Reusable Palladium N-Heterocyclic Tetracarbene for Aqueous Suzuki-Miyaura Cross-Coupling Reaction: Homogeneous Catalysis and Heterogeneous Recovery

Article abstract of DOI:10.1021/acs.organomet.8b00195

A pH-responsive Pd(II) N-heterocyclic tetracarbene complex synthesized by a solvothermal method was reported. It can be a highly active reusable catalyst to homogeneously catalyze the Suzuki-Miyaura cross-coupling reaction in water and can be heterogeneously recovered by simply adjusting the pH value of the aqueous reaction media.

Full text of DOI:10.1021/acs.organomet.8b00195

Communication
Cite This: Organometallics XXXX, XXX, XXX−XXX
Reusable Palladium N‑Heterocyclic Tetracarbene for Aqueous
Suzuki−Miyaura Cross-Coupling Reaction: Homogeneous Catalysis
and Heterogeneous Recovery
Yue Li, Ying Dong,* Yong-Liang Wei, Jing-Jing Jv, Yun-Qi Chen, Jian-Ping Ma, Jia-Jia Yao,
and Yu-Bin Dong*
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for
Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong
Normal University, Wenhua East Road 88#, Jinan, Shandong 250014, People’s Republic of China
S
* Supporting Information
ABSTRACT: A pH-responsive Pd(II) N-heterocyclic tetracarbene
complex synthesized by a solvothermal method was reported. It can be
a highly active reusable catalyst to homogeneously catalyze the
Suzuki−Miyaura cross-coupling reaction in water and can be
heterogeneously recovered by simply adjusting the pH value of the
aqueous reaction media.
the aqueous phase. This provides a unique opportunity to
design and prepare pH-driven Pd-NHCs for homogeneous
aqueous catalysis and heterogeneous catalyst recovery. In this
way, the requirements of highly efficient conversion, sustain-
ability, and environmental friendliness for Pd-catalyzed C−C
coupling would be met simultaneously.
alladium-catalyzed cross-coupling has provided a powerful
1
Ptool in organic synthesis for C−C formation.
As
palladium is a noble metal, its recovery and reuse are highly
imperative. One useful way to address such an issue is to
fabricate Pd-based heterogeneous catalysts. So far, various Pd
heterogeneous catalysts of this type have been prepared by
loading Pd species into porous supports such as polymers,
silica, MOFs, COFs, and so on, which made Pd available for
reuse.2 The efficiency of heterogeneous catalysis, as is known, is
generally lower than that of homogeneous catalysis due to its
inherent nature. In addition, the Pd leaching from porous
supports often occurs during heterogeneous catalytic processes.
Thus, the most ideal case for a Pd-based catalytic procedure
would be a homogeneous catalysis and a heterogeneous
recovery.
In this contribution, we report for the first time the novel
pH-responsive palladium N-heterocyclic tetracarbene complex
PdII-NHTC (3), which was prepared under solvothermal
conditions. The obtained PdII-NHTC (3) catalyst is air- and
water-stable and can be reused to highly promote aqueous
Suzuki−Miyaura cross-coupling in a homogeneous way on the
basis of its unique pH-responsive aqueous solubility. By simply
adjusting the pH value, the catalyst can be readily recovered
heterogeneously from an aqueous reaction system and reused
for the next catalytic run at least 10 times without loss of the
catalytic activity.
