Pd Nanoparticles Embedded Into MOF-808: Synthesis, Structural Characteristics, and Catalyst Properties for the Suzuki–Miyaura Coupling Reaction

Article abstract of DOI:10.1007/s10562-021-03731-4

Abstract: A heterogeneous single-site catalyst Pd@MOF-808 was successfully synthesized by water-based, green synthesis procedure. The catalytic experiments exhibited the Pd@MOF-808 promoted efficiently the Suzuki–Miyaura coupling reaction without the assistance of organic phosphine ligands at atmospheric pressure conditions. The catalyst also could be applied in the gram-scale synthesis of industrially anti-inflanmatory analgestic Fenbufen. Graphic Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-021-03731-4

Catalysis Letters
https://doi.org/10.1007/s10562-021-03731-4
Pd Nanoparticles Embedded Into MOF‑808: Synthesis, Structural
Characteristics, and Catalyst Properties for the Suzuki–Miyaura
Coupling Reaction
Jie Wang1 · Tang Li1 · Zesheng Zhao1 · Xiaoli Zhang1 · Wan Pang1
Received: 21 April 2021 / Accepted: 4 July 2021
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
Abstract
A heterogeneous single-site catalyst Pd@MOF-808 was successfully synthesized by water-based, green synthesis procedure.
The catalytic experiments exhibited the Pd@MOF-808 promoted efciently the Suzuki–Miyaura coupling reaction without
the assistance of organic phosphine ligands at atmospheric pressure conditions. The catalyst also could be applied in the
gram-scale synthesis of industrially anti-infanmatory analgestic Fenbufen.
Graphic Abstract
Pd@MOF-808
X
B(OH)2
B(OH)2
+
+
R1
MeOH,40°C
R1
Pd@MOF-808
O
I
O
MeOH,40°C
R2
R2
Keywords Heterogeneous single-site catalyst · Pd@MOF-808 · Pd nanoparticles · Suzuki–Miyaura coupling reaction ·
Fenbufen
1 Introduction
they are compounds with high afnity and can bind to multiple
receptors. Consequently, they are extensively used in pharma-
ceutical products as a key step in producing bioactive molecules
for medicines. SMC reaction is best described as a catalytic
cycle where the catalyst is regenerated. Many metal catalytic
systems have been investigated in SMC reaction, such as nickel
[5–7], copper [8], cobalt [9–11], ruthenium, argent, iron [12,
13] etc. However, palladium remains the most versatile [14].
With high activity and high selectivity, Pd nanoparticles
(NPs) have been extensively applied as chemical catalysts
for several organic transformations [15]. In the past 20 years,
though some exciting progresses have already been made,
Since its discovery in 1979, the Suzuki–Miyaura coupling
(SMC) reaction has become one of the most prevalent and
efective methods to create carbon–carbon bond [1]. Its cou-
pling products, especially asymmetric biaryl compounds [2,
3], are classed as privileged structural motifs [4], which means
* Wan Pang
pangwan@sit.edu.cn
1
School of Chemical and Environmental Engineering,
Shanghai Institute of Technology, Haiquan Road,
Shanghai 201418, China
Vol.:(0123456789)
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J. Wang et al.
yet, the feld of Pd NPs catalyst is still under intensive
investigation and there are still some challenges [16]. For
example, single Pd NPs are easily aggregated during the
homogenous catalytic process, which results in the poor
catalyst stability, catalyst deactivation, difculty in recov-
ery and reuse [17]. Heterogeneous catalysts are reusable
and conducive to the separation of products and catalysts
from the medium. However, for inert substrates or substrates
with large steric hindrance, they often lack sufcient activity
and stability, and need the assistance of organic phosphine
ligands. Accordingly, highly efcient, reusable, accessible
and eco-friendly Pd catalysts for SMC-type reaction are
needed.
functionalized biaryls have been successfully synthesized.
