Construction of heterometallic M2Pd3 supramolecular cages via a metalloligand strategy as heterogeneous catalyst for Suzuki–Miyaura coupling reaction

Article abstract of DOI:10.1016/j.ica.2018.07.009

On the basis of hard soft acid base theory, two neutral heterometallic M₂Pd₃ supramolecular cages, [Al₂Pd₃(L)₆Cl₆] (1) and [Fe₂Pd₃(L)₆Cl₆] (2) (where HL is 1-(4-(1H-imidazol-1-yl)phenyl)butane-1,3-dione), have been constructed by using the tripodal M(L)₃ as metalloligands in combination with PdCl₂ or Pd(MeCN)₂Cl₂. The supramolecular cage can be described as a trigonal bipyramid with two M³⁺ ions occupying at the two axial sites in ΔΔ or ΛΛ configurations and three Pd²⁺ ions sitting in the three equatorial positions with square planar geometry in trans configuration. The supramolecular cages exhibit high catalytic activity for the Suzuki–Miyaura coupling with arylbromide or arylchrolide and phenylboronic acid in biorenewable solvent glycerol under mild conditions. Moreover, the catalyst can be readily recycled and reused at least five times without loss of catalytic activity. The high catalytic performance may be attributed to the distinct properties of the cage structure with uniformly distributive and well-defined Pd active centres on the cage surfaces. The high stability in the cage structure also prevents Pd leaching out and agglomeration.

Full text of DOI:10.1016/j.ica.2018.07.009

Accepted Manuscript
Construction of Heterometallic M2Pd3 Supramolecular Cages via a Metalloli-
gand Strategy as Heterogeneous Catalyst for Suzuki–Miyaura Coupling Reac-
tion
Xi-Ren Wu, Su-Yang Yao, Lian-Qiang Wei, Li-Ping Li, Bao-Hui Ye
PII:
S0020-1693(18)30771-0
https://doi.org/10.1016/j.ica.2018.07.009
ICA 18355
DOI:
Reference:
Inorganica Chimica Acta
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Received Date:
Revised Date:
Accepted Date:
18 May 2018
2 July 2018
4 July 2018
Please cite this article as: X-R. Wu, S-Y. Yao, L-Q. Wei, L-P. Li, B-H. Ye, Construction of Heterometallic
M2Pd3 Supramolecular Cages via a Metalloligand Strategy as Heterogeneous Catalyst for Suzuki–Miyaura Coupling
Reaction, Inorganica Chimica Acta (2018), doi: https://doi.org/10.1016/j.ica.2018.07.009
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Construction of Heterometallic M2Pd3 Supramolecular Cages via
a
Metalloligand Strategy as Heterogeneous Catalyst for Suzuki–Miyaura Coupling
Reaction
Xi-Ren Wu,a,b Su-Yang Yao,a Lian-Qiang Wei,a Li-Ping Li,a and Bao-Hui Ye*a
aMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry
and Chemical EngineeringSun Yat-senUniversity, Guangzhou 510275 (P. R. China).
E-mail: cesybh@mail.sysu.edu.cn
bSchool of Pharmacy, Guangdong Medical University, Dongguan, 523808, China

ABSTRACT
On the basis of hard soft acid base theory, two neutral heterometallic M2Pd3
supramolecular cages, [Al2Pd3(L)6Cl6](1) and [Fe2Pd3(L)6Cl6] (2) (where HL is
1-(4-(1H-imidazol-1-yl)phenyl)butane-1,3-dione), have been constructed by using the
tripodal M(L)3 as metalloligands in combination with PdCl2 or Pd(MeCN)2Cl2. The
supramolecular cage can be described as a trigonal bipyramid with two M3+ ions
occupying at the two axial sites in ΔΔ or ΛΛ configurations and three Pd2+ ions sitting
in the three equatorial positions with square planar geometry in trans configuration.
The supramolecular cages exhibit high catalytic activity for the Suzuki–Miyaura
coupling with arylbromide or arylchrolide and phenylboronic acid in biorenewable
solvent glycerol under mild conditions. Moreover, the catalyst can be readily recycled
and reused at least five times without loss of catalytic activity. The high catalytic
performance may be attributed to the distinct properties of the cage structure with
uniformly distributive and well-defined Pd active centres on the cage surfaces. The
high stability in the cage structure also prevents Pd leaching out and agglomeration.
Keywords:
Supramolecular
cages;
Metalloligand;
Palladiumcomplexes;
Heterogeneous catalyst; Suzuki-Miyaura coupling.