On the other hand, water is a safe, abundant, eco-friendly,
and low-cost solvent. The development of Pd-catalyzed cross-
coupling reactions in neat water is significant. However, the
limited stability and deactivation of Pd catalysts in aqueous
media has largely impeded the practical application of Pd-based
aqueous catalysis, although some remedies such as cosolvents/
phase-transfer catalysts have been recently suggested.3
In addition, N-heterocyclic carbene (NHC) based Pd-NHC
complexes are stable due to their high Pd−C dissociation
energies. Moreover, they have exhibited remarkable catalytic
performance in C−C coupling such as the Suzuki−Miyaura
reaction.4 To date, an increasing number of studies on aqueous
metal NHC based catalysis have appeared in the literature.5
However, reusable Pd-NHC catalysts for aqueous C−C cross-
coupling have been very rarely reported.6
As shown in Scheme 1, PdII-NHTC (3) was prepared via two
steps. First, the palladium N-heterocyclic dicarbene PdII-
NHDC (2) was synthesized as a light yellow solid by the
Scheme 1. Synthesis of the Multiple Carboxyl-Attached Pd
N-Heterocyclic Tetracarbene Complex of 3
In principle, the water solubility of Pd-NHCs which contain a
hydrophilic functional group such as carboxyl with active
hydrogen atoms can be tuned by controlling the pH value of
Received: April 3, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00195
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combination of Pd(OAc)2 and a methylene-bridged bis-
(imidazolium) salt (1) with terminal carboxylate groups in
95% yield.6,7 Second, the obtained 2 was heated under
solvothermal conditions (THF/MeOH, 90 °C, 72 h) to
generate the palladium N-heterocyclic tetracarbene 3 as
colorless crystals with four terminal carboxylate groups in
50% yield (Supporting Information).
In comparison to 1, the absence of a signal for the
1
imidazolium methine protons at 10.65 ppm in the H NMR
spectra of 2 and 3 (Figure S1) indicated that the corresponding
carbene species was successfully formed. Meanwhile, a single
peak at 6.97 ppm for the methylene linkage in 1 was upshifted
to 6.51−6.78 ppm as two doublets with geminal coupling
signals in 2 and 3 (Figure 1). In the 13C NMR spectra (Figures
Figure 2. (a) ORTEP figure of 3. (b) pH-driven solubility of 3 in neat
water. (c) pH-induced aqueous solubility changes of 3 before and after
the model coupling reaction of 4-chlorobenzotrifluoride (4b) with
phenylboronic acid (5a).
once the pH value was adjusted to 5 with dilute HCl (Figure
2b). Such a phenomenon made the 3-based aqueous
homogeneous catalysis under alkaline conditions and hetero-
geneous catalyst recovery under acidic conditions feasible.
Our initial PdII-NHTC (3) catalytic activity test for the
Suzuki−Miyaura coupling started with 4-chlorobenzotrifluoride
(4b) and phenylboronic acid (5a). Optimization of the reaction
was first conducted at different temperatures such as 50, 80, and
100 °C to furnish the desired product 6b under the given
reaction conditions (Table 1, entries 1−3). The best result was
Table 1. Optimization of the Model Suzuki−Miyaura Cross-
Coupling Reaction of 4-Chlorobenzotrifluoride (4b) with
a
Phenylboronic Acid (5a)
1
Figure 1. H NMR spectra of 1−3.
S2 and S3), the signals for carbene carbons appeared at 158.5
(2) and 168.7 ppm (3), respectively.8 The IR spectra of 2 and 3
displayed strong carboxyl absorption bands at 1711−1715 cm−1
(Figure S4). The existence of a Pd species in 3 was further
confirmed by inductively coupled plasma (ICP) analysis. The
Pd amount in 3 was determined to be 11.21 wt % (calcd 11.81
wt %), which is quite consistent with its molecular formula of
C42H32N8O8PdCl2. The Pd valence was characterized by X-ray
photoelectron spectroscopy (XPS). The main peaks at 337.9
and 343.1 eV could be assigned to the bivalent Pd binding
energy (Figure S5).9
cat.
cocat.
yield
b
entry (mol %) t (h)
base
(1.0 equiv)
T (°C)
(%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
1
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Et3N
TBAB
50
80
50
74
99
74
56
20
99
50
59
70
92
1
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
c
1
100
100
100
100
100
100
100
100
100
0.5
0.1
0.01
1
1
The structure of PdII-NHTC (3) was finally determined by a
single-crystal analysis (CCDC 1815220, Table S1). As
indicated in Figure 2, 3 crystallized in the triclinic space
1
Cs2CO3 TBAB
K2CO3
d
10
11
1
1
K2CO3
TBAB
(0.8 equiv)
group P1. The Pd(II) center was surrounded by two twisted
̅
carboxyl-attached and methylene-bridged bis(imidazolium)
ligands to form a Pd(II)−tetracarbene complex. The Pd(II)
center adopted a quasi-square-planar coordination sphere with
Pd−C bond distances of 2.020(4) and 2.037(5) Å, respectively.
