Controlling the Activity of a Caged Cobalt-Porphyrin-Catalyst in Cyclopropanation Reactions with Peripheral Cage Substituents

Article abstract of DOI:10.1002/ejic.202100384

In this study, three novel cubic cages were synthesized and utilized to encapsulate a catalytically active cobalt(II) meso-tetra(4-pyridyl)porphyrin guest. The newly developed caged catalysts (Co-G@Fe₈(Zn-L ? 1)₆, Co-G@Fe₈(Zn-L ? 2)₆ and Co-G@Fe₈(Zn-L ? 3)₆) can be easily synthesized and differ in exo-functionalization, which are either none, polar or apolar groups. This leads to a different polarity of the peripheral environment surrounding the cage, which affects the (relative) local concentration of the substrates surrounding the cage and hence indirectly influences the substrate availability of the catalysis embedded in the active site of the caged catalyst systems. The resulting increased local substrate concentrations give rise to higher catalytic activities of the respective caged catalyst in metalloradical catalyzed cyclopropanation reactions. Interestingly, the catalytic activity is the highest when the apolar cage catalyst (Co-G@Fe₈(Zn-L ? 1)₆) is used, and lowest with the polar analog (Co-G@Fe₈(Zn-L ? 3)₆). In addition, the catalytic activity of the cage without exo-functionalities (Co-G@Fe₈(Zn-L ? 2)₆) is nearly two times lower than that of Co-G@Fe₈(Zn-L ? 1)₆ and three times higher than that of Co-G@Fe₈(Zn-L ? 3)₆, which further demonstrates the effect of the peripheral functionalities on the cyclopropanation reaction.

Full text of DOI:10.1002/ejic.202100384

European Journal of Inorganic Chemistry
Accepted Article
Title: Controlling the Activity of a Caged Cobalt–Porphyrin-Catalyst in
Cyclopropanation Reactions with Peripheral Cage Substituents
Authors: Valentinos Mouarrawis, Eduard O. Bobylev, Bas de Bruin,
and Joost N.H. Reek
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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content of this Accepted Article.
To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.202100384
Link to VoR: https://doi.org/10.1002/ejic.202100384
01/2020

10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
Controlling the Activity of a Caged Cobalt–Porphyrin-Catalyst in
Cyclopropanation Reactions with Peripheral Cage Substituents
Valentinos Mouarrawis,[a] Eduard O. Bobylev,[a] Bas de Bruin,*[a] and Joost N. H. Reek*[a]
[a]
V. Mouarrawis, E. O. Bobylev, Prof. dr. B. de Bruin, Prof. dr. J. N. H. Reek
Homogeneous and Supramolecular Catalysis Group
Van’ t Hoff Institute for Molecular Science (HIMS)
University of Amsterdam (UvA), Science Park 904
1098 XH Amsterdam (The Netherlands)
E-mail: b.debruin@uva.nl, J.N.H.Reek@uva.nl
Homepage URL: http://homkat.nl/People/Scientific%20Staff/Bas%20de%20Bruin/Bas%20de%20Bruin.htm, http://homkat.nl
Supporting information for this article is given via a link at the end of the document
Abstract: In this study, three novel cubic cages were synthesized
and utilized to encapsulate a catalytically active cobalt(II) meso-
tetra(4-pyridyl)porphyrin guest. The newly developed caged
been developed as supramolecular catalysts, where catalytic
activity and/or selectivity are controlled by the second
coordination sphere.[5] Several studies have been reported were
coordination cages with well-defined confined spaces impose
so-called second coordination sphere effects, which can
influence the activity and selectivity of the catalytic reaction.[6] An
interesting feature of a reaction taking place in a confined space
is the increased proximity of substrate(s) and the catalyst active
site, thereby enhancing overall reaction rates by pre-
organization.[7] Secondly, selective substrate binding can lead to
substrate selectivity and selective conversion of one of the
substrates.[8] Thirdly, the pre-organization of a substrate in a
higher energy conformation can accelerate the reaction and
promote reactivity.[4b] Most importantly, the stabilization of a
transition state or intermediate can alter reaction mechanisms
and lead to reactivity not observed in the bulk.[9]
catalysts
(Co-G@Fe8(Zn-L∙1)6,
Co-G@Fe8(Zn-L∙2)6
and
Co-G@Fe8(Zn-L∙3)6) can be easily synthesized and differ in exo-
functionalization, which are either none, polar or apolar groups. This
leads to
a different polarity of the peripheral environment
surrounding the cage, which affects the (relative) local concentration
of the substrates surrounding the cage and hence indirectly
influences the substrate availability of the catalysis embedded in the
active site of the caged catalyst systems. The resulting increased
local substrate concentrations give rise to higher catalytic activities
of the respective caged catalyst in metalloradical catalyzed
cyclopropanation reactions. Interestingly, the catalytic activity is the
highest when the apolar cage catalyst (Co-G@Fe8(Zn-L∙1)6) is used,
and lowest with the polar analog (Co-G@Fe8(Zn-L∙3)6). In addition,
the catalytic activity of the cage without exo-functionalities (Co-
G@Fe8(Zn-L∙2)6) is nearly two times lower than that of Co-
G@Fe8(Zn-L∙1)6 and three times higher than that of Co-G@Fe8(Zn-
L∙3)6, which further demonstrates the effect of the peripheral
functionalities on the cyclopropanation reaction.