1. Introduction
Palladium catalysis carbon-carbon coupling reactions, such as Suzuki–Miyaura,
Heck and Sonogashira reactions, have numerous potential applications in synthesis of
biologically active compounds and pharmaceuticals.[1-6] However, many of Pd
catalysts are limited to homogeneous reactions, in which the catalysts suffer from
recovery, leading to the loss of the expensive Pd metal and organic ligands. The use of
a heterogeneous catalyst instead provides the possibility to easily separate and recycle
the catalyst. Great efforts have been devoted to the preparation of actively recyclable
Pd catalysts via immobilization of catalysts on the solid supports, such as magnetic
nanoparticles, activated carbon, silica, zeolites, carbon nanotubes, metal oxides, clays,
organic polymers and metal-organic frameworks.[7-16] In spite of great advances, the
active sites on these solid supports are not always accessible for the reactions and very
few achieve uniform distribution as an isolated single-site. In many cases, the
catalytic activities are lower than those in the homogeneous counterparts and harsh
reaction conditions are always required. Therefore, high efficient, easily separable and
reusable catalyst systems are still highly desired.
To overcome these problems, we pay our attention to supramolecular cage that not
only arranges the catalytic center in an isolated single-site with a well-defined
structure but also maximally exposes the active sites to the substrates to enhance the
catalytic activity due to the discrete structure. In fact, many homonuclear Pd
supramolecular cages have been assembled,[17-24] and some of them have also been

used as catalysts for carbon-carbon coupling reactions.[25-35] However,
heterometallic Pd supramolecular cage is still rare.[36-42] On the basis of hard soft
acid base (HSAB) theory, Raymond, Shionoya and Wang have successfully
constructed heterometallic Pd supramolecular cages via a metalloligand strategy
(Scheme 1).[36-40] But the catalytic activity of these heterometallic Pd complexes
has never been exploited. Specifically, the synthesis of heterometallic Pd coordination
polymers with the selected metalloligands is a very attractive area concerning the
applications as catalysts.[43-46] The synergistic effect between Pd and the other metal
ion through the ligand in promotion of catalytic activity has been observed.[47-49]
Follow these synthetic strategies, a exotopic bifunctional ligand with N-donor and
β-diketone chelating donors at the terminal were employed to construct
heterometallic supramolecular cages. Each ligand may bind to two separated metal
β-diketone ensures to bind to a hard metal ion in high
stability and a negative charge on each ligand allows access to neutral tripodal
metalloligand with a M3+ metal ion. Furthermore, the N-donor may bind to a Pd2+ ion
as a potential catalytic center and the vector angle between the N-donor lone pair and
β-diketone chelate in an appropriate angle allows to form a cage structure. The
long and rigid rod-like ligand would make sure the supramolecular cages possess big
windows that the substrates could readily pass through and the catalytic centers locate
in the appropriate sites separately. Such structure feature would help the active
component PdCl2 to promote both the in-cage and out-cage reactions with high
efficiency. It can be anticipated that such a rational design will lead to excellent

catalytic activity because the cages allow maximum exposure of the active sites to
reactants. Indeed, two heterometallic M2Pd3 supramolecular cages [Al2Pd3(L)6Cl6] (1)
and
[Fe2Pd3(L)6Cl6]
(2),
(where
HL
=
1-(4-(1H-imidazol-1-yl)phenyl)butane-1,3-dione) were constructed via the
metalloligand strategy. The catalytic experiments showed that the M2Pd3 cages were
highly efficient for the Suzuki−Miyaura cross-coupling reaction in biorenewable
solvent glycerol under mild conditions. The catalyst could be recycled at least five
times without loss of catalytic activity.
Scheme 1. The diagram of metalloligands for heterometallic supramolecular cages
2. Experimental
2.1. General procedures
All commercial reagents and solvents were used without further purification.
Electrospray ionization mass spectra (ESI-MS) were obtained on a Shimadzu

