Synthesis of N-heterocyclic carbene-PdCl-[(2-Pyridyl)alkyl carboxylate] complexes and their catalytic activities towards arylation of (benzo)oxazoles with aryl bromides

Article abstract of DOI:10.1016/j.jorganchem.2018.07.029

Four well-defined N-heterocyclic carbene-PdCl-[(2-Pyridyl)alkyl carboxylate] complexes have been conveniently synthesized through bridge-cleavage reactions of [Pd(μ-Cl)(Cl)(NHC)]₂ with (2-pyridyl)alkyl carboxylic acids [2-(pyridin-2-yl)acetic acid and 3-(pyridin-2-yl)propanoic acid]. The new complexes have been fully characterized by NMR, elemental analysis, HR-MS and X-ray single-crystal diffraction. The catalytic performance of the complexes was screened and the obtained palladium (II) complexes shown effective catalytic activities for direct arylation of (benzo)oxazoles with aryl bromides. Moreover, the 2-(pyridin-2-yl)acetate stabilized NHC–Pd complexes were more efficient than the 3-(pyridin-2-yl)propanoate stabilized NHC–Pd analogues. Further studies exhibited that 2-(pyridin-2-yl)acetate, as ancillary ligand, could easily decarboxylate and transform into 2-methylpyridine in the reaction condition.

Full text of DOI:10.1016/j.jorganchem.2018.07.029

Journal of Organometallic Chemistry 872 (2018) 24e30
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of N-heterocyclic carbene-PdCl-[(2-Pyridyl)alkyl
carboxylate] complexes and their catalytic activities towards
arylation of (benzo)oxazoles with aryl bromides
Wei Chen, Jin Yang*
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui, 235000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Four well-defined N-heterocyclic carbene-PdCl-[(2-Pyridyl)alkyl carboxylate] complexes have been
conveniently synthesized through bridge-cleavage reactions of [Pd(m-Cl)(Cl)(NHC)]2 with (2-pyridyl)
Received 25 May 2018
Received in revised form
11 July 2018
Accepted 25 July 2018
Available online 26 July 2018
alkyl carboxylic acids [2-(pyridin-2-yl)acetic acid and 3-(pyridin-2-yl)propanoic acid]. The new com-
plexes have been fully characterized by NMR, elemental analysis, HR-MS and X-ray single-crystal
diffraction. The catalytic performance of the complexes was screened and the obtained palladium (II)
complexes shown effective catalytic activities for direct arylation of (benzo)oxazoles with aryl bromides.
Moreover, the 2-(pyridin-2-yl)acetate stabilized NHCePd complexes were more efficient than the 3-
(pyridin-2-yl)propanoate stabilized NHCePd analogues. Further studies exhibited that 2-(pyridin-2-yl)
acetate, as ancillary ligand, could easily decarboxylate and transform into 2-methylpyridine in the re-
action condition.
Keywords:
N-Heterocyclic carbene palladium
complexes
(2-Pyridyl)alkyl carboxylic acids
Arylation of (benzo)oxazoles
© 2018 Published by Elsevier B.V.
1. Introduction
with transition metal ions. Recently, Jin and Lu have reported the
heteroleptic palladium (II) complexes containing both NHCs and 2-
Since Herrmann demonstrated that N-heterocyclc carbene
(NHC) palladium complexes possess high thermal stability and are
suitable for use in catalysis, considerable effort has been extended
to the synthesis of various NHC‒Pd complexes that lead to high
catalytic activities [1]. Thus NHCs have played an important role in
homogeneous catalysis and coordination chemistry, partially
replacing the well-known tertiary phosphine ligands [2]. Among
them, a particularly successful family of well-defined Pd(II) com-
plexes was reported by Organ: (NHC)PdCl2(3-chloropyridine), the
mixed coordination of NHCs with monodentate pyridyl ligand was
developed, which exhibited high catalytic activities and robust
ability [3]. Extensive studies suggest that the catalytic performance
of their complexes was affected greatly by the properties of the
NHCs, however, the coordination of the ancillary ligand also affects
the catalytic activities [4]. Therefore, modification of the pyridyl
moieties by other N-donors have emerged great interest in order to
increase the catalytic performance of the NHC‒Pd complexes [5]. In
the majority of coordination chemistry, the N-atoms of pyridines
and O-atoms of carboxylates were widely engage in coordination
pyridine carboxylate ligand, which shown high catalytic activities
for Buchwald-Hartwig amination [6]. It is well-known that the
catalytic activities of the well-defined NHCePd complexes mainly
depend on the balance of the ancillary ligand disassociating from
the [NHCePd0] complex and further re-coordinating to it in solu-
tion [4a,7]. The decreased strength of the PdeN bond could lead to
easier activation of the complex [4a,4d]. As a result, we envisioned
that by introducing of an electron-withdrawing group (COOꢀ) can
decrease the charge density of pyridine ring, furthermore, by
increasing the distance between the N-atom of pyridine and the O-
atom of carboxylate can adjust the coordination of the N,O-biden-
tate ligand. Thus the incorporation of the [N,O] chelate ligands into
the NHCePd(II) complex might fine tune the electronic and steric
properties of the coordination sphere of the NHC‒Pd complexes,
which facilitates ancillary ligand dissociation and recoordination in
the catalytic process, and accelerated formation of the active
[(NHC)Pd0] species. As part of our ongoing project aimed to explore
new types of well-defined NHC‒Pd complexes, herein, we intro-
duced the semi-rigid ligands [2-(pyridin-2-yl)acetate and 3-(pyr-
idin-2-yl)propanoate] into the coordination with NHC‒Pd
complexes and preliminarily examined their catalytic activities for
direct arylation of (benzo)oxazoles with aryl halides.
