Confinement Self-Assembly of Metal-Organic Cages within Mesoporous Carbon for One-Pot Sequential Reactions

Full text of DOI:10.1016/j.chempr.2020.06.038

ll
Article
Confinement Self-Assembly of Metal-Organic
Cages within Mesoporous Carbon for One-Pot
Sequential Reactions
Fan-Fan Zhu, Li-Jun Chen,
Shangjun Chen, ..., Yi Qin, Lin
Xu, Hai-Bo Yang
lijun.chen@sydney.edu.au (L.-J.C.)
hbyang@chem.ecnu.edu.cn (H.-B.Y.)
HIGHLIGHTS
Combined features of discrete
metal-organic complexes and
mesoporous carbon materials
Improved stability of metal-
organic cages after confinement
self-assembly
Othogonal feature of isolated
catalytically active sites within the
bifunctional catalyst
Enhanced catalytic activities,
selectivity, and recyclability for
one-pot reactions
The introduction of well-defined M12L24 cages into amino-functionalized
mesoporous carbon has resulted in a new heterogeneous catalyst for one-pot
sequential reaction with the improved stability and activity in transferring alcohols
to a, b-unsaturated dinitriles. This system was found to be highly active, selective,
and recyclable, thereby opening a new avenue for the development of metal-
organic assemblies for heterogeneous catalysis in sequential reaction.
Zhu et al., Chem 6, 1–12
September 10, 2020 ª 2020 Elsevier Inc.
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Please cite this article in press as: Zhu et al., Confinement Self-Assembly of Metal-Organic Cages within Mesoporous Carbon for One-Pot
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Article
Confinement Self-Assembly of Metal-Organic
Cages within Mesoporous Carbon
for One-Pot Sequential Reactions
1
1,
2
1
1
1
Fan-Fan Zhu, Li-Jun Chen, * Shangjun Chen, Gui-Yuan Wu, Wei-Ling Jiang, Ji-Chuang Shen,
Yi Qin, Lin Xu, and Hai-Bo Yang1,3,*
1
1
SUMMARY
The Bigger Picture
Well-defined discrete metal-organic cages have been widely explored
in the field of supramolecular catalysis. However, these metal-organic
cages have been rarely explored as heterogeneous catalysts for
one-pot reactions. Herein, we present the first successful confinement
self-assembly of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)-
containing metal-organic cages within amino-functionalized mesopo-
rous carbon to realize a new family of bifunctional heterogeneous
catalyst (Cage@FDU-ED) for one-pot reactions. The orthogonal fea-
tures of the isolated catalytically active sites within the obtained
bifunctional catalyst lead to enhanced catalytic activities, selectivity,
and recyclability with the overall transformation yielding up to 96%
conversion. These results demonstrate that continuous chemical
transformation with high efficiency is possible through careful design
of catalytic sites in both metal-organic cages and mesoporous matrix
isolatedly. This study paves a new way toward metal-organic cages as
a promising platform for heterogeneous sequential reactions.
Well-defined discrete metal-
organic cages have been very
attractive in the field of
supramolecular catalysis.
However, their potential to serve
as heterogeneous catalysts for
one-pot reactions remains
unexplored. Herein, we present
the success of confinement self-
assembly of TEMPO-containing
12
M L24 cage within the cavity of
amino-functionalized
mesoporous carbon FDU-ED,
which gave rise to a highly
efficient heterogeneous catalyst
for one-pot oxidation-
Knoevenagel condensation
reaction. The orthogonal feature
of the isolated catalytic sites
within the obtained bifunctional
heterogeneous catalyst leads to
enhanced catalytic activities,
selectivity, and recyclability for
the overall transformation, which
provides valuable information and
methodology for design of the
next-generation heterogeneous
catalysts based on
INTRODUCTION
Well-defined discrete metal-organic cages have been very appealing in the field of
supramolecular catalysis because they can provide relatively rigid and hydrophobic
1
–8
cavities that may mimic binding pockets in enzymes.
Well-known examples
include Fujita’s ‘‘molecular flasks’’ for unusual regioselectivity in a Diels–Alder reac-
9
tion, Reek’s pre-organization of substrate inside coordination nanospheres to
1
0
accelerate cyclization, and Raymond’s faster alkyl–alkyl reductive elimination
1
1
4 6
within a Ga L cavity, etc. However, due to the dynamic nature of coordination
bonds, their instability has inhibited their catalytic activity in some cases. Moreover,
for efficiently catalyzing a reaction through recovery and recycling of catalyst, the
fabrication of heterogeneous catalysts is generally required but is still a great chal-
1
2–15
supramolecular architectures. The
longer-term ambition is to put
forward a new platform for the
advent of catalysts with unique
and exciting reactivity.
lenge for supramolecular catalysis.
formance lies in the confinement of metal-organic architectures in porous materials,
One possible strategy to improve their per-
1
6–20
including metal-organic frameworks (MOFs), mesoporous carbon and silica.
In
2
0
18
19
the earlier reports by Zhou, Li and our group, it is found that the stability of
metal-organic assemblies have been significantly enhanced in the confined meso-
pores. Therefore, self-assembly of discrete metal-organic architectures within a
confined space has recently evolved to be one of the most attractive topics within
supramolecular chemistry and materials science.
It should be noted that, although great achievements have been obtained in the
field of confinement self-assembly, only very limited examples have been explored
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Scheme 1. Schematic Presentation of Bifunctional Heterogeneous Catalyst for One-Pot
Sequential Reaction via Confinement Self-Assembly
1
8–20
as heterogeneous catalysts.