LCMS-2010A Liquid Chromatography Mass spectrometer. The C, H, and N
1
microanalyses were carried out with a Vario EL elemental analyser. H NMR spectra
were recorded with a Bruker AV 400 spectrometer by using the solvent as an internal
standard. Thermogravimetric data were collected on a NETZSCH TG 209
F3analyserin nitrogen atmosphere at a heating rate of 10 °C min−1 from ambient
temperature to 850 °C. Powder X-ray diffraction patterns were recorded on a D8
ADVANCE diffractometer with Cu-Kα radiation (λ = 1.5409 Å) at a scanning rate of 4°
min−1 with 2θ ranging from 5 to 35°. Transmission electron microscopy (TEM)
images were taken with a FEI Tecnai G2 F20 transmission electron microscope
operating at an accelerated voltage of 200 kV. X-ray photoelectron spectroscopy (XPS)
measurements were made on a Thermo Fisher Scientific ESCALAB250 machine with
a monochromatic Al-K source operated at 150W and the pass energy of the analyser
was kept at 10 eV. All the binding energies were calibrated by using the contaminant
carbon (C1s = 284.6 eV) as a reference. Pd elemental analyses were performed by
inductively coupled plasma atomic emission spectroscopy (ICP-AES) using a TJA
IRIS HR ICP instrument. The ligands HL was prepared according to our previously
published procedures.[50]
2.2. Syntheses of metalloligands [Al(L)3] and [Fe(L)3]
M(NO3)3·9H2O (1mmol), HL (3.5mmol) and NaHCO3 (3.5mmol, 0.294 g) were
dissolved in 100 mL of MeOH/H2O (1:1 v/v) and stirred until a white or red product
precipitated (about 24 h). The resultant precipitate was filtered and washed with water.

The crude product was extracted with CHCl3 and dried over anhydrous MgSO4. The
CHCl3 solvent was removed under reduced pressure to afford product as a white or
red solid. Yields for Al(L)3, 0.556 g, 78%, MS: m/z = 709 [M+H]+; for Fe(L)3, 0.473 g,
64%,MS: m/z= 738 [M+H]+.
2.3. Syntheses of heterometallic cages [Al2Pd3(L)6Cl6] (1) and [Fe2Pd3(L)6Cl6] (2)
A mixture of DMSO/CH2Cl2 solvent (2 mL, v:v = 1:1) was carefully layered over a
solution of Al(L)3 in CH2Cl2 (0.01 mmol, 1 mL). Then, a solution of PdCl2 in DMSO
(0.015 mmol, 2 mL) was layered on the top of the buffer. Yellowish, prism-shaped
X-ray quality crystals of 1·5DMSO·3CH2Cl2 was obtained after 10 days. The
dark-red block crystals of 2·solvent was obtained via layering a solvent of
DMF/MeOH (2 mL, v:v = 1:1) over a solution of Pd(CH3CN)2Cl2 in DMF (1 mL,
0.015 mmol), then, a solution of Fe(L)3 in MeOH (1 mL, 0.01 mmol) on the top of the
buffer. Crystals 1 and 2 were filtered and washed with DMSO three times, followed
by soaking in methanol for two days. Subsequently, solids 1 and 2 were collected via
centrifugation and dried at 150 °C under vacuum for 24 h. Yield for 1·2DMSO, 7.6
mg, 72%, Anal. Calcd for C82H78Cl6Al2N12O14S2Pd3: C 46.77, H 3.73, N 7.98. Found:
C 46.61, H 4.01, N 7.73; for 2·2DMF, 5.0 mg, 49%, Anal. Calcd for
C84H80Cl6Fe2N14O14Pd3: C 46.85, H 3.74, N 9.11. Found: C 46.67, H 3.54, N 9.01.
2.4. General procedure for the Suzuki-Miyaura coupling reaction
Aryl halide (1.0 mmol), aryl boronic acid (1.1 mmol), K2CO3 (1.5 mmol) and

catalyst (0.02 mol%) were mixed together in 4.0 mL glycerol and allowed to react at
80 °C for 2 h. After that, the reaction mixture was cooled to room temperature and the
organic residue was extracted from glycerol phase by CH2Cl2 (3 × 5 mL). Removal of
solvent CH2Cl2, the crude residue was purified by silica gel chromatography to afford
pure product, which was identified using 1H NMR and 13C NMR analyses (see ESI).
2.5. General procedure for catalyst recovery
Once the reaction was stopped, the organic residues were extracted from glycerol
phase by CH2Cl2 (3 × 5 mL). Then, the glycerol phase was maintained under reduced
pressure with stirring at 80 °C for 30 min. The fresh substrates were directly added to
the recovered glycerol phase in the same tube for the next run reaction under the
corresponding conditions.
2.6. Crystallographic analysis
The diffraction intensities for 1 and 2 were collected on an Oxford Gemini S Ultra
CCD Area detector diffractometer with graphite-monochromated Cu Kα radiation (λ
=1.54178 Å). All of the data were corrected for absorption effect using the
CrysAlisPro software.[51] The structures were solved by direct methods with
SHELXT[52] and refined with full-matrix least squaresrefinements using
SHELXL[53] within the Olex2 suite.[54] All non-hydrogen atoms were refined
anisotropically. All hydrogen atoms were included in the final structure factor
calculation at idealized positions and were allowed to ride on the neighbouring atoms.