* Corresponding author. Tel.: þ86 561 380 2235; fax: þ86 561 380 2235.
E-mail address: yangjinlz@163.com (J. Yang).
https://doi.org/10.1016/j.jorganchem.2018.07.029
0022-328X/© 2018 Published by Elsevier B.V.

W. Chen, J. Yang / Journal of Organometallic Chemistry 872 (2018) 24e30
25
2. Experimental section
668.2241. Anal. Calc. for (SIPr)PdCl [2-(pyridin-2-yl)acetate]
(C34H44ClN3O2Pd): C, 61.08; H, 6.63; N, 6.28%. Found: C, 61.37; H,
6.97; N, 6.01%.
2.1. General remarks
All reactions were carried out under air atmosphere. Dimeric
2.3.3. (IPr)PdCl[(3-(pyridin-2-yl)propionate] (1c)
compounds [Pd(
m
-Cl)(Cl)(IPr)]2 and [Pd(
m
-Cl)(Cl)(SIPr)]2 [IPr ¼
The procedure yielded 232 mg (85%) of the pure product 1c as a
N,N0-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene; SIPr ¼ N,N0-
bis-(2,6-diisopropylphenyl)imidazolidin-2-ylidene] were prepared
according to literature method [8]. NMR spectra were performed in
CDCl3 with tetramethylsilane (TMS) as an internal standard and
recorded on a Bruker Avance NMR spectrometer. High-resolution
mass spectra were recorded on Agilent 6550 iFunnel Q-TOF MS
System. The C, H, and N analyses were performed with a Vario El III
elementar.
yellow powder. 1H NMR (CDCl3, 500 MHz)
d
(ppm) ¼ 8.15 (d,
J ¼ 5.5 Hz, 1H, o-CH-pyridyl), 7.57 (m, 2H, m-CH-pyridyl), 7.50 (t,
J ¼ 7.5 Hz, 1H, p-CH-pyridyl), 7.43 (d, J ¼ 8.0 Hz, 4H, m-CH-aniline),
7.18 (s, 2H, NCH¼CHN), 6.98 (t, J ¼ 8.0 Hz, 2H, p-CH-aniline), 3.30 (s,
2H, CH2COOꢀ), 3.06 (br, 4H, CH(CH3)2), 2.08 (t, J ¼ 6.5 Hz, 2H,
CH2CH2COOꢀ), 1.46 (d, J ¼ 6.5 Hz, 12H, CH(CH3)2), 1.13 (d, J ¼ 4.5 Hz,
12H, CH(CH3)2). 13Ce{1H} NMR (CDCl3, 125 MHz)
d
(ppm) ¼ 176.7
(COOꢀ), 161.6, 156.1 (Ccarbene), 151.0, 138.4, 134.9, 130.2, 124.6, 124.1,
124.0, 122.5, 107.9, 37.9 (CH2COOꢀ), 34.2 (CH2CH2COOꢀ), 28.8
(CH(CH3)2), 26.4 (CH(CH3)2), 22.9 (CH(CH3)2). HR-MS (ESI): calcd
for C35H45ClN3O2Pd [M þ Hþ]þ 681.6340; found 681.6352. Anal.
Calc. for (IPr)PdCl [(3-(pyridin-2-yl)propionate] (C35H44ClN3O2Pd):
C, 61.76; H, 6.52; N, 6.17%. Found: C, 61.48; H, 6.24; N, 6.55%.
2.2. General procedure for preparation of (NHC)PdCl[(2-(pyridin-2-
yl)acetate] complexes 1a and 1b
In air,
a round bottom flask was charged with [Pd(m-
Cl)(Cl)(NHC)]2 (0.2 mmol, 225 mg), 2-pyridylacetic acid hydro-
chloride (0.4 mmol, 70 mg), KOtBu (1.0 mmol, 112 mg) and THF
(2.0 mL). After stirring for 6 h at room temperature, the mixture
was condensed under vacuum. The solid residue was filtered by
flash chromatography on short silica gel with CH2Cl2 and recrys-
tallized from n-hexane/CH2Cl2 to provide the desired products.