Most importantly, the authors noted that Pd@MIL-101-NH2
can be run continuously for many days in a fowing reactor
without loss of activity. Another example was reported by
Ahn for Pd NPs immobilized inside MIL-125-NH2 as a het-
erogeneous single-site catalyst exhibited good performance
towards SMC reaction and the catalyst could be reused 4
times without loss of activity [41]. In addition to Pd@MIL,
the family of Pd@UiO also showed remarkably catalytic
activity for the SMC reaction. For example, Pd@UiO-66
and Pd@UiO-67 can efciently catalyze the SMC reaction
of diferent halogenated aromatic hydrocarbons with arylbo-
ronic acid at mild conditions [42, 43]. Not all Pd@MOFs
are stable, Liang and co-workers developed Pd@MOF-5, a
composite catalyst that was unstable [44]. Although the Pd@
MOF-5 materials showed a good activity in the frst catalytic
run, its crystal structure was completely destroyed during the
following reaction runs and caused a big loss of the catalytic
activity. As mentioned above, despite great eforts, synthesis
of Pd@MOF with high stability, high activity, low cost, and
long service life is still a bit challenge for its wide application
in industry and commerce.
Heterogeneous single-site catalysts have come into wide-
spread use over the past decades as a remarkable new tool
to combine the precise active site design of organometallic
catalysts with the stability and recyclability of solid cata-
lysts, essentially bridging the gap between homogeneous
and traditional heterogeneous catalysis [18–20]. Heteroge-
neous single-site catalysts use the rigid pores of the porous
material to provide space limitations for the catalytically
metal NPs and prevent aggregation and leaching [21, 22].
Many inert porous solid materials, such as porous polymers
[23], mesoporous solids, carbon polymorphs [24–26], metal
oxides [27], and their variants are widely used as support-
ing materials for Heterogeneous single-site catalysis [28].
Compared to MOFs materials, these porous materials can
provide good support and space limitations, but the pores of
these materials are not uniform and are easily clogged. This
afects the difusion of reactants and products, resulting in
reduced catalytic activity [29].
Based on recent progress on the new MOF-808 material
[45], large specifc surface area, high porosity with large
adamantine cages and chemical and thermal stability, we
here develop a scalable metal − organic framework-based
heterogeneous single-site catalyst Pd@MOF-808 for the
SMC reaction. MOF-808 can be produced cheaply on a large
scale via a facile “green” synthesis route.
Metal − organic frameworks (MOFs), which were dis-
covered in the early 1990s [30], are coordination polymers
made up of metal ions and organic linkers [31, 32]. The
adjustable and uniform nature of pour size to mesoporous
range in MOFs is a notable advantage and good for the trans-
formation into heterogeneous single-site catalysts [33, 34].
Pd@MOF is one of the best cases to illustrate the poten-
tial of MOFs as excellent supports for metal NPs [35–37].
These applications include typical C−C coupling reaction,
alcohol oxidation reaction, olefn hydrogenation reaction, and
reduction reaction of nitrobenzene compounds [38]. Pd@
MOFs as excellent heterogeneous single-site catalysts have
great catalysis performance for the SMC reaction. Wang and
coworkers reported the synthesis and characterization of Pd
NPs supported on stable micro-crystal DUT-67 MOFs [39].
Pd@DUT-67 had high catalytic activity and could achieve
99% conversion and 89% selectivity under optimized con-
ditions in the SMC reaction. In another excellent example,
well-dispersed Pd NPs in MIL-101-NH2 were prepared by
Martín-Matute et al. in 2015 [40]. The catalyst with a Pd
loading of 8 wt% showed excellent performance in the SMC
reaction under optimized reaction conditions. More than 40
2 Experimental
2.1 Preparation of Support
MOF-808 was synthesized using a water-based, green syn-
thesis procedure according to previous report with slight
modifcations [46, 47]. ZrOCl2·8H2O (5.85 g, 18.15 mmol)
and H3BTC (1.27 g, 6.05 mmol) was dissolved in a mixture
solvent of H2O/acetic acid (50 mL/50 mL). The mixture was
then stirred at 100 °C for 3 days in a 250 mL three-necked
fask under the nitrogen atmosphere. Afterwards, the result-
ing white microcrystalline MOF powder was obtained by
centrifugation and washed with acetic acid (3 times) and
rinsed with deionized water (3 times) and ethanol (3 times)
for 3 h each time. After that, the solid was dried in an oven
at 80 °C under normal pressure for 8 h, and fnally dried at
120 °C under vacuum for 12 h (Scheme 1).