The structure of 2 contains accessible voids that are filled in a spot of diffuse electron
density belonging to uncoordinated solvent. The SQUEEZE routine of PLATON was
used to remove remaining electron density corresponding to solvent not reported in
the calculated formula.[55] The crystal data and the details of data collection and
refinement for the complexes are summarized in Table 1. The selected bond distances
and angles are listed in Table S1 in the Supporting Information.
Table 1. Crystallographic data for complexes
1 and 2.
Complex
Molecular formula
Mr
Crystal system
Space group
a [Å]
15DMSO3CH2Cl2
C91H102Cl12Al2N12O17S5Pd3
23DMFMeCNH2O
C89H93Cl6Fe2N16O16Pd3
2286.40
triclinic
P-1
17.1396(4)
19.0469(5)
19.1412(8)
111.923(3)
101.723(2)
104.074(2)
2594.71
triclinic
P-1
16.7428(16)
18.0798(14)
20.8624(16)
70.613(7)
b [Å]
c [Å]
a []
[]
89.475(7)
g []
V [Å3]
68.511(9)
5497.3(9)
2
1.568
5314.4(3)
2
1.418
Z
Dc(g cm-3)
 (mm-1)
8.195
17020
13619
8.070
16972
12886
Data collected
Observed reflections
aR1[I>2(I)]
0.0609
0.0717
b
WR2(F2) [I>2(I)]
0.1762
1.029
0.1850
1.010
GOF on F2
2
2 2 1/2
aR1 = Fo-Fc/Fo, bwR = [w(Fo -Fc2)2/w(Fo ) ]
CCDC-1586307 and 15866312 contain the crystallographic information for this paper. All these
data can be obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_requests/cif.

3. Results and Discussion
3.1. Ligand Design and Synthesis of Complexes via a Metalloligand Strategy
The bifunctional ligand HL containing a terminal N-donor imidazole group and a
β-diketone chelate linking via a phenyl spacer was successfully synthesized by
Claisen condensation of N-donor substituted acetophenone and ethyl acetate.[50] It
can beseen as three potential exotopic donors with distinctly coordinated feature
binding to two different metal ions, the chelating nature of β-diketone is hard with
negative charge and favors a hard M3+ metal ion to form a neutral octahedral geometry.
On the other hand, the N-donor ligand is relative soft and bind to a Pd ion as a
potential catalytic center. A ligand containing dual these functional groups arranged in
a proper geometry can generate a cage structure. The introduction of phenyl ring
between the N-donor and β-diketone as a space allows the potential catalytic centers
separately.
Though hard metal ions can exclusively bind at the β-diketone site, softer metal
centers such as Pd2+ and Zn2+ may not discriminate sufficiently between the
β-diketone and N-donor coordination modes. Thus, Zn2+ or Pd2+ reacted with HL like
ligand, resulting in a product containing indiscriminate N-donor and β-diketone
coordination to Zn2+ or Pd2+ ions.[50, 56-58] Here, we opted to synthesize
β-diketone-hard metal complex first as a metalloligand (see Scheme 2).[36-40, 59-62]
Indeed, when the ligand reacted with M(NO3)3 (M= Al3+ or Fe3+) in a 3:1 ratio in the

presence of NaHCO3 as a base, a neutral metalloligand M(L)3 was afford as a white or
red powder. Each of the tripodal M(L)3 metalloligand with three N-donors can
coordinate to three Pd2+ ions, leading to a heterometallic supramolecular complex, in
which each Pd2+ ion may be further coordinated by two labile chlorides to meet
charge balance and coordination saturation. It should be pointed out that the
introduction of labile ligand such as chloride will be benefit for catalysis. Neutral
complex 1 was prepared by layering a solution of PdCl2 in DMSO over a solution of
Al(L)3 in CH2Cl2. While complex 2 was obtained by layering a solution of Fe(L)3 in
MeOH over a solution of Pd(MeCN)2Cl2 in DMF.
Scheme 2. Synthesis of heterometallic M2Pd3 supramolecular cages via the
metalloligand strategy.
Complexes 1 and 2 are not soluble in common solvents such as MeOH, CHCl3 and
DMF. Due the crystals easy effloresce under atmosphere, the lower boiling point
solvent molecules are tried to be removed by drying at 150 °C under vacuum for 24 h
before analysis.Elemental analyses and thermogravimetric analysis (TGA, see Figures
S1 and S2) were used to determine the number of the solvent molecules. It was found
that there were two DMSO and two DMF molecules in complexes 1·2DMSO (7.41%