2.3.4. (SIPr)PdCl[(3-(pyridin-2-yl)propionate] (1d)
The procedure yielded 235 mg (86%) of the pure product 1d as a
yellow powder. 1H NMR (CDCl3, 500 MHz)
d
(ppm) ¼ 8.06 (d,
J ¼ 5.5 Hz, 1H, o-CH-pyridyl), 7.49e7.47 (m, 3H, m,p-CH-pyridyl),
7.37 (d, J ¼ 7.5 Hz, 4H, m-CH-aniline), 6.95 (t, J ¼ 7.5 Hz, 2H, p-CH-
aniline), 4.11 (d, J ¼ 9.0 Hz, 4H, NCH2CH2N), 3.51 (br, 2H, CH(CH3)2),
3.38 (br, 2H, CH(CH3)2), 3.14 (br, 2H, CH2CH2COOꢀ), 2.00 (t,
J ¼ 6.5 Hz, 2H, CH2COOꢀ), 1.52 (d, J ¼ 6.0 Hz, 12H, CH(CH3)2), 1.28 (d,
J ¼ 6.5 Hz, 6H, CH(CH3)2), 1.24 (d, J ¼ 6.5 Hz, 6H, CH(CH3)2). 13Ce
2.3. General procedure for preparation of (NHC)PdCl[(3-(pyridin-2-
yl)propionate] complexes 1c and 1d
The synthesis of 1c and 1d were performed following the same
procedure employed for the preparation of 1a and 1b, starting from
{1H} NMR (CDCl3, 125 MHz)
d
(ppm) ¼ 186.5 (Ccarbene), 176.9
(COOꢀ), 161.4, 150.9, 147.9, 147.7, 138.3, 135.0, 129.4, 124.5, 124.3,
123.9, 122.4, 53.5 (NCH2CH2N), 34.0 (CH2COOꢀ), 28.8 (CH(CH3)2),
27.0 (CH2CH2COOꢀ), 26.9 (CH(CH3)2), 23.7 (CH(CH3)2), 23.4
(CH(CH3)2). HR-MS (ESI): calcd for C35H47ClN3O2Pd [M þ Hþ]þ
682.2392; found 682.2407. Anal. Calc. for (SIPr)PdCl [(3-(pyridin-2-
yl)propionate] (C35H46ClN3O2Pd): C, 61.58; H, 6.79; N, 6.16%. Found:
C, 61.35; H, 6.52; N, 6.43%.
[Pd(m-Cl)(Cl)(NHC)]2 (0.2 mmol, 225 mg), 3-(2-pyridyl)propionic
acid (0.4 mmol, 61 mg), KOtBu (0.5 mmol, 56 mg) and THF (2.0 mL)
to give the desired products.
2.3.1. (IPr)PdCl[(2-(pyridin-2-yl)acetate] (1a)
The procedure yielded 242 mg (91%) of the product 1a as a
yellow powder. 1H NMR (CDCl3, 500 MHz)
d
(ppm) ¼ 8.44 (dd,
J ¼ 5.5 and 1.0 Hz, 1H, o-CH-pyridyl), 7.54e7.51 (m, 3H, m,p-CH-
pyridyl), 7.39 (d, J ¼ 7.5 Hz, 4H, m-CH-aniline), 7.17 (s, 2H,
NCH¼CHN), 7.05 (t, J ¼ 7.5 Hz, 1H, p-CH-aniline), 7.03 (t, J ¼ 7.5 Hz,
1H, p-CH-aniline), 3.49 (s, 2H, CH2COOꢀ), 3.00 (br, 4H, CH(CH3)2),
1.46 (d, J ¼ 6.5 Hz,12H, CH(CH3)2),1.13 (br, 12H, CH(CH3)2). 13Ce{1H}
2.4. General procedure for the arylation of (benzo)oxazoles with
aryl bromides
The direct arylation reactions were carried out under aerobic
conditions. In the parallel reaction, aryl bromide (0.5 mmol),
(benzo)oxazoles (0.75 mmol), LiOtBu (1.0 mmol) and the NHC-
PdCl-[(2-pyridyl)alkyl carboxylate] complex (1% mol) and DMF
(2.0 mL) were introduced in a reaction tube. The reaction mixture
was stirred for 12 h at 130 ꢁC. After completion of the reaction, the
reaction mixture was cooled to room temperature and then evap-
orated under vacuum. The residue was subjected to purification via
column chromatography with petroleum ethereEtOAc (20:1) as
eluent to give the products.
NMR (CDCl3, 125 MHz)
d
(ppm) ¼ 171.9 (COOꢀ), 156.4, 156.3 (Ccar-
bene), 150.8, 146.6, 138.6, 134.6, 130.3, 124.8, 124.2, 124.1, 122.4, 49.7
(CH2COOꢀ), 28.7 (CH(CH3)2), 26.3 (CH(CH3)2). HR-MS (ESI): calcd
for C34H43ClN3O2Pd [M þ Hþ]þ 666.2079; found 666.2098. Anal.