The corresponding ∠C(10)−Pd(1)−C(10)#1 and ∠C(10)−
Pd(1)−C(12) angles are 180.000 and 94.58(18)°, respectively
(Table S2).8
12
1
1
K2CO3
TBAB
(0.5 equiv)
100
75
a
Reaction conditions: 4-chlorobenzotrifluoride (4b, 1.0 mmol),
phenylboronic acid (5a, 1.1 mmol), base (2.0 mmol), H2O (2 mL),
b
c
in air. Isolated yield. The TON and TOF values are 99 and 99 h−1,
d
respectively. Pd black appeared during the reaction.
As is known, Pd-NHC complexes are stable to air and
moisture. For the application of 3 in aqueous homogeneous
catalysis and heterogeneous recovery in the Suzuki−Miyaura
coupling, its pH-driven aqueous solubility was tested. As shown
in Figure 2b, with the aid of K2CO3 (pH 8), 3 readily dissolved
in neat water due to the carboxyl−carboxylate conversion.
However, it was easily precipitated out from aqueous solution
observed when the reaction was performed at 100 °C to give 6b
in 99% yield (Table 1, entries 3 and 7), which placed 3 in a
strong position among the reported Pd-NHC catalysts for
aqueous Suzuki−Miyaura cross-coupling.5 In addition, when
the reaction was carried out in water with a lower catalyst
loading, 0.5, 0.1, and 0.01 mol % instead of 1 mol %, the
coupled product of 6b was isolated in lower yields (Table 1,
B
DOI: 10.1021/acs.organomet.8b00195
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Communication
entries 4−6), but with improved TON values (i.e., TON values
changed from 99 to 148, 560, and 2000, respectively).
Furthermore, K2CO3 and K3PO4 were found to be superior
over Cs2CO3 and Et3N (Table 1, entries 7−9). Without the aid
of tetra-n-butylammonium bromide (TBAB), 6b was isolated in
only 70% yield because TBAB can suppress Pd leaching6 and
the formed Bu4NPhB(OH)3 can facilitate the Suzuki−Miyaura
cross-coupling reaction (Table 1, entry 10).10 A lower amount
of TBAB would also lead to lower yield (Table 1, entries 11 and
12).
Table 2. Suzuki−Miyaura Cross-Coupling Reactions of
a
Various Aryl Halides and Aryl Boric Acids Catalyzed by 3
yield of 6
b
entry
substrate 4
substrate 5
5a: R2 = H
5a: R2 = H
t (h)
(%)
1
2
3
4
4a: R1 = H, X = Cl
1
1
1
1
6a: 99
6b: 99
6c: 99
6d: 99
4b: R1 = 4-CF3, X = Cl
4c: R1 = 4-NO2, X = Cl 5a: R2 = H
Once the reaction was finished, the product was easily
separated by ether extraction. Then, the pH value of the
residual aqueous solution was tuned to 5 with dilute HCl. The
regenerated 3 was obtained as a white solid (Figure 2c), and it
could be reused for the next run after water washing. On the
other hand, an aqueous solution containing deprotonated 3
could also be directly reused for the next run without isolation.
Notably, 3 can be reused at least 10 times without loss of its
catalytic activity under the optimized conditions (Figure S6). In
addition, 1H NMR (Figure S7), 13C NMR (Figure S8), and IR
spectra (Figure S9) demonstrated that 3 is stable after 10
catalytic runs. The Pd amount in 3 after 10 catalytic cycles was
still up to 11.15 wt % (determined by ICP), indicating that no
Pd species leaching occurred during the reuse process. On the
other hand, no valence change for Pd(II) was detected on the
basis of XPS measurements after 10 catalytic cycles (Figure
S10). On the basis of the above observations, the Pd-based
tetracarbene complex 3 herein is very stable (Figure S11) under
the reaction conditions; moreover, it showed much better
catalytic performance in comparison to that of a reported Pd-
based dicarbene complex (Table S3).6 The robust, highly
active, and facile recyclable nature of 3 make it an important
candidate for the practical applications in C−C cross-coupling.