in theory vs 7.75% in experiment) and 2·2DMF (6.80% in theory vs 7.20% in
experiment), respectively, from the TGA curves.
3.2. Structural Analysis and Characterization
In order to observe the structure of the heterometallic supramolecular cage, single
crystal structures of 1·5DMSO·3CH2Cl2 and 2·3DMF·MeCN·H2O were measured by
X-ray crystallography, respectively. They crystallize in the P-1 space group. The
heterometallic supramolecular cages are indeed confirmed as shown in Figure 1. Each
cage consists of two homochiral M(L)3 fragments in ΔΔ or ΛΛ configurations that are
linked by three PdCl2 units. Thus each cage molecule is chiral, indicating that the
homochiral assembly between M(L)3 metalloligands occurs during the course of
reaction with Pd2+. The similar case was also observed in [Al2Zn3Br6(L1)6] (L1 is
1-(4-pyridyl)butane-1,3-dione) cage,[40] but a mesocate was reported in
[Ti2Pd3Br6(L2)6]4+ (L2 is 4-PPh2-catechol) cage,[36, 37] this may relate to the ligand
structure. However, there are a pair of enantiomeric molecules (ΔΔ and ΛΛ) in each
unit cell, they are racemate and crystallize in achirality. The M2Pd3 heterometallic
supramolecular cage may be described as a trigonal bipyramid, two M3+ cations
situate at the axial corners with a M⋯M distance of 19.71 Å for 1 and 20.11 Å for 2
and three Pd2+ cations locate in the equatorial plane with a Pd⋯Pd distance of
9.99-11.04 Å for 1 and 9.78-10.43 Å for 2. The M⋯Pd distances are in the rang
11.43-11.75 Å and 11.47-11.98 Å for 1 and 2, respectively. These much enlongate the

distances between Pd2+ ions and form larger rhombic windows, comparison with
those of the reported heterometallic cages [Al2Zn3Br6(L1)6] (Al···Al = 11.26 Å)[40]
and [Ti2Pd3Br6(L2)6]4+ (Ti···Ti = 6.76 Å).[36, 37] Each M3+ ion is triply chelated by
the β-diketonate moieties of L ligand in a slightly distorted octahedral geometry with
the fac configuration, indicating that an isomerization process (from mer to fac) may
occurs during the course of assembly to form cage structure. The Al–O and Fe–O
distances are in the range 1.860(5)–1.893(5) Å and 1.968(6)–2.017(6) Å, respectively,
which are consistent with the reports.[40] Each of Pd2+cation is coordinated by two
N-donors from the imidazolate of L ligand and two chloride anions in a square planar
with a trans configuration (Cl-Pd-Cl = 174-179°, N-Pd-N = 174-178°). The bond
distances of Pd–N and Pd–Cl are in the range of 1.998(5)–2.015(6) Å and
2.2896(17)–2.3141(19) Å for 1, and 1.994(7)–2.024(6) Å and 2.282(2)–2.299(3) Å
for 2, respectively.
Figure1. Crystal structures of homochiralheterometallic [M2Pd3(L)6Cl6] supramolecular cages
-atomsand solvents are omitted for clarity. Color code: gray, C; blue,
N; red, O; green, Cl; orange, Pd; teal, M (Al, Fe). Selected bond distances (Å) and angles (°) for 1
and 2 (in parentheses):M1⋯Pd1 = 11.655(2) (11.569(5)), M1⋯Pd2 = 11.605(2) (11.556(4)),
M1⋯Pd3 = 11.458(2) (11.840(3)), M2⋯Pd1 = 11.494(2) (11.581(3)), M2⋯Pd2 = 11.434(2)
(11.473(4)), M2⋯Pd3 = 11.759(2) (11.982(6)), Pd1⋯Pd2 = 9.999(1) (10.354(2)), Pd1⋯Pd3 =
10.332(1) (9.787(4)), Pd2⋯Pd3 = 11.044(1) (10.429(3)) and M1⋯M2 = 19.713(2) (20.110(2));