In particular, their potential to serve as heteroge-
neous catalysts for one-pot reactions remains unexplored. Note that one-pot reac-
tion can avoid tedious isolation and purification of the reaction intermediates,
2
1,22
thus allowing for a simpler and greener process.
A methodology that enables
continuous chemical transformation in a manner reminiscent of enzymatic catalysis
2
3–25
is catalytic site-isolation within one system to facilitate one-pot catalysis.
We
envision that careful introduction of catalytic sites in both metal-organic cages and
mesoporous matrix separately (Scheme 1) might provide a new approach to realize
continuous chemical transformations. The advantages of mesoporous structures
2
6–32
containing metal-organic structures include size control, sites adjustment
and
unique confinement effects on a molecular scale, thus allowing for spatially isolated
catalysis akin to enzyme catalysis. Besides, the thermally stable, porous, solid nature
of the obtained hybrids facilitates easy access of substrates to the catalytic sites and
separation of products from the catalyst.
RESULTS
Design and Synthesis of Cage@FDU-ED
The coordination metal-organic cages we explored in this study are M12L24 cages
decorated with TEMPO catalytic moieties (Cat. Site I) that show catalytic activity
4
toward oxidation reactions. Following the literature reported strategy, the
TEMPO-containing M12
ditopic ligands (L, Scheme S1) and 12 Pd(II) ions in MeNO
Scheme S2). The formation of M12 24 complexes was successfully confirmed by
L
24 cage C can quantitatively self-assemble from 24 bent
2
or H O-MeNO mixtures
2
2
(
L
electrospray ionisation time-of-flight mass (ESI-TOF-MS) spectrum, in which the
peaks were isotopically resolved and agreed well with theoretically predicted distri-
bution (Figure S1). The size distribution profile in dynamic light scattering (DLS) anal-
ysis was in good agreement with the theoretical dimension of M12
ure S2), thus ruling out the formation of polymeric species. Taking into account
that the dimension of the TEMPO-containing M12
24 cage C is ꢀ4.6 nm, a mesopo-
rous carbon material with three-dimensional (3D) cage-type cubic (Im3m) struc-
L24 cage (Fig-
1Shanghai Key Laboratory of Green Chemistry
and Chemical Processes, Chang-Kung Chuang
Institute, School of Chemistry and Molecular
Engineering, East China Normal University,
Shanghai 200062, China
L
3
3–37
ture
was adopted as substrate, and an amine modification of mesoporous sub-
3
7
2
Department of Chemistry, Shanghai Normal
strate (FDU-ED) was performed to provide Cat. Site II. The synthesis of FDU-ED
was presented in experimental procedures (see detailed structure information about
FDU-ED in Scheme S4). As evidenced by powder X-ray diffraction (PXRD, Figure S8),
small-angle X-ray scattering (SAXS, Figure S9), transmission electron microscope
University, Shanghai 200234, China
3Lead Contact
*Correspondence:
lijun.chen@sydney.edu.au (L.-J.C.),
hbyang@chem.ecnu.edu.cn (H.-B.Y.)
(
TEM, Figure S10), as well as the N
2
adsorption-desorption tests (Figure S11; Table
S2), FDU-ED possess structures and cavities similar to those of parental mesoporous
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Scheme 2. Self-Assembly of M12L24 Cage C in Cavities of Mesoporous Carbon FDU-ED to
Generate Cage@FDU-ED
carbon material FDU-16. It should be noted that the cavity of FDU-ED was ꢀ6.0 nm,
which is large enough to accommodate the TEMPO-containing M12L24 cage within
the confined space. Moreover, the organic element analysis results (Table S1) and
Fourier transform infrared (FTIR) spectra (Figure S12) of FDU-ED supported the ex-
istence of amino moieties in FDU-ED substrate. In order to check whether the amino
units will interfere with the formation of metal-organic M12
L24 cage, we first per-
formed the self-assembly of M12 24 cage C in the presence of diethylamine. It was
L
1
found that the H NMR signal with diethylamine was consistent with that of pure
cage (Figure S3). However, due to the paramagnetic shifts derived from the nitroxyl
radical, no significant signal was detected in either cases. Thus, a ditopic precursor
0
0
ligand L was used to construct a model M12
L
24 cage C (Scheme S3) under different
1
conditions to give more evidences. In the H NMR spectrum, the notably identical
0
downfield shifts of the pyridine protons compared with free ligand L were observed
in MeNO
amine (Figure S4), indicating that the sphere cage formation was not interfered with
water or amines. The formation of M12 24 complex was further successfully
2 3 2 3 2
-d , or in a mixture of MeNO -d -D O, as well as in the presence of diethyl-
L
confirmed by ESI-TOF-MS spectrum, in which a series of peaks with continuous
4ꢁ
charge states corresponding to losing different numbers of BF counterions were
detected and peaks were isotopically resolved in good agreement with theoretical
simulations (Figure S5). The observation of a distinct band at log D = ꢁ10.02 in
2
D diffusion-ordered spectroscopy (DOSY) (Figure S6) and well size matching with
theoretical dimension of M12
L24 cage in DLS measurement (Figure S7) suggested
the formation of a sphere cage product rather than polymetric species.
To perform the confinement self-assembly of M12
mesoporous substrate, FDU-ED was first added into H
.0 h, followed by addition of a small amount of hydrophobic nitromethane solution
containing [Pd(CH CN) ](BF , and then to which a minimum amount nitromethane
solution of dipyridyl ligand was added dropwise (Scheme 2; Figure S13). Based on
the above experiments results, self-assembly of M12 24 cage can then take place
L
24 cage inside the cavities of the
2
O with vigorous stirring for
2
3
4
4 2
)
L
in FDU-ED pores. Moreover, presumably, according to the sizes of cage C and cav-
ities in FDU-ED, the migration and leaching of the cage C can be prohibited because
the pore windows (ꢀ 3.0 nm) are smaller than the dimension of the cage (ꢀ 4.6 nm).
