various analytical and spectroscopic
techniques including single‐crystal X‐ray diffraction. The
catalytic activities of the new complexes 3a and 3b were
investigated in the carbonylative Sonogashira coupling
reactions of various aryl iodides with arylalkynes and
alkylalkynes including dialkynes. Excellent isolated yields
of the expected alkynones were obtained for aryl iodides
with both arylalkynes and alkylalkynes and very good
yields were achieved for the carbonylative coupling of
aryl diiodide with arylalkynes. Worth noting is the syn-
thesis of a new compound, 1,1′‐benzene‐1,4‐diylbis(4,4‐
dimethylpent‐2‐yn‐1‐one), from the carbonylative
Sonogashira coupling reaction of 1,4‐diiodobenzene with
4,4‐dimethylpent‐2‐yne using the new catalytic system
based on complex 3a.
[15] J. B. Peng, F. P. Wu, C. L. Li, X. Qi, X.‐F. Wu, Eur. J. Org. Chem.
2017, 1434.
[16] Y. Wang, X. Yang, J. Yu, RSC Adv. 2017, 7, 31850.
[17] F.‐P. Wu, J. B. Peng, X. Qi, X. F. Wu, Cat. Sci. Technol. 2017, 7,
4924.
[18] P. Gautam, B. M. Bhanage, Chemistry Select 2016, 1, 5463.
[19] G. Martra, Appl. Catal. A 2014, 80, 1.
[20] X. Qi, L. B. Jiang, C. L. Li, R. Li, X. F. Wu, Chem. Asian J. 2015,
10, 1870.
[21] W. Li, X. F. Wu, Org. Biomol. Chem. 2015, 13, 5090.
[22] X.‐F. Wu, H. Neumann, M. Beller, Chem. A Eur. J. 2010, 16,
12104.
[23] S. Perrone, F. Bona, L. Troisi, Tetrahedron 2011, 67, 7386.
[24] T. Kobayashi, M. Tanaka, J. Chem. Soc. Chem. Commun. 1981,
333.
[25] S.‐K. Kang, H.‐C. Ryu, Y.‐T. Hong, J. Chem. Soc. Perkin Trans.
2001, 1, 736.
ACKNOWLEDGEMENTS
This project was funded by the National Plan for Science,
[26] X.‐F. Wu, H. Neumann, M. Beller, Org. Biomol. Chem. 2011, 9,
Technology and Innovation (MARIFAH)
–
King
8003.
Abdulaziz City for Science and Technology – through
the Science and Technology Unit at King Fahd University
of Petroleum and Minerals (KFUPM), the Kingdom of
Saudi Arabia (award no. 14‐PET165‐04) and also by the
NUS/KFUPM collaboration.
[27] M. T. Rahman, T. Fukuyama, N. Kamata, M. Sato, I. Ryu,
Chem. Commun. 2006, 2236.
[28] M. S. M. Ahmed, A. Mori, Org. Lett. 2003, 5, 3057.
[29] B. Liang, M. W. Huang, Z. J. You, Z. C. Xiong, K. Lu, R. Fathi, J.
H. Chen, Z. Yang, J. Org. Chem. 2005, 70, 6097.
[30] B. M. O'Keefe, N. Simmons, S. F. Martin, Org. Lett. 2008, 10,
5301.
ORCID
[31] P. J. Tambade, Y. P. Patil, N. S. Nandurkar, B. M. Bhanage,
Bassam El Ali http://orcid.org/0000-0003-4005-6386
Synlett 2008, 886.

IBRAHIM ET AL.
11 of 11
[32] A. Park, K. Park, Y. Kim, S. Lee, Org. Lett. 2011, 13, 944.
[53] M. B. Ibrahim, R. Suleiman, M. Fettouhi, B. El Ali, RSC Adv.
2016, 6, 78826.
[33] A. Brennführer, H. Neumann, M. Beller, Angew. Chem. Int. Ed.
2009, 48, 4114.
[54] Bruker, Smartm Saint, Bruker Axs Inc., Madison, WI, 2008.
[55] G. M. Sheldrick, SADABS, Program for Empirical Absorption
Correction of Area Detector Data, University of Gottingen,
Germany 1996.
[34] J. H. Liu, J. Chen, W. Sun, C. G. Xia, Cuihua Xuebao 2010, 1, 31.