2.2 Synthesis of Pd@MOF‑808
1.1 g PVP and 2.0 g activated MOF-808 were dissolved
in 200 mL deionized water with ultrasound for 10 min.
1 3

Pd Nanoparticles Embedded Into MOF-808: Synthesis, Structural Characteristics, and Catalyst…
ZrOCl2•8H2O
+
Wash (H2O,C2H5OH)
Vacuum drying (120°C)
H2O/HAc(1/1)
N2
O
OH
100°C,3d
MOF-808
O
O
OH
OH
H3BTC
1)PdCl2
Wash (H2O,C2H5OH)
PVP, H2O
Ultrasound(10min)
2)L-AA,KBr
Vacuum drying (120°C)12h
3)N2,80°C,3h
Pd@MOF-808
1
Scheme 1 Preparation of Pd@MOF-808
Sequentially, 0.2 g (10 wt %) PdCl2 was added to the above
solution, then 0.6 g L-AA and 9.0 g KBr were added as
reducing agent and to control the reduced monomer Pd
morphology, reacted at 80 °C for 3 h under nitrogen atmos-
phere. The black powder was obtained by centrifugation and
rinsed with deionized water (3 times) and ethanol (3 times)
for 30 min each time. The as-prepared Pd@MOF-808 was
obtained by drying in an oven at 80 °C under normal pres-
sure for 8 h, and fnally dried at 120 °C under vacuum for
12 h. (Scheme 1).
Fig. 1 PXRD spectrum for Pd, as simulated MOF-808, as synthe-
sized MOF-808, Pd@MOF-808, and as reused Pd@MOF-808
by silica gel chromatography with a mixture of petroleum
ether and ethyl acetate.
Typical procedure for recycling of catalysts: the reac-
tions were performed under the same reaction conditions as
described above, except using the recovered catalyst. Each
time, the catalyst was isolated from the reaction solution by
centrifugation after every reaction at the end of the reaction,
washed with methanol, ethanol and deionized water, and
then heated at 120 °C under vacuum.
2.3 Characterization Methods
The crystal structure of the prepared Pd@MOF-808 was
characterized by PXRD using a Bragg–Brentano difrac-
tometer with a scan range of 5°–80° and a step size of 0.02.
On the automatic specifc surface and porosity analyzer, the
BET specifc surface area of Pd@MOF-808 was character-
ized by N2 adsorption at a temperature of 77 K. The gravi-
metric analysis was performed in air with a heating rate of
10 °C min−1 and heating from 35 °C to 650 °C. The elec-
tronic structure of Pd@MOF-808 was characterized by an
X-ray photoelectron spectrometer, in which the X-ray exci-
tation source was monochromatic Al Ka (hv= 1486.6 eV,
power = 150 W). The microscopic morphology of Pd@
MOF-808 was observed by scanning electron microscope
and transmission electron microscope.
