Synthesis of novel pillar[5]arene-based N-heterocyclic carbene ligands for Pd-catalysed Heck reactions

Article abstract of DOI:10.1016/j.tetlet.2016.06.083

Pillar[5]arene-based 1-benzylimidazole and 1-(9-anthracenylmethyl)imidazole salts were prepared for the first time as novel class supramolecular NHC ligands. These ligands, together with PdCl₂(CH₃CN)₂, were used as catalysts in the Heck coupling reactions of styrene and aryl halide derivatives. The 1-(9-anthracenylmethyl)imidazole salt exhibited better catalytic activity than the 1-benzylimidazole salt, owing to the steric bulk of the ligand. The novel pillar[5]arene-based imidazolium salt is a promising supramolecular skeleton for the construction of highly active catalysts.

Full text of DOI:10.1016/j.tetlet.2016.06.083

Tetrahedron Letters 57 (2016) 3385–3388
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of novel pillar[5]arene-based N-heterocyclic carbene
ligands for Pd-catalysed Heck reactions
⇑
Xue-Dong Xiao, Ya-Li Bai, Jia-Qi Liu, Jun-Wen Wang
Department of Chemistry, Shanxi Normal University, Linfen 041004, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Pillar[5]arene-based 1-benzylimidazole and 1-(9-anthracenylmethyl)imidazole salts were prepared for
the first time as novel class supramolecular NHC ligands. These ligands, together with PdCl2(CH3CN)2,
were used as catalysts in the Heck coupling reactions of styrene and aryl halide derivatives. The 1-(9-
anthracenylmethyl)imidazole salt exhibited better catalytic activity than the 1-benzylimidazole salt,
owing to the steric bulk of the ligand. The novel pillar[5]arene-based imidazolium salt is a promising
supramolecular skeleton for the construction of highly active catalysts.
Received 24 March 2016
Revised 16 June 2016
Accepted 20 June 2016
Available online 21 June 2016
Keywords:
Ó 2016 Elsevier Ltd. All rights reserved.
Pillar[5]arene
N-Heterocyclic carbene
Heck reaction
Catalyst
Introduction
we have found that pillar[5]arene-based imidazolium salts, being
N-heterocyclic carbene precursors, are promising organocatalysts.
The Heck reaction, or palladium-catalysed arylation of olefins,
has attracted increasing attention in the past decade and has
become one of the most important selective C–C bond forming
methods.1–6 In recent years, N-heterocyclic carbenes (NHCs) have
started to play a more important role than phosphine ligands in
organometallic chemistry,7–13 being easily modifiable and exhibit-
ing outstanding catalytic performance in a variety of reactions.14–16
Pillar[n]arenes, first reported by Tomoki Ogoshi in 2008,17 are a
new class of macrocyclic hosts, which not only show unique sym-
metrical pillar-shaped architectures, but also exhibit other
supramolecular macrocyclic host compounds excellent proper-
ties.18–21 Just a few years after their discovery, pillar[n]arenes have
already been widely used in molecular recognition,22 self-assem-
bly,23 preparation of liquid crystals24 and other fields. With the
development of organometallic chemistry, many supramolecular
organometallic complexes, such as metallacrown ethers (Fig. 1A),25
metallacalixarenes (Fig. 1B)26 and metalloporphyrins (Fig. 1C)27
have been successfully obtained by coordination of transition met-
als to the supramolecular skeleton. These metal-containing macro-
cycles are widely applicable in the area of catalysis. Despite their
widespread applications in supramolecular chemistry, the utiliza-
tion of pillararenes in catalytic processes just begun.28 As part of
our current research on supramolecular N-heterocyclic carbenes,
Results and discussion
In this work, we prepared two novel pillar[5]arene-NHC
ligands: 1-benzylimidazole hexafluorophosphate (ligand 3a) and
1-(9-anthracenylmethyl)imidazole hexafluorophosphate (ligand
3b) according to previously reported procedures.29,30 The synthesis
of NHC ligands is outlined in Scheme 1. Bromoethoxy pillar[5]
arene 2 was prepared by stirring a mixture of 1,4-bis(2-bro-
moethoxy)benzene 1, BF3ÁEt2O, and paraformaldehyde in dry CH2-
Cl2 for 150 min under N2 atmosphere. Ligand 3b was prepared by
refluxing 2 with excess 1-(9-anthracenylmethyl)imidazole in 1,4-
dioxane, followed by anion exchange with PFÀ6 .31,32 Moreover, since
the melting point of 1-benzylimidazole is relatively low, a solvent-
free method was used to obtain high-purity 3a. Compound 2 and
excess 1-benzylimidazole were stirred at 150 °C in the absence of
solvent, yielding 3a after anion exchange with PFÀ6 . The pillar[5]
arene-NHC ligands were characterized by 1H NMR, 13C NMR, and
IR spectroscopy. In the 1H NMR spectra, the appearance of the imi-
dazolium proton resonance at d 9.50 and 9.43 (NCHN) supports the
formation of the expected carbene precursors.
To evaluate the catalytic activity of novel pillar[5]arene-NHC
ligands, they were tested in the Heck cross-coupling of styrene
and aryl halide derivatives. We first chose ligand 3b and PdCl2
(CH3CN)2 as a catalytic system to determine optimum conditions,
including base, solvent, temperature, etc. Further investigations
showed that the model substrates (styrene and aryl halide)
⇑
Corresponding author.
E-mail address: wangjunwen2013@126.com (J.-W. Wang).
http://dx.doi.org/10.1016/j.tetlet.2016.06.083
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