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The obtained hybrid materials Cage@FDU-ED were subsequently separated by
centrifugation and washed with a large quantity of nitromethane to remove the phys-
isorbed cages on the FDU-ED surface.
Characterization of Cage@FDU-ED
The actual Pd contents doped within the FDU-ED were measured by ICP, from which
the doping mass fraction of cage was determined to be 7.89% (Figure S14; Table S3).
The incorporation of M12L24 cage in FDU-ED was further confirmed by FTIR spectros-
copy, in which the spectrum of Cage@FDU-ED exhibited the characteristic bonds of
both cage and FDU-ED (Figure S15). For example, the peaks at 1,738 and
ꢁ
1
1
,605 cm were assigned to the C=C and C=N stretching frequencies in FDU-
ꢁ1
ED, respectively, and the peak at 2,220 cm was assigned to ChC stretching in
the cage skeleton. No obvious shifts were observed between the Cage@FDU-ED
and pristine cage C, indicating that the cage in FDU-ED pores preserved its original
structure.
The crystallinity of Cage@FDU-ED was examined by PXRD and SAXS. In both PXRD
(
Figure S16) and SAXS patterns (Figure 1A), Cage@FDU-ED showed diffraction
peaks similar to the parent pristine FUD-ED, thus demonstrating the well maintain-
ing of crystalline mesostructures after the cage incorporation. The TEM images of
Cage@FDU-ED viewed along the [100], [110], and [111] directions, together with
the corresponding fast Fourier transform (FFT) patterns (Figures 1D–1F and S17),
verified its highly ordered cubic structure. The N
of the parent FDU-ED and the composited sample Cage@FDU-ED both exhibited a
typical IV type isotherm and a H -type hysteresis loop in the P/P region of 0.4–0.6
Figures 1B and S18), which demonstrated again that the well-ordered mesostruc-
2
adsorption-desorption isotherms
2
0
(
tures were precisely maintained after the cage incorporation. Meanwhile, compared
with the parent samples FDU-ED, the hysteresis loop of shifts to the lower relative
2
pressure with BET surface areas decreased from 515 to 395 m /g after the introduc-
tion of cages (Table S4), indicating the successful incorporation of the cage within
the FDU-ED cavities.
In addition, N and Pd elements were presented obviously in the X-ray photoelectron
spectroscopy (XPS) survey spectrum of Cage@FDU-ED (Figure S19) and the Pd XPS
spectra of both cage and Cage@FDU-ED exhibited the typical characteristics of Pd
(
II) ions at ꢀ338.8 eV (Pd 3d5/2) and ꢀ344.0 eV (Pd 3d3/2), respectively, without
apparent differences (Figure 1C). This result revealed no strong electron interaction
between the cage and substrate present in the composites Cage@FDU-ED. The el-
ements Pd and N are homogeneously distributed in the whole sample in energy-
dispersive X-ray spectroscopy (EDS) elemental mapping (Figures 2H and S22) of
Cage@FDU-ED. Besides, no distinct aggregation was observed in both TEM (Fig-
ures S20B–S20D) and high-angle annular dark-field scanning transmission electron
microscopy (HAADF-STEM) (Figures 2G and S20A), suggesting that the cages
were uniformly dispersed in the mesopores without aggregation. These results
were further confirmed by scanning electron microscopy (SEM) and the correspond-
ing mapping analysis (Figure S21).
All above results evidenced the homogeneously distributed of Pd-organic species
inside the mesoporous substrate, however, some may argue that those Pd-organic
species are polymeric species rather than defined cages. Since direct evidence of
the exact structure of the species inside the cavity is very challenging to obtain,
0
we designed a series of control experiments by using model cage C which can be
1
characterized by H NMR to provide more information. First, a similar cage-type
4
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Figure 1. Structural Characterization of Composite Materials Cage@FDU-ED
(
(
(
(
(
2
A and B) (A) SAXS patterns and (B) N sorption isotherms of Cage@FDU-ED and mesoporous matrix FDU-ED.
C) XPS spectrum of cage C and Cage@FDU-ED.
D–F) TEM image with the corresponding FFT pattern (top right inset) of ultrathin cuts from hybrid materials Cage@FDU-ED recorded along the [100]
D), [110] (E), and [111] (F) directions.
G and H) (G) HAADF-STEM image and (H) the corresponding elemental mapping images.
0
mesoporous substrate FDU-ED , which process a cavity size of about 4.0 nm (Fig-
ure S23A) was adopted as a control substrate. In this case, the dimension of
M
12
L
24 cage (ꢀ4.6 nm) is larger than the pore size (ꢀ 4.0 nm), thus, cage cannot
self-assemble inside the cavities. Indeed, no Pd contents were detected in ICP
test (Figure S23B) of solid materials obtained from the same procedure following
1
prepare Cage@FDU-ED. At the same time, the H NMR spectra of the filtrate
0
composition were identical to those of pure cage C (Figure S24), demonstrating
the mesoporous substrate themselves did not interfere the self-assembly of
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Figure 2. Catalytic studies of Cage@FDU-ED
(
(
(
(
A) Scheme for the sequential reaction of alcohol (Cage@FDU-ED as catalyst).
B) Oxidation-Knoevenagel condensation profile of alcohol 1.
C) The kinetic monitoring of the oxidation reaction under different control experiments.
