Asymmetric Hydroformylation Using a Rhodium Catalyst Encapsulated in a Chiral Capsule

Article abstract of DOI:10.1002/asia.201901771

Supramolecular capsules can be used to change the activity and selectivity of a catalyst through the influence of the second coordination sphere, reminiscent of how enzymes control the selectivity of their processes. In enzymes, this approach is used to also control the enantioselectivity of reactions in which the active catalytic site is often not chiral but the second coordination sphere is. We are interested in the possibility to generate a chiral second coordination sphere around an otherwise achiral transition metal complex for asymmetric catalysis. In this paper we show that the ligand template approach can be used to generate a chiral second coordination sphere around a rhodium complex, which is used in asymmetric hydroformylation.

Full text of DOI:10.1002/asia.201901771

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Asymmetric hydroformylation using a rhodium catalyst
encapsulated in a chiral capsule
Authors: Lukas J. Jongkind and Joost Reek
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
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
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Asian J. 10.1002/asia.201901771
Link to VoR: http://dx.doi.org/10.1002/asia.201901771
A Journal of
A sister journal of Angewandte Chemie
and Chemistry – A European Journal

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
Asymmetric hydroformylation using a rhodium catalyst
encapsulated in a chiral capsule
Lukas J. Jongkind [a] and Joost N. H. Reek*[a]
Abstract: Supramolecular capsules can be used to change the
activity and selectivity of a catalyst through the influence of the second
coordination sphere, reminiscent of how enzymes control the
selectivity of their processes. In enzymes, this approach is used to
also control the enantioselectivity of reactions in which the active
catalytic site is often not chiral but the second coordination sphere is.
We are interested in the possibility to generate a chiral second
coordination sphere around an otherwise achiral transition metal
complex for asymmetric catalysis. In this chapter we show that the
ligand template approach can be used to generate a chiral second
coordination sphere around a rhodium complex, which is used in
asymmetric hydroformylation.
ligand bears a central donor atom, usually a phosphorus atom, for
coordination to a transition metal atom. Orthogonal donor atoms,
predominantly harder donors such as nitrogen, are present in the
ligand that can coordinate to bulky molecular building blocks in
order to encapsulate the central donor atom of the ligand and the
transition metal center bound to it. Using this approach, we have
encapsulated several transition metal complexes to demonstrate
the effect of encapsulation in catalysis.
The first example of the ligand template approach involves
the encapsulation of the tris-3-pyridyl phosphine ligand template
with zinc tetraphenyl porphyrin (Zn(II)TPP).[26–29] The phosphine
atom selectively coordinates to rhodium, while the pyridine donor
atoms coordinate to the zinc atoms of the Zn(II)TPP,
encapsulating the rhodium complex. When this capsule is applied
in the rhodium catalyzed hydroformylation of unfunctionalized
alkenes, the formation of aldehyde products on the innermost
position of the alkene as the major product. As no traditional
ligand system is known that shows a similar product selectivity,
this capsule was studied in detail, which revealed that the unique
product selectivity is caused by hindered rotation enforced by the
One of the most important challenges in catalysis is to control the
outcome of chemical reactions to produce key molecules in an
efficient and selective manner. In homogeneous catalysis
researchers mainly use ligands to control the activity and
selectivity of transition metal complexes that are applied as
catalysts in reactions.[1] The development of different ligand
structures and the increased understanding of the chemical
reactions that occur during catalysis has allowed researchers to
develop specific ligand structures required for selective processes
for different transition metals. In recent years, the development of
supramolecular strategies in homogeneous catalysis has gained
popularity as a new way to control the activity and selectivity of
transition metal complexes.[2–8] Some supramolecular strategies
aim to control the selectivity and activity of a catalytic reaction
through the second coordination sphere of transition metal
catalysts, which resembles the way enzymes control catalytic
reactions. These efforts resulted in systems that operate via
enzyme-like mechanisms such as substrate preorganization,
[28]
capsule during hydride migration . Encapsulation of the ligand
template changes the sterics, which leads to the formation of a
rhodium catalyst coordinated to a single phosphine ligand, which
partially explains the tenfold increase in activity as compared to
[26]
the non-encapsulated ligand template observed.
Transition
state stabilization induced by the encapsulation of the catalyst
also contributes to the rate acceleration observed upon
encapsulation.[28,30]
The ligand template approach was also successfully applied
in
enantioselective
hydroformylation
reactions,
where
encapsulation of a chiral ligand template led to increased
enantioselectivity
hydroformylation.
for
both
styrene
and
2-octene
[
9–
transition state stabilization and cofactor controlled regulation.
[31–33]
In these examples the ligand template is
1
8]
These effects can be achieved by the encapsulation of
the source of chirality, with encapsulation increasing the
enantioselectivity of the catalyst.
Enzymes achieve perfect enantioselectivity solely through
the chirality of second coordination sphere.[34] Inspired by this, we
transition metal complexes in supramolecular cages and
capsules.[5,19–24] For these types of systems the confinement
effect that is induced by the encapsulation is important, as
different product selectivity and rate enhancement may be
induced as an effect of catalyst encapsulation.
In our group we have used functionalized ligands to facilitate
the encapsulation of transition metal complexes in a strategy we
coined the ligand template approach.[25] In this approach, the
were interested whether the use of an achiral ligand template and
chiral capsule building blocks could generate a chiral capsule for
enantioselective hydroformylation. Because the application of the
tris-3-pyridyl phosphine ligand template (ligand template 1)
encapsulated by Zn(II)TPP in rhodium catalyzed hydroformylation
of unfunctionalized alkenes produces chiral aldehydes (as a
racemic mixture) as major products, we chose the encapsulation
of ligand template 1 with chiral porphyrins to form a chiral capsule
for enantioselective hydroformylation (Figure 1). Here we discuss
the synthesis of suitable porphyrin building blocks, the
encapsulation of ligand template 1 with these porphyrins and the
application of the formed capsules in rhodium catalyzed
hydroformylation.
[
a] L. J. Jongkind and Prof. dr. J. N. H. Reek
Homogeneous, Supramolecular and Bio-Inspired Catalysis, Van ’t
Hoff Institute for Molecular Sciences
University of Amsterdam
Science Park 904, 1098 XH Amsterdam (The Netherlands)
*
E-mail: j.n.h.reek@uva.nl
Supporting information for this article is given via a link at the end of the
document.