3 Result and Discussion
3.1 Characterization of Support and Catalyst
The PXRD spectrum of the as-synthesized Pd@MOF-
808 series materials was shown in Fig. 1. It could be seen
that powder XRD pattern of the as-synthesized MOF-808
matched well with the simulated and already published
XRD patterns. There is no signifcant diference between
the crystallinity of MOF-808 and Pd@MOF-808 except the
peak intensity. After loading Pd NPs, the crystal structure
of Pd@MOF-808 remained good, and the crystallinity of
MOF-808 did not lose, which indicated that the dispersion
of Pd nanoparticles was high after entering MOF-808, but
the color of the samples changed from white to gray. In addi-
tion, comparing the spectrum of Pd and Pd@MOF-808, it
could be clearly seen that the characteristic peaks of Pd are
around 40° and 46°, which indicates that Pd NPs has been
successfully loaded into MOF-808. Moreover, it could be
seen that the PXRD characteristic peak of the as-recycled
catalyst remains intact, and the crystallinity remained good.
As shown in Fig. 2, the N2 adsorption isotherm of Pd@
MOF-808 at 77 K shows the isotherm characteristics of
2.4 Catalytic Reactions
Typical procedure for SMC reaction: a defnite amount of
palladium catalyst (1) and base were placed in a dried 25 mL
round bottom fask, aromatic halide (1.0 mmol), phenylbo-
ronic acid (1.5 mmol) and solvent (6.0 mL) were added, and
the mixture was stirred at 40 °C for a desired time. After
that, the reaction mixture was quenched with water and
extracted with ethyl acetate. The combined organic layers
were dried over anhydrous Na2SO4. Solvent was removed
under a reduced pressure and the crude product was purifed
1 3

J. Wang et al.
Zr all appeared in the experimental materials, and the 3d5/2
and 3d3/2 peaks in Pd0 appeared in 341.9 eV and 336.8 eV,
respectively. These test results were almost perfectly consist-
ent with the characteristic peaks reported in the literature
[48].
Figure 4 showed the TGA curve of Pd@MOF-808 series
materials, same as the facts recently reported. Distinctly,
the frst weight loss of the specimen materials is about 3%
at 150 °C, which is mainly due to the evaporation of organic
solvents and water which is absorbed on the surface of Pd@
MOF-808. The other two weight loss peaks were located at
350 °C and 550 °C, respectively. Therefore, it could be con-
cluded that the minimum thermal stability of Pd@MOF-808
is about 350 °C, and the skeleton of MOF-808 completely
collapses at 550 °C.
Fig. 2 N2 adsorption and desorption isotherms for MOF-808 and
The scanning electron microscopy (SEM) image (Fig. 5a)
showed that the sample was formed by octahedral crystals
with size ranging between 0.9 and 1 um. Bright feld trans-
mission electron microscopy (TEM) images (Fig. 5b–f)
acquired on the crystal of Pd@MOF-808 show black spots
that are attributed to the Pd nanoparticles. Figure 5d–f
showed that the size of as-synthesized Pd nanoparticles is
about 7 nm without any visible agglomeration.
Pd@MOF-808
microporous/mesoporous materials. In the relatively low
pressure region between 0.001 and 0.1, the adsorption
capacity of MOF-808 series materials adsorbed by N2 rap-
idly increased from 0 to 300 cm3/g, which was mainly attrib-
uted to the pores of MOF-808 were flled with N2 under the
pressure. Hysteresis loop was formed when the pressure area
was P/P0= 0.9–1. It could also be seen from Fig. 2, Pd@
MOF-808 was occupied by highly dispersed Pd nanoparti-
cles, resulting in a sharp drop of specifc surface area.
