Synthesis of silver(I) and palladium(II) N-heterocyclic carbene complexes and their use as catalysts for the direct C5 arylation of heteroaromatic compounds

Article abstract of DOI:10.1007/s11243-016-0075-y

Silver(I) N-heterocyclic carbene complexes were synthesized in good yields by the reactions of 1,3-dialkylperhydrobenzimidazolium salts with silver(I) oxide in dichloromethane. The silver complexes were used as carbene-transfer agents to synthesize pallad

Full text of DOI:10.1007/s11243-016-0075-y

Transition Met Chem
DOI 10.1007/s11243-016-0075-y
Synthesis of silver(I) and palladium(II) N-heterocyclic carbene
complexes and their use as catalysts for the direct C5 arylation
of heteroaromatic compounds
1
Beyhan Yigit Murat Yigit Zeynep Dagdeviren Ismail Ozdemir
1
1
•
2
¨
˙
•
•
˘
˘
˘
Received: 8 April 2016 / Accepted: 20 June 2016
Ó Springer International Publishing Switzerland 2016
Abstract Silver(I) N-heterocyclic carbene complexes were
synthesized in good yields by the reactions of 1,3-di-
alkylperhydrobenzimidazolium salts with silver(I) oxide in
dichloromethane. The silver complexes were used as car-
bene-transfer agents to synthesize palladium(II) N-hetero-
cyclic carbene complexes. All of the complexes were
characterized by physicochemical and spectroscopic
methods. The new palladium complexes were tested as
catalysts in the direct C5 arylation of 2-n-butylfuran, 2-n-
butylthiophene and 2-n-propylthiazole with aryl bromides
at 130 °C in N,N-dimethylacetamide. The arylation reac-
tions proceeded selectively at the C5 position of the
heteroaromatic compounds, and the corresponding cou-
pling products were obtained in moderate to good yields by
using 0.5 mol% of the palladium complex.
carbenes exhibit good r-donor and weak p-acceptor
properties, and they are very strong nucleophiles. Due to
their strong r-electron-donating properties, NHC ligands
form stronger bonds with transition metals than classical
ligands such as phosphines, often giving stable transition
metal complexes that are generally resistant to decompo-
sition [5, 6]. Additionally, the NHC ligands can be easily
modified by changing the substituents on the nitrogen
atoms or the carbene ring, which provides various ligands
for organometallic chemistry [7–9]. Metal complexes of N-
heterocyclic carbenes have received much interest as cat-
alysts and display higher stabilities and reactivities than the
corresponding phosphine complexes in various catalytic
processes [10–15]. In particular, palladium NHC com-
plexes have been successfully developed as highly active
precatalysts for C–C and C–N coupling, CO-ethylene
copolymerization and direct arylation reactions [16–19].
In recent years, the synthesis of arylated heterocycles
has received much attention due to their biological and
physical properties [20]. Such compounds can be prepared
by conventional methods such as Stille, Suzuki, Kumada
or Negishi couplings [21–24]. However, these methods
require the preliminary synthesis of organometallic
nucleophiles and produce stoichiometric amounts of side
products. In addition, the high reactivities of these reagents
as both nucleophiles and bases sometimes give rise to
limitations in the synthesis. In 1990, Ohta et al. [25]
reported the direct arylation of heteroaromatics (thio-
phenes, furans and thiazoles) with aryl halides in moderate
to good yields, using [Pd(PPh3)4] as the catalyst. Since
then, the palladium-catalyzed direct arylation of heteroaryl
derivatives with aryl halides has become a valuable
method for the synthesis of arylated heterocycles [26–30].