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
Figure 1. Achiral ligand template 1 encapsulated with chiral capsule building
blocks, explored as asymmetric catalysts in hydroformylation in this work
Results and discussion
Ligand template 1 has been studied thoroughly in previous
research, providing guidelines for encapsulating this ligand
template in a fashion that would allow for chiral induction in
catalysis.[30,35,36] The ligand template in solution is highly dynamic,
as the pyridine groups can rotate freely in solution. When the
ligand template is encapsulated by porphyrins the number of
possible conformations the ligand template can adopt is
decreased due to steric restrictions imposed by the coordination
of the porphyrins.[35,36] The capsule formed by encapsulation of
ligand template 1 with Zn(II)TPP is present in only two different
Figure 2. Encapsulation of ligand template 1 with Zn(II)TPP limits the amount
of possible conformations of the ligand template to two distinct conformations,
as observed in the crystal structure (top), two enantiomeric propeller
conformations of the ligand template (middle and bottom)
conformation in the crystal structure.[30] Inspection of these
structures shows that for both structures the pyridine groups are
pointing in the same direction, creating a propeller shape. The
difference between the two propeller conformations is the
handedness of the propeller, making these two observed
conformations a pair of enantiomeric conformers (Figure 2).
Interconversion between the two enantiomeric forms can only
occur when one of the capsule building blocks is dissociated,
whereafter the conformation can flip to the propeller conformation
of opposite handedness. Porphyrin association and dissociation
and therefore the interconversion between the two enantiomeric
conformations is fast on the NMR timescale, also at low
temperatures down to -90 °C, and as such both enantiomeric
forms of ligand template 1 are present in solution.[35,36]
When ligand template 1 could be encapsulated by chiral
porphyrin building blocks, the two resulting conformers of
opposite handedness would be diastereoisomers that may have
different energies. In that case, the ligand template adapts to form
the lower energy conformer as the major product, essentially
creating a diastereomeric excess of that conformation, resulting
in a capsule that can be applied in enantioselective catalysis.
Synthesis
From previous research it is known that the shape of the
capsule is essential for achieving highly branched selectivity in
Scheme 1. Synthesis of chiral porphyrin 2 using Buchwald-Hartwig amination
We synthesized several chiral porphyrins to serve as
capsule building blocks for the generation of encapsulated
catalysts. These porphyrins were synthesized using two
strategies. The synthesis of chiral porphyrin 2 was achieved
through introduction of a chiral carboxamide onto a bromo-
substituted porphyrin using similar Buchwald-Hartwig amination
conditions as described in literature (see experimental section for
details),[37] followed by methylation of the amide functionalities in
order to obtain desirable solubility properties, and metalation
hydroformylation.
The
shape
suitable
for
selective
hydroformylation catalysis is only preserved for capsules based
on substituted porphyrins with the substituent at the meta position
of the phenyl rings of the tetraphenyl porphyrin.[28] The meta
substituent is known not to disrupt the intermolecular CH-π
interactions required for the formation of the capsule, as the
substituents are pointing away from the center of the capsule.[30]
When porphyrins with ortho or para substituents are used, steric
hindrance causes deformation of the capsule.
(
scheme 1). All intermediates in these reactions were
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
characterized by NMR spectroscopy and high-resolution mass
spectrometry (HR-MS, for the spectra see SI). Similar to
porphyrins reported in literature, no diastereoisomers were
1
observed in the H NMR, indicating that no racemization of the
chiral groups had occurred during the synthesis.[37]
Figure 3. DFT calculations show that the energy difference between the two
enantiomeric states of ligand template 1 is 3 kcal/mol when encapsulated with
porphyrin 2, lower energy structure depicted on the right
Scheme 2. Synthesis of porphyrin 3-5 through ester condensation
Porphyrins 3-5 were synthesized by ester condensation of
the hydroxyl substituted porphyrins with chiral acids and
subsequently metalated to provide the chiral zinc porphyrins
(
scheme 2). For porphyrins 3-5, the intermediate species (not
depicted in scheme 2) and the final products were characterized
by NMR spectroscopy and HR-MS (for spectra see SI). No
1
diastereoisomers were observed according to H NMR, indicating
retention of the chiral configuration of the substituents throughout
these reactions.
Formation of encapsulated catalysts
DFT calculations of the capsule formed from ligand template
1
and porphyrin 2 indicate that the computed structures are similar
to the structures known for the Zn(II)TPP capsule (Figure 3 and 4,
Carthesian coordinates provided in the SI). The chiral
substituents are pointing outwards, unable to have direct contact
with a metal that is coordinated at the inside of the capsule. The
source for any chiral induction in catalysis should therefore
originate from the chirality of the conformation of ligand template
1
in combination with the chiral shape of the porphyrin capsule.
Figure 4. Overlay structure of the chiral enantiomeric states of the capsule
formed by ligand 1 and porphyrin 2 with the capsule formed by encapsulation of
ligand 1 with ZnTPP, viewed from the top (upper pictures) and from the bottom,
showing that one of the porphyrins in the capsule formed with porphyrin 2 is
rotated compared to the ZnTPP based capsule (lower pictures)
The two calculated structures of the diasteomeric forms of the
capsule have an energy difference of 3 kcal/mol, indicating that if
the capsule forms in solution one of the diastereomeric forms will
be the major conformer present. The calculated structures were
compared with the structure of the ZnTPP based capsule (figure
between the porphyrin and the other porphyrin building blocks are
observed. This suggests that for the capsule based on porphyrin
4). The overlay of the structures shows that for the capsules
2
the binding of the last porphyrin building blocks may not exhibit
based on porphyrin 2 (in red and yellow) two of the porphyrins are
in a similar conformation as is observed for the ZnTPP capsule
the cooperative binding effect observed for the ZnTPP
capsule.[28,30] The distortion of the capsule shape when using
porphyrin 2 as a capsule building block is a result of the chiral
(
in blue). The third porphyrin is rotated compared to the ZnTPP
capsule and for the rotated porphyrins no CH-π
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
substituents on the porphyrin building block, which are in close
proximity in several locations in the calculated structure. The
influence of close proximity between the chiral substituents on the
distorted binding of the third equivalent of porphyrin 2 to ligand
template 1 explains why one of the diastereomeric conformations
is lower in energy.