Calc. for (IPr)PdCl [2-(pyridin-2-yl)acetate] (C34H42ClN3O2Pd): C,
61.26; H, 6.35; N, 6.30%. Found: C, 61.55; H, 6.15; N, 6.17%.
2.3.2. (SIPr)PdCl[(2-(pyridin-2-yl)acetate] (1b)
The procedure yielded 245 mg (92%) of the pure product 1b as a
yellow powder. 1H NMR (CDCl3, 500 MHz)
d
(ppm) ¼ 8.37 (d,
J ¼ 5.5 Hz, 1H, o-CH-pyridyl), 7.53 (t, J ¼ 7.5 Hz, 2H, p-CH-pyridyl),
7.47e7.44 (m, 2H, m-CH-pyridyl), 7.34 (d, J ¼ 7.5 Hz, 4H, m-CH-an-
iline), 7.02 (t, J ¼ 7.5 Hz, 2H, p-CH-aniline), 4.13 (d, J ¼ 6.5 Hz, 2H,
NCH2CH2N), 4.08 (d, J ¼ 6.0 Hz, 2H, NCH2CH2N), 3.57 (sept,
J ¼ 6.5 Hz, 2H, CH(CH3)2), 3.29 (sept, J ¼ 6.5 Hz, 2H, CH(CH3)2), 3.24
(s, 2H, CH2COOꢀ),1.52 (br, 12H, CH(CH3)2), 1.29 (d, J ¼ 6.5 Hz, 6H,
CH(CH3)2), 1.24 (d, J ¼ 6.0 Hz, 6H, CH(CH3)2). 13Ce{1H} NMR (CDCl3,
2.5. General procedure for preparation of (NHC)PdCl2[(2-
methylpyridine] complexes 2a and 2b
In air,
a round bottom flask was charged with [Pd(m-
Cl)(Cl)(NHC)]2 (0.2 mmol, 225 mg), 2-pyridylacetic acid hydro-
chloride (0.4 mmol, 70 mg), K2CO3 (1.0 mmol, 138 mg) and THF
(2.0 mL). The reaction mixture was stirred for 6 h at 70 ꢁC. After
completion of the reaction, the reaction mixture was cooled to
room temperature and then evaporated under vacuum. The solid
residue was filtered by flash chromatography on short silica gel
with CH2Cl2 and recrystallized from n-hexane/CH2Cl2 to provide
the desired products.
125 MHz)
d
(ppm) ¼ 187.1 (Ccarbene), 171.9 (COOꢀ), 156.3, 150.8,
147.8, 147.7, 138.6, 134.8, 129.5, 124.6, 124.4, 124.2, 122.3, 53.6
(NCH2CH2N), 49.2 (CH2COOꢀ), 28.9 (CH(CH3)2), 28.8 (CH(CH3)2),
26.9 (CH(CH3)2), 26.8 (CH(CH3)2), 24.1 (CH(CH3)2), 23.3 (CH(CH3)2).
HR-MS (ESI): calcd for C34H45ClN3O2Pd [M þ Hþ]þ 668.2235; found

26
W. Chen, J. Yang / Journal of Organometallic Chemistry 872 (2018) 24e30
12H, CH(CH3)2), 1.25 (d, J ¼ 6.8 Hz, 12H, CH(CH3)2). 13Ce{1H} NMR
(CDCl3, 100 MHz)
d
(ppm) ¼ 188.3 (Ccarbene), 159.4, 150.3, 148.2,
136.8, 129.3, 125.2, 124.5, 124.2, 121.4, 53.7 (NCH2CH2N), 28.8
(CH(CH3)2), 27.0 (CH(CH3)2), 24.7 (CH3-Pyridine), 23.8 (CH(CH3)2).
HR-MS (ESI): calcd for C33H45Cl2N3Pd [M þ Hþ]þ 659.2025; found
659.2041.
Anal.
Calc.
for
(SIPr)PdCl2(2-methylpyridine)
(C33H44Cl2N3Pd): C, 59.96; H, 6.86; N, 6.36%. Found: C, 60.21; H,
7.04; N, 6.19%.
2.6. X-ray crystallography
Scheme 1. Synthesis route for the well-defined NHC‒Pd complexes 1a‒1d: [Pd(m-
Cl)(Cl)(NHC)]2, (2-Pyridyl)alkyl carboxylic acid, KOtBu, THF, r.t., 6 h.