These supramolecular catalysts are inspired by the working
principles of enzymes,[10] and in an effort to design and prepare
catalysts with further control over chemical reactivity, enzymes
can further serve as sources of inspiration. The active site of
many enzymes is often located deep within the substrate binding
cavity of the protein, and for any catalytic transformation to take
place the substrate must diffuse through the body of the protein
via a tunnel.[11] The difference with proteins where the active site
is located on the surface is the additional protein-substrate
interactions, as the substrate must diffuse through tunnel
residues before binding to the active active site.[12] For example,
the structure of cytochrome P450, which consists of a long
hydrophobic tunnel, regulates the substrate access and product
release.[13] Although these tunnels consist of highly complex
molecular structures that contribute to enzyme function, less
sophisticated abiological catalytic systems can mimic their
properties and function for the development of catalysts with
high efficiencies in terms of selectivity and/or activity.[14]
Introduction
Catalysis occupies a pivotal role in the modernization of our
chemical industry, because it ensures more efficient use of
natural resources and also aids in the minimization of waste
production.[1] Traditionally, catalytic efficiency is controlled
through ligand design, also known as the first coordination
sphere.[2] Despite significant progress in the field of catalysis,
there are still many reactions for which high catalytic efficiency
cannot be achieved, and development of new approaches that
lead to catalyst improvement are therefore important. In recent
years, great efforts have been devoted to the development of
supramolecular strategies as complementary approach to
control catalytic performance.[3] Within this field, ‘caged catalysts’
have shown interesting prospects. A catalyst under confinement
conditions often imposes reactivity and selectivity not observed
in the bulk bulk.[4] Thus far, many self-assembled capsules have
We previously demonstrated the effect of the second-
coordination sphere on catalysis, wherein a caged catalyst
functionalized with apolar groups was shown to increase the
catalytic activities in the cobalt-catalyzed cyclopropanation of
styrene when compared to the free catalyst.[15] In this work, we
demonstrate an unprecedented strategy for controlling catalytic
1
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
performance, in which differences in peripheral functionalization
polarities (Figure 1). The previously reported Fe8(Zn-L∙1)6 cage
is functionalized with apolar aliphatic tails (Figure 1, left),[15] the
Fe8 (Zn-L∙3)6 cage is decorated with polar groups at the
periphery (Figure 1, right) and the reference Fe8(Zn-L∙2)6 cage
(Figure 1, middle). We envisioned that the different peripheries
of these caged systems could be used to control the affinity of
caged catalyst for the substrate and thus lead to different
activities. As such the cage serves as a mimic of the active site
of cubic supramolecular cages hosting
a cobalt catalyst
influences the catalytic activity for cyclopropanation of styrene.
To our best knowledge there are no previous examples reported
wherein the periphery of a cage was shown to influence the
activity of a (wo)man-made catalyst.
For the purpose of studying effects of the cage periphery, we
explored three different caged catalyst with different exo-
Figure 1. Modeled structures of Fe8(Zn-L∙1)6 (left), Fe8(Zn-L∙2)6 (middle), and Fe8(Zn-L∙3)6 (right), showing their inner cavity (red) and the different peripheral
substituents (grey).
pocket of an enzyme whereas the periphery of the cage (light
grey surface) provides a synthetic equivalent of the substrate
binding site tunnel (Figure 1).
with the obtained diameters of the self-assembled cages (36 Å
for Fe8(Zn-L∙2)6 and 43 Å for Fe8(Zn-L∙3)6) based on molecular
modeling studies (vide infra).
High resolution electrospray ionization mass spectrometry (HR-
ESI-MS) reveals various peaks belonging to the two new cubic
cages (Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6) with different charges, in
line with the formation of the desired multicationic species
(Figure 2A and B). For each cage, the experimental spectra and
simulated isotope patterns overlap perfectly, unambiguously
confirming the formation of M8L6 cage structures. Our efforts to
grow single crystals suitable for X-ray diffraction were
unsuccessful (solvent layering and vapor diffusion at different
temperatures only led to solid powders, not suitable for X-ray).
Cage Fe8(Zn-L∙1)6 was synthesized by following the same
synthetic protocol and all analytical data are in line with the
formation of a species identical to the previously reported
cage.[15]
To confirm that the central cavity size of Fe8(Zn-L∙2)6 and
Fe8(Zn-L∙3)6 is similar to Fe8(Zn-L∙1)6 and able to bind
metalloporhyrins such as the catalytically active paramagnetic
Co-tetrapyridyl porphyrin (Co-G) or the non-catalytic
diamagnetic model compound Zn-tetrapyridyl porphyrin (Zn-G),
we performed molecular modeling studies. The molecular model
of Fe8(Zn-L∙1)6 was used to generate the new coordinates with
different peripheral functionalization, and the geometry was
optimized using a semi-empirical extended tight-binding method
((GFN2-xTB).[16] This provided an estimated volume of 3300 Å3
and 3250 for Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6, respectively. As
anticipated the obtained models reveal similar cavity volumes for
Results and Discussion
Next to our previously reported apolar Fe8(Zn-L∙1)6 cage, we
synthesized two new cages (Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6)
without any peripheral functional groups and with polar
peripheral substituents. This was done by following our recently
reported synthetic protocol for the synthesis of Fe8(Zn-L∙1)6
(Figure 2). For the preparation of the polar cage analog,
component 3 was readily synthesized in one step in 65% yield
by the nucleophilic aromatic substitution of 5-fluoro-2-
formylpyridine with Bis[2-(2-hydroxyethoxy)ethyl]ether (see
Supporting information). The reaction between subcomponent
Zn-L (6 equiv.), 2 or 3 (24 equiv.) and iron(II) triflimide (8 equiv.)
in dry DMF at 70 ˚C overnight resulted in the formation of single
discrete species via the complexation of iron with the formed
pyridyl-imine functionality (Figure 2A and 2B). Typical shifts in
1
the H NMR spectra are in line with the formation of Fe8(Zn-L)6
type cages. Importantly, 1H NMR diffusion-ordered spectroscopy
(DOSY) shows a narrow band with a diffusion constant of 3.4∙10-
6
cm2s-1 for Fe8(Zn-L∙2)6 and 2.9∙10-6 cm2s-1 for Fe8(Zn-L∙3)6
confirming the formation of a single species in solution that is
much larger than the corresponding subcomponents (Figure 2A
and B). The value of the diffusion constant is in good agreement
2
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6 as the Fe8(Zn-L∙1)6 cage and
therefore have an optimal internal volume to bind Co-G or Zn-G.
We first explored encapsulation of the diamagnetic Zn-G guest
in the new cages, as the resulting assemblies can be readily
studied by NMR techniques (in contrast to encapsulation studies
of paramagnetic Co-G). The overnight reaction of pre-formed
Fe8(Zn-L∙2)6 in DMF with 1 equivalent of Zn-G, results in a 4:2
splitting of the 1H-NMR signals of the cage, consistent with
desymmetrization of the host induced by binding of the guest.
Additionally, the 1H NMR peaks of the free Zn-G disappeared
and three new strongly upfield shifted guest peaks appeared a
6.59, 5.6, and 2.49 ppm indicating internal binding of Zn-G
(Figure 3B). When Fe8(Zn-L∙3)6 was stirred in the presence of
Zn-G, the empty cage and free Zn-G were still in solution and
no new signals belonging to the encapsulated guest were
observed by HR-ESI-MS and NMR spectroscopy. In contrast, a
Figure 2. Synthetic procedures of (A) Fe8(Zn-L∙2)6 and (B) Fe8(Zn-L∙3)6 and their geometry optimized structure using GFN2-xTB.[16] Calculated inner cavity
volume of Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6 displayed in red, using Voss Volume Voxelator. Obtained (red) and calculated (black) HR-ESI-MS for the 7+ (left) and
14+ (right) species of Fe8(Zn-L∙2)6 and 9+ (left) and 12+ (right) species of Fe8(Zn-L∙3)6. 1H-DOSY NMR of Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6 showing diffusion
constants of 3.4∙10-6 and 2.9∙10-6 cm2s-1 , respectively.