D) Recyclability experiments of Cage@FDU-ED.
12
M L24 cage. These results also indicted that the cavity size of mesoporous substrate
is importance when performing confinement self-assembly to produce hybrid mate-
rials. Another mesoporous substrate FDU-15-ED, which displayed a highly ordered
2
-D p6m hexagonal structure, was also used to perform confinement self-assembly.
In this case, the relatively larger pores and channels of the structure make it possible
to elute the self-assembled species inside the channel after the confinement self-as-
sembly by washing with a large quantity of solvent. As shown in Figure S25, self-
assembled species (presumably M12L24 cages) were dispersed in the mesopores
without aggregation in TEM measurements. After wash with nitromethane for
several times, the Pd contents almost disappeared (Figure S26; Table S5). The ob-
0
1
tained eluent displayed characteristic signals as pure cage C in H NMR test, indi-
cating that the self-assembled species inside the channel were M12 24 cages
Figure S27). Since FDU-ED has chemical components and environment similar
to FDU-15-ED, combing all above results, we concluded that the self-assembled
L
(
Pd-organic species inside the cavities were M12
species.
L24 cages rather than polymeric
Thermal stability of M12L24 cage C was then studied by using differential scanning
calorimetry (DSC) and thermal gravimetric analysis (TGA) measurements, in which
thermal effects are observed separately but in parallel with the mass loss over a
wide range of temperatures. The DSC thermogram for pure cage C shows a strong
ꢂ
endothermic effect around 215 C (Figure S28B, blue line) which may relate to cage
collapses, but still does not involve mass loss. At a higher temperature, above
ꢂ
2
45 C, the exothermic signal is now correlated with the mass loss of this sample
as recorded in TGA (Figure S28A, blue line). In the case of Cage@FDU-ED, no endo-
ꢂ
ꢂ
thermic or exothermic effects appeared in temperatures of 200 C–280 C. Instead,
ꢂ
the endothermic effects initiated at the temperature around 330 C appear (Fig-
ꢂ
ure S28B, red line), while mass loss starts at temperature 350 C (Figure S28A, red
6
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Table 1. Catalyst Evaluation in the One-Pot Reaction
a
b
Ent.
Subs.
Cat.
step 1
ꢁ
Cat. Loading
Time
Total Conv. [%]
Yield [%]
c
d
e
f
step 2
[%]
[%] or mg
A (h)
4
B (min)
10
ꢁ
2
3
1
2
3
4
5
6
7
8
9
1
1
1
2
1
1
2
2
1
1
1
1
1
1
1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
<2
88
90
ꢁ
<1
88
90
ꢁ
ꢁ
ligand L
cage C
ꢁ
10
10
ꢁ
ꢁ
4
ꢁ
ꢁ
4
ꢁ
ꢁ
cage C
diethylamine
diethylamine
FDU
10%
ꢁ
4
10
10
10
10
10
10
10
10
10
10
10
10
<2
78
83
<1
98
ꢁ
ligand L
cage C
ꢁ
10
10
ꢁ
10%
87
90
<2
98
<2
<2
88
89
90
90
96
9
10%
4
7
20 mg
20 mg
20 mg
20 mg
20 mg
20 mg
20 mg
20 mg
(23 mg)
ꢁ
ꢁ
4
ꢁ
ꢁ
FDU-ED
FDU
ꢁ
ꢁ
ꢁ
ꢁ
<1
<1
88
89
4
10
11
12
13
14
15
ꢁ
FDU-ED
FDU
ꢁ
4
ꢁ
ligand L
cage C
ligand L
cage C
Cage@FDU-ED
10
10
10
10
10
4
ꢁ
FDU
4
ꢁ
FDU-ED
FDU-ED
4
86
88
96
4
2
g
4
ꢁ
a
ꢂ
Reaction performed in CH
3
CN (1.0 mL) for A h at room temperature and/or B min at 60 C.
Amount of substance (50.0 mmol), with concentration 50 mM.
(60.0 mmol) was added as co-oxidant.
Malononitrile (60.0 mmol) was added as reactant.
b
c
PhI(OAc)
2
d
e
Calculation based on TEMPO units.
f
When mesoporous materials were added as catalyst, the amount of catalyst demonstrated in mass (mg).
g
Total mass of the hybrid material Cage@FDU-ED composite.
line). The combined results demonstrate that M12L24 cage C starts to decompose at
ꢂ
3
30 C after being confined in mesopores which is much higher than pure cage
ꢂ
(
215 C), indicating the improved thermal stability of the M12
L24 cage within the
confined space.
Catalytic Performance of Cage@FDU-ED Catalyst toward One-Pot Sequential
Reaction
To demonstrate the utility of our bifunctional Cage@FDU-ED catalyst, a one-pot
3
8,39
alcohol oxidation/Knoevenagel condensation
(Figure 2A), which can be viewed
as two separate steps: a TEMPO-promoted alcohol oxidation followed by an amine-
promoted Knoevenagel reaction, was studied. Initially, we employed a simple
alcohol (4-nitrobenzyl alcohol 1) as a model substrate to evaluate the oxidative cat-
alytic activity of M12
of catalyst gave no conversion of the starting material (Table 1, entry 1). With
PhI(OAc) as a co-oxidant, ligand L (Table 1, entry 2) and cage C (Table 1, entry 3)
L24 cage C homogeneously. The control reaction in the absence
2
exhibited 88% and 90% conversion, respectively, after 4 h of reaction. The kinetic
study for the oxidation reaction (Figure 2C blank line, red line and Figures S31a
and S31b) revealed that cage C retained the same level of reactivity as free ligand
ꢁ1
L and the reactive rate was slightly faster (TOFini of cage C = 53.88 min , TOFini
ꢁ1
of ligand L = 46.80 min (Table S6).