Data collection was performed on a Bruker-AXS SMART CMOS
area detector diffractometer at 296 K using
u rotation scans with a
scan width of 0.5ꢁ and Mo-K
a
radiation (
l
¼ 0.71073 Å). Multi-scan
2.5.1. (IPr)PdCl2(2-methylpyridine) (2a)
The procedure yielded 221 mg (84%) of the pure product 2a as a
corrections were applied using SADABS [9]. Structure solutions and
refinements were performed with the SHELX-2014 package [10]. All
non-hydrogen atoms were refined anisotropically by full-matrix
least-squares on F2. The hydrogen atoms to carbon were included
in idealized geometric positions with thermal parameters equiva-
lent to 1.2 times those of carbon atoms. CCDC 1841674‒1841679
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/
structures/.
yellow powder. 1H NMR (CDCl3, 400 MHz)
d
(ppm) ¼ 8.22 (d,
J ¼ 5.2 Hz, 1H, CH-pyridyl), 7.53 (t, J ¼ 7.6 Hz, 2H, p-CH-aniline),
7.40e7.38 (m, 5H), 7.15 (s, 2H, NCH¼CHN), 6.96e6.91 (m, 2H), 3.19
(br, 4H, CH(CH3)2), 2.55 (s, 3H, CH3-Pyridine), 1.46 (d, J ¼ 4.8 Hz,
12H, CH(CH3)2), 1.11 (d, J ¼ 6.4 Hz, 12H, CH(CH3)2). 13Ce{1H} NMR
(CDCl3, 100 MHz)
d
(ppm) ¼ 159.4 (Ccarbene), 157.3, 150.4, 147.0,
136.8, 130.1, 125.3, 124.8, 124.0, 123.8, 121.4, 28.8 (CH(CH3)2), 26.4
(CH(CH3)2), 25.0 (CH3-Pyridine), 22.9 (CH(CH3)2). HR-MS (ESI):
calcd for C33H44Cl2N3Pd [M þ Hþ]þ 658.1947; found 658.1959. Anal.
Calc. for (IPr)PdCl2(2-methylpyridine) (C33H44Cl2N3Pd): C, 60.14; H,
6.58; N, 6.38%. Found: C, 60.43; H, 6.87; N, 6.21%.
3. Results and discussion
2.5.2. (SIPr)PdCl2(2-methylpyridine) (2b)
3.1. Synthesis and characterization of the complexes
The procedure yielded 212 mg (80%) of the pure product 2b as a
yellow powder. 1H NMR (CDCl3, 400 MHz)
d
(ppm) ¼ 8.13 (d,
As shown in Scheme 1, reactions of [Pd(m-Cl)(Cl)(NHC)]2 with
J ¼ 4.8 Hz, 1H, CH-pyridyl), 7.46 (t, J ¼ 7.6 Hz, 2H, p-CH-aniline),
7.36e7.38 (m, 5H), 6.92e6.87 (m, 2H), 4.12 (s, 4H, NCH2CH2N), 3.61
(sept, J ¼ 6.8 Hz, 4H, CH(CH3)2), 2.40 (s, 3H, CH3-Pyridine), 1.53 (br
(2-pyridyl)alkyl carboxylic acids in the presence of KOtBu in THF at
room temperature afforded the (NHC)PdCl[(2-pyridyl)alkyl
carboxylate] complexes 1a‒1d in good yields. The compounds were
Fig. 1. ORTEP diagrams of complexes 1a‒1d with thermal displacement parameters drawn at 30% probability. Parts of the hydrogen atoms and solvent molecules have been omitted
for clarity.

W. Chen, J. Yang / Journal of Organometallic Chemistry 872 (2018) 24e30
27
Table 1
Selected bond lengths [Å] and angles [o] for complexes 1aꢀ1d.
1a
1b
1c
1d
Pd1eC1
Pd1eN3
Pd1eO1
Pd1eCl1
C1ePd1eO1
O1ePd1eN3
C1ePd1eCl1
N3ePd3eCl1
PdCONCl/carbene dihedral angle
1.968(5)
1.940(4)
2.062(4)
2.022(3)
2.2633(15)
89.94(14)
88.82(14)
89.11(12)
92.39(11)
68.35
1.965(4)
2.079(4)
2.017(3)
2.2615(14)
89.84(15)
91.94(13)
88.49(12)
90.19(11)
67.44
1.975(5)
2.098(4)
2.047(4)
2.2821(18)
89.91(19)
91.64(17)
88.74(15)
90.22(13)
69.67
2.094(4)
2.034(3)
2.2714(16)
91.27(16)
87.82(16)
87.87(14)
92.96(14)
79.76
fully characterized by 1H, 13C NMR, HR-MS and elemental analysis.
The 1H NMR spectra of complexes 1a‒1d in CDCl3 reveals the
complete disappearance of the proton signals of carboxylic acids
and the stoichiometric proton signals of NHCs with (2-pyridyl)alkyl
carboxylates. In addition, the 13C NMR spectra revealed the
appearance of diagnostic carbene carbon peaks (156.3 and
156.1 ppm for IPr-bearing complexes 1a and 1c; 187.1 and
186.5 ppm for SIPr-bearing complexes 1b and 1d) and the carbonyl
carbon peaks at a range of 171.9e176.9 ppm. All of the complexes
were further characterized by high-resolution mass spectrometry.