The results of powder X-ray difraction experiment and
N2 desorption showed that Pd NPs were successfully intro-
duced into the pores of MOF-808. Furthermore, the XPS
spectrum of Pd@MOF-808 series materials was shown in
Fig. 3, and the chemical composition and chemical state of
the elements of the sample were determined. It could be
obviously seen that the characteristic peaks of C, Pd, O and
3.2 Pd@MOF‑808 Catalyzed Suzuki–Miyaura
Coupling Reaction
The performance of the Pd@MOF-808 material as a single-
site heterogeneous catalyst for the Suzuki–Miyaura coupling
reaction was tested by employing p-iodoanisole and phe-
nylboronic acid as model substrates and performing the
reaction under optimized reaction conditions. As listed in
Table 1, without catalyst and the parent MOF-808 gave no
conversion in the reaction (Table 1, entries 1–2), confrming
as expected the need of palladium to perform the coupling
Fig. 3 XPS spectrum of Pd@MOF-808, the inset plot is a magnifed
view of the partial area
Fig. 4 TGA curve of Pd@MOF-808 series materials
1 3

Pd Nanoparticles Embedded Into MOF-808: Synthesis, Structural Characteristics, and Catalyst…
Fig. 5 SEM image of MOF-808
(a); TEM images of Pd@MOF-
808 (b-f)
Table 1 Performance of the catalyst for the Suzuki–Miyaura cross-
when 3 mol% Pd@MOF-808 was used as catalyst. On the
coupling reaction of p-iodoanisole and phenylboronic acid
contrary, 10 wt% Pd/C only gave 60% yield (Table 1, entry
6). Under the same experimental conditions except for the
absence of p-iodoanisole, there was no biphenyl product was
observed. Which meant that the biphenyl product would do
not come from the homocoupling of phenylboronic acid
(Table 1, entry 7).
Subsequently, the efect of catalyst loading on the cross-
coupling reaction was investigated under air atmosphere at
40 °C for 4 h and the results are shown in Table 2. With
the highest loading of 5 mol%, the reaction gave a yield of
74% after 4 h. Decreasing the catalyst loading to 3 mol% still
gave the same yield (72%) after 4 h (Table 2, entry 3). By
further decreasing the amount of Pd catalyst to 2 mol% and
1 mol%, the yield dropped substantially to about 55% and
45% (Table 2, entries 1–2). It is well known that acidic prod-
ucts are formed in the palladium-catalyzed coupling reaction
of aryl halides, which may increase the solution acidity and
subsequently suppress the reactions. Therefore, some suit-
able bases are usually needed to neutralize the acidic prod-
ucts generated. With the optimized catalysts, the infuence
of base on the catalytic performance of the present reaction
system was investigated, and the results are summarized in
Table 2 (entries 5–12). The reaction did not proceed at all
when bases were absent (Table 2, entry 13), demonstrating
the signifcance of bases in this transformation. The results
with the addition of various bases indicated that potassium
salts could be used as efcient bases for the Pd@MOF-808
catalyzed coupling reaction of iodobenzene, and the use of
potassium acetate furnished the highest conversion and yield
of biphenyl (entry 6). The use of sodium salts also promoted
Entry
Additive
Solvent
Yield %a
1
2
3
4
5
6
7b
Nothing
MOF-808
PdCl2
PdCl2,MOF-808
Pd@MOF-808
Pd/C
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
N.R
N.R
29
32
71
60
N.R
Pd@MOF-808
Reaction conditions: p-iodoanisole (0.5 mmol), phenylboronic acid
(0.75 mmol), K3PO4(1 mmol) and 3 mol% additive in solvent (3.0 ml)
at 40 °C (oil temperature) for 4 h
aThe yield was determined by H NMR spectroscopy using Dibro-
1
momethane as an internal standard
bReaction was performed without p-iodoanisole
reaction. The catalytic efciency was also observed to be
reduced remarkably when the same amount of PdCl2 (29%
yield) (Table 1, entry 3) was used to replace Pd@MOF-
808. Compared with the reaction with Pd@MOF-808, only
32% yield was obtained when 3 mol% PdCl2 and 3 mol%
MOF-808 were added separately (Table 1, entry 4). A sig-
nifcantly higher yield (71%) (Table 1, entry 5) was obtained
1 3

J. Wang et al.
Table 2 Optimization of the cross-coupling reaction with Pd@MOF-
the reaction (entries 7 and 9), but they were less efcient
than the corresponding potassium salts in the coupling reac-
tions. As shown in Table 2, the biphenyl yield increased in
the order: K2CO3 ≈ Cs2CO3 >K3PO4 > >Na2CO3 >NaOAc.