3386
X.-D. Xiao et al. / Tetrahedron Letters 57 (2016) 3385–3388
tBu
tBu
tBu
But
O
O
O
O
R
N
R
N
O
O
O
O
O
O
N
O
N
N
O
O
3
3
porphyrin
O
N
3
3
-
4PF6
Me2
Me2
N
N
R
Cl
Pd
Cl
N
R
N
N
N
Pd
N
Pd
N
C
N
C
N
N
Me2
Me2
(B)
(A)
(C)
Figure 1. Structures of the complexes A, B and C.
R
N
Br
Br
N
R
O
O
N
N
O
H2
C
(HCHO)n, BF3 Et2O
CH2Cl2
H2
C
NH4PF6/CH3OH
5
O
O
5
O
-
10PF6
R
Br
Br
N
N
1
2
3
Yields䠖 3a 90%
R1=
R2=
3b 70%
Ligand 3a
Ligand 3b
Scheme 1. Preparations of ligand 3a and ligand 3b.
efficiently formed the trans-stilbene coupling product (4a), with the
results shown in Table 1.
improved (Table 1, entry 4), Therefore, KOH, an inorganic strong
base, was determined to be most suitable. Our re-optimization
efforts were then focused on testing different types of solvents,
Non-polar and polar protic solvents, afforded 4a in less than 40%
yield, whereas polar aprotic solvents (e.g., THF, DMF, or NMP) gave
relatively high conversions (Table 1, entries 5–10). After some
experimentation, we found NMP to be the best solvent for this
reaction (Table 1, entry 10). More screening conditions are listed
in the Supplementary data (Table S1).
Initially, among the several bases examined, a 30% yield of 4a
was obtained by using KOtBu and NEt3 in DMF at 120 °C for 5 h
(Table 1, entries 1, and 2). Subsequently, we turned our attention
to inorganic bases, known to be useful in Heck coupling.33 K2CO3
(120 °C, 5 h) gave a low yield (Table 1, entry 3). However, when
KOH was accidentally used as a base, the yield was significantly
With the optimized reaction conditions in hand, we set out to
explore the substrate scope. A wide range of aryl halide derivatives
were coupled with two different styrenes (R2 = H, OMe), ligand 3b
and PdCl2(CH3CN)2 as a catalytic system. The results are summa-
rized in Table 2.
Table 1
Optimization of reaction conditionsa
1.3 mol% Ligand 3b,
1.3 mol% PdCl2(CH3CN)2
+
Br
As shown in Table 2, all iodobenzene and bromobenzene
derivatives were converted to the corresponding coupling products
in excellent yields, despite the aromatic rings having electron-
donating groups (Table 2, entries 2, 3, 5, 6, 8, 9, 11, 12, 14, and
15). The coupling of chlorobenzene derivatives also proceeded
smoothly, furnishing the coupling products in moderate yields
(Table 2, entries 1, 4, 7, 10, and 13). Additionally, we examined
the coupling of various aryl bromides with 4-methoxystyrene,
and found that aryl bromides bearing different substituents were
efficiently converted to the corresponding coupling products in
good yields (Table 2, entries 16–19).
In the last part of the study, we tried to explore the catalytic
performance of different ligands; For this purpose, the perfor-
mance of pillar[5]arene-based imidazolium salts 3a and 3b was
compared for the coupling of aryl halides with styrene, with the
results summarized in Table 3.
solvent, base, 5h, N2
4a
Entry
Solvent
Base
Temp (°C)
Yieldb (％)
1
2
3
4
5
6
7
8
9
10
DMF
DMF
DMF
DMF
Ethanol
DMSO
CH3CN
THF
NMP
NMP
KOtBu
NEt3
K2CO3
KOH
KOH
KOH
KOH
KOH
KOH
KOH
120
120
120
120
100
100
85
100
140
160
24
33
25
71
30
34
31
44
90
95
a
Reaction condition: 0.73 mmol of aryl halide, 0.87 mmol styrene, 2.19 mmol of
base, 1.3 mol% (9.49 Â 10À3 mmol) of ligand 3b, 1.3 mol% (9.49 Â 10À3 mmol) of
PdCl2(CH3CN)2, 5 h, N2.
b
Isolated yields after chromatographic purification.