So far, a few examples of (NHC)Pd(II)-catalyzed arylation
of heterocycles using aryl halides have been described
Introduction
The first metal complexes bearing N-heterocyclic carbene
(NHC) ligands were independently reported by Wanzlick
¨
[1] and Ofele [2] in 1968. After these initial reports, most
chemists except Lappert et al. [3] directed little attention
toward NHC ligands for the next two decades. The isola-
tion of the first stable NHC species in 1991 by Arduengo
[4] and utilization of NHC complexes in catalysis led to a
renewed interest in NHC chemistry. N-heterocyclic
˘
& Murat Yigit
myigit@adiyaman.edu.tr
1
Department of Chemistry, Faculty of Science and Art,
Adıyaman University, 02040 Adıyaman, Turkey
2
¨ ¨
Department of Chemistry, Faculty of Science and Art, Inonu
University, 44260 Malatya, Turkey
123

Transition Met Chem
Synthesis of silver(I) complexes 2
[31–35]. To the best of our knowledge, however, Pd-car-
bene complexes bearing a perhydrobenzimidazol-2-ylidene
ligand for direct arylation of heteroaromatic compounds
have not been reported to date. The number, nature, and
position of the substituents on the nitrogen atoms or NHC
ring have considerable influence on the rate of catalysis
and stability of the NHC complexes against heat, moisture
and air. Therefore, thousands of free and metal-coordi-
nated N-heterocyclic carbenes have been reported,
although NHCs with cyclohexyl carbene backbones are
still relatively rare. We now report the synthesis and
characterization of new silver(I) and palladium(II) com-
plexes with perhydrobenzimidazol-2-ylidene as a ligand,
and the use of the palladium complexes as catalysts for the
direct C5-arylation of heteroaromatics with various aryl
halides.
A solution of the appropriate perhydrobenzimidazolium
chloride (0.94 mmol), Ag2O (0.47 mmol) and activated
˚
4 A molecular sieves in dichloromethane (20 mL) was
stirred for 24 h at room temperature in the dark under
argon. The reaction mixture was filtered through Celite,
and the solvent was removed under reduced pressure. The
crude product was recrystallized from dichloromethane/
hexane (1:2) at room temperature. The resulting white solid
was isolated by filtration and dried in vacuum.
Chloro-1,3-bis(4-isopropylbenzyl)perhydrobenzimida-
zol-2-ylidenesilver(I) 2a. Yield: 0.415 g, 83 %; en: 158 °C.
IR: m(NCN) = 1663 cm-1. Anal. Calc. for C27H37AgClN2:
C, 60.84; H, 6.94; N, 5.25. Found: C, 60.89; H, 6.97; N,
5.29 %. 1H NMR (CDCl3) d: 1.12–1.23 (m, 4H, NCHCH2-
CH2CH2CH2CHN), 1.66–1.83 and 2.03–2.11 (m, 4H,
NCHCH2CH2CH2CH2CHN),
2.83–2.94
(m,
2H,
NCHCH2CH2CH2CH2CHN), 1.26 (d, 12H, J = 7.03 Hz,
CH2C6H4CH(CH3)2-p), 3.12–3.22 (m, 2H, CH2C6H4-
CH(CH3)2-p), 4.44, 4.61, 4.91 and 5.07 (d, 4H,
J = 15.0 Hz, CH2Ar), 7.08 and 7.36 (d, 8H, J = 8.1 Hz,
Ar–H). 13C NMR (CDCl3) d: 23.86 (NCHCH2CH2CH2-
CH2CHN), 28.06 (NCHCH2CH2CH2CH2CHN), 50.28
(NCHCH2CH2CH2CH2CHN), 23.95 (CH2C6H4CH(CH3)2-
p), 33.97 (CH2C6H4CH(CH3)2-p), 66.42 (CH2Ar), 126.41,
128.02, 132.35 and 147.58 (Ar–C).