3
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
a in situ approach in which, Zn-G and Zn-L, 3, and the iron(II)
triflimide were mixed in the correct stoichiometric ratios yielded
the encapsulated catalyst, as no 1H-NMR signals of the free
guest (Zn-G) could be identified. In addition, similar upfield
shifted peaks as in Fe8(Zn-L∙2)6 were observed (6.58, 5.62 and
2.5 ppm, Figure 3C). The observed Δδ values of Zn-G upon
encapsulation in the two novel cages are consistent with
previous encapsulation studies of Zn-G in Fe8(Zn-L∙1)6 and with
similar cubic self-assembled cages.[17] HR-ESI-MS of Zn-
G@Fe8(Zn-L∙2)6 and Zn-G@Fe8(Zn-L∙3)6 yields spectra with
signals in line with the desired species and associated only to
structures in which one molecule of Zn-G is encapsulated inside
the molecular cube (Zn-G@Fe8(Zn-L∙2)6 and Zn-G@Fe8(Zn-
L∙3)6, Figure 3B and C). Importantly, DOSY of the two cages
(Zn-G@Fe8(Zn-L∙2)6 and Zn-G@Fe8(Zn-L∙3)6) features
a
uniquely observed product with the same diffusion constant
(3.35∙10-6 cm2s-1 and 2.86∙10-6 cm2s-1) as the empty cages
(Fe8(Zn-L∙2)6 and Fe8(Zn-L∙3)6), but now including the upfield
NMR signals that are from protons of the Zn-G guest (Figure 3B
and C). Interestingly, the preparation of Zn-G@Fe8(Zn-L∙2)6 can
be done via either the encapsulation of Zn-G in Fe8(Zn-L∙2)6 or
via the one-pot reaction of all the subcomponents, whereas the
synthesis of Zn-G@Fe8(Zn-L∙1)6 and Zn-G@Fe8(Zn-L∙3)6 is
only feasible by the one-pot synthetic protocol. We ascribe this
to the more electron-rich O-functionalized building blocks used
for the synthesis of Zn-G@Fe8(Zn-L∙1)6 and Zn-G@Fe8(Zn-L∙3)6
leading to stronger pyridine binding to iron and therefore
decreasing the dynamicity of the pyridyl-imine iron(II) moieties.
Figure 3. (A) Synthetic procedures of M-G@Fe8(Zn-L∙2)6 (left) and M-G@Fe8(Zn-L∙3)6 (right). (B) Obtained (red) and calculated (black) HR-ESI-MS for the 9+
(left) and 12+ (right) species of Co-G@Fe8(Zn-L∙2)6 and (C) for 9+ (left) and 12+ (right) species of Co-G@Fe8(Zn-L∙3)6. (B) 1H-DOSY NMR of Zn-G@Fe8(Zn-L∙2)6
and of (C) Zn-G@Fe8(Zn-L∙3)6 showing diffusion constants of 2.86∙10-6 cm2s-1 and 3.35∙10-6 cm2s-1, respectively. Guest peaks are indicated with a circle.
4
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
With the optimized synthetic protocols for encapsulation of Zn-G
in hand, and having established the characterization of the
diamagnetic assemblies Zn-G@Fe8(Zn-L∙1)6, Zn-G@Fe8(Zn-
L∙2)6 and Zn-G@Fe8(Zn-L∙3)6 based on the non-catalytic
metalloporphyrin Zn-G, we next explored the encapsulation of
catalytically active and paramagnetic cobalt(II)-tetra(4-
pyridyl)porphyrin Co-G via the same approach (Figure 3A).
Confirmation of encapsulation of the catalysts came from the
HR-ESI-MS of the assemblies, and the spectra reveal signals
corresponding to the expected elemental composition [(Co-
G@Fe8(Zn-L∙2)6)(NTf2)16 - x(NTf2)]x+
and
[(Co-G@Fe8(Zn-
L∙3)6)(NTf2)16 - x(NTf2)]x+ of both caged-systems (Co-G@Fe8(Zn-
L∙2)6 and Co-G@Fe8(Zn-L∙3)6 Figure 3B and C). Additional
support for the formation of the host-guest systems was
provided by EPR, which reveals typical signals for an isolated
(non-interacting) S = ½ CoII(por) species with clearly resolved
cobalt hyperfine. In contrast, the EPR signal of free Co-G itself is
Table 1. Control experiments and optimization of the reaction conditions or the cyclopropanation of styrene in cages.[a], [b]
Entry
Catalyst
T [˚C]
Conversion [%]
P1 [%]
P2 [%]
1
Fe8(Zn-L∙1)6
40
65
40
65
40
65
40
65
40
65
40
65
40
65
40
40
65
40
40
65
40
—
—
—
—
—
—
—
—
—
—
—
—
—
—
14
17
12
8.5
12
5.5
6
2
Fe8(Zn-L∙1)6
—
—
3
Fe8(Zn-L∙2)6
—
—
4
Fe8(Zn-L∙2)6
—
—
5
Fe8(Zn-L∙3)6
—
—
6
Fe8(Zn-L∙3)6
—
—
7
Zn-G@Fe8(Zn-L∙1)6
Zn-G@Fe8(Zn-L∙1)6
Zn-G@Fe8(Zn-L∙2)6
Zn-G@Fe8(Zn-L∙2)6
Zn-G@Fe8(Zn-L∙3)6
Zn-G@Fe8(Zn-L∙3)6
Co-G@Fe8(Zn-L∙1)6
Co-G@Fe8(Zn-L∙1)6
Co-G@Fe8(Zn-L∙1)6
Co-G@Fe8(Zn-L∙2)6
Co-G@Fe8(Zn-L∙2)6
Co-G@Fe8(Zn-L∙2)6
Co-G@Fe8(Zn-L∙3)6
Co-G@Fe8(Zn-L∙3)6
Co-G@Fe8(Zn-L∙3)6
—
—
8
—
—
9
—
—
10
11
12
13[c]
14
15
16[c]
17
18
19[c]
20
21
—
—
—
—
—
—
90
95
96
65.5
70
73
51
57
63.5
76
78
84
57
58
67.5
45
48.5
60
8.5
3.5
[a] Reaction conditions: Catalyst (0.25 mol %) with respect to S2, Styrene (S1, 0.16 mmol), ethyl diazoacetate (S2, 0.08 mmol) in DMF-d7 (1 mL), 30 h under N2
atmosphere. [b] Conversion of S2 and yields with respect to S2 were determined by 1H NMR spectroscopy, using 1,3,5-trimethoxybenzene as internal standard.