By adding diethylamine, a small molecule catalyst for Knoevenagel condensation,
substantial transformation from aldehyde 2 to benzylidene malononitrile 3 was real-
ized with 90% total conversion and 83% yield of 3 (Table 1, entry 6). The amino con-
taining matrix FDU-ED indeed can act a solid catalyst for Knoevenagel condensation
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as show in Table 1 (entry 8), while the parental material FDU displayed no activity
(
Table 1, entry 7). A control reaction by using aldehyde 2 as starting material (Table 1,
entry 4) indicated that cage C can only promote the first oxidation step. Starting from
alcohol 1, both FDU (Table 1, entry 9) and FDU-ED (Table 1, entry 10) gave no con-
version of starting material, indicating that both the mesoporous matrix and func-
tional amino units did not interfere the first oxidation step. This was also evidenced
by the results from simple mixing ligand L or cage C with mesoporous matrix FDU
(
Table 1, entry 11 and 12) to perform the one-pot reaction, in which only the interme-
diate aldehyde product 2 generated in both cases. Combing the ligand L or cage C
with amino containing matrix FDU-ED gave the formation of finial product benzyli-
dene malononitrile 3 with good yield (86% for ligand L and 88% for cage C). In
this case, the relationship between conversion and reaction time (Figure 2C, blue
line and green line, respectively, and Figures S31c and S31d) for the first oxidation
step are similar to those performed in homogenous solutions (Table S6). Note that
the second step Knoevenagel condensation in all one-pot sequential reactions here-
in went very fast (finished in 10 min). Thus, we only monitored kinetic data of the
oxidation step to compare the catalyst’s activities.
Then, we set out to evaluate the performance of composites Cage@FDU-ED as a
bifunctional heterogeneous catalyst for this one-pot sequential reaction. As shown
in Figure 2B, the alcohol 1 conversion and aldehyde 2 yields gradually increased
to the maximum values within 4 h. After introducing malononitrile into the reaction
solution, the intermediate benzaldehyde 2 yield rapidly decreased with the forma-
tion of benzylidene malononitrile 3 in 96% yield within 10 min (Figures S29 and
S30, NMR&GC). The results verified the capacity of Cage@FDU-ED for one-pot
catalysis. As observed in above control experiments, the one-pot synthesis occurred
in a consecutive manner, and the oxidation being the rate-controlling step. Interest-
ingly, the kinetic monitoring of the oxidation reaction (Figure S31) revealed that
Cage@FDU-ED (Figure 2C purple line) displayed the fastest oxidation rate and high-
est turnover frequency value (Table S6) among all the tests herein. For example, the
ꢁ1
TOFini value of Cage@FDU-ED (261.18 min ) was about five times of those ob-
ꢁ1
tained by simple mixing cage C and FDU-ED (54.54 min ) or in homogenous solu-
ꢁ1
tion (53.88 min ). Taking into account that these catalysts have similar amounts of
catalytic components, we propose that the improved activities should be ascribed to
the high dispersion and good isolation of catalytically active sites inside the compos-
ites Cage@FDU-ED, as M12L24 cages themselves may form aggregates when mixed
with the mesoporous matrix or in homogenous solution.
It should be noted that no further reaction took place without composites Cage@FDU-
ED after ignition of the oxidation reaction at 10 min in leaching test (Figure 2C orange
line and Figure S32), thus demonstrating a typical heterogeneous catalyst nature of
Cage@FDU-ED in this study. Moreover, the Cage@FDU-ED catalyst showed good
reusability for this one-pot reaction sequence. After each catalytic run, the solid cata-
ꢂ
lyst was easily collected by centrifugation, washed with acetonitrile, dried at 90 C, and
reused in the next run under the same conditions. As shown in Figures 2D and S33a, no
obvious decrease in activity was observed and, in fact, the yield of the desired 2-ben-
zylidene malononitrile product 3 remained over 90% after five runs. In contrast, as for
the controlled heterogeneous catalysts ligand L+FDU-ED and cage C+FDU-ED (Fig-
ures 2D, S33b, and S33c), the activities dramatically decreased from the second run,
because of the leaching problem. Besides, the PXRD (Figure S34), TEM (Figure S35),
and ICP (Figure S36; Table S7) measurements of Cage@FDU-ED catalyst after the re-
action did not show obvious changes, suggesting that the bifunctional Cage@FDU-ED
catalytic systems are stable and reusable during the reaction.
8
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Article
Table 2. Cage@FDU-ED Catalyzed One-Pot Sequential Oxidation-Knoevenagel Condensation
Reactions from Alcohols to a, b--Unsaturated Dinitriles
A
B
C
Reaction condition: alcohol (0.05 mmol), Cage@FDU-ED (10 mol % based on TEMPO units) PhI(OAc)
2
ꢂ
(
0.06 mmol), CH CN (1.0 mL) at room temperature and after A h malononitrile (0.06 mmol) at 60 C for B min.