The promoting efect of these bases is probably related to the
sizes of the metal cations because the potassium and Cae-
sium ions with a relatively larger size will have a weaker
ion-pairing interaction than sodium, leading to higher solu-
bility and basicity. A brief survey of the bases revealed that
the addition of organic bases had signifcantly reduced the
product formation (Table 2, entries 10–12). The investigation
of some solvents usually used in Suzuki–Miyaura cross-cou-
pling, such as MeOH, EtOH and H2O, revealed that MeOH
was the best solvent (Table 2, entry 6). In sharp contrast,
the yield of the model reaction was dramatically decreased
when H2O or EtOH were used as solvent (Table 2, entry 21).
The use of mixed solvents such as MeOH/H2O enhanced the
yield of biphenyl (Table 2, entries 22–25). When increasing
the amount of methanol to reach a MeOH/H2O ratio of 10:1,
93% yield of biphenyl could be achieved under the condi-
tions (entry 25). The results suggested that methanol played
an important role in the arylation, which might facilitate the
oxidative addition and promote the subsequent dissociation
of iodide from Pd (II) to give a cationic Pd(II)-iodobenzene
species. On the other hand, it was found that organic solvents
such as DMSO, DMF, CH2Cl2 and CH3CN were inefective
for this reaction (Table 2, entries 14–20). Temperature obvi-
ously infuenced the reaction yields too. 40 °C was found to
be suitable temperature (Table 2, entry 6). Reducing the reac-
tion temperature from 40 °C to 25 °C, the product yield was
decreased (Table 2, entries 26–27). Moreover, a brief inves-
tigation of the substrate ratio revealed that the yield reached
the highest when 1f:2=1:1.5 (Table 2, Entries 28–29). After
these extensive and systematic experiments, it was discovered
that the optimal reaction conditions employed 3 mol% Pd@
MOF-808 and 2 equivalents of K2CO3 in MeOH at 40 °C
with the substrate ratio (1a:2=1:1.5), which provides biphe-
nyl at 99% isolated yield.
808 catalyst
Entry Pd@
Solvent
Bases
Ta/°C Yieldb %
MOF-808
(mol %)
1
2
3
4
1
2
3
5
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
DMF
K3PO4
K3PO4
K3PO4
K3PO4
KF
K2CO3
Na2CO3
Cs2CO3
NaAc
Et3N
40
40
40
40
40
40
40
40
40
40
40
45
55
72
74
25
99
47
99
20
25
N.R
N.R
N.R
<5
<3
9
<5
<3
40
19
36
78
83
88
93
86
80
90
96
5
6c
7
8
9
10
11
12
13
14
15
16
17d
18
19
20
21
22
23
24
25
26
27
28e
29f
Py
NH3·H2O 40
–
40
40
40
40
40
40
40
40
40
40
40
40
40
30
25
40
40
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMSO
H2O
H2O
THF
CH2Cl2
CH3CN
C2H5OH
MeOH/H2O(1/1) K2CO3
MeOH/H2O(2/1) K2CO3
MeOH/H2O(5/1) K2CO3
MeOH/H2O(10/1) K2CO3
MeOH
MeOH
MeOH
MeOH
K2CO3
K2CO3
K2CO3
K2CO3
Having established the optimized reaction conditions, the
scope of the reaction with respect to the aryl halide cou-
pling partner was examined (Table 3). Various aryl iodides
bearing variety of functional groups underwent the reaction
successfully. Electron-donating groups (Table 3, 3b-3i) such
as -CH3, -C2H5, -OCH3, -OC2H5 and electron-withdrawing
groups such as ester, nitro, cyano, acetyl, halogen were
all well tolerated. Heteroaromatic iodides, only thiophene
derivatives proved efective coupling partners. Additionally,