[c] S2 was added without prior stirring of styrene and the catalyst.
very broad and does not show any hyperfine couplings due to
self-aggregation causing substantial signal broadening as a
result of spin-spin exchange coupling interactions.[17b]
Encapsulation of Co-G within the cage assemblies leads to
much sharper signals because the protective environment of the
cage prevents self-aggregation. Interestingly, the formation of
three different caged-systems with different exo-polarities shows
that our strategy can be used to encapsulate metalloporphyrins
with different metals (Zn and Co) inside cages with polar, apolar,
and no peripheral functionalization.
Having established the preparation of three novel caged catalyst
systems, we investigated the solubility in order to find a
compatible solvent to perform our catalysis studies. Cages
Co-G@Fe8(Zn-L∙2)6 and Co-G@Fe8(Zn-L∙3)6 proved to be
5
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
soluble in DMF, acetone and acetonitrile, whereas
Co-G@Fe8(Zn-L∙1)6 is soluble in a wide range of solvents
(dimethylformamide, acetone, tetrahydrofuran, dichloromethane,
toluene, and dichloromethane/hexane mixtures). As such, we
focussed our catalysis investigation on utilizing DMF, as all the
cages are soluble in this solvent and we have previously shown
that DMF is a suitable solvent for these type of cobalt catalyzed
cyclopropanation reactions.
Next, we conducted a series of control experiments, and
optimized the reaction conditions. The results are summarized in
Table 1. In a typical reaction, S1 (2 equiv.) and the catalyst were
dissolved in DMF and stirred for 30 minutes before the addition
of the diazo compound S2 (1 equiv.), as it generally led to lower
dimer P2 formation (Table 1, entries 13, 16, 19 vs 15, 18, 21).
Importantly, Fe8(Zn-L∙1)6, Fe8(Zn-L∙2)6 Fe8(Zn-L∙3)6 and Zn-
G@Fe8(Zn-L∙1)6, Zn-G@Fe8(Zn-L∙2)6, Zn-G@Fe8(Zn-L∙3)6 are
not catalytically active, as performing the reaction at 40 or 65 ˚C
did not yield any product (Table 1, entries 1-12). Following
investigations on the effect of the temperature, a better catalytic
performance was found when the reaction was done at 40˚C vs
65 ˚C. (Table 1, entries 14, 17, and 20 vs 15, 18, and 21).
Similar observations were obtained for all the caged catalysts
(Co-G@Fe8 (Zn-L∙1)6, Co-G@Fe8 (Zn-L∙2)6 and Co-G@Fe8 (Zn-
L∙3)6), displaying an optimal reaction temperature of 40 ˚C, and
revealing the importance of stirring the styrene with the
supramolecular catalysts prior to addition of the diazo compound
S2 for our catalysis investigations.
With optimized reaction conditions for the three caged catalysts
Co-G@Fe8 (Zn-L∙1)6, Co-G@Fe8 (Zn-L∙2)6 and Co-G@Fe8 (Zn-
L∙3)6, we studied the catalytic performance in terms of stability,
activity, and selectivity. Table 2 shows the catalytic results for
the cyclopropanation of S1 by using caged catalysts (0.25
mol %) with a hydrophobic (Co-G@Fe8(Zn-L∙1)6), neutral (Co-
G@Fe8(Zn-L∙2)6),
and
hydrophilic
(Co-G@Fe8(Zn-L∙3)6)
peripheral environment. As we previously showed that Co-
G@Fe8(Zn-L∙1)6 outperforms both [Co(TPP)] and the free
catalyst (Co-G), as encapsulation of Co-G leads to steric
protection of cobalt-porphyrin catalyst (Co-G) from pyridine-
cobalt coordination and therefore hinders self-deactivation via
the blockage of the catalytic cobalt center. We ascribe the
increased conversion when using Co-G@Fe8(Zn-L∙1)6
compared to [Co(TPP)] to the increased local concentration of
ethyl diazoacetate S2 and styrene S1 in the hydrophobic
periphery environment of the cage, and hence also inside the
cage, when compared to the bulk. In agreement with this
hypothesis, interestingly, the enhanced performance of Co-
G@Fe8(Zn-L∙1)6 is accompanied with more dimer P2 formation
when compared to [Co(TPP)] and the guest catalyst (Co-G).
Table 2. Cyclopropanation of styrene with different cages and guests.[a], [b]
Entry
Catalyst
Conversion [%]
P1 [%]
P2 [%]
P1/P2
TON[c]
1
2
3
4
5
Co-G@Fe8(Zn-L∙1)6
Co-G@Fe8(Zn-L∙2)6
Co-G@Fe8(Zn-L∙3)6
Co-G
96
73
63.5
5
84
67.5
60
3
12
5.5
3.5
2
7
384
292
254
10
12
17
1.5
70
[Co(TPP)]
71
70
1
284
[a] Reaction conditions: Catalyst (0.25 mol %) with respect to S2 , ethyl diazoacetate (S2, 0.32 mmol) and styrene (S1, 0.64 mmol) in solvent (1 mL), 40 ˚C, 30 h
under N2 atmosphere. [b] Conversion of S2 and yields with respect to S2 were determined by NMR spectroscopy, using 1,3,5-trimethoxybenzene as internal
standard, and averaged from three measurements. [c] Turnover number (TON) was determined by dividing the conversion through the catalyst loading
(conv/0.25).
Having concluded that the caged catalyst with apolar exo-
functionalities (Co-G@Fe8(Zn-L∙1)6) enhances catalytic
than Co-G@Fe8 (Zn-L∙3)6 (Table 2, entries 1 and 2). The apolar
cage catalyst Co-G@Fe8(Zn-L∙1)6 leads to a P1/P2 ratio of 7,
whereas this ratio is 12.3 and 17 for the non-functionalized
Co-G@Fe8(Zn-L∙2)6 and polar Co-G@Fe8(Zn-L∙3)6 analogs,
respectively (Table 2, entries 1, 2 and 3). Remarkably, the
selectivity towards the desired product P1 decreases upon
increasing the polarity of the cage periphery. These results
indicate that the peripheral modification of the cage from polar to
apolar increases the catalytic performance of the system in the
cyclopropanation reaction. We ascribe this to a different local
concentration of ethyl diazoacetate and styrene in the two cages,
thus leading to different catalytic activities for the formation of
both P1 and P2.