Pd1-M1-Pd3 = 58.1(1) (49.4(1)), Pd1-M1-Pd2 = 50.9(2) (53.2(2)), Pd2-M1-Pd3 = 57.2(1)
(52.9(2)), Pd1-M2-Pd3 = 52.8(1) (49.1(2)), Pd1-M2-Pd2 = 51.7(2) (53.4(2)), Pd2-M2-Pd3 =
56.8(1) (52.8(2)), Cl-Pd1-Cl = 175.5(1) (178.1(1)), N-Pd1-N = 177.3(1) (178.1(2)),
Cl-Pd2-Cl = 178.7(2) (174.6(2)), N-Pd2-N = 174.2(1) (178.4(1)), Cl-Pd3-Cl = 179.0(1)
(178.5(2)) and N-Pd3-N = 174.6(1) (177.7(1)).
The powder X-ray diffraction (PXRD) of complexes 1 and 2 were also collected,
respectively (see Figure S3). The discrepancies in PXRD patterns based on the
stimulation from single-crystal structures and the as-synthesized samples remain,
these might result from preferred crystallite orientation and anisotropic particle
broadening. TGA of the as-synthesized samples showed that they lost solvent
molecules as the temperature was elevated. Complex 1 decomposed when the
temperature reached about 250 °C, and 2 at about 290 °C, indicating that they have
good thermal stability.
3.3. Catalysis for the Suzuki-Miyaura Coupling Reaction
To evaluate the catalytic activity of the synthetic catalysts, 4-bromoacetophenone
and phenylboronic acid were used as model compounds for the Suzuki–Miyaura cross
coupling reaction in the presence of 1 (0.05 mol%) as a catalyst and K2CO3 as a base
in H2O under ambient atmosphere at 60 °C for 1 h (Table 2, entry 1). However, the
yield was found only in 14%. To our delight, when EtOH was used as a solvent, the
monitor experiment revealed that the halide substrate was completely converted into
target product (entry 2), indicating that complex 1 is an efficient catalyst for the
Suzuki–Miyaura coupling. We also found that catalyst 1 is high activity for the
Suzuki–Miyaura coupling in the mixture solvent of EtOH and water (entry 3-5).

However, the catalyst turned from pale yellow to grey black, indicating Pd2+ ion may
be leached out in some degree during the reaction. That is unfavorable to recycle and
reuse the catalyst. Form the view of green chemistry, the eco-friendly and
biorenewable solvents, such as water, ethanol and glycerol, are welcome.[63] When
biorenewable solvent glycerol was used instead of EtOH, the target product was
afforded in 46%, but increase to 99% at 80 °C. Importantly, catalyst 1 maintained pale
yellow initial color after reaction. Base has been regarded as a significant factor in the
Suzuki–Miyaura coupling, thus, we turned our attention to test the impact of base
(entry 7-12). The experiments revealed that K2CO3 is the best one. Na2CO3 has a
similar effect and is superior to other bases, such as KOH, NaOH, K3PO4 and
NaHCO3. Moreover, low catalyst loading tests were performed in order to find out the
efficiency of the catalyst. We found that the conversion of the reaction would be
completed in 2 h in the presence of 0.02 mol% catalyst 1, but the yield was decreased
to 84% when 0.01 mol% 1 was used in 4 h.
Table 2. Optimization of the Suzuki-Miyauracoupling conditions under ambient atmosphere a
Entry
1
2
3
4
5
6
7
8
Catalyst
Solvent
H2O
EtOH
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaHCO3
K3PO4
KOH
Yield (%)b
14
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
99
94
90
99
EtOH/H2O(1:1)
EtOH/H2O(2:3)
EtOH/H2O(3:2)
glycerol
46
99c
96c
61c
55c
15c
19c
91c,d
99d,e
84f
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
9
10
11
12
13
14
15
NaOH
K2CO3
K2CO3
K2CO3
glycerol