Furthermore, the crystals of complexes 1a‒1d, which were
grown in the mixture of dichloromethane and n-hexane, have been
subjected to single crystal X-ray diffraction to determine the crystal
structures. The solid-state molecular structures of the complexes
are depicted in Fig. 1 and selected bond lengths and angles are
listed in Table 1. As commonly observed for Pd(II)-complexes, all
NHC-PdCl-[(2-pyridyl)alkyl carboxylate] complexes feature slightly
distorted square-planar Pd centers and the adjacent bite angles
around the Pd centers are close to 90ꢁ. The coordination spheres
contain the NHCs, the bidentate N,O-donors of (2-pyridyl)alkyl
found in natural products, bioactive compounds and pharmaceu-
ticals [11]. There is a considerable attention in the development of
practical methods for the construction of these compounds [12].
Recently the transition metal-catalyzed direct CꢀH bond arylation
of (benzo)oxazoles with aryl halides emerged as a straight forward
approach for the synthesis of these compounds [13]. In most cases,
excessive tertiary phosphine ligands with the Pd‒complexes were
used as efficient catalysts for the reaction. Due to the stronger s-
donor electronic ability and fine-tuning steric, NHCs were consid-
ered as simple phosphane mimics in organometallic chemistry.
However, so far, only a few examples of well-defined NHC‒Pd
complexes catalyzed arylation of (benzo)oxazoles using aryl halides
have been described [14]. With the isolation and characterization of
this series of (NHC)PdCl [(2-pyridyl)alkyl carboxylate] complexes,
we were able to test and compare their catalytic activities in the
arylation of (benzo)oxazoles with aryl halides. As an initial exper-
iment, a model reaction of benzoxazole with 4-bromoanisole was
tested in the presence of 1.0 mol % of complex 1a as precatalyst and
2 equiv of K2CO3 as base in N,N-dimethylformamide (DMF) at
130 ꢁC for 24 h, to our delight, the arylation product, 2-(4-
methoxyphenyl)benzoxazole was isolated in 47% yield (Table 2,
entry 1). This preliminary result encouraged us to further optimize
the reaction conditions. In most cases, C‒H activation of azoles was
carboxylates and the respective chlorides. The neutral s-donating
pyridine nitrogen atom is located trans to NHCs, while the
carboxylate oxygen is situated cis to NHCs and in a direction
opposite to the chloride. In order to satisfy the square-planar ge-
ometry of the central planes around the Pd centers, the (2-pyridyl)
alkyl carboxylates are twisted and the six or seven-membered
chelate ring are non-coplanar and show the bent geometry. The
slightly distorted square-planar coordination planes of the Pd
centers are approximately perpendicular to the carbene ring planes
with the dihedral angles are 79.76, 68.35, 67.44 and 69.67ꢁ,
respectively. The Pd‒C bond distances in IPr-bearing complexes
(1.968(5) Å for 1a and 1.965(4) Å for 1c) are similar with the
analogous distances in their corresponding SIPr-bearing analogues
(1.940(4) Å for 1b and 1.975 (5) Å for 1d). Generally, the Pd‒C bonds
distances indicated the single bond character, which is in good
Table 2
Influence of the reaction conditions for complex 1a catalyzed arylation of benzox-
azole with 4-bromoanisolea.
Entry
[Pd] [%]
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (1.0%)
1a (0.5%)
DMF
DMF
DMF
DMF
CH3CN
DMF
DMF
DMF
DMF
DMF
DMAc
NMP
1,4-dioxane
toluene
DMF
DMF
DMF
DMF
K2CO3
LiOtBu
NaOtBu
KOtBu
LiOMe
NaOMe
KOMe
NaOH
KOH
Cs2CO3
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
47
92
84
77
70
75
75
60
65
55
88
85
75
65
50
91
72
65
accordance with their
s-donor properties. Among the obtained
complexes, complex 1d has the slightly longer distances of Pd‒C
[1.975 (5) Å], Pd‒N [2.098 (4) Å], and Pd‒O [2.047 (4) Å] bonds, as
well as the Pd‒Cl bond [2.2821(18) Å] and were similar with those
found in (IPr)PdCl(pyridine-2-carboxylate) [6]. The Pd‒C bond
distances were between the obtained complexes [1.940(4)‒
1.975(5) Å)] and the Pd-PEPPSI-(NHC) complexes (1.969(3) Å for
{(IPr)PdCl2(3-chloropyridine) [3a], 1.990 (3) Å for (SIPr)PdCl2(3-
chloropyridine) [4a]} have no evident differences. However, due
to the chelation of the bidentate N,O-donors and trans arrangement
of the N-donors and the NHCs, the Pd‒N bond distances [2.062(4)‒
2.098(4) Å)] are significantly shorter than the Pd-PEPPSI-(NHC)
complexes.
9
10
11
12
13
14
15c
16d
17e
18d
a
Reaction conditions: benzoxazole (0.75 mmol), 4-bromoanisole (0.50 mmol),
NHC‒Pd 1a (1.0% mol), base (1.0 mmol), solvent (2.0 mL) at 130 ꢁC for 24 h.
b
Isolated yield.