Experimental
All reactions for the preparation of the Ag(I) and Pd(II)
NHC complexes were carried out under argon in flame-
dried glassware using standard Schlenk techniques. The
solvents were purified by distillation over the drying agents
indicated and were transferred under Ar: THF, Et2O (Na/K
alloy), CH2Cl2 (P4H10), hexane, toluene (Na). All reagents
1
were purchased from Sigma-Aldrich, Merck or Fluka. H
Chloro-1,3-bis(4-tert-butylbenzyl)perhydrobenzimida-
zol-2-ylidenesilver(I) 2b. Yield: 0.44 g, 91 %, en:
202–204 °C, IR: m(NCN) = 1645 cm-1. Anal. Calc. for
C29H41AgClN2: C, 62.08; H, 7.31; N, 4.99. Found: C,
62.01; H, 7.37; N, 4.92 %. 1H NMR (CDCl3) d 1.13–1.32
(m, 4H, NCHCH2CH2CH2CH2CHN), 1.75–1.78 and
and 13C NMR spectra were recorded in CDCI3 using a
Bruker AC300P FT spectrometer operating at 300.13 MHz
(1H) or 75.47 MHz (13C). Chemical shifts (d) are given in
ppm relative to TMS, coupling constants (J) in hertz. FTIR
spectra were recorded as KBr pellets between 400 and
4000 cm-1 on
a
Mattson 1000 spectrophotometer
2.04–2.07
(m,
4H,
NCHCH2CH2CH2CH2CHN),
(wavenumbers, cm-1). Chromatograms were recorded by
GC-FID on an Agilent 6890 N gas chromatograph equip-
ped with an HP-5 column of 30 m length, 0.32 mm
diameter and 0.25 lm film thickness. Melting points were
measured in open capillary tubes with an Electrothermal-
9200 melting point apparatus and are uncorrected. Ele-
2.95–2.98 (m, 2H, NCHCH2CH2CH2CH2CHN), 1.33 (s,
18H, CH2C6H4C(CH3)3-p), 4.60 and 4.91 (d, 4H,
J = 15.0 Hz CH2Ar), 7.24 and 7.38 (d, 8H, J = 8.2 Hz,
Ar–H). 13C NMR (CDCl3) d: 23.84 (NCHCH2CH2CH2-
CH2CHN), 28.04 (NCHCH2CH2CH2CH2CHN), 53.08
(NCHCH2CH2CH2CH2CHN), 31.32 (CH2C6H4C(CH3)3-
p), 34.60 (CH2C6H4C(CH3)3-p), 66.42 (CH2Ar), 125.83,
127.35, 132.00 and 151.23 (Ar–C).
¨ ¨
mental analyses were performed at Inonu University
research center.
Chloro-1,3-bis(2,4,6-trimethoxybenzyl)perhydrobenz-
imidazol-2-ylidenesilver(I) 2c. Yield: 0.687 g, 77 %, en:
180–182 °C, IR: m(NCN) = 1610 cm-1. Anal. Calc. for
C27H37AgClN2O6: C, 51.55; H, 5.88; N, 4.45. Found: C,
Synthesis of perhydrobenzimidazolium salts 1
A mixture of the required N,N0-dialkyl-1,2-diaminocyclo-
hexane (6.2 mmol), NH4Cl (6.2 mmol) and triethyl ortho-
formate (10 mL) was heated for 12 h at 110°C. Upon
cooling to room temperature, colorless crystals were
obtained. These were filtered off, washed with diethyl ether
(3 9 15 mL) and dried under vacuum. The crude product
was recrystallized from EtOH/Et2O.
1
51.50; H, 5.83; N, 4.49 %. H NMR (CDCl3) d: 1.34–1.49
(m, 4H, NCHCH2CH2CH2CH2CHN), 1.64–1.71 and
1.75–1.85 (m, 4H, NCHCH2CH2CH2CH2CHN), 3.57–3.69
(m, 2H, NCHCH2CH2CH2CH2CHN), 3.80 and 3.82 (s,
18H, CH2C6H2(OCH3)3-2,4,6), 4.35, 4.46, 4.75 and 4.90
(d, 4H, J = 14.5 Hz, CH2Ar), 6.08 and 6.12 (s, 4H, Ar–H).
13C NMR (CDCl3) d: 22.10 (NCHCH2CH2CH2CH2CHN),
123

Transition Met Chem
24.69 (NCHCH2CH2CH2CH2CHN), 40.96 (NCHCH2-
CH2CH2CH2CHN), 55.47 and 55.97 (CH2C6H2(OCH3)3-
2,4,6), 59.28 (CH2Ar), 90.27, 101.68, 105.12, 159.63,
159.77 and 161.21 (Ar–C).
0.84–1.16 (m, 8H, NCHCH2CH2CH2CH2CHN), 1.34–1.63
and 1.71–1.84 (m, 8H, NCHCH2CH2CH2CH2CHN),
3.31–3.42 (m, 4H, NCHCH2CH2CH2CH2CHN), 3.80 and
3.83 (s, 36H, CH2C6H2(OCH3)3-2,4,6), 4.49, 4.84, 5.42 and
5.60 (d, 8H, J = 14.1 Hz, CH2Ar), 6.04 and 6.11 (s, 8H,
Ar–H). 13C NMR (CDCl3) d: 22.44 (NCHCH2CH2CH2-
CH2CHN), 24.24 (NCHCH2CH2CH2CH2CHN), 38.46
(NCHCH2CH2CH2CH2CHN), 55.43 and 55.96 (CH2C6
H2(OCH3)3-2,4,6), 59.69 (CH2Ar), 89.90, 101.90, 106.92,
159.68, 160.39 and 162.21 (Ar–C), 200.53 (Pd–C).