16
17
18
19
2
2
glycerol
glycerol
glycerol
glycerol
K2CO3
K2CO3
K2CO3
K2CO3
99d,e
82f
<5e
83e
PdCl2
PdCl2+HL
a
Reaction conditions: 4-bromoacetophenone (1.0 mmol),
phenylboronic acid (1.1 mmol), catalyst (0.05 mol%), and base (1.5
mmol) in solvent (4.0 mL) under ambient atmosphere at 60 °C for 1
h.bYield was determined by 1HNMR with mesitylene as internal
standard.c 80 °C,1h. dcatalyst 0.02 mol%. e80 °C, 2 h.fcatalyst 0.01
mol%, 80 °C, 4 h.
The catalytic activity of catalyst 2 was also evaluated under the optimal conditions
(entries 16 and 17). The yield is 99% in the identical conditions, indicating that
catalysts 1 and 2 have excellent catalytic activity for the Suzuki-Miyaura coupling
under the reaction conditions. These may be attributed to the stronger electron-rich
effect of imidazolyl group in HL ligand, which favors both the oxidative addition and
reductive elimination steps in the catalytic cycle.[25, 64-66] Moreover, the control
experiments were also performed. When PdCl2 was employed as a catalyst, only a
little product was found. The addition of ligand HL to the above reaction solution, the
yield markedly increased to 83% under the reaction conditions, but the catalyst turned
to black at the end of reaction and hard to be reused, indicating that the formation of
heterometallic cage benefits to increase the stability of catalyst and catalytic activity.
With the optimized reaction conditions in hand, the scopes and limitations of the
catalytic reaction were examined. Under the optimal conditions, a variety of
substitutions of electron-withdrawing such as COCH3, CHO, CN, and NO2 groups on
arylbromide completely converted into the corresponding target products in yield of
99% (Table 3, entry 1-4). These functional groups would be readily used as sources
for further derivations. Moreover, the reaction activity of the electron-neutral
substrate bromobenzene is slightly inferior, affording in 83% yield, but increase to 99%

via extension the reaction time to 4 h. For more challenging electron-donating aryl
bromides, with the exception of ortho-methyl aryl bromide (15%), the yields were
good in 86–96% (entry 6-9) when the temperature was set at 90 °C for 4 h. The lower
yield of the ortho-substituent demonstrated that steric effect of the aryl bromide was
sensitive to the reaction. In addition, reactions using other aryl boronic acids (entry
10-14) were also performed, and the corresponding biaryl products were obtained in
good to excellent yields, regardless of electron-deficient and electron-rich
phenylboronic acid, suggesting the electronic character of the substituents has
minimal impact on the reaction. Finally, a dual Suzuki-Miyaura coupling formation of
a polyaromatic compound in one-pot was also performed under the optimal conditions.
1,4-dibromobenzene reacted with phenylboronic acid efficiently, affording the target
product p-terphenyl in yield of 99% in 4 h (entry 15). No monocoupling product was
observed.
Encouraged by the high activity of the catalyst 1, the coupling reactions of aryl
chlorides with phenylboronic acid were observed (entry 16-21), which is much more
difficult than aryl bromide because of the lager bond energy of C-Cl bond, and
harsher reaction conditions are required. To our delight, the activated aryl chlorides
with electron-withdrawing groups gave 98-99% yield in the presence of 0.1% catalyst
1 at 110 °C, whereas an inactivated one gave 66-90% yield. Unfortunately, only trace
product was obtained for the strong electron-rich aryl chloride (entry 21).
These results demonstrate the broad substrate scope and high catalytic efficiency of
catalyst 1 for the Suzuki-Miyaura coupling reaction. The highly catalytic activity of

the catalyst 1 may be attributed to the distinct cage structure with rigid geometry that
allows the catalytic center in a single site and maximum exposure to substrates.
Notably, the catalytic reactions are under mild conditions, not requiring the exclusion
of air and water.
Table 3. The Suzuki-Miyaura coupling catalysed by 1.
a Reaction conditions: aryl halide (1.0 mmol), aryl boronic acid (1.1mmol), catalyst 1 (0.02 mol%), and K2CO3 (1.5 mmol) in
glycerol (4.0 mL) under ambient atmosphere at 80 °C for 2 h. b Yield was determined by 1HNMR with mesitylene as internal
standard. c80 °C, 4 h. d 90 °C, 4 h. e Phenylboronic acid 2.2 mmol, 3.0 equivK2CO3. f catalyst 0.1 mol%, 110 °C, 4 h.

3.4. Heterogeneity Test and Catalyst Reuse
Leaching of Pd from the catalyst is a vital topic in coupling reaction in
heterogeneous reaction. To verify this matter, a hot filtration test was performed.[67]
When the coupling reaction of 4-bromoacetophenone and phenyl boronic acid was
triggered under the optimal conditions in about 30 min (ca. 51% conversion
1
determined by H NMR), the liquid phase was collected by hot filtration at the
reaction temperature to remove the catalyst. Then, 1.5 equiv of K2CO3 was added to
the filtrate, and the mixture was stirred for another 1.5 h at the reaction temperature.
1
After that, H NMR analysis of the reaction solution indicated that no further
cross-coupling occurred (see Figure 2), demonstrating that catalyst 1 has a good
heterogeneous natureand no active species leached into the liquid phase under the
reaction conditions. In addition, ICP-AES analysis showed that no detectable
palladium was observed in the filtrate after reaction. These result simply that the Pd is
not leached out from the supramolecular cage 1 during the reaction because of the
strong interaction between Pd(II) ion and ligand via coordination bonds and catalyst 1
seems to catalyze the couplingin a truly heterogeneous manner.