We distance ourselves from any type of explanation and frankly
say that we do not know the detailed mechanism of 3 for this
aqueous Suzuki−Miyaura cross-coupling at this stage, but we
believe it might go through a catalytic pathway similar to those
of reported palladium N-heterocyclic dicarbene catalysts.4,5
On the basis of the above optimized reaction conditions, the
scope of the reaction was explored (Table 2). To our delight, 3
could tolerate various functional groups such as −CF3, −NO2,
−COCH3, −CH3, −OCH3, −OH, −CO2Me, and −CN at
different substituent positions. As shown in Table 2, the
electronic effect of the substituents appeared to be crucial. For
aryl chlorides without substituents or with electron-with-
drawing groups at different positions (Table 2, entries 1−11),
the target cross-coupling products were obtained in excellent
yields (93−99%) within 1 h. Meanwhile, the substituent groups
on the aryl boric acids have no obvious effect on the coupling
reactions under the reaction conditions (Table 2, entries 7−
11). However, aryl chlorides with electron-donating groups, for
example, 4-chloroanisole (4h) and phenylboronic acid (5a)
coupling (Table 2, entry 12), gave an exceptionally low yield
(56%) even at a prolonged reaction time (3 h). Further study
indicated that Pd leaching occurred during this reaction (Figure
S12), and the leaching amount in aqueous solution was 4.84
ppm (determined by ICP). This observation was further
supported by high-resolution transmission electron microscopy
measurements (Figure S13). The low reactivity of 4h with an
electron-donating −OCH3 group in the reaction might be due
to the reluctance of its C−Cl bond to oxidatively add to the Pd
center, and Pd was likely to be reduced by boric acid.11
4d: R1 = 4-COCH3, X = 5a: R2 = H
Cl
5
6
7
8
9
4e: R1 = 2-CN, X = Cl
4f: R1 = 2-CH3, X = Cl
4b: R1 = 4-CF3, X = Cl
4c: R1 = 4-NO2, X = Cl 5c: R2 = 4-F
4g: R1 = 3-COCH3, X = 5d: R2 = 4-OCH3
5a: R2 = H
1
1
1
1
1
6e: 97
6f: 97
6g: 95
6h: 94
6i: 93
5a: R2 = H
5b: R2 = 3-CN
Cl
10
11
4e: R1 = 2-CN, X = Cl
4b: R1 = 4-CF3, X = Cl
5e: R2 = 3-OCH3
5f: R2 = 2-OCH3
5a: R2 = H
1
1
3
6j: 97
6k: 96
6l: 56
c
12
4h: R1 = 4-OCH3,
X = Cl
d
13
4i: R1 = H, X = Br
5a: R2 = H
5a: R2 = H
0.5
0.5
0.5
6a: 99
6c: 97
6d: 99
14
15
4j: R1 = 4-NO2, X = Br
4k: R1 = 4-COCH3, X = 5a: R2 = H
Br
16
17
4l: R1 = 4-OCH3, X = Br 5a: R2 = H
0.5
0.5
6l: 95
4m: R1 = 4-CO2CH3, X 5a: R2 = H
6m: 99
= Br
18
19
20
21
22
23
4n: R1 = 3-OH, X = Br
5a: R2 = H
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
6n:90
6f: 99
6o: 99
6e: 95
6p: 95
6l: 99
6a: 99
6q: 95
6r: 99
6s: 98
6o: 97
6l: 98
6p:99
6m:99
4o: R1 = 2-CH3, X = Br 5a: R2 = H
4p: R1 = 3-NO2, X = Br 5a: R2 = H
4q: R1 = 2-CN, X = Br
4i: R1 = H, X = Br
4i: R1 = H, X = Br
4r: R1 = H, X = I
5a: R2 = H
5g: R2 = 4-CN
5d: R2 = 4-OCH3
5a: R2 = H
d
24
25
26
27
28
29
30
31
4s: R1 = 2-OCH3, X = I 5a: R2 = H
4t: R1 = 2-CF3, X = I
4u: R1 = 3-CH3, X = I
4v: R1 = 3-NO2, X = I
5a: R2 = H
5a: R2 = H
5a: R2 = H
4w: R1 = 4-OCH3, X = I 5a: R2 = H
4x: R1 = 4-CN, X = I
5a: R2 = H
5a: R2 = H
4y: R1 = 4-CO2CH3,
X = I
32
33
34
4s: R1 = 2-OCH3, X = I 5a: R2 = H
0.5
0.5
0.5
6q: 95
6p: 93
6l: 98
4r: R1 = H, X = I
4r: R1 = H, X = I
5g: R2 = 4-CN
5d: R2 = 4-OCH3