Synthesis of palladium(II) complexes 3
A solution of the required silver(I) NHC complex
(0.74 mmol) and PdCl2(PhCN)2 (0.37 mmol) in dichlor-
omethane (20 mL) was stirred for 24 h at room tempera-
ture in the dark. The resulting mixture was filtered through
Celite, and the solvent was removed under reduced pres-
sure. The crude product was recrystallized from dichlor-
omethane/diethyl ether (1:2) at room temperature. The
white crystals were filtered off, washed with diethyl ether
(3 9 10 mL) and dried under vacuum.
General procedure for direct C5 arylations
The required heteroaryl derivative (2 mmol), aryl halide
(1 mmol), Pd complex 3a–c (0.005 mmol), KOAc
(1 mmol) and DMAc (2 mL) were placed in a Schlenk tube
equipped with a magnetic stirring bar. The Schlenk tube
was purged several times with argon and then placed in a
preheated oil bath at 130 °C, and the reaction mixture was
stirred for 1 h. The mixture was analyzed by gas chro-
matography to determine the conversion of the aryl bromide
and the yield of product. The solvent was removed by
heating the reaction vessel under vacuum, and the residue
was charged directly onto a silica gel column. The products
were eluted using diethyl ether/pentane (1:3).
Bis[1,3-di(4-isopropylbenzyl)perhydrobenzimidazol-2-
ylidene]dichloropalladium(II) 3a. Yield: 0.28 g, 81 %, en:
268–270 °C. IR: m(NCN) = 1511 cm-1. Anal. Calc. for C54-
H74N4PdCl2: C, 67.85; H, 7.74; N, 5.86. Found: C, 67.93; H,
1
7.71; N, 5.81 %. H NMR (CDCl3) d: 0.99–1.02 (m, 8H,
NCHCH2CH2CH2CH2CHN), 1.59–1.61 and 1.84–1.88 (m,
8H, NCHCH2CH2CH2CH2CHN), 2.83–2.85 (m, 4H,
NCHCH2CH2CH2CH2CHN), 1.22 (d, 24H, J = 6.92 Hz,
CH2C6H4CH(CH3)2-p), 2.87–2.92 (m, 4H, CH2C6H4-
CH(CH3)2-p), 4.94, 5.03, 5.45 and 5.57 (d, 8H, J = 15.3 Hz,
CH2Ar), 7.01 and 7.52 (d, 16H, J = 8.1 Hz, Ar–H). 13C
NMR (CDCl3) d: 23.99 (NCHCH2CH2CH2CH2CHN), 28.12
(NCHCH2CH2CH2CH2CHN), 51.92 (NCHCH2CH2CH2-
CH2CHN), 23.97 (CH2C6H4CH(CH3)2-p), 33.73 (CH2C6-
H4CH(CH3)2-p), 66.27 (CH2Ar), 126.35, 128.54, 133.60 and
147.73 (Ar–C), 203.72 (Pd–C).