compared with the corresponding meta- and para-substituted
aryl iodide, the yields of the orhto-substituted derivatives
gave the lowest yields in longer reaction times (Table 3, 3c,
3d, 3h), the stereo-hindrance efect played a key role in the
reaction. Halogen atoms such as F and Cl were also tolerated
under the reaction conditions in excellent yields (Table 3,
Reaction conditions: to the reaction mixture of p-iodoanisole 1f
(0.5 mmol) and Phenylboronic acid 2 (0.75 mmol) in solvent (3 ml)
for 4 h
aOil temperature
bThe yield and conversion rate was determined by 1H NMR spectros-
copy using Dibromomethane as an internal standard
cThe optimal reaction conditions
d2 equiv. of TBAB were added
eThe ratio of 1f:2 was 1:1
fThe ratio of 1f:2 was 1:1.2
1 3

Pd Nanoparticles Embedded Into MOF-808: Synthesis, Structural Characteristics, and Catalyst…
Table 3 Pd@MOF-808 catalyzed Suzuki–Miyaura cross-coupling reaction of aryl halide derivatives with phenylboronic acid
Reaction conditions: aryl iodide 1a-r (1 mmol) and phenylboronic acid 2 (1.5 mmol) in solvent (6.0 ml), Pd@MOF-808
(3 mol%), 40 °C Oil temperature
a1r=4-bromo iodobenzene, 2=phenylboronic acid (3 equiv.). As another product of the reaction, 1,1’:4’,1’’-terphenyl(3 s) with
a yield of 59% was obtained
3p-3q). However, Br and I had brilliant adaptability, there
was an obvious competition mechanism, the coupling with
the iodine substituted side was always preferred (Table 3,
3r).
In the meantime, arylboronic acids having diferent sub-
stituents were examined and the results are listed in Table 4.
As shown in Table 4, a series of substituted arylboronic
acids bearing either electron-donating (4a-4e) or electron-
withdrawing (4f-4 g) functional groups aforded the desired
products in good to excellent yields. Notably, boronic acid
substrates bearing electron donating groups, such as p-OMe,
p-Me gave higher yields of the corresponding adducts in
shorter reaction times (Table 4, 4a and 4d). The steric efect
on the reaction was also investigated. The yields of the para-
substituted derivatives gave better yields in shorter reaction
times (Table 4, 4a-4c), demonstrating that steric efect of
boronic acid was sensitive to the reaction (Table 4, 4h-4i).
However, there was an unexpected low (29%) yield when
p-hydroxy phenylboronic acid participated in this reaction,
probably because of the acidity of para-phenolic hydroxyl
group (Table 4, 4e). Heteroaromatic boronic acid, including
furan, thiophene, 1-naphthylboronic acid, 4-Triphenylamine
In addition, the reactions of some aryl chlorides and aryl
bromides were studied. When bromobenzene, 4-Bromo-
toluene, 4-Bromoanisole and 4-bromoacetophenone were
employed as substrates, the products of coupling reaction
with phenylboronic acid were formed in 99% (1.5 h), 76%
(4 h), 94% (3.5 h) and 89% (6 h), respectively. The experi-
ment results in Table 3 showed that the catalytic system
lacked sufcient activity for chloride benzene. Chloroben-
zene gave the low yields (21%) in longer reaction times
(12 h) (Table 3, 3a). When the substrate was substituted
with 4-chloroanisole, 4-methylchlorobenzene and 4-chloro-
acetophenone, only trace amounts of biphenyl products were
detected (Table 3. 3b, 3f, 3 m).