[35] S. T. Gadge, B. M. Bhanage, RSC Adv. 2014, 4, 10367.
[36] X.‐F. Wu, B. Sundararaju, H. Neumann, P. H. Dixneuf, M.
Beller, Chem. A Eur. J. 2011, 17, 106.
[56] G. M. Sheldrick, Acta Crystallogr. 2008, 64, 112.
[57] Y.‐C. Lin, H. H. Hsueh, S. Kanne, L.‐K. Chang, F.‐C. Liu, I. J. B.
Lin, G.‐H. Lee, S.‐M. Peng, Organometallics 2013, 32, 3859.
[37] C. Bai, S. Jian, X. Yao, Y. Li, Sci. Technol. 2014, 4, 3261.
[38] Y. Wang, J. H. Liu, C. G. Xia, Tetrahedron Lett. 2011, 52, 1587.
[58] L. Ray, M. M. Shaikh, P. Ghosh, Dalton Trans. 2007, 4546.
[59] K. Y. Lee, M. J. Lee, J. N. Kim, Tetrahedron 2005, 61, 8705.
[60] C. Chowdhury, N. G. Kundu, Tetrahedron 1999, 55, 7011.
[39] M. Genelot, V. Dufaud, L. Djakovitch, Synth. Catal. 2013, 355,
2604.
[40] J. H. Liu, J. Chen, C. G. Xia, J. Catal. 2008, 253, 50.
[61] Q. Wei, H. Deng, Y. Cai, J. W. Y. Lam, J. Li, J. Sun, M. Gao, A.
[41] J. M. Liu, X. G. Peng, W. Sun, Y. W. Zhao, C. G. Xia, Org. Lett.
2008, 10, 3933.
Qin, N. Z. Tang, Macromol. Rapid Commun. 2012, 33, 1356.
[62] D. J. D. Wilson, S. A. Couchman, J. L. Dutton, Inorg. Chem.
2012, 51, 7657.
[42] W. Y. Hao, J. C. Sha, S. R. Sheng, M. Z. Cai, J. Mol. Catal. A
2009, 298, 94.
[63] J. Jover, N. Fey, M. Purdie, G. C. Lloyd‐Jones, J. N. A. Harvey,
J. Mol. Catal. A 2010, 39, 324.
[43] F. Rajabi, W. R. Thiel, Adv. Synth. Catal. 2014, 356, 1873.
[44] C. Zhang, J. Liu, C. Xia, Org. Biomol. Chem. 2014, 12, 9702.
[64] M. Bakherad, A. Keivanloo, B. Bahramian, S. Jajarmi, Synlett
2011, 3, 311.
[45] A. Chartoire, A. Boreux, A. R. Martin, S. P. Nolan, RSC Adv.
2013, 3, 3840.
[46] T. Wang, H. Xie, L. Liu, W. X. Zhao, J. Org. Chem. 2016, 804, 73.
SUPPORTING INFORMATION
[47] K. Natte, J. Chen, H. Neumann, M. Beller, X. Wu, Biomol.
Chem. 2014, 12, 5590.
Additional Supporting Information may be found online
in the supporting information tab for this article.
[48] A. Chartoire, X. Frogneux, S. P. Nolan, Adv. Synth. Catal 2012,
354, 1897.
[49] V. H. Nguyen, M. B. Ibrahim, W. W. Mansour, B. M. El Ali, H.
How to cite this article: Ibrahim M, Malik I,
Mansour W, Sharif M, Fettouhi M, El Ali B. Novel
(N‐heterocyclic carbene)Pd(pyridine)Br2 complexes
for carbonylative Sonogashira coupling reactions:
Catalytic efficiency and scope for arylalkynes,
alkylalkynes and dialkynes. Appl Organometal
Chem. 2018;e4280. https://doi.org/10.1002/aoc.4280
V. Huynh, Organometallics 2017, 36, 2345.
[50] M. B. Ibrahim, B. El Ali, M. Fettouhi, L. Ouahab, Appl.
Organomet. Chem. 2015, 29, 400.
[51] M. B. Ibrahim, S. M. S. Hussain, A. Fazal, M. Fettouhi, B. El Ali,
J. Coord. Chem. 2015, 68, 432.
[52] S. M. S. Hussain, M. B. Ibrahim, A. Fazal, R. Suleiman, M.
Fettouhi, B. El Ali, Polyhedron 2014, 70, 39.