To investigate if a capsule is formed around the rhodium
atom when porphyrins 2-5 are used as capsule building blocks,
we used high-pressure infrared (HP-IR) spectroscopy.[27,29,38] HP-
IR can be used to observe IR stretch vibrations of the carbonyl
ligands present around the rhodium center, which provides
information about the geometry of the coordination complex. The
electron density of the rhodium is influenced by the other ligands
present in the complex, and this in turn influences the positions of
the carbonyl IR bands. In the absence of porphyrin building blocks,
are within one reciprocal centimeter the same as for catalyst 6,
indicating that the carbonyl ligands have identical electronic
properties. Below 2000 cm-1 no peaks are observed, ruling out the
formation of a bis-coordinated species similar to catalyst 7. These
spectra indicate that under catalytic conditions, the species
formed by encapsulation of ligand template 1 with porphyrins 2-5
are nearly identical to catalyst 6, a monophosphine-coordinated
rhodium species with three carbonyl ligands, encapsulated by
three chiral porphyrin capsule building blocks.
2 2
a RhH(ligand 1) (CO) complex forms under syngas pressure,
which will convert to a monocoordinated complex when the ligand
template is successfully encapsulated by the porphyrin building
blocks. The species formed under syngas pressure for ligand
template 1 and various equivalents of Zn(II)TPP are well-
known.[27–29] For the encapsulated catalyst, leading to
RhH(ligand 1)(CO) complex, three carbonyl frequencies are
observed. For the non-encapsulated complex (RhH(ligand
(CO) ), two sets of two peaks are observed as a result of the
formation of the ee and ea coordination complexes (figure 5).
a
3
1)
2
2
[
27–
2
9]
Previous research also showed that formation of a bis-(3-
pyridyl)phenylphosphine ligand template encapsulated with two
Zn(II)TPP capsule building blocks leads to the formation of a
mono-coordinated rhodium catalyst with three carbonyl peaks
2 3
observed. The spectrum for the RhH(1·(ZnTPP) )(CO) has not
been recorded, but the HP-IR spectrum in that case will likely
deviate by several wavenumbers from the spectrum observed for
catalyst 6.
Figure 6. HP-IR spectra recorded for the active species formed by
encapsulation of ligand template 1 in presence of a rhodium precursor and
under syngas pressure ([Rh]=1.0 mM, [phosphine 1] = 2.5 mM, [Chiral porphyrin
Figure 5. Active catalyst 6 is formed upon encapsulation of ligand template 1
with Zn(II)TPP in presence of a rhodium precursor under catalytic conditions,
the HP-IR spectrum shows three characteristic carbonyl peaks at 2089, 2039
and 2011 cm (top, [Rh]=1.0 mM, [phosphine 1]=2.5 mM, [ZnTPP]=7.5 mM).
Catalyst 7 is formed by ligand template 1 and a rhodium precursor under
catalytic conditions in absence of capsule building blocks, with the equatorial-
apical (ea) and the equatorial-equatorial (ee) isomers leading to four peaks in
the HP-IR at 2058, 2006, 1987 and 1953 cm-1 (bottom, taken from ref. [29])
building blocks] = 7.5 mM in DCM) with porphyrin
2 (top left, carbonyl
-
1
-1
frequencies: 2089, 2038 and 2010 cm ), porphyrin 3 (top right, carbonyl
-
1
frequencies: 2089, 2038 and 2012 cm ), porphyrin 4 (bottom left, carbonyl
-
1
frequencies: 2089, 2038 and 2011 cm ) and porphyrin 5 (bottom right, carbonyl
-
1
frequencies: 2089, 2038 and 2012 cm )
The HP-IR spectra recorded for porphyrins 2-5 are all nearly
identical to the spectrum recorded for catalyst 6 (see figure 6).
Three peaks are observed, characteristic for the formation of a
Catalysis
The selectivity of the encapsulated catalysts based on
ligand template 1 in the hydroformylation of 1-octene is strongly
influenced by capsule formation.
mono-coordinated rhodium species with three carbonyl
ligands.[
27,28]
The IR stretch frequencies of the carbonyl ligands
[26–28,30]
Previous research has
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
shown that when the ligand template is encapsulated with only
two Zn(II)TPP building blocks, the resulting ratio between the
linear and the branched aldehyde product (the l/b ratio) is 1.1.[27]
with the previously reported results in which a tetra-3-nitrophenyl
porphyrin was used to form the encapsulated catalyst which was
applied in 2-octene hydroformylation, resulting in no conversion
When three Zn(II)TPP molecules are bound to the ligand template, of the 2-octene. In that case the electron-withdrawing effect of the
a full capsule is formed around the rhodium atom, which leads to
a characteristic l/b ratio of 0.60 when applied in 1-octene
hydroformylation. Similar l/b ratios have been observed when
meta substituted tetraphenyl porphyrins were used as capsule
building blocks.[26,30] Because the difference in selectivity between
nitro substituent leads to the formation of a more stable capsule
that blocked the conversion pathway for 2-octene and other
internal alkenes.[28,30] For the capsules based on porphyrins 2-5 a
combination of increased steric interaction caused by the
substituents present and the electron-withdrawing nature of the
substituents is likely to have the same effect.
the RhH((1)(TPP)
3
)(CO)
3
2 3
and the RhH((1)(TPP) )(CO)
complexes in 1-octene hydroformylation is large, we first used our
new capsules in this reaction to confirm proper capsule formation
under catalytic conditions (table 1). The catalytic results show that
when three equivalents of porphyrin 2 are present in the catalytic
mixture, the l/b ratio of the product aldehydes is 0.90, suggesting
that full encapsulation was not achieved. When porphyrin 2 is
added in excess compared to ligand template 1 the l/b ratio of the
product aldehydes is 0.56, which is the characteristic selectivity
obtained for a capsule based on a three-to-one porphyrin to ligand
template ratio. These results show that an excess of porphyrin
can be used to ensure formation of a fully encapsulated catalyst
when using porphyrin 2 as the capsule building block. The
formation of three-to-one complexes of porphyrins 3-5 with ligand
template 1 was also confirmed when an excess of porphyrin
building blocks is present and the formed capsule are applied in
Because no conversion was obtained for 2-octene
hydroformylation, the capsule based on chiral porphyrin 2 was
applied in styrene hydroformylation. The amount of porphyrin
equivalents needed for the formation of a three-to-one capsule
around ligand template 1 with porphyrin 2 was also investigated
for this substrate. Application of three equivalents of porphyrin 2
in styrene hydroformylation showed that chiral induction is
possible, yielding the product in 9% enantiomeric excess (ee)
(Table 2). Adding porphyrin 2 in excess yielded a maximum ee of
13% when six equivalents of porphyrin are present. Addition of a
larger excess of porphyrin 2 did not further increase the ee.