Results and discussion
Synthesis of the complexes
In general, silver(I) NHC complexes can be easily prepared
by deprotonation of two equivalents of azolium salt with
the mild base Ag2O [36]. This method is very useful
because the free carbene ligand, which is often hard to
handle, does not need to be isolated. Our previously
reported [37, 38] symmetrical 1,3-dialkylperhydrobenzi-
midazolium salts were synthesized in high yields from the
N,N0-dialkylcyclohexan-1,2-diamines, triethyl orthofor-
mate and ammonium chloride. The silver(I) NHC com-
plexes 2a–c were prepared by reaction of the 1,3-
dialkylperhydrobenzimidazolium salts as NHC ligand
precursors with Ag2O in dichloromethane at room tem-
perature in the dark (Scheme 1). The silver NHC com-
plexes 2a–c were obtained in high yields as white solids,
soluble in halogenated solvents. The formation of com-
plexes 2a–c was confirmed by the loss of the perhy-
drobenzimidazolium C2 proton resonance, observed at
10.74 ppm for 1a and 1b, 8.62 ppm for 1c in the 1H NMR
spectra. In the 13C NMR spectra of 1a, 1b and 1c, the C2
carbon is observed at 161.90, 162.02 and 162.28 ppm,
respectively; for complexes 2a–c, the equivalent reso-
nances for the carbene carbon were not detected, which has
Bis[1,3-di(4-tert-butylbenzyl)perhydrobenzimidazol-2-
ylidene]dichloropalladium(II) 3b. Yield: 0.33 g, 89 %,
en: 297–298 °C. IR: m(NCN) = 1514 cm-1. Anal. Calc. for
C58H82N4PdCl2: C, 68.84; H, 8.11; N, 5.53. Found: C,
68.90; H, 8.18; N, 5.59 %. 1H NMR (CDCl3) d: 0.99–1.15
(m, 8H, NCHCH2CH2CH2CH2CHN), 1.59–1.61 and 1.84–
1.87 (m, 8H, NCHCH2CH2CH2CH2CHN), 2.87–2.88 (m,
4H, NCHCH2CH2CH2CH2CHN), 1.27 (s, 36H, CH2C6-
H4C(CH3)3-p); 4.95, 4.99, 5.49 and 5.54 (d, 8H,
J = 15.3 Hz, CH2Ar); 7.26, 7.27, 7.50 and 7.54 (d, 16H,
J = 8.4 Hz, Ar–H). 13C NMR (CDCl3) d: 23.99
(NCHCH2CH2CH2CH2CHN), 28.12 (NCHCH2CH2CH2-
CH2CHN), 51.92 (NCHCH2CH2CH2CH2CHN), 31.39
(CH2C6H4C(CH3)3-p); 34.44 (CH2C6H4C(CH3)3-p);
66.41 (CH2Ar); 125.20, 128.16, 133.28 and 149.95 (Ar–
C), 203.79 (Pd–C).
Bis[1,3-di(2,4,6-trimethoxybenzyl)perhydrobenzimida-
zol-2-ylidene]dichloropalladium(II) 3c. Yield: 0.30 g,
70 %, en: 247–249 °C. IR: m(NCN) = 1498 cm-1. Anal.
Calc. for C54H74N4O12PdCl2: C, 56.49; H, 6.45; N, 4.88.
Found: C, 56.40; H, 6.49; N, 4.81 %. 1H NMR (CDCl3) d:
123

Transition Met Chem
Ar
Ar
Ar
Ag2O, CH2Cl2
RT, 24 h
[PdCl2(PhCN)2], CH2Cl2
RT, 24 h
N
N
+)
N
N
N
Cl-
PdCl2
AgCl
2
N
Ar
Ar
Ar
3a-c
1
2a-c
b
c
a
H3CO
H3CO
Ar:
OCH3
Scheme 1 Synthesis of the palladium(II) NHC complexes
Catalytic studies
also been mentioned in the literature and given as an
indicator of the fluxional behavior of such NHC complexes
[39]. The silver NHC complexes exhibit characteristic
t(C=N) bands, at 1663, 1645 and 1610 cm-1, for 2a, 2b
and 2c, respectively.
Use of benzimidazol-2-ylidene or imidazolin-2-ylidene
ligands in the palladium-catalyzed direct arylation of thi-
azoles, thiophenes and furans was originally reported by
Doucet et al. [31]. They found that the treatment of aryl
bromides with thiazoles, thiophenes or furans in the pres-
ence of 1 mol% of a Pd-NHC complex in N,N-dimethy-
lacetamide at 150 °C for 20 h under argon gave the
corresponding arylation products in moderate to good
yields. In this study, we performed catalytic experiments
under mild conditions including short reaction time, low
catalyst loading and relatively low temperature. Based on
previous results, in this study, we chose N,N-dimethylac-
etamide (DMAc) as the solvent and potassium acetate as
the base. The catalytic reactions were performed at 130 °C
for 1 h in the presence of complexes 3a–c. Under these
reaction conditions, 2-n-butylfuran, 2-n-butylthiophene and
2-n-propylthiazole were allowed to react with four aryl
bromides bearing electron-donating or electron-withdraw-
ing groups at the para position to furnish the arylated
products in moderate to good yields (Tables 1, 2, 3). In the
absence of palladium complex, the reactions of 4-bro-
moacetophenone with 2-n-butylfuran, 2-n-butylthiophene
or 2-n-propylthiazole resulted in only 1 % yields under
these reaction conditions. When aryl chlorides were used as
substrate, the reactivities dropped significantly and longer
reaction times were required to afford the arylated prod-
ucts. For example, 4-chloroacetophenone was coupled with
2-n-butylfuran in the presence of 3c to give 5-(4-acet-
ylphenyl)-2-n-butylfuran in 52 % yield at 130 °C after
Various synthetic methods for the synthesis of Pd(II)
NHC complexes have been described in the literature. One
of these is the generation of a silver(I) NHC complex,
followed by transfer of the carbene ligand to palladium.