1 3

J. Wang et al.
Table 4 Pd@MOF-808 catalyzed Suzuki–Miyaura cross-coupling reaction of p-iodoanisole with arylboronic acids derivatives
Reaction conditions: p-iodoanisole 1f (1 mmol) and arylboronic acids derivatives 2a-p(1.5 mmol) in solvent (6.0 ml), Pd@MOF-
808 (3 mol%), 40 °C Oil temperature
through the Suzuki–Miyaura cross-coupling of p-iodoani-
sole and phenylboronic acid under the optimal conditions. It
could be seen that the yield of 3f was not decreased signif-
cantly after the catalyst was recycled 5 times (Fig. 6). Base
on the TGA, PXRD testing results and the new chemical
deactivation mechanism reported by Persson’s group [49],
we speculated that the irreversible deactivation of the stable
heterogeneous single-site catalysis Pd@MOF-808 is neither
caused by the leaching of the Pd NPs active material nor
by the decomposition of the crystal structure of MOF-808.
Instead, the halide ions cover the surface of active material
Pd NPs.
To further demonstrate the functional group compatibil-
ity and practicality of the catalytic method, it was used to
prepare a selection of pharmaceutical drugs bearing biaryl
scaffold. Fenbufen is a long-acting non-steroidal anti-
Fig. 6 Recycling of the Pd@MOF-808
infammatory analgesic developed by American Cyanamid
Company that possesses analgesic, anti-infammatory and
and trimethylsilca derivaties, all proved efective coupling
antipyretic efects, which has less irritative efect on gastro-
partner. It was found that the reactivity of β-naphthalene
intestinal tract and stronger anti-infammatory efect than
boronic acid was much higher than α-naphthalene boronic
ibuprofen. Our synthesis of fenbufen was accomplished in
acid (Table 4, 4m-4p).
two steps (Scheme 2). First, intermediate 1 was obtained
The recycling of the catalyst was investigated to fur-
through Friedel–Crafts acylation reaction of bromobenzene
ther confrm the persistence of the catalytic activity. The
and succinic anhydride catalyzed by anhydrous aluminum
Pd@MOF-808 catalytic recycling experiment was studied
1 3

Pd Nanoparticles Embedded Into MOF-808: Synthesis, Structural Characteristics, and Catalyst…
O
O
Br
O
1) AlCl3,0°C,4h
2) 25°C,4d
COOH
Phenylboronic acid
O
COOH
yield = 89%
+
3 mol %Pd@MOF-808
K2CO3, MeOH,40°C
yield = 90%
Br
O
Fenbufen
Intermediate 1
Scheme 2 Synthesis of Fenbufen
8. Thapa S, Shrestha B, Gurung SK, Giri R (2015) Org Bio Chem
13:4816–4827
trichloride (89% yield), then intermediate 1 was subjected
to Suzuki cross-coupling reaction with phenylboronic acid
catalyzed by Pd@MOF-808 and the corresponding coupling
products Fenbufen was successfully obtained with a yield of
up to 90% in a short time in high yield.
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4 Conclusions
15. Trzeciak AM, Augustyniak AW (2019) Coord Chem Rev
384:1–20
In summary, we have synthetized a stable and highly ef-
cient heterogeneous single-site catalyst for SMC reactions
by immobilizing Pd nanoparticles on MOF-808. The char-
acterized testing results showed that the synthesized Pd
nanoparticles have been successfully introduced into the
cavity and channel of MOF-808, and the structure of Pd@
MOF-808 could remain stable at 350 °C. The Pd@MOF-
808 catalyst was highly efcient in SMC reaction of various
aryl/heteroaryl iodides without the aid of phosphine ligands.
Furthermore, the catalyst was reusable, showed negligible
metal leaching, and maintained high catalytic activities over
a number of cycles. The combination of advantages of both
molecular Pd NPs catalysts and solid MOFs in this system
may bring new opportunity in the development of highly
efcient heterogeneous single-site catalysis for C–C cou-
plings or other Pd-catalyzed transformations.
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Acknowledgements The authors are grateful for fnancial supports
from National Natural Science Foundation of China (Grant No.
21602135). Middle and Youth teachers Scientifc and Technological
Talents Developing Fund (No. ZQ2020-9).
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