Figure 2. Time conversion plot for the Suzuki-Miyaura reaction conditions (Table 3, entry 1).
One of the reactions (black) was carried out in the presence of catalyst 1, for the other (red),
catalyst 1 was filtered and the reaction mixture was allowed to continue the reaction.
The recovery and reuse of a heterogeneous catalyst are of great importance from
the views of industry, economy and green chemistry. Therefore, tests of the
recyclability of catalyst 1 were carried out using the model reactions,
4-bromoacetophenone and phenylboronic acid under the optimal conditions. After
each cycle, the final product was extracted with dichloromethane several times and
1
analysed by H NMR. As depicted in Figure 3, the recovered catalyst 1 was
subsequently used in at least five successive cycles without loss of catalytic activity.
PXRD pattern of the reused catalyst 1 showed that the structural integrity of the
framework was mostly maintained (see Figure 4), indicating that the supramolecular
cages are robust and stable under the reaction conditions. To observe the state of Pd
after catalytic reaction, XPS analysis was performed for the recovered catalyst 1 after
the first and the fifth run of the Suzuki−Miyaura coupling reactions. They both exhibit
a Pd 3d5/2 band at338 eV and a Pd 3d3/2 band at 343 eV, respectively, which are
characteristic of Pd2+.[68] The weak peaks at 335 and 341 eV are ascribed to the Pd(0)
3d5/2 and 3d3/2, respectively (see Figure S4).[69] Meanwhile, transmission electron
microscopy (TEM) images of the recycled catalyst 1 also showed that a spot of Pd(0)
particles in situ generation during the coupling reaction were uniformly dispersed on
the surface of the supramolecular cages and no aggregation Pd(0) nanoparticles were
observed (see Figure S5). Therefore, the catalyst is still highly efficient and can be
reused.

On the basis of the aforementioned studies, a plausible mechanism is suggested. In
the coupling reaction, the Pd2+ in catalyst 1 seems to undergo a reversible process, in
which Pd2+ is reduced to Pd(0) and immediately oxidized back to the initial Pd2+ state
in situ after the catalytic cycle under the air atmosphere. The distinct coordination and
stable structure in supramolecular cage of catalyst 1 plays a key role to reserve the
chemical microenvironment of the Pd2+ center sites, not only isolating Pd2+ in a single
site, but also preventing the agglomeration of active Pd(0) species into Pd black.
Figure 3. Durability test of catalyst 1 in the Suzuli-Miyaura reactionof 4-bromoacetophenone and
phenylboronic acid under the optimal
Figure 4. PXRD patterns of the as-synthesized sample of 1 and the recovery catalyst 1.

Conclusions
In summary, neutral heterometallic M2Pd3 supramolecular cages with a trigonal
bipyramid geometry have been successfully assembled via metalloligand strategy on
the basis of HSAB theory. Homochiral assembly and isomerization of the tripodal
M(L)3 metalloligands occurred during the course of assembly with Pd2+. The
molecular cages exhibit high catalytic activity for the Suzuki–Miyaura coupling
reaction under mild conditions and can be readily recycled and reused at least five
times without loss of catalytic activity. The excellent catalytic activity can be
attributed to the distinct properties of the cage structure in uniformly distributive and
well-defined Pd active centers on the cage surfaces. This finding would provide a
complementary strategy on design and synthesis of new catalyst for heterogeneous
reaction.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant
no. 21272284 and 21571195).
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Graphical abstract
Neutral heterometallic M2Pd3 supramolecular cages with a trigonal bipyramid
geometry have been successfully assembled via the metalloligand strategy on the
basis of HSAB theory and exhibit high catalytic activity for the Suzuki–Miyaura
coupling reaction in a biorenewable solvent under mild conditions.

Highlights
·Developed heterogeneous single-site M2Pd3 catalyst to prolong catalyst lifetime.
·Highly efficient and recyclable supramolecular catalyst for Suzuki–Miyaura reaction
·Both aryl bromine and aryl chloride were suitable substrates.
·Mild recation conditions and environment-friendly