Table 2. Styrene hydroformylation with porphyrin 2 at different concentration
1-octene hydroformylation (table 1).
Table 1. Hydroformylation of 1-octene with porphyrins 2-5
Porphyrin[a]
Equivalents of porphyrin[b]
ee[c]
Substrate
Styrene
Styrene
Styrene
Styrene
2
2
2
2
3
6
9%
13%
13%
13%
9
Equivalents of
l/b
ratio
Porphyrin[a]
Substrate
Yield[c]
porphyrin[
b]
[c]
12
2
2
3
4
5
1-octene
1-octene
1-octene
1-octene
1-octene
3
6
6
6
6
>99%
>99%
>99%
>99%
>99%
0.90
0.56
0.49
0.50
0.49
[
a] Conditions: [Rh(acac)(CO)
2
] = 0.18 mM, [Rh]:[Phosphine 1] = 1:5, T = 25 °C,
t = 96h, p = 20 bar (CO:H =1:1), solvent: Toluene, [b] with respect to ligand
template 1, [c] ee determined with chiral GC, see experimental section for
details
2
After having established the required conditions for
successful capsule formation with the chiral porphyrins, the
capsules based on porphyrins 2-5 were applied in the
hydroformylation of several benchmark substrates (table 3, for
further control experiments and examples of GC traces see SI).
The encapsulated catalyst formed with porphyrin 2 shows the
highest ee of all reactions performed, with 33% ee observed for
the aldehyde product of vinyl acetate hydroformylation. Vinyl
benzoate and vinyl pivalate hydroformylation products are formed
with 16% and 15% ee respectively, at similar yield as for vinyl
acetate. The product of styrene hydroformylation was formed in
[
a] Conditions: [Rh(acac)(CO)
octene] = 1:400, T = 25 °C, t = 96h, p = 20 bar (CO:H
b] with respect to ligand template 1, [c] yield and l/b ratio determined with GC
2
]=0.18 mM, [Rh]:[Phosphine 1] = 1:5, [Rh]:[1-
2
=1:1), solvent: Toluene,
[
using decane as an internal standard, see experimental section for details
The 2-aldehyde was the major product formed during the
hydroformylation of 1-octene, however we were unable to
determine the enantioselectivity of the product formed (for
attempts at separating the enantiomers see experimental section).
Therefore the hydroformylation of 2-octene was attempted.[40] The
capsule based on Zn(II)TPP has been shown to be an excellent
catalyst for 2-octene hydroformylation, yielding up to 90% of the
-aldehyde product.[ Application of porphyrins 2-5 as capsule
building blocks in the hydroformylation of 2-octene yielded no
products, even when the catalyst loading (up to 1 mol%) and the
temperature were increased (up to 40°C). These results are in line
1
3% ee with 92% yield. The capsule based on porphyrin 3
produces the aldehyde products of vinyl acetate, vinyl benzoate
and vinyl pivalate in similar yields, around 70% and with an ee of
around 20%. Compared to the capsule based on porphyrin 2, the
encapsulated catalyst formed with porphyrin 3 has a higher
product yield, with lower ee observed for the products of vinyl
acetate and styrene hydroformylation, but a higher ee for the
products of vinyl benzoate and vinyl pivalate hydroformylation.
The encapsulated catalyst formed with porphyrin 4 shows very
28]
3
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
low product yields with low ee of the product aldehydes. The
capsule based on porphyrin 5 produces good yields, comparable
to the capsules based on porphyrins 2 and 3, but no significant
amount of ee is observed in any of the product aldehydes.
a capsule that is too stable to accommodate catalysis, a results of
the electronic and steric properties of the camphanic acid
substituent on the capsule building blocks which is not a flexible
or dynamic substituent. Porphyrin 5, like porphyrins 3 and 4,
contains an ester bond to attach the chiral substituent to the
porphyrin core. When porphyrin 5 is used for the formation of an
encapsulated catalyst, no ee is detected in the product aldehydes.
This is a result of the small size of the chiral substituents on
porphyrin 5, which are unable to steer the capsule formation
process towards a chiral capsule.
Table 3. Asymmetric hydroformylation of several substrates with chiral
porphyrin based capsules
Porphyrin[a]
Substrate
Vinyl acetate
Styrene
Yield[b]
45%
96%
52%
45%
71%
99%
63%
76%
11%
13%
<1%
<1%
56%
98%
58%
69%
ee[c]
33%
13%
16%
15%
19%
6%
2
2
2
2
3
3
3
3
4
4
4
4
5
5
5
5
Conclusion
Vinyl benzoate
Vinyl pivalate
Vinyl acetate
Styrene
We have shown that it is possible to perform
enantioselective hydroformylation by encapsulating an achiral
ligand template with chiral capsule building blocks. For this
purpose several chiral porphyrins have been synthesized and
characterized. Computational studies show that encapsulation of
ligand template 1 limits the amount of conformations to two
distinct conformations, which are diastereoisomers of one another
that have different energies. The energy difference between the
two diastereomeric conformations is 3 kcal/mol, which suggests
that the capsule is almost exclusively present in that conformation.
HP-IR spectra show that mono-coordinated catalysts are formed
by ligand template 1 with chiral porphyrins 2-5 in presence of
rhodium under syngas pressure. Titrations combined with
catalysis data show that the chiral porphyrins have to be added in
excess to form a three porphyrin to one ligand template
encapsulated state in catalysis. Application of the capsules based
on porphyrins 2-5 in 1-octene hydroformylation yielded a linear to
branched product ratio typical for these type of porphyrin based
encapsulated catalysts. Application of the capsules based on
porphyrins 2-5 in 2-octene hydroformylation gave no conversion
of the substrate, which is caused by the formation of a more rigid
capsule caused by the electronic properties and the increase
steric interaction of the chiral substituents. When these catalysts
are applied in asymmetric hydroformylation of various substrates,
a maximum ee of 33% is achieved in the hydroformylation of vinyl
acetate for the capsule formed by encapsulation with porphyrin 2.