3.2. Direct arylation of (benzo)oxazoles with aryl halides
c
The reaction was performed at 100 ꢁC for 24 h.
d
The reaction was performed at 130 ꢁC for 12 h.
e
Arylated (benzo)oxazoles are important structural scaffolds
The reaction was performed at 130 ꢁC for 6 h.

28
W. Chen, J. Yang / Journal of Organometallic Chemistry 872 (2018) 24e30
carried out in the presence of strong bases. Herein, the high yields
were obtained when LiOtBu was used as the base instead of K2CO3
(Table 2, entry 2). In addition, the replacement of LiOtBu by two
alternative bases (NaOtBu and KOtBu) was also gave high yields but
less effective than LiOtBu (Table 2, entries 3‒4). Other inorganic
bases, such as LiOMe, NaOMe, KOMe, NaOH, KOH and Cs2CO3 were
also examined for the reaction, and all proved to be inferior as
bases, affording the product in low yields (Table 2, entries 5‒10).
Further screening of solvents revealed that DMF was the optimal
solvent. Other polar solvent, such as N,N-dimethylacetamide
(DMAc), N-methyl pyrrolidone (NMP), 1,4-dioxane and toluene,
were less effective than that of DMF (Table 2, entries 11‒14). In this
solvent, decreasing the reaction temperature from 130 ꢁC to 100 ꢁC
had detrimental effect on the yield (Table 2, entry 15). Furthermore,
when the reaction time was reduced from 24 h to 12 h, no notice-
able effect on the yield was observed, but when the reaction time
was reduced to 6 h, the yield dropped significantly (Table 2, entries
16‒17). The loading of the precatalyst was also examined, in the
presence of 1 mol% of 1a as precatalyst, LiOtBu as base, DMF as
solvent at 130 ꢁC for 12 h, the arylated benzoxazoles was obtained
in 91% isolated yield, but when the precatalyst loading was reduced
from 1 mol% to 0.5 mol%, the yield decreased to 65% (Table 2, entry
18). Finally, the best result was obtained when the reaction was
carried out in DMF in the presence of LiOtBu at 130 ꢁC for 12 h with
the precatalyst loading of 1.0% mol.
After the optimization of the reaction conditions, arylation of
(benzo)oxazoles with a variety of aryl bromides catalyzed by
complexes 1a‒1d under the optimum reaction condition were
carried out and the results are given in Scheme 2. Firstly, several
substituted aryl bromides were applied to the arylation reactions
with benzoxazole. As shown in Scheme 2, most of the aryl bro-
mides, both with electron-donating substituents, such as 2-Me, 3-
Me, 4-Me, 4-OMe and 4-OEt groups, and with electron-
withdrawing group, such as 4-F group, on the benzene rings,
could react smoothly with benzoxazole to give the corresponding
products in good yields. Notably, simple benzoxazoles with various
substituents on the heterocyclic (5-F, 6-Me and 4-Me groups) were
also employed for the reaction with aryl bromide under the opti-
mized reaction condition. The results indicated that the reaction
proceeded smoothly and were tolerated a number of substituted
groups. The corresponding 2-aryl substituted benzoxazoles were
obtained in good yields. Moreover, the reactions of 4-bromotoluene
and 4-bromoanisole with ethyl oxazole-4-carboxylate were highly
efficient to generate the corresponding products in high yields,
respectively. The reaction showed a good tolerance of different
groups on the aromatic ring. However, both complexes gave poor
Scheme 2. Arylation of (benzo)oxazoles with aryl bromides catalyzed by the (NHC)-PdCl-[(2-Pyridyl)alkyl carboxylate] complexes 1a‒1da.
a
Reaction conditions: (benzo)oxazoles (0.75 mmol), aryl bromide (0.50 mmol), LiOtBu (1.0 mmol), NHC‒Pd complex (1.0% mol) in DMF (2.0 mL) at 130 ꢁC for 12 h.

W. Chen, J. Yang / Journal of Organometallic Chemistry 872 (2018) 24e30
29
transformed into the Pd-PEPPSI precatalyst (NHC)PdCl2(2-
methylpyridine) under the reaction condition. Due to its easier
dissociation from the Pd-centre thus forming the active [(NHC)Pd0]
species or higher tendency to recoordinate to the [(NHC)Pd0] spe-
cies, the monodentate 2-methylpyridine stabilized NHC‒Pd com-
plexes exhibited more active than 3-(pyridin-2-yl)propanoate
stabilized NHC‒Pd analogues. In order to obtain more information
and to explain the influence factor for the higher catalytic activities
of complexes 1a and 1b, we tried to identify the catalytically active
species present in solution. Unfortunately, we have not separated
the [(NHC)Pd0] intermediate product. In another way, we found
that treatment of 2-(pyridin-2-yl)acetic acid hydrochloride with
Scheme 3. Synthesis route for the well-defined NHC‒Pd complexes 2a and 2b: [Pd(
Cl)(Cl)(NHC)]2, 2-pyridylacetic acid hydrochloride, K2CO3, THF, reflux, 6 h.