X.-D. Xiao et al. / Tetrahedron Letters 57 (2016) 3385–3388
3387
Table 2
Heck coupling reaction catalysed by ligand 3ba
1.3 mol% Ligand 3b,
R2
X
1.3 mol% PdCl2(CH3CN)2
R1
+
R2
R1
NMP, KOH, 160䉝, 5h
4a-4h
Entry
Product
R1
X
R2
Yieldb (%)
1
2
3
4
5
6
7
8
4a
4a
4a
4b
4b
4b
4c
4c
4c
4d
4d
4d
4e
4e
4e
4d
4f
H
H
H
Cl
Br
I
Cl
Br
I
Cl
Br
I
Cl
Br
I
Cl
Br
I
Br
Br
Br
Br
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
4-H
79
95
99
71
90
90
74
90
94
70
91
95
82
97
99
92
89
84
95
2-Me
2-Me
2-Me
4- Me
4- Me
4- Me
4-OMe
4-OMe
4-OMe
4-F
4-F
4-F
4-H
4-Me
4-OMe
4-F
9
10
11
12
13
14
15
16
17
18
19
4-OMe
4-OMe
4-OMe
4-OMe
4g
4h
a
Reaction condition: 0.73 mmol of Ar-X derivatives, 0.87 mmol styrene (R2 = H, OMe), 2.19 mmol of KOH, 1.3 mol% (9.49 Â 10À3 mmol) of ligand 3b, 1.3 mol%
(9.49 Â 10À3 mmol) of PdCl2(CH3CN)2, 160 °C, 5 h.
b
Isolated yields after chromatographic purification.
As shown in Table 3, the activity of the two catalysts in the sim-
ple coupling of bromobenzene derivatives and styrene is quite dif-
ferent. It is surprising that the steric bulk of the ligand seems to
have a large impact on the Heck coupling. Notably, when 1.3 mol
% of the NHC-pillar[5]arene 3b was used, all coupling reactions of
bromobenzene derivatives and styrene afforded the desired prod-
ucts in considerable yields (entries 2, 4, 6, 8, and 10). However,
the reaction yields were significantly reduced when 2.0 mol% of
the NHC-pillar[5]arene 3a were used (entries 1, 3, 5, 7, and 9).
These facts suggest that the pillar[5]arene-based imidazolium salt
3b exhibits higher catalytic activity, since the steric bulk of the
NHC ligand may facilitate the formation of a catalytically active
species, and enhance the reductive elimination step.14,34,35
Conclusions
In this paper, we report the first-time synthesis of pillar[5]
arene-based 1-benzylimidazole hexafluorophosphate (ligand 3a)
and pillar[5]arene-based 1-(9-anthracenylmethyl)imidazole hex-
afluorophosphate (ligand 3b). The novel NHC-pillar[5]arene 3b
exhibited good catalytic activity in the Heck cross-coupling of styr-
ene and aryl halide derivatives. The activities of the two catalysts
were compared, showing the steric bulk of the ligand plays a very
important role in this coupling reaction. Inspired by this, we are
now pursuing the search for highly active supramolecular catalytic
systems.
Table 3
Heck coupling of aryl halide with different catalystsa
Acknowledgments
X mol% Ligand 3,
R
Br
+
1.3 mol% PdCl2(CH3CN)2
R
We are grateful for the support provided by the Research Fund
for the Shanxi Natural Science Foundation of China for the project
(No. 2011011006-4).
NMP, KOH, 160䉝, 5h
4a-4e
Entry
R
Ligands
Yieldb (％)
1
2
3
4
5
6
7
8
9
10
H
H
Ligand 3a
Ligand 3b
Ligand 3a
Ligand 3b
Ligand 3a
Ligand 3b
Ligand 3a
Ligand 3b
Ligand 3a
Ligand 3b
85
95
72
90
80
90
80
91
89
97
Supplementary data
2-Me
2-Me
4-Me
4-Me
4-OMe
4-OMe
4-F
Supplementary data (full experimental procedures and 1H NMR,
13C NMR and IR spectra for compounds) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/j.
tetlet.2016.06.083.
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