3
Universality of Substrate
Encouraged by the results described above, we extended the study on Cage@FDU-ED
catalyzed one-pot sequential synthesis to other a, b-unsaturated dinitriles from alco-
hols. First, a series of substituted aromatic alcohols were selected as the substrates
and reacted with malononitrile. As monitored by NMR and GC-MS analysis (see
detailed data in Figures S37–S52), both electron-rich and electron-deficient alcohols
were converted into the corresponding Knoevenagel condensation products effi-
ciently in 89%–96% yield (Table 2A), indicating the good tolerance of the resultant cat-
alytic system to a variety of substituent on aromatic nuclei. Compared to benzyl
alcohol, we found that naphthyl methanol needed the longer reaction time and gave
relative lower overall conversions (85%–88%) probably because of the steric conges-
tion of the aromatic group. Furthermore, for trans-cinnamyl alcohol, although the final
condensation products were obtained in moderate yield (68%), the selectivity was well
maintained (Table 2B). At the same time, the catalyst can also convert aliphatic alcohols
into the corresponding condensation products (Table 2C), verifying the general utility
of Cage@FDU-ED for the successive selective oxidation-Knoevenagel reaction.
DISCUSSION
In conclusion, we present a new bifunctional heterogeneous catalyst toward one-pot
sequential reaction through confinement self-assembly of discrete metal-organic ca-
ges in amine-modified cavity-structured mesoporous carbon materials FDU-ED.
Chem 6, 1–12, September 10, 2020
9

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Sequential Reactions, Chem (2020), https://doi.org/10.1016/j.chempr.2020.06.038
ll
Article
With the precise control over the location of different catalytically active sites in
both M12L24 spherical cages and on the FDU-ED matrix separately, the resultant
catalyst Cage@FDU-ED demonstrated excellent performance in the sequential
oxidation-Knoevenagel condensation reaction from alcohols to a, b-unsaturated
dinitriles. By combing the attractive features of metallosupramolecular complexes
and mesoporous heterogeneous catalysts, the resultant Cage@FDU-ED displayed
excellent stability, activity, and recyclability. Because of the easy preparation, fine-
tuned sizes, shapes, and functionalities of both metallosupramolecular complexes
and mesoporous matrix, the confinement self-assembly strategy demonstrated
herein have the potential to allow chemists to easily predict and therefore
design one-pot multistep syntheses based on new heterogeneous catalysts.
Studies aimed at designing new metallosupramolecular complexes-based catalysts
for advanced sequential catalysis applications are currently underway in our
laboratory.
EXPERIMENTAL PROCEDURES
Resource Availability
Lead Contact
Further information and requests for resources and reagents should be directed to
and will be fulfilled by the Lead Contact, Hai-Bo Yang (hbyang@chem.ecnu.edu.cn).
Materials Availability
This study did not generate new unique reagents.
All reagents were of analytical purity and used without further treatment. TLC ana-
lyses were performed on silica-gel plates, and flash chromatography was conducted
using silica-gel column packages. All solvents were dried according to standard pro-
2
cedures and all of them were degassed under N for 30 min before use.
Data and Code Availability
This study did not generate/analyze datasets/code.
Synthesis of FDU-ED
Two-step chemical functionalization strategy was adopted for the preparation of
amine-modified ordered mesoporous carbon. First, the chloromethylation reaction
was carried out by stirring 500.0 mg of mesopolymer in 5.0 mL of chloromethyl
3
methyl ether in the presence of 100.0 mg of anhydrous AlCl catalyst at room tem-
perature for 5.0 h. The chloromethylated sample was washed repeatedly with
distilled water and acetone to remove the physisorbed organic species, and dried
for 2.0 h under dynamic vacuum. The products incorporated with chloromethyl
groups on the inner surfaces of mesopores are denoted as FDU-16-CH
second step, FDU-16-CH Cl was further functionalized with amines under mild con-
ditions. The amination reaction was carried out by stirring 500.0 mg of FDU-16-
CH Cl with 3.0 mL ethylenediamine (ED) at 333.0 K for 6.0 h. The obtained material
2
Cl. In the
2
2
was washed with distilled water and ethanol to remove physisorbed amines, and
finally dried under vacuum at 353.0 K for 6.0 h. Then solid base mesoporous carbon
was obtained, which is denoted as FDU-ED.
Synthesis of Cage@FDU-ED
The double solvent strategy was used for the introduction of cage to amino-function-
alized carbon FDU-ED. FDU-ED was added to H
lowed by addition of a small amount of hydrophobic nitromethane solution contain-
ing [Pd(CH CN) ](BF (Vsolution < Vpore of FDU-ED). The suspension was stirred at room
2
O, stirring vigorously for 2.0 h, fol-
3
4
4 2
)
10
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Please cite this article in press as: Zhu et al., Confinement Self-Assembly of Metal-Organic Cages within Mesoporous Carbon for One-Pot
Sequential Reactions, Chem (2020), https://doi.org/10.1016/j.chempr.2020.06.038
ll
Article
temperature for 30 min, to which a minimum amount nitromethane solution of ligand
L was added dropwise in 10 min under continuous vigorous stirring. Because the in-
ner surface of FDU-ED is more hydrophobic than the outer surface, the small amount
of hydrophobic nitromethane solution easily enters the pores by capillary force. Self-
assembly of M12L24 cage C thus takes place in FDU-ED pores. Afterwards, the sus-
pension was stirred for another 2.0 h. Then, the dark solids were separated by centri-
fugation and wash with a large quantity of nitromethane to remove physisorbed cage
until no Pd traces could be detected in the filtrate. The obtained hybrids solid was
dried for 12.0 h under dynamic vacuum and named as Cage@FDU-ED.
Catalysis Experiments
The experiments were carried out on reaction condition: Alcohol (50.0 mmol),
PhI(OAc)
2
(60.0 mmol), Cat. (10 mol %, (based on TEMPO content) and/or 20 mg
solid matrix), CH
3
CN(1.0 mL) at room temperature and after A h malononitrile
ꢂ
(
60.0 mmol) at 60.0 C for B min. The product and yield of the reaction were moni-
tored by NMR. The crude product was also quantified by GC-MS analysis.