To gain more insight on the effect of the cage periphery, the
reaction was monitored over time by 1H NMR spectroscopy,
from which the kinetic profiles in DMF for Co-G@Fe8(Zn-L∙1)6,
Co-G@Fe8(Zn-L∙2)6, Co-G@Fe8(Zn-L∙3)6 and [Co(TPP)] were
obtained (Figure 4). As the peripheral environment of the three
novel cages differs in polarity, different kinetics are expected for
activities compared to the non-encapsulated catalysts (free Co-
G and [Co(TPP)]), we were interested to investigate the effect of
the peripheral groups on the catalytic performance. The use of
the exo-decorated cage analog Co-G@Fe8(Zn-L∙3)6 with 24
PEG-4 groups, in the cyclopropanation reaction, lowered the
conversion to 63.5% (TON=254, Table 2, entry 2). Interestingly,
P2 formation was decreased, as Co-G@Fe8(Zn-L∙3)6
suppressed dimerization by 2-fold compared to Co-G@Fe8(Zn-
L∙1)6 (Table 2, entries 1 and 3). Compared to [Co(TPP)], the
polar cage catalyst (Co-G@Fe8(Zn-L∙3)6) results in lower
conversions and cyclopropane yields (Table 2, entries 3 and 5),
and a higher amount of dimer product P2 (1% vs 3.5%).
Further evidence that this is an effect of the cage periphery was
obtained by the use of a cage without exo-funtionalities (Co-
G@Fe8 (Zn-L∙2)6). Importantly, this catalyst system converted
S2 to cyclopropane P1 in a yield of 67.5% (TON=292, Table 2,
entry 2), which is lower than Co-G@Fe8(Zn-L∙1)6 and higher
6
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
each catalyst system. As shown in Figure 4, Co-G@Fe8(Zn-
L∙1)6 is substantially more active than Co-G@Fe8(Zn-L∙2)6 and
Co-G@Fe8(Zn-L∙3)6, as evidenced by the initial TOF at 15%
conversion (Figure 4). This indicates a higher degree of
substrate accumulation in Co-G@Fe8(Zn-L∙1)6 compared to both
Co-G@Fe8(Zn-L∙2)6 and Co-G@Fe8(Zn-L∙3)6, thus leading to
higher catalytic activity due to higher local concentrations of both
S1 and S2. As is clear from Figure 4, reaction rates for both
cyclopropanation and carbene dimerization are enhanced. The
presence of 24 icosyl groups in the periphery of the cage
(Co-G@Fe8(Zn-L∙1)6) leads to higher substrate affinity for the
periphery, and thereby the interior of the cage, and
demonstrates the influence of the peripheral polarity of the cage
Figure 4. (A) Reaction profile of Co-G@Fe8(Zn-L∙1)6, (B) Co-G@Fe8(Zn-L∙2)6, (C) Co-G@Fe8(Zn-L∙3)6 and (D) [Co(TPP)] in the cyclopropanation of styrene at
0.25 % catalyst loading. (E) Plot of TOFini for the formation of P1 calculated at 15% conversion. Data is obtained by fitting the initial part of the reaction rate curve
of Co-G@Fe8(Zn-L∙1)6, Co-G@Fe8(Zn-L∙2)6, Co-G@Fe8(Zn-L∙3)6 and [Co(TPP)] (see Supporting Info). (F) TON for Co-G@Fe8(Zn-L∙1)6, Co-G@Fe8(Zn-L∙2)6,
Co-G@Fe8(Zn-L∙3)6 and [Co(TPP)] after 30 h.
on the catalytic rates. This trend shows that the exo-
hydrophobicity of the cage framework has an indirect, but
nonetheless significant impact on the affinity of the substrate
towards the inner environment of the cage. If correct, inverse
7
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
detection was done in positive-ion mode and the source voltage was
between 4 and 6 kV. The flow rate was 18 uL/hr. The machine was
calibrated prior to every measurement via direct infusion of a TFA-Na
solution. For geometry optimizations of cages and caged-catalysts,
Grimme’s GFN2-xTB (Geometry, Frequency, Noncovalent, extended
tight, binding) software was used.[16] Figures and images of the
geometry-optimized structures were generated with UCSF Chimera
software.[18] EPR spectra were recorded on a Bruker EMX X-band
spectrometer equipped with an ER 4112HV-CF100 helium cryostat.
polarity is expected to lead to slower catalytic rates in the
cyclopropanation reaction. Indeed, lower activity is observed
with the increased peripheral polarity of Co-G@Fe8(Zn-L∙3)6,
due to lower local substrate concentration in the cavity of the
cage. Importantly, the catalytic activity of the cage with no exo-
functionalities (Co-G@Fe8(Zn-L∙2)6) is nearly two times lower
than Co-G@Fe8(Zn-L∙1)6 and three times higher than that of
Co-G@Fe8(Zn-L∙3)6 (Figure 4E). Additionally, the catalytic
activity of the confined catalyst Co-G@Fe8(Zn-L∙2)6 compared to
the non-encapsulated catalyst [Co(TPP)] is similar, whereas the
activity of Co-G@Fe8(Zn-L∙3)6 is 2 times lower than that of
[Co(TPP)]. As cages Co-G@Fe8(Zn-L∙1)6, Co-G@Fe8(Zn-L∙2)6
and Co-G@Fe8(Zn-L∙3)6 similarly confine the catalyst (Co-G),
we attribute the differences in activity to different (relative)
substrate affinities to the periphery of the cage catalysts, and
thereby the interior of the cages, as a result of the peripheral
functionalities.
3: PEG-4 (1.7 mL, 9.73 mmol), cesium carbonate (3.2 g, 9.74 mmol), and
dry DMF (230 mL) were added to a Schlenk flask under N2. The mixture
was stirred at 100 ˚C for 1 h, after which 5-fluoropicolinaldehyde (1.2 g,
9.6 mmol) was added. The reaction mixture was heated at 100°C for 18 h,
followed by cooling down to room temperature. The brown suspension
was filtered through a celite pad and the DMF was removed under
reduced pressure. The crude product was purified by flash column
chromatography (SiO2 Ethyl acetate/MeOH ( 100:1 to 100:5, v/v) which
afforded the desired product 2 (1.9 g, 65%) as a yellow oil. 1H-NMR (400
MHz, 298 K, CDCl3) δ (ppm) = 9.98 (d, J = 0.8 Hz, 1H), 8.46 (d, J = 2.8
Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.34 (ddd, J = 8.8, 2.8, 0.7 Hz, 1H),
4.30 – 4.27 (m, 2H), 3.92 – 3.89 (m, 2H), 3.75 – 3.65 (m, 11H), 3.62 –
3.59 (m, 2H). 13C NMR (101 MHz, 298 K, CDCl3) δ (ppm) = 61.68, 68.21,
69.37, 70.29, 70.53, 70.64, 70.90, 72.52, 77.06, 120.80, 123.34, 138.94,
146.35, 158.36, 192.01. HR-MS (ESI) theoretical calculation for
Conclusion
In conclusion, we prepared three novel cubic cages that can
bind catalytically active cobalt(II) meso-tetra(4-pyridyl)porphyrin.