The capsules based on porphyrin 2 and porphyrin 3 were found
to produce the product aldehydes of all substrates with some
amount of enantiomeric excess. Porphyrin 4 gave low conversion
for all substrates owing to the formation of a cavity around the
rhodium atom that cannot facilitate catalysis, similar to what was
observed for all chiral porphyrins in 2-octene hydroformylation.
Porphyrin 5, which bears small chiral substituents, gave no ee for
any of the substrates used, showing that the steric definition and
size of the chiral substituents play an important role in
enantioselective hydroformylation with these catalysts.
Vinyl benzoate
Vinyl pivalate
Vinyl acetate
Styrene
21%
18%
12%
3%
Vinyl benzoate
Vinyl pivalate
Vinyl acetate
Styrene
6%
4%
2%
<1%
<1%
<1%
Vinyl benzoate
Vinyl pivalate
[
2
a] Conditions: [Rh(acac)(CO) ] = 0.18 mM, [Rh] : [Phosphine 1] = 1 : 5,
[
Phosphine 1] : [Porphyrin] = 1 : 6, [Rh]:[substrate] = 1:1600, T = 25 °C, t = 96h,
1
p = 20 bar (CO:H
2
=1:1), solvent, : Toluene, [b] determined with H NMR using
1,3,5-trimethoxybenzene as an internal standard, [c] ee determined with chiral
GC, see experimental section for details
The results show that the influence of the chiral group
attached to the porphyrin building block of the encapsulated
catalyst is very important for the activity and selectivity of the
reaction. The capsule based on porphyrin 2 has the highest ee
aldehyde product for vinyl acetate, which is not increased by using
a more sterically demanding substrate such as vinyl benzoate or
vinyl pivalate. For the encapsulated catalyst formed with
porphyrin 3 the ee and yield observed for all vinyl esters is similar,
showing that for the encapsulated catalyst increasing the size of
the substrate does not increase the selectivity of the reaction or
inhibit the activity of the catalyst, as is observed for the catalyst
formed with porphyrin 2. The activity of the encapsulated catalyst
is inhibited by the substituents on the capsule building blocks, as
is observed for the capsule formed with porphyrin 4. Similar to
porphyrin 3, the chiral groups of porphyrin 4 are connected to the
porphyrin via ester bonds. The capsule based on porphyrin 4
yields low amounts of products for each substrate used, although
the HP-IR of the encapsulated catalyst shows formation of the
active rhodium hydride species. The low yield observed for the
capsule based on porphyrin 4 is likely caused by the formation of
Experimental section
General procedures. All reactions were performed under an inert
atmosphere (N
otherwise. Toluene was distilled over sodium under N
2
or Ar) using standard Schlenk techniques unless stated
atmosphere before
2
use. Styrene, vinyl acetate, vinyl benzoate and vinyl pivalate were filtered
over basic alumina prior to use, 1,3,5-trimethoxybenzene and
Rh(acac)(CO)
synthesized using literature procedures.
2
was used as received. Tris-3-pyridyl phosphine 1 was
[41]
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
HP-FTIR. High-pressure IR spectra were recorded using a specially
modified autoclave.[42] The autoclave was flushed with Ar for 20 minutes
prior to use. The samples were then injected under Ar flow, after which the
autoclave was flushed with syngas (CO/H =1:1, 10 bar, 3x) and
2
pressurized to the required pressure. Addition of Rh proceeded through a
separate container in the autoclave under slight overpressure of syngas
purple solid (109.0 mg, 0.1 mmol) in 97% yield. 1H NMR (300 MHz,
Acetone-d ) δ 9.73 (s, 4H), 8.97 (s, 8H), 8.58 (d, J = 8.3 Hz, 4H), 8.21 (d,
6
J = 8.1 Hz, 4H), 7.94 (d, J = 7.6 Hz, 4H), 7.73 (t, J = 7.9 Hz, 4H), 1.75 (t, J
= 6.7 Hz, 4H), 1.23 (s, 12H), 1.16 (s, 12H), 1.11 (d, J = 5.0 Hz, 4H), 0.80
(dd, J = 8.0, 3.9 Hz, 4H), -2.74 (s, 2H). 13C NMR (75 MHz, Acetone-d
6
) δ
169.8, 142.5, 138.3, 129.3, 128.9, 128.2, 127.3, 127.1, 125.3, 120.1, 118.2,
(
25 bar). A background was measured of the phosphine ligand, the zinc
26.5, 22.0, 19.8, 18.1. HR-MS (CSI+): calculated for [MH]+ (C68
1059.5285, found: 1059.5330
66 8 4
H N O ):
porphyrin, after which Rh(acac)(CO) was added and formation of the
2
active species was monitored overnight. Concentrations used: [Rh]=1.0
mM, [ligand template 1]=2.5 mM, [porphyrin]=7.5 mM
Porphyrin intermediate i2
Catalysis. Catalysis was performed in
a stainless steel autoclave
2
Under N atmosphere, porphyrin intermediate i1 (101.8 mg, 0.10 mmol)
equipped with an eight vial insert, in which small GC vial (1.5 ml) were
and NaH (60% dispersion in mineral oil, 40.7 mg, 1.7 mmol) were
dissolved in dry THF (10 ml), after which the solution was stirred for 3h at
RT. Subsequently, MeI (120 μl, 1.9 mmol) was added and the mixture was
stirred overnight. After evaporating the solvent, the product was purified
place loaded with
a
stirring bar. Porphyrins were weighed on
a
microbalance and added to the vials as solids. Rh(acac)(CO)
2
and 1,3,5-
trimethoxybenzene were added as a stock solution in dry toluene and tris-
-pyridylphosphine was added as a stock solution in dry toluene prepared
3
using column chromatography (SiO
product as a purple solid (87.1 mg, 0.08 mmol) in 81% yield. H NMR (300
2
, DCM:Acetone=3:1) yielding the