SUPPLEMENTAL INFORMATION
Supplemental Information can be found online at https://doi.org/10.1016/j.chempr.
2
020.06.038.
ACKNOWLEDGMENTS
This work was financially supported by the 973 Program, China (no. 2015CB856600),
NSFC/China (nos. 21625202, 21871092, 21672070), Innovation Program of
Shanghai Municipal Education Commission, China (no. 2019-01-07-00-05-
E00012), and Shanghai Pujiang Program (18PJD015).
AUTHOR CONTRIBUTIONS
F.-F.Z. and L.-J.C. carried out the design, synthesis, and structure characterization;
F.-F.Z. systematic study of the catalytic properties of materials. S.C. was responsible
for the preparation of mesoporous materials FDU-16; G.-Y.W., W.-L.J., and L.X. gave
a lot of help on the drawing diagram and data collection; samples for TEM were pre-
pared by J.-C.S. and Y.Q.; F.-F.Z., L.-J.C., and H.-B.Y. co-wrote the manuscript. All
authors discussed the results and commented on the manuscript at all stages.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: December 4, 2019
Revised: January 10, 2020
Accepted: June 29, 2020
Published: July 27, 2020
REFERENCES
1
2
. Brown, C.J., Toste, F.D., Bergman, R.G., and
Raymond, K.N. (2015). Supramolecular
catalysis in metal-ligand cluster hosts. Chem.
Rev. 115, 3012–3035.
3. Mal, P., Breiner, B., Rissanen, K., and
Nitschke, J.R. (2009). White phosphorus
is air-stable Within a self-assembled
tetrahedral capsule. Science 324, 1697–
5. Mondal, B., and Mukherjee, P.S. (2018).
Cage encapsulated gold nanoparticles as
heterogeneous photocatalyst for facile and
selective reduction of nitroarenes to azo
compounds. J. Am. Chem. Soc. 140, 12592–
12601.
1699.
. Yoshizawa, M., Klosterman, J.K., and
Fujita, M. (2009). Functional molecular
flasks: new properties and reactions
within discrete, self-assembled hosts.
Angew. Chem. Int. Ed. Engl. 48, 3418–
4. Ueda, Y., Ito, H., Fujita, D., and Fujita, M. (2017).
Permeable self-assembled molecular
containers for catalyst isolation enabling two-
step cascade reactions. J. Am. Chem. Soc. 139,
6090–6093.
6. Jiao, J.J., Tan, C.X., Li, Z.J., Liu, Y., Han, X., and
Cui, Y. (2018). Design and assembly of chiral
coordination cages for asymmetric sequential
reactions. J. Am. Chem. Soc. 140, 2251–2259.
3
438.
Chem 6, 1–12, September 10, 2020
11

Please cite this article in press as: Zhu et al., Confinement Self-Assembly of Metal-Organic Cages within Mesoporous Carbon for One-Pot
Sequential Reactions, Chem (2020), https://doi.org/10.1016/j.chempr.2020.06.038
ll
Article
7
8
9
. Cullen, W., Misuraca, M.C., Hunter, C.A.,
Williams, N.H., and Ward, M.D. (2016). Highly
efficient catalysis of the Kemp elimination in
the cavity of a cubic coordination cage. Nat.
Chem. 8, 231–236.
the pores of a metal–organic framework. J. Am.
Chem. Soc. 138, 1138–1141.
metallosupramolecular construction. Chem.
Soc. Rev. 42, 1728–1754.
1
9. Chen, L.J., Chen, S.J., Qin, Y., Xu, L., Yin, G.Q.,
Zhu, J.L., Zhu, F.F., Zheng, W., Li, X.P., and
Yang, H.B. (2018). Construction of porphyrin-
containing metallacycle with improved stability
and activity within mesoporous carbon. J. Am.
Chem. Soc. 140, 5049–5052.
30. Yamashina, M., Sei, Y., Akita, M., and
Yoshizawa, M. (2014). Safe storage of radical
initiators within a polyaromatic nanocapsule.
Nat. Commun. 5, 4662.
. Lu, Z., Lavendomme, R., Burghaus, O., and
Nitschke, J.R. (2019). A Zn L capsule with
4 6
enhanced catalytic CꢁC Bond formation
activity upon C60 binding. Angew. Chem. Int.
Ed. Engl. 131, 9171–9175.
31. Saha, R., Devaraj, A., Bhattacharyya, S., Das, S.,
Zangrando, E., and Mukherjee, P.S. (2019).
Unusual behavior of donor–acceptor
2
2
2
2
2
0. Feng, L., Lv, X.L., Yan, T.H., and Zhou, H.C.
(2019). Modular programming of hierarchy and
Stenhouse adducts in confined space of a
. Yoshizawa, M., Tamura, M., and Fujita, M.
diversity in multivariate polymer/metal–organic
framework hybrid composites. J. Am. Chem.
Soc. 141, 10342–10349.
II
water-soluble Pd
8
molecular vessel. J. Am.
(2006). Diels-alder in aqueous molecular hosts:
Chem. Soc. 141, 8638–8645.
unusual regioselectivity and efficient catalysis.
Science 312, 251–254.
3
3
3
2. Takezawa, Y., M u¨ ller, J., and Shionoya, M.
1. Parsons, P.J., Penkett, C.S., and Shell, A.J.
(1996). Tandem reactions in organic synthesis:
novel strategies for natural product elaboration
and the development of new synthetic
(
2017). Artificial DNA base pairing mediated by
1
1
0. Wang, Q.Q., Gonell, S., Leenders, S.H., D u¨ rr,
diverse metal ions. Chem. Lett. 46, 622–633.