This reaction has been successfully applied for a variety
of metals, including ruthenium, rhodium, iridium, gold
and nickel [40]. The palladium(II) NHC complexes 3a–c
were prepared in good yields by treatment of the corre-
sponding silver complexes with PdCl2(PhCN)2 in
dichloromethane at room temperature (Scheme 1). These
complexes are stable both in solution and in the solid state
against air, light and moisture and are soluble in chlori-
nated solvents. Suitable single crystals of these complexes
for X-ray diffraction studies could not be obtained. The
1
new complexes were therefore characterized by H NMR,
13C NMR, IR spectroscopy and elemental analysis, which
support the proposed structures. They show a character-
istic t(NCN) band at 1511, 1514 and 1498 cm-1 for 3a,
3b and 3c, respectively. NMR analyses of the complexes
showed that the N-heterocyclic carbene ligands had suc-
cessfully transferred from silver to palladium. The 13C
NMR spectra of the Pd complexes exhibited a singlet
assigned to the C2 carbon at 203.72, 203.79 and
200.53 ppm for 3a, 3b and 3c, respectively. This is con-
sistent with reported values for other [PdCl2(NHC)2]
complexes.
123

Transition Met Chem
Table 1 Direct C5 arylation of 2-n-propylthiazole using aryl bromides
N
N
Pd-NHC (0.005 mmol)
+
R
Br
R
nPr
nPr
DMAc (2 mL), KOAc (1 mmol), 1 h
S
S
Entry
R
Complex
Conv. (yield %)
1
MeC(O)–
MeO–
Me–
3a
3b
3c
3a
3b
3c
3a
3b
3c
3a
3b
3c
89(69)
87(66)
94(78)
98(80)
95(77)
99(84)
97(78)
92(73)
99(83)
94(74)
90(71)
97(76)
2
3
4
5
6
7
8
9
10
11
12
H–
Reaction conditions: 2-n-propylthiazole (2 mmol), aryl bromide (1 mmol), Pd-NHC (3a–c) (0.005 mmol), KOAc (1 mmol), N,N-dimethylac-
etamide (2 mL), 130 °C, 1 h. Product purity was checked by GC and NMR. Conversions were calculated based on aryl bromide
Table 2 Direct C5 arylation of 2-n-butylthiophene using aryl bromides
Pd-NHC (0.005 mmol)
+
R
Br
R
nBu
DMAc (2 mL), KOAc (1 mmol), 1 h
S
nBu
S
Entry
R
Complex
Conv. (yield %)
1
MeC(O)–
MeO–
Me–
3a
3b
3c
3a
3b
3c
3a
3b
3c
3a
3b
3c
89(66)
86(63)
92(72)
97(81)
94(76)
98(87)
98(82)
91(75)
96(80)
92(72)
89(70)
95(76)
2
3
4
5
6
7
8
9
10
11
12
H–
Reaction conditions: 2-n-butylthiophene (2 mmol), aryl bromide (1 mmol), Pd-NHC (3a–c) (0.005 mmol), KOAc (1 mmol), N,N-dimethylac-
etamide (2 mL), 130 °C, 1 h. Product purity was checked by GC and NMR. Conversions were calculated based on aryl bromide
20 h. The arylation reactions were regioselective, such that
in all cases, only the C5-arylated products were formed.