under inert conditions. All constituents were added to the vials after which
the volume was completed to the required volume with dry toluene
1
MHz, Chloroform-d) δ 9.06 – 8.67 (m, 8H), 8.32 – 8.02 (m, 8H), 7.85 (td, J
(
typically 0.7 ml). These solutions were then stirred for 20 minutes under
aerobic conditions, after which the vials were placed in the autoclave and
the autoclave was flushed with syngas (CO:H =1:1, 3x20 bar) and
=
8
2
1
7.8, 3.2 Hz, 4H), 7.68 (d, J = 8.0 Hz, 4H), 3.60 (s, 12H), 1.36 – 1.25 (m,
H), 1.13 (s, 12H), 0.94 (s, 12H), 0.74 (dd, J = 7.9, 4.2 Hz, 4H), -2.77 (s,
H). 13C NMR (75 MHz, Chloroform-d) δ 171.5, 143.3, 143.0, 133.1, 130.9,
2
pressurized to the required pressure. The autoclave was then placed in an
oil bath set at the required temperature and stirred (750 rpm). After the
required time, the reaction was halted by venting the syngas from the
28.8, 127.7, 119.2, 37.7, 29.7, 28.8, 26.5, 22.3, 20.4, 19.0, 18.1. HR-MS
+
(CSI+): calculated for [MH] (C72
74 8 4
H N O ): 1115.5911, found: 1115,5932
autoclave, after which the vials were removed and the solutions were used
Chiral porphyrin 2
1
for analysis with H NMR (take ~0.1 ml of solution and add 0.5 ml of CDCl
3
)
and chiral GC (Supelco β-dex 225 capillary column). Methods: Vinyl
Acetate: 100°C, hold for 10 min. then 4°C/min to 140°C; Styrene: 100°C,
hold for 5 min., then 4°C/min to 160°C, hold for 2 min.; Vinyl Benzoate:
Porphyrin intermediate i2 (87.1 mg, 0.07 mmol) and Zn(OAc)
2
(179.9 mg,
0.98 mmol) were dissolve in a mixture of DCM (25 ml) and Acetone (10
ml) and stirred for 1h at RT, after which the solvent was evaporated. The
residue was then dissolved in EtOAc (50 ml) and washed with water (3x50
ml), after which the organic layer was dried with Na SO , filtered and
2 4
evaporation yielded the product as a purple solid (90.4 mmol, 0.07 mmol)
in quantitive yield. 1H NMR (300 MHz, Chloroform-d) δ 8.88 (br m, 8H),
135°C, hold for 60 min.; Vinyl Pivalate: 77°C, hold for 22 min. GC
separation of the 1-octene hydroformylation products was performed on
an Interscience Trace GC Ultra machine with a RTX-1 column (30 meter
column, 0.25 mm internal diameter, 0.25 μm film thickness), initial
temperature: 50 °C, hold for 2 minutes, ramp 10 °C/min to 300 °C, hold for
8
.27 – 8.06 (m, 4H), 7.96 (d, J = 12.4 Hz, 4H), 7.78 (q, J = 6.2, 5.2 Hz, 4H),
.55 (s, 4H), 3.32 (br s, 12H), 1.33 – 1.20 (m, 4H), 0.94 (br m, 14H), 0.60
3
minutes.
7
(
s, 5H). 13C NMR (75 MHz, Methylene Chloride-d
) δ 170.5, 149.9, 149.8,
2
Separation of 2-methyl octanal enantiomers. To separate the branched
product isomer of the 1-octene hydroformylation several methods were
attempted. Separation of the enantiomers with the Supelco β-dex 225
capillary column gave no separation of the products. Attempts at reduction
1
2
1
44.5, 142.2, 132.8, 132.6, 131.7, 131.5, 127.2, 126.3, 119.5, 29.7, 28.0,
5.9, 21.6, 18.3. HR-MS (CSI+): calculated for [MH]+ (C72
72 8 4
H N O Zn):
178.4968, found 1178.5046
4
of the aldehyde with NaBH followed by either GC or HPLC were unreliable.
Porphyrin i3
Under
(
(
Condensation of the product aldehydes with a chiral amine resulted in the
1
formation of highly complex H NMR spectra, for which we were unable to
N
2
atmosphere, 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin
294.3 mg, 0.43 mmol), (S)-(+)-Ibuprofen (481.9 mg, 2.4 mmol), DCC
532.4 mg, 2.6 mmol) and DMAP (29.2 mg, 0.24 mmol) were dissolved in
determine which peaks belonged to which products.
DFT calculations. Geometry optimizations were performed with the
Amsterdam Density Functional (ADF) program using the BLYP functional
and the DZP basis set similar to with previous calculations performed on
these type of capsules.[30] The structures were generated using the two
3
conformations observed in the X-ray structure of 1(Zn(II)TPP) .
dry THF (15 ml) and stirred for 120h at RT. After this, the solvent was
evaporated and the product was isolated using column chromatography
(SiO
2
, DCM:Hexane=10:1) yielding the product as a purple solid (505 mg)
1
in 79% yield. H NMR (300 MHz, Methylene Chloride-d
2
) δ 8.93 (s, 8H),
8
8
7
.10 (d, J = 7.7 Hz, 4H), 7.92 (s, 4H), 7.79 (t, J = 7.9 Hz, 4H), 7.50 (d, J =
.0 Hz, 4H), 7.37 (d, J = 7.7 Hz, 8H), 7.15 (d, J = 7.7 Hz, 8H), 4.08 (q, J =
.1 Hz, 4H), 2.44 (d, J = 7.2 Hz, 8H), 1.80 (hept, J = 7.0 Hz, 4H), 1.67 (dd,
Synthesis
J = 7.1, 2.4 Hz, 12H), 0.85 (d, J = 6.6 Hz, 24H), -2.91 (s, 2H). 13C NMR (75
MHz, Chloroform-d) δ 173.4, 149.5, 143.2, 140.8, 137.2, 132.1, 130.9,
Porphyrin intermediate i1
1
29.6, 127.6, 127.5, 127.2, 120.9, 119.0, 45.4, 45.0, 30.1, 29.7, 22.4, 18.6,
+
Under N
2
atmosphere, 5,10,15,20-tetrakis(3-bromophenyl)porphyrin (99.0
14.1. HR-MS (CSI+): calculated for [MH] (C96
94 4 8
H N O ): 1432.7183, found
mg, 0.1 mmol), (S)-(+)-2,2-Dimethylcyclopropanecarboxamide (364.2 mg,
1432.7149
3
.2 mmol), Pd
2
dba
3
(34.8 mg, 0.033 mmol), Xantphos (49.1 mg, 0.08
(517.4 mg, 1.6 mmol) were added to a flame-dried
mmol) and Cs
2
CO
3
Zinc porphyrin 3
Schlenk flask, followed by the addition of dried THF (6 ml) after which the
mixture was stirred for 60h at 100°C. After the reaction was cooled down
to RT, DCM (50 ml) was added and solids were removed through filtration.