M., Ivanovi ꢀc -Burmazovi ꢀc , I., and Reek, J.N.
(2016). Self-assembled nanospheres with
3. Ryoo, R., Joo, S.H., Kruk, M., and Jaroniec, M.
multiple endohedral binding sites pre-
organize catalysts and substrates for highly
efficient reactions. Nat. Chem. 8, 225–230.
methodology. Chem. Rev. 96, 195–206.
(
2001). Ordered mesoporous carbons. Adv.
Mater. 13, 677–681.
2. Huang, Y.B., Liang, J., Wang, X.S., and Cao, R.
(2017). Multifunctional metal–organic
4. Ma, T.Y., Liu, L., and Yuan, Z.Y. (2013). Direct
synthesis of ordered mesoporous carbons.
Chem. Soc. Rev. 42, 3977–4003.
1. Kaphan, D.M., Levin, M.D., Bergman, R.G.,
Raymond, K.N., and Toste, F.D. (2015). A
supramolecular microenvironment strategy for
transition metal catalysis. Science 350, 1235–
framework catalysts: synergistic catalysis and
tandem reactions. Chem. Soc. Rev. 46,
126–157.
3. Hecht, S., and Fr e´ chet, J.M.J. (2001). Dendritic
encapsulation of function: applying nature’s
site isolation principle from biomimetics to
materials science. Angew. Chem. Int. Ed. Engl.
40, 74–91.
35. Deng, Y., Wei, J., Sun, Z., and Zhao, D. (2013).
Large-pore ordered mesoporous materials
templated from non-pluronic amphiphilic
block copolymers. Chem. Soc. Rev. 42, 4054–
4070.
1238.
1
1
1
1
1
2. De, S., Mahata, K., and Schmittel, M. (2010).
Metal-coordination-driven dynamic
heteroleptic architectures. Chem. Soc. Rev. 39,
1555–1575.
4. Wiester, M.J., Ulmann, P.A., and Mirkin, C.A.
(2011). Enzyme mimics based Upon
supramolecular coordination chemistry.
Angew. Chem. Int. Ed. Engl. 50, 114–137.
36. Meng, Y., Gu, D., Zhang, F.Q., Shi, Y.F., Yang,
H.F., Li, Z., Yu, C.Z., Tu, B., and Zhao, D.Y.
(2005). Ordered mesoporous polymers and
homologous carbon frameworks: amphiphilic
surfactant templating and direct
3. Sun, L.B., Liu, X.Q., and Zhou, H.C. (2015).
Design and fabrication of mesoporous
heterogeneous basic catalysts. Chem. Soc.
Rev. 44, 5092–5147.
2
5. Ghosh, S., and Isaacs, L. (2010). Biological
catalysis regulated by cucurbit[7]uril molecular
containers. J. Am. Chem. Soc. 132, 4445–4454.
transformation. Angew. Chem. Int. Ed. Engl.
4. Farrusseng, D., Aguado, S., and Pinel, C. (2009).
Metal–organic frameworks: opportunities for
catalysis. Angew. Chem. Int. Ed. Engl. 48, 7502–
44, 7053–7059.
3
7. Xing, R., Wu, H.H., Li, X.H., Zhao, Z.L., Liu, Y.M.,
Chen, L., and Wu, P. (2009). Mesopolymer solid
base catalysts with variable basicity:
preparation and catalytic properties. J. Mater.
Chem. 19, 4004–4011.
2
6. Chakrabarty, R., Mukherjee, P.S., and Stang,
P.J. (2011). Supramolecular coordination: self-
assembly of finite two- and three-dimensional
ensembles. Chem. Rev. 111, 6810–6918.
7513.
5. Hong, C.M., Bergman, R.G., Raymond, K.N.,
and Toste, F.D. (2018). Self-assembled
tetrahedral hosts as supramolecular catalysts.
Acc. Chem. Res. 51, 2447–2455.
2
7. Chen, L.J., Yang, H.B., and Shionoya, M. (2017).
Chiral metallosupramolecular architectures.
Chem. Soc. Rev. 46, 2555–2576.
3
8. Samanta, D., Mukherjee, S., Patil, Y.P., and
Mukherjee, P.S. (2012). Self-assembled Pd
6
6. Leenders, S.H.A.M., Gramage-Doria, R., de
Bruin, B.D., and Reek, J.N.H. (2015). Transition
metal catalysis in confined spaces. Chem. Soc.
Rev. 44, 433–448.
open cage with triimidazole walls and the use
of its confined nanospace for catalytic
Knoevenagel- and Diels–alder reactions in
aqueous medium. Chemistry 18, 12322–12329.
2
8. Chen, L.J., and Yang, H.B. (2018). Construction
of stimuli-responsive functional materials via
hierarchical self-assembly involving
coordination interactions. Acc. Chem. Res. 51,
2699–2710.
1
7. Galan, A., and Ballester, P. (2016). Stabilization
of reactive species by supramolecular
3
9. Samanta, D., and Mukherjee, P.S. (2013).
Multicomponent self-sorting of a Pd
7
encapsulation. Chem. Soc. Rev. 45, 1720–1737.
2
9. Smulders, M.M.J., Riddell, I.A., Browne, C., and
Nitschke, J.R. (2013). Building on architectural
principles for three-dimensional
molecular boat and its use in catalytic
Knoevenagel condensation. Chem. Commun.
(Camb.) 49, 4307–4309.
1
8. Qiu, X., Zhong, W., Bai, C., and Li, Y. (2016).
Encapsulation of a metal–organic polyhedral in
12
Chem 6, 1–12, September 10, 2020