The cages differ in exo-decoration, which can be polar or apolar
tails. By encapsulation of cobalt porphyrins as catalysts, this
strategy provides three supramolecular caged catalyst systems
with only different peripheral environment, which effect was
probed in catalysis. For the cyclopropanation of styrene with
ethyl diazoacetate, we observed an effect of these peripheral
groups on the catalytic activity, with the exo-functionalized cage
catalyst with apolar icosyl groups providing a higher activity
(TOFini) compared to the free bulk catalyst and cages with no or
polar exo-functionalization (Co-G@Fe8(Zn-L∙2)6 and Co-
G@Fe8(Zn-L∙3)6). The catalytic activity of the non exo-
functionalized cage catalysts (Co-G@Fe8(Zn-L∙2)6) was nearly
two times lower than Co-G@Fe8(Zn-L∙1)6 and three times higher
than that of Co-G@Fe8(Zn-L∙3)6. Remarkably, the peripheral
modification of the cage catalysts from polar to apolar increases
the catalytic activities in the cyclopropanation reaction and
dimerization. We ascribe this effect to different (relative)
substrate affinities to the cage that lead to different substrate
local concentrations and thus to altered catalytic activities. The
affinity of the substrates proved to be the highest when the
apolar decorated cage (Co-G@Fe8(Zn-L∙1)6) is used and the
lowest for the polar analog (Co-G@Fe8(Zn-L∙3)6).
C14H21NO6, m/z [M+H]+: 300.1402, experimental result m/z [M+H]+
300.1387.
=
Fe8(Zn-L∙2)6: Zn-L (0.144 g, 0.150 mmol) together with picolinaldehyde
(0.062 g, 0.57 mmol), iron(II)triflimide (0.118 g, 0.191 mmol) and dry
DMF (11 ml) were added to a Schlenk flask. The mixture was degassed
by three cycles of freeze-pump-thaw, and heated at 70 ˚C for 18 h. The
reaction mixture was cooled down to room temperature and stirred for 1
h. The purple-red solution was passed through a short pad of celite and
precipitated in diethyl ether. The precipitates were collected by filtration
and washed with diethyl ether (10 ml) and DCM (10 ml). The solids were
collected by washing the filter with acetonitrile (100 ml) and the solvent
was removed under reduced pressure afford Fe8(Zn-L∙2)6 as dark purple
solid. (0.255 g, 80%). 1H NMR (300 MHz, Acetonitrile-d3) δ (ppm) = 9.07
(s, 24H), 8.88 (s, 34H), 8.65 (d, J = 7.6 Hz, 28H), 8.51 (s, 24H), 8.42 –
8.32 (m, 38H), 8.18 (dd, J = 19.0, 7.5 Hz, 44H), 8.03 (d, J = 8.2 Hz, 48H),
7.87 (s, 36H), 7.53 (d, J = 5.3 Hz, 24H), 5.69 (d, J = 7.7 Hz, 60H). 13C
NMR (75 MHz, Acetonitrile-d3) δ 174.90, 158.48, 156.04, 149.70, 149.62,
142.97, 139.81, 137.88, 135.12, 131.64, 131.18, 129.88, 127.99, 1265.4,
124.6, 122.
Fe8(Zn-L∙3)6: Zn-L (0.100 g, 0.095 mmol) together with 3 (0.114 g, 0.38
mmol), iron(II)triflimide (0.078 g, 0.127 mmol) and dry DMF (12 ml) were
added to a Schlenk flask. The mixture was degassed by three cycles of
freeze-pump-thaw, and heated at 70 ˚C for 20 h. The reaction mixture
was cooled down to room temperature and stirred for 1 h. The purple-red
solution was passed through a short pad of celite and precipitated in
diethyl ether. The precipitates were collected by filtration and washed
with diethyl ether (100 ml) and DCM (100 ml). The solids were collected
by washing the filter with acetonitrile (100 ml) and the solvent was
removed under reduced pressure to afford Fe8(Zn-L∙3)6 as dark purple
solid. (0.292 g, 77%).1H NMR (500 MHz, Acetonitrile-d3) δ (ppm) 8.95 (s,
24H), 8.86 (d, J = 7.7 Hz, 38H), 8.58 (d, J = 8.9 Hz, 28H), 8.44 – 8.27 (m,
42H), 8.27 – 8.09 (m, 44H), 8.00 (s, 74H), 7.20 (s, 18H), 5.71 (s, 42H),
4.37 (s, 42H), 3.88 (s, 62H), 3.81 – 3.35 (m, 330H). 13C NMR (75 MHz,
Acetonitrile-d3) δ (ppm) = 173.44, 146.78, 135.77, 135.55, 132.77,
132.25, 128.51, 126.41, 125.21, 123.11, 122.9, 72.56, 71, 69.56, 61.85.
Experimental Section
General considerations: All reactions involving air- or moisture-
sensitive compounds were carried out under nitrogen using standard
Schlenk and vacuum line techniques. Unless noted otherwise, all
reagents were of commercial grade and used without further purification.
Dry DMF was kept under N2 over molecular sieves. Styrene was filtered
over basic alumina prior to use. 1H NMR spectra were recorded on a
Bruker AMX 400, Varian Mercury 300, Bruker DRX 500, Bruker DRX
300 or spectrometer, and they are referenced to the solvent residual
signal (5.32 ppm for CD2Cl2, 7.32 ppm for CDCl3, 8.03 ppm for DMF-d7,
1.32 ppm for CD3CN and 2.08 ppm for toluene-d8). The temperature and
the magnetic gradient were calibrated prior the measurement for 2D 1H-
DOSY NMR. High-resolution mass spectra were recorded on a HR-ToF
Bruker Daltonik Gmbh Impact II, as ESI-ToF MS capable of a resolution
of at least 4000 FWHM, coupled to a Bruker cryospray unit. The
Zn-G@Fe8(Zn-L∙2)6: To an oven-dried Schleck flask under nitrogen
atmosphere were added Fe8(Zn-L∙2)6 (0.080 g, 0.006 mmol), Zn-G (4.1
mg, 0.006 mmol) and dry DMF (4 ml). The mixture was degassed by
three cycles of freeze-pump-thaw, and heated at 70 ˚C for 18 h. The
reaction mixture was cooled down to room temperature and stirred for 1
8
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
h. The purple-red solution was passed through a short pad of celite and
precipitated in diethyl ether. The precipitates were collected by filtration
and washed with diethyl ether (100 ml) and DCM (100 ml). The
remaining solids on the filter were collected by washing the filter
acetonitrile (100 ml). The solvent was removed under reduced pressure
to afford Zn-G@Fe8(Zn-L∙2)6 as a dark purple solid. (0.059 g, 69 %). 1H-
NMR (400 MHz, Acetonitrile-d3) δ (ppm) 9.12 – 8.86 (m, 48H), 8.63 (s,
34H), 8.48 (s, 28H), 8.41 – 8.22 (m, 50H), 8.21 – 7.66 (m, 134H), 7.51 (d,
J = 19.9 Hz, 32H), 6.59 (s, 8H), 5.67 (dd, J = 17.9, 8.1 Hz, 34H), 5.6 (s,
8H) 2.49 (s, 8H).