The solvent was then removed and the product was purified using column
2 2
Porphyrin i3 (505.3 mg, 0.34 mmol) and Zn(OAc) ·2H O (1.1g, 5.0 mmol)
were dissolved in a mixture of DCM (15 ml) and Acetone (10 ml) and stirred
for 1.5h at RT. After this, the solvent was evaporated, the residue was
2
chromatography (SiO , DCM:Acetone=20:1) yielding the product as a
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
dissolved in EtOAc (50 ml) and washed with H
2
O (3x 50 ml), dried with
Zinc porphyrin 5
4
MgSO and filtered. The product was obtained by evaporation of the
solvent, yielding the product as a purple solid (520 mg) in quantative yield.
H NMR (300 MHz, Chloroform-d) δ 9.01 (s, 8H), 8.07 (d, J = 7.5 Hz, 4H),
2 2
Porphyrin i5 (100.2 mg, 0.10 mmol) and Zn(OAc) ·2H O were dissolved in
a mixture of DCM (25 ml) and Acetone (10 ml) and stirred for 1.5h at RT.
After this, the solvent was evaporated, the residue was dissolved in EtOAc
1
7.91 (s, 4H), 7.73 (t, J = 7.9 Hz, 4H), 7.47 (d, J = 8.2 Hz, 4H), 7.41 – 7.32
(m, 8H), 7.19 – 7.03 (m, 8H), 4.05 (q, J = 7.6 Hz, 4H), 2.43 (d, J = 7.2 Hz,
2 4
(50 ml) and washed with H O (3x 50 ml), dried with MgSO and filtered.
8
2
1
4
H), 1.94 – 1.75 (m, 4H), 1.68 (d, J = 3.7 Hz, 12H), 0.86 (d, J = 6.5 Hz,
4H). 13C NMR (75 MHz, Chloroform-d) δ 173.4, 150.1, 149.4, 143.9,
40.8, 137.2, 132.2, 131.9, 129.5, 127.5, 127.3, 127.2, 120.7, 120.0, 45.4,
5.0, 30.1, 22.4, 18.6. HR-MS (CSI+): calculated for [MH]+
The product was obtained by evaporation of the solvent, yielding the
product as a purple solid (89.9 mg) in 89% yield. 1H NMR (300 MHz,
Methylene Chloride-d
2
) δ 9.07 (br s, 8H), 8.14 (d, J = 7.6 Hz, 4H), 7.99 (s,
H), 7.82 (t, J = 7.9 Hz, 4H), 7.56 (d, J = 8.1 Hz, 4H), 2.75 (q, J = 6.9 Hz,
H), 1.91 (dt, J = 14.3, 7.2 Hz, 4H), 1.70 (dt, J = 14.3, 7.2 Hz, 4H), 1.35 (d,
) δ 175.3,
149.5, 143.9, 132.1, 131.9, 127.9, 127.4, 120.8, 120.0, 41.2, 26.8, 16.4, 14.0, 11.4.
HR-MS (CSI+): calculated for [MNa]+ (C64
Zn): 1099.3600, found:
099.3670
4
4
(
C
96 92 4 8
H N O Zn): 1494.6224, found 1494.6271
J = 6.9 Hz, 12H), 1.06 (t, J = 7.4 Hz, 12H). 13C NMR (126 MHz, CDCl
3
Porphyrin i4
Under
60 4 8
H N O
1
N
2
atmosphere, 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin
(
200.0 mg, 0.29 mmol), (-)-camphanic acid chloride (286.6 mg, 1.3 mmol)
and DMAP (13.2 mg, 0.12 mmol) were added to a Schlenk flask and
dissolved in THF (10 ml), after which NEt (0.2 ml, 1.5 mmol) was added
and the mixture was stirred for 72h at RT. After this, the solvent was
removed and the mixture was purified using column chromatography (SiO
3
Acknowledgements
2
,
We thank the European Research Council (ERC Adv. Grant
339786-NAT_CAT to Reek) for financial support. We would like
to thank dr. J. Heinen for DFT calculations and P.R. Linnenbank
for performing control experiments.
DCM:Hexane=20:1), yielding the product after evaporation of the solvent
1
as a purple solid (327.4 mg) in 83% yield. H NMR (300 MHz, Chloroform-
d) δ 8.95 (s, 8H), 8.15 (d, J = 7.6 Hz, 4H), 8.03 (s, 4H), 7.83 (t, J = 7.9 Hz,
4
2
1
H), 7.62 (d, J = 8.5 Hz, 4H), 2.87 – 2.50 (m, 4H), 2.39 – 2.20 (m, 4H),
.03 (td, J = 12.1, 10.9, 4.4 Hz, 4H), 1.91 – 1.74 (m, 4H), 1.21 (s, 12H),
.18 (s, 12H), 1.16 (s, 12H), -2.86 (s, 2H). 13C NMR (75 MHz, Methylene
Keywords: catalyst encapsulation • hydroformylation •
supramolecular chemistry • asymmetric catalysis • bio-inspired
catalysis
2
Chloride-d ) δ 177.7, 166.5, 148.7, 143.4, 132.7, 128.0, 127.6, 123.0,
19.0, 91.0, 30.9, 29.0, 16.7, 9.5. HR-MS (CSI+): calculated for [MNa]+
1
84 78 4
(C H N O16): 1421.5310, found: 1421.5351
Zinc porphyrin 4
[
[
1]
2]
P. W. N. M. van Leeuwen, Focus Catal. 2005, 2005, 8.
M. Raynal, P. Ballester, A. Vidal-Ferran, P. W. N. M. Van Leeuwen,
Chem. Soc. Rev. 2014, 43, 1660–1733.
2 2
Porphyrin i4 (100.6 mg, 0.075 mmol) and Zn(OAc) ·2H O (327.7 mg, 1.5
mmol) were dissolved in a mixture of DCM (25 ml) and Acetone (10 ml)
and stirred for 1.5h at RT. After this, the solvent was evaporated, the
[3]
[4]
[5]
[6]
[7]
[8]
[9]
M. Raynal, P. Ballester, A. Vidal-Ferran, P. W. N. M. van Leeuwen, Chem.
Soc. Rev. 2014, 43, 1734–1787.
residue was dissolved in EtOAc (50 ml) and washed with H
dried with MgSO and filtered. The product was obtained by evaporation
of the solvent, yielding the product as a purple solid (76.3 mg) in 73% yield.