Initially, we investigated the reactions of 2-n-propylth-
iazole with 4-bromoacetophenone, 4-methoxybromoben-
zene, 4-methylbromobenzene and bromobenzene for the
direct C5 arylation reactions using complexes 3a–c as
catalysts. The arylation products were obtained in good
yields for all three catalysts (Table 1, entries 1–12). Aryl
bromides with an electron-donating group such as methoxy
or methyl on the aromatic ring reacted with 2-n-propylth-
iazole to give the coupled products in excellent yields
(Table 1, entries 4–9). However, aryl bromides without an
electron-donating group on the aromatic ring showed
slightly lower reactivities, as demonstrated in the arylation
123

Transition Met Chem
Table 3 Direct C5 arylation of 2-n-butylfuran using aryl bromides
Pd-NHC (0.005 mmol)
+
R
Br
R
nBu
DMAc (2 mL), KOAc (1 mmol), 1 h
nBu
O
O
Entry
R
Complex
Conv. (yield %)
1
MeC(O)–
MeO–
Me–
3a
3b
3c
3a
3b
3c
3a
3b
3c
3a
3b
3c
96(78)
93(76)
98(83)
93(74)
89(70)
96(78)
92(72)
87(66)
94(76)
93(72)
88(69)
95(78)
2
3
4
5
6
7
8
9
10
11
12
H–
Reaction conditions: 2-n-butylfuran (2 mmol), aryl bromide (1 mmol), Pd-NHC (3a–c) (0.005 mmol), KOAc (1 mmol), N,N-dimethylacetamide
(2 mL), 130 °C, 1 h. Product purity was checked by GC and NMR. Conversions were calculated based on aryl bromide
reactions using 4-bromoacetophenone and bromobenzene
(Table 1, entries 1–3 and 10–12). For all aryl bromides, the
best conversion (of 93–99 %) was achieved with complex
3c.
electron-deficient 4-bromoacetophenone (Table 3, entries
1–4) as compared to direct arylation of 2-n-propylthiazole
or 2-n-butylthiophene. Among the three complexes, com-
plex 3c bearing NHC ligands with methoxy substituents
exhibited better catalytic activity than the others.
Next, we examined the reactivity of 2-n-butylthiophene
using the same coupling partners under similar reaction
conditions (Table 2). As with 2-n-propylthiazole, aryl
bromides with an electron-donating group coupled with
2-n-butylthiophene to give the corresponding arylation
products in good yields (Table 2, entries 4–9). Thus, the
5-arylated thiophenes were obtained in high yields.
4-Bromoacetophenone was successfully coupled with 2-n-
butylthiophene using complexes 3a–c as catalysts to give
5-(4-acetylphenyl)-2-n-butylthiophene in 66–72 % yields.
High conversions for 2-n-butylthiophene were obtained
using the electron-rich 4-bromoanisole and 4-methylbro-
mobenzene in the presence of all three complexes (Table 2,
entries 5–8). The catalytic activities of complexes 3a–c in
these reactions were similar to those in the direct C5 ary-
lation of 2-n-propylthiazole.
Conclusion
In summary, silver(I) and palladium(II) NHC complexes
were successfully synthesized and characterized by
physicochemical and spectroscopic methods. The catalytic
activities of the palladium complexes were investigated in
direct C5 arylation of thiazole, thiophene and furan
derivatives in the presence of potassium acetate. All three
complexes demonstrated excellent catalytic activities in
these reactions. Furthermore, the catalyst loading and
reaction temperature were both lower, and the reaction
time shorter, compared to previous reports. It should be
noted that these arylation reactions are very selective, such
that in all cases, only the C5-arylated products were
formed; the 3- or 4-arylated products were not detected by
GC analysis of the reaction mixtures.
Finally, for the direct arylation reactions, in place of
2-n-propylthiazole or 2-n-butylthiophene, 2-n-butylfuran
was used. The reactions were performed with 4-substituted
aryl bromides at 130 °C for 1 h in DMAc to obtain 5-aryl-
2-n-butylfurans with the results summarized in Table 3.
Four aryl bromides were used successfully. Reactivities of
these aryl bromides using complexes 3a–c were also
examined for the direct arylation of 2-n-butylfuran. All of
the aryl bromides gave moderate to high yields of C5
arylation products in the presence of 0.5 mol% of catalyst.
High conversions for 2-n-butylfuran were obtained using
Acknowledgments We thank the Adıyaman University Research
Fund (FEFMAP/2015-0004) for financial support of this work.
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