m-
yields in reactions with aryl chlorides as substrates. For example,
under the same catalytic condition, complexes 1a‒1d afford only
27e38% yields for the reaction between 4-chloroanisole and ben-
zoxazole. In this regard, complexes 1a‒1d are inferior to the well-
defined (IPr)PdCl2(1-methylimidazole) complex, which is more
effective with aryl chlorides [14c].
dimeric compounds [Pd(m-Cl)(Cl)(NHC)]2 in THF under reflux with
K2CO3 as the base led to the (NHC)PdCl2(2-methylpyridine) com-
plexes, which confirmed our conjecture. As shown in Scheme 3, the
reaction of 2-(pyridin-2-yl)acetic acid hydrochloride with 0.5
equivalent of [Pd(m
-Cl)(Cl)(IPr)]2 in THF at 60 ꢁC generated the (IPr)
PdCl2(2-methylpyridine) in 84% yield. The structures of the com-
plexes were unequivocally established by the X-ray single-crystal
analysis of the crystals (Fig. 2).
As seen in Scheme 2, complexes 1a‒1d were effective in the
arylation of (benzo)oxazoles with aryl bromides and the IPr-
bearing complexes showed the slightly higher catalytic activities
than their SIPr-bearing analogues. Although the superior reactivity
of SIPr-bearing complexes compared to IPr-bearing analogues has
been previously reported for the coupling reactions using the well-
defined NHC‒Pd complexes [15], however, this is in contrast to the
general trends found in our work. We cannot attribute the reac-
tivity differences to disparities in the electronic and steric proper-
ties of the ligands, which have been proven to be very similar [16].
With the results in hand, we believe that in our system, due to the
[N, O] bidentate-chelating coordination of the (2-pyridyl)alkyl
carboxylate, the unsaturated IPr‒Pd complexes may be favourable
when generating the IPr‒Pd0 active catalyst species [6a]. Further-
more, the [2-(pyridin-2-yl)acetate complexes 1a and 1b are more
active than the 3-(pyridin-2-yl)propanoate stabilized NHC‒Pd an-
alogues 1c and 1d. According to the previous reports for the well-
defined NHC‒Pd complexes, higher catalytic activities of 1a and
1b appear to be due to an easier departure of the “throw-away”
ligand to form the active [(NHC)Pd0] species or a higher tendency of
the “throw-away” ligand to recoordinate to [(NHC)Pd0] during the
activation process [4a,4d]. The coordination and dissociation ability
of the ancillary ligand is significantly influence the catalytic activ-
ities. Herein, in our system, the ancillary ligands 2-(pyridin-2-yl)
acetate and 3-(pyridin-2-yl)propanoate have the similar structure
and coordination mode (N,O-bidentate chelate ligands). Never-
theless, the decarboxylation of the 2-(pyridin-2-yl)acetate into 2-
methylpyridine is easily taken place in the solvent under reflux.
Therefore, the complexes 1a and 1b possibly have been
Moreover, to further examine the structureeactivity relation-
ship, we have selected complexes 1a‒1d and 2a, 2b as models for
time-conversion study (Fig. 3). The reaction of benzoxazole with 4-
bromoanisole were performed in the presence of 1 mol% of the
complex as precatalyst, LiOtBu as base, DMF as solvent at 130 ꢁC for
12 h and the yields were monitored by GC (with dodecane used as
an internal standard). In these conditions, complexes 1a and 1b
show a similar level of catalytic activity compared with 2a and 2b,
but a slightly higher activity in comparison with 1c and 1d. These
results hinted that the well-defined (NHC)PdCl2(2-methylpyridine)
complexes should be the precatalysts in the reaction. In addition, as
ancillary ligands, the coordination modes significantly influenced
the catalytic activities of the well-defined NHC‒Pd complexes.
4. Conclusions
In conclusion, a series of heteroleptic palladium complexes
containing both NHCs and (2-pyridyl)alkyl carboxylates [2-(pyr-
idin-2-yl)acetate and 3-(pyridin-2-yl)propanoate] were synthe-
sized and fully characterized. The catalytic behaviours of the
complexes was investigated in direct arylation of (benzo)oxazoles
with aryl bromides. The [NHC)PdCl(2-pyridyl)alkyl carboxylate]
complexes were found to be suitable catalysts for arylation of
(benzo)oxazoles with aryl bromides. Further studies exhibited that
2-(pyridin-2-yl)acetate stabilized NHC-Pd complexes exhibited
more active than 3-(pyridin-2-yl)propanoate stabilized NHC-Pd
Fig. 2. ORTEP diagrams of 2a and 2b with thermal displacement parameters drawn at 30% probability. Parts of the hydrogen atoms have been omitted for clarity.

30
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