a
Reaction conditions: aryl halide (1.0 mmol), boric acid (1.1 mmol),
K2CO3 (2.0 mmol), 3 (1.0 mol %), TBAB (1.0 mmol), H2O (2 mL),
b
c
in air. Isolated yield. Pd black was found after the reaction
(Supporting Information). For PhBr and PhI with phenylboronic
d
acid, a 99% yield could also be reached with 0.2 mol % of 3, but lower
catalyst loading (0.1 mol %) would decrease the yields within 0.5 h
(Table S4). The characterization data for the coupled products are
provided in the Supporting Information.
Aryl bromides were more active for the cross-coupling
reaction. As shown in Table 2 (entries 13−23), the yields for
the target coupled products were in the range of 90−99%
within only 0.5 h. Similar to the case for aryl chlorides, lower
yields were obtained for an electron-donating group attached to
an aryl bromide (Table 2, entry 18). In addition, aryl iodides
exhibited even higher reactivity, and all the aryl iodides
employed under the optimized conditions furnished excellent
C
DOI: 10.1021/acs.organomet.8b00195
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3, 2757−2759. (c) Alonso, D. A.; Naj
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coupling yields (93−99%) within 0.5 h (Table 2, entries 24−
34). Again, electron-withdrawing or electron-donating groups
on the arylboronic acid counterparts did not significantly affect
the coupling yields between aryl bromides or aryl iodides with
corresponding arylboronic acids.
In summary, we reported herein a novel Pd(II)−tetracarbene
complex which was synthesized under solvothermal conditions.
The obtained PdII-NHTC (3) is air- and water-stable and
exhibits an interesting pH-responsive aqueous solubility. More
importantly, it is able to highly promote the aqueous Suzuki−
Miyaura cross-coupling homogeneously and can be readily
recovered heterogeneously by simply adjusting the pH value of
the aqueous reaction solution. We expect this approach to be
viable for the construction of many more new and interesting
metal-NHC-containing catalytic systems for organic trans-
formations in this way.
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ASSOCIATED CONTENT
* Supporting Information
■
S
́
(10) (a) Botella, L.; Naera, C. Angew. Chem., Int. Ed. 2002, 41, 179−
181. (b) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi, U.
J. Org. Chem. 1997, 62, 7170−7173.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00195.
(11) Gaikwad, V.; Kurane, R.; Jadhav, J.; Salunkhe, R.; Rashinkar, G.
Appl. Catal., A 2013, 451, 243−250.
Synthesis, characterization, catalytic activity, and catalytic
cycle of 3, single-crystal data of 3, comparison of 3 with
the reported N-heterocyclic dicarbene Pd(II) complex,
and product characterization for the 3-catalyzed cross-
coupling reactions (PDF)
Accession Codes
CCDC 1815220 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
*E-mail for Y.D.: dongyinggreat@163.com.
*E-mai for Y.-B.D.:yubindong@sdnu.edu.cn.
■
ORCID
Jian-Ping Ma: 0000-0002-5300-3307
Yu-Bin Dong: 0000-0002-9698-8863
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the NSFC (Grant
Nos. 21671122 and 21475078) and the Shandong Taishan
Scholar’s Construction Project.
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