Kirchhoff, T. C. Williamson, Appl. Catal. A Gen. 2001, 221, 3-13; d) B.
Plietker, Synlett 2010, 14, 2049-2058; e) C. Adams, in Top. Catal.,
2009, 52, 924-934 ; f) E. S. Beach, Z. Cui, P. T. Anastas, Energy
Environ. Sci. 2009, 2, 1038-1049; g) M. Beller, G. Centi, L. Sun,
ChemSusChem 2017, 10, 6-13; h) S. Chu, A. Majumdar, Nature 2012,
488, 294-303; i) G. Centi, J. Čejka, ChemSusChem 2019, 12, 621-632.
a) B. Cornils, W. A. Herrmann, M. Beller, R. Paciello, Applied
[2]
Homogeneous Catalysis with Organometallic Compounds:
A
Comprehensive Handbook in Three Volumes, Vol. 2, Wiley‐VCH Verlag
GmbH & Co. KGaA, 2012, pp 23-90; b) D. J. Gorin, B. D. Sherry, F. D.
Toste, Chem. Rev. 2008, 108, 3351–3378; c) E. Peris, Chem. Rev.
2018, 118, 9988-10031; d) J. El Karroumi, A. El Haib, E. Manoury, A.
Benharref, J. C. Daran, M. Gouygou, M. Urrutigoïty, J. Mol. Catal. A
Chem. 2015, 401, 18-26; e) O. R. Luca, R. H. Crabtree, Chem. Soc.
Rev. 2013, 42, 1440-1459.
Zn-G@Fe8(Zn-L∙3)6: To an oven-dried Schleck flask under nitrogen
atmosphere were added Zn-G (8.45 mg, 0.012 mmol), Zn-L (0.078 g,
0.075 mmol), 3 (0.090 g, 0.3 mmol), iron(II)triflimide (0.062 g, 0.1 mmol)
and dry DMF (7 ml). The mixture was degassed by three cycles of
freeze-pump-thaw, and heated at 70 ˚C for 18 h. The reaction mixture
was cooled down to room temperature and stirred for 1 h. The purple-red
solution was passed through a short pad of celite and precipitated in
diethyl ether. The precipitates were collected by filtration and washed
with diethyl ether (100 ml) and DCM (100 ml). The remaining solids on
the filter were collected by washing with acetonitrile (150 ml). The solvent
was removed under reduced pressure to afford Zn-G@Fe8(Zn-L∙3)6 as a
dark purple solid. (0.169 g, 73 %). 1H-NMR (400 MHz, 298 K,
Acetonitrile-d3) δ (ppm) = 8.99 (d, J = 15.6 Hz, 58H), 8.61 (dd, J = 17.2,
9.0 Hz, 48H), 8.35 (dd, J = 21.5, 7.1 Hz, 62H), 8.24 – 7.76 (m, 114H),
7.22 (d, J = 17.2 Hz, 30H), 6.58 (s, 8H), 5.73 (s, 46H), 5.62 (s, 8H), 4.37
(s, 42H), 3.88 (s, 58H), 3.75 – 3.42 (m, 286H), 2.50 (s, 8H).
[3]
[4]
a) T. Keijer, T. Bouwens, J. Hessels, J. N. H. Reek, Chem. Sci. 2021, 12,
50-70; b) S. H. A. M. Leenders, R. Gramage-Doria, B. De Bruin, J. N. H.
Reek, Chem. Soc. Rev. 2015, 44, 433-448; c) K. Wang, J. H. Jordan, X.
Y. Hu, L. Wang, Angew. Chemie - Int. Ed. 2020, 59, 13712-13721.
a) M. Morimoto, S. M. Bierschenk, K. T. Xia, R. G. Bergman, K. N.
Raymond, F. D. Toste, Nat. Catal. 2020, 3, 969-984; b) V. Mouarrawis,
R. Plessius, J. I. van der Vlugt, J. N. H. Reek, Front. Chem. 2018, 6,
623; c) Q. Fu, X. Bao, Nat. Catal. 2019, 2, 834-836; d) A. B. Grommet,
M. Feller, R. Klajn, Nat. Nanotechnol. 2020, 15, 256-271; e) B.
Mitschke, M. Turberg, B. List, Chem 2020, 6, 2515-2532; f) L. Catti, Q.
Zhang, K. Tiefenbacher, Chem. Eur. J. 2016, 22, 9060-9066; g) I.
Sinha, P. S. Mukherjee, Inorg. Chem. 2018, 57, 4205-4221; h) Y. Fang,
J. A. Powell, E. Li, Q. Wang, Z. Perry, A. Kirchon, X. Yang, Z. Xiao, C.
Zhu, L. Zhang, F. Huang, H. C. Zhou, Chem. Soc. Rev. 2019, 48,
4707-4730.
Co-G@Fe8(Zn-L∙2)6: To an oven-dried Schleck flask under nitrogen
atmosphere were added Fe8(Zn-L∙2)6 (0.080 g, 0.006 mmol), Co-G (4
mg, 0.006 mmol) and dry DMF (4 ml). The mixture was degassed by
three cycles of freeze-pump-thaw, and heated at 70 ˚C for 18 h. The
reaction mixture was cooled down to room temperature and stirred for 1
h. The purple-red solution was passed through a short pad of celite and
precipitated in diethyl ether. The precipitates were collected by filtration
and washed with diethyl ether (100 ml) and DCM (100 ml). The
remaining solids on the filter were collected by washing the filter
acetonitrile (100 ml). The solvent was removed under reduced pressure
to afford Co-G@Fe8(Zn-L∙2)6 as a dark purple solid. (0.062 g, 74 %).
[5]
[6]
a) C. Tan, D. Chu, X. Tang, Y. Liu, W. Xuan, Y. Cui, Chem. - A Eur. J.
2019, 25, 662-672; b) R. J. Severinsen, G. J. Rowlands, P. G. Plieger,
J. Incl. Phenom. Macrocycl. Chem. 2020, 96, 29-42.
a) Y. Xue, X. Hang, J. Ding, B. Li, R. Zhu, H. Pang, Q. Xu, Coord. Chem.
Rev. 2021, 430, 213656. b) M. D. Ward, C. A. Hunter, N. H. Williams,
Acc. Chem. Res. 2018, 51, 2073-2082. c) L. Catti, Q. Zhang, K.
Tiefenbacher, Chem. - A Eur. J. 2016, 22, 9060-9066. d) C. J. Brown,
F. D. Toste, R. G. Bergman, K. N. Raymond, Chem. Rev. 2015, 115,
3012-3035. e) J. Jiao, C. Tan, Z. Li, Y. Liu, X. Han, Y. Cui, J. Am.
Chem. Soc. 2018, 140, 2251-2259. f) W.-X. Gao, H.-N. Zhang, G.-X.
Jin, Coord. Chem. Rev. 2019, 386, 69-84.
Co-G@Fe8(Zn-L∙3)6: To an oven-dried Schleck flask under nitrogen
atmosphere were added Co-G (8.8 mg, 0.013 mmol), Zn-L (0.081 g,
0.078 mmol), 3 (0.093 g, 0.31 mmol), iron(II)triflimide (0.064 g, 0.1 mmol)
and dry DMF (7 ml). The mixture was degassed by three cycles of
freeze-pump-thaw, and heated at 70 ˚C for 18 h. The reaction mixture
was cooled down to room temperature and stirred for 1 h. The purple-red
solution was passed through a short pad of celite and precipitated in
diethyl ether. The precipitates were collected by filtration and washed
with diethyl ether (100 ml) and DCM (100 ml). The remaining solids on
the filter were collected by washing with acetonitrile (150 ml). The solvent
was removed under reduced pressure to afford Co-G@Fe8(Zn-L∙3)6 as a
dark purple solid. (0.191 g, 79 %).
[7]
a) L. Li, L. Yang, X. Li, J. Wang, X. Liu, C. He, Inorg. Chem. 2021, DOI
10.1021/acs.inorgchem.1c00745. b) Q. Q. Wang, S. Gonell, S. H. A. M.
Leenders, M. Dürr, I. Ivanovic-Burmazovic, J. N. H. Reek, Nat. Chem.
2016, 137, 2680-2687.
[8] a) S. S. Nurttila, W. Brenner, J. Mosquera, K. M. van Vliet, J. R. Nitschke,
J. N. H. Reek, Chem. - A Eur. J. 2019, 25, 609-620. b) M. Otte, P. F.
Kuijpers, O. Troeppner, I. Ivanović-Burmazović, J. N. H. Reek, B. de
Bruin, Chemistry 2014, 20, 4880-4884.
[9]
a) C. J. Hastings, M. D. Pluth, R. G. Bergman, K. N. Raymond, J. Am.
Chem. Soc. 2010, 132, 6938-40. b) W. M. Hart-Cooper, K. N. Clary, F.
D. Toste, R. G. Bergman, K. N. Raymond, J. Am. Chem. Soc. 2012,
134, 17873-7876.
[10]
[11]
a) M. J. Wiester, P. A. Ulmann, C. A. Mirkin, Angew. Chemie - Int. Ed.
2011, 50, 114-137; b) E. Kuah, S. Toh, J. Yee, Q. Ma, Z. Gao, Chem. -
A Eur. J. 2016, 22, 8404-8430; c) J. Meeuwissen, J. N. H. Reek, Nat.
Chem. 2010, 2, 615-621.
Acknowledgements
L. J. Kingsley, M. A. Lill, Proteins Struct. Funct. Bioinforma. 2015, 83,
599-611.
A Financial support from The Netherlands Organization for
Scientific Research (NWO TOP-PUNT) and the University of
Amsterdam (Research Priority Area Sustainable Chemistry) is
gratefully acknowledged.
[12] X. Yu, V. Cojocaru, R. C. Wade, Biotechnol. Appl. Biochem. 2013, 60,
134-145.
[13] S. Kaushik, S. M. Marques, P. Khirsariya, K. Paruch, L. Libichova, J.
Brezovsky, Z. Prokop, R. Chaloupkova, J. Damborsky, FEBS J. 2018,
285, 1456-1476.
Keywords: Confinement • cyclopropanation • homogeneous
catalysis • Metal-coordination cages • cage effects
[14] M. Raynal, P. Ballester, A. Vidal-Ferran, P. W. N. M. van Leeuwen,
Chem. Soc. Rev. 2014, 43, 1734–87.
[15] V. Mouarrawis, E. Bobylev, B. de Bruin, J. Reek, Chem. Eur. J. 2021, 27,
8390-8397.
[1]
a) G. Centi, S. Perathoner, Catal. Today 2008, 138, 69-76; b) Y. Kim,
C.-J. Li, Green Synth. Catal. 2020, 1, 1-11; c) P. T. Anastas, M. M.
9
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10.1002/ejic.202100384
European Journal of Inorganic Chemistry
FULL PAPER
[16] C. Bannwarth, S. Ehlert, S. Grimme, J. Chem. Theory Comput. 2019,
1652-1671.
[17] a) M. Otte, P. F. Kuijpers, O. Troeppner, I. Ivanovic
Reek, B. de Bruin, Chem. - A Eur. J. 2014, 136, 1090-1096; b) M. Otte,
P. F. Kuijpers, O. Troeppner, I. Ivanovic-Burmazovic, J. N. H. Reek, B.
̈ ̈
-Burmazovic, J. N. H.
̈
̈
de Bruin, Chem. Eur. J. 2013, 19, 10170-10178; c) F. J. Rizzuto, W. J.
Ramsay, J. R. Nitschke, J. Am. Chem. Soc. 2018, 140, 11502-11509.
E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M.
Greenblatt, E. C. Meng, T. E. Ferrin, J. Comput. Chem. 2004, 25, 1605-
1612.
[18]
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Entry for the Table of Contents
Three novel cubic cages were synthesized and utilized to encapsulate a catalytically active cobalt(II) meso-tetra(4-pyridyl)porphyrin
guest. The different polarity of the peripheral cage substituents influences the substrate availability of the catalysts embedded in the
active site of the caged catalyst systems. This is demonstrated on the on the cyclopropanation reaction wherein the catalytic activity
is the highest when the apolar cage catalyst (Co-G@Fe8(Zn-L∙1)6) is used, and lowest with the polar analog (Co-G@Fe8(Zn-L∙3)6).
Institute and/or researcher Twitter usernames: @bruin_bas and @JoostReek
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