1H NMR (300 MHz, Methylene Chloride-d
) δ 9.09 (s, 8H), 8.23 (d, J = 7.5
Hz, 4H), 8.09 (s, 4H), 7.89 (td, J = 7.9, 1.6 Hz, 4H), 7.72 – 7.56 (m, 4H),
2
O (3x 50 ml),
S. H. A. M. Leenders, R. Gramage-Doria, B. de Bruin, J. N. H. Reek,
Chem. Soc. Rev. 2015, 44, 433–448.
4
C. J. Brown, F. D. Toste, R. G. Bergman, K. N. Raymond, Chem. Rev.
2015, 115, 3012–3035.
2
W. X. Gao, H. N. Zhang, G. X. Jin, Coord. Chem. Rev. 2019, 386, 69–
84.
3
.03 – 2.42 (m, 4H), 2.37 – 2.16 (m, 4H), 2.14 – 1.95 (m, 4H), 1.76 (dt, J
13.2, 3.4 Hz, 4H), 1.22 (br s, 12H), 1.14 (br m, 12H), 1.12 (br s, 12H).
C NMR (126 MHz, Chloroform-d) δ 177.7, 166.4, 150.1, 148.6, 144.4,
32.6, 127.7, 127.5, 127.5, 120.6, 119.68, 91.0, 30.8, 29.0, 20.6, 16.7,
=
C. Tan, D. Chu, X. Tang, Y. Liu, W. Xuan, Y. Cui, Chem. Eur. J. 2019,
25, 662–672.
13
1
1
1
C. M. Hong, R. G. Bergman, K. N. Raymond, F. D. Toste, Acc. Chem.
Res. 2018, 51, 2447–2455.
3.9, 9.4. HR-MS (CSI+): calculated for [MNa]+ (C84
483.4445, found: 1483.4431
76 4
H N O16Zn):
V. Blanco, D. A. Leigh, V. Marcos, Chem. Soc. Rev. 2015, 44, 5341–
5
370.
10] M. J. Wiester, P. A. Ulmann, C. A. Mirkin, Angew. Chem. Int. Ed. 2011,
0, 114–137.
[
Porphyrin i5
5
[
[
[
11] U. Lüning, Angew. Chem. Int. Ed. 2012, 51, 8163–8165.
12] T. Imahori, S. Kurihara, Chem. Lett. 2014, 43, 1524–1531.
13] A. J. McConnell, C. S. Wood, P. P. Neelakandan, J. R. Nitschke, Chem.
Rev. 2015, 115, 7729–7793.
Under
N
2
atmosphere, 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin
(332.0 mg, 0.49 mmol), (R)-2-methyl butyric acid (432 μl, 2.7 mmol),
DMAP (32.9 mg, 0.27 mmol) and DCC (604.7 mg, 2.9 mmol) were added
to a Schlenk flask and dissolved in dry THF (20 ml) and stirred at RT for
[
[
[
[
[
14] M. Vaquero, L. Rovira, A. Vidal-Ferran, Chem. Commun. 2016, 52,
4
8h. After evaporation of the solvent the mixture was purified using column
chromatography (SiO , Hexane:DCM=30:700:100) yielding the product
as a purple solid (294 mg) in 59% yield. 1H NMR (300 MHz, Methylene
Chloride-d ) δ 8.99 (s, 8H), 8.14 (d, J = 7.6 Hz, 4H), 7.99 (s, 4H), 7.83 (t,
J = 7.9 Hz, 5H), 7.58 (ddd, J = 8.3, 2.4, 1.1 Hz, 4H), 2.89 – 2.57 (m, 4H),
1
1038–11051.
15] M. Vlatković, B. S. L. Collins, B. L. Feringa, Chem. Eur. J. 2016, 22,
7080–17111.
2
1
2
16] J. A. A. W. Elemans, E. J. A. Bijsterveld, A. E. Rowan, R. J. M. Nolte,
Eur. J. Org. Chem. 2007, 751–757.
1
6
.91 (dt, J = 13.6, 7.3 Hz, 4H), 1.70 (dt, J = 13.7, 6.9 Hz, 4H), 1.36 (d, J =
.9 Hz, 12H), 1.06 (t, J = 7.4 Hz, 12H), -2.87 (s, 2H). 13C NMR (75 MHz,
17] L. J. Jongkind, J. A. A. W. Elemans, J. N. H. Reek, Angew. Chem. Int.
Ed. 2019, 58, 2696–2699.
Methylene Chloride-d
19.1, 41.2, 26.8, 16.4, 11.4. HR-MS (CSI+): calculated for [MH]+
): 1015.4646, found 1015.4659
2
) δ 175.3, 149.6, 143.1, 132.0, 128.0, 127.6, 121.1,
18] A. C. H. Jans, A. Gómez-Suárez, S. P. Nolan, J. N. H. Reek, Chem. Eur.
J. 2016, 22, 14836–14839.
1
64 62 4 8
(C H N O
[
[
19] M. Yoshizawa, M. Tamura, M. Fujita, Science 2006, 312, 251–255.
20] J. Kang, J. Rebek J., Nature 1996, 382, 239–241.
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
[
[
[
[
21] Q. Zhang, L. Catti, K. Tiefenbacher, Acc. Chem. Res. 2018, 51, 2107–
114.
[32] R. Bellini, J. N. H. Reek, Chem. Eur. J. 2012, 18, 13510–13519.
[33] R. Bellini, S. H. Chikkali, G. Berthon-Gelloz, J. N. H. Reek, Angew. Chem.
Int. Ed. 2011, 50, 7342–7345.
2
22] S. H. A. M. Leenders, R. Gramage-Doria, B. de Bruin, J. N. H. Reek,
Chem. Soc. Rev. 2015, 44, 433–448.
[34] D. Ringe, G. A. Petsko, Science 2008, 320, 1428–1429.
[35] I. Jacobs, A. C. T. van Duin, A. W. Kleij, M. Kuil, D. M. Tooke, A. L. Spek,
J. N. H. Reek, Catal. Sci. Technol. 2013, 3, 1955.
23] Q. Q. Wang, S. Gonell, S. H. A. M. Leenders, M. Dürr, I. Ivanovic-
Burmazovic, J. N. H. Reek, Nat. Chem. 2016, 8, 225–230.
24] R. Gramage-Doria, J. Hessels, S. H. A. M. Leenders, O. Tröppner, M.
Dürr, I. Ivanović-Burmazović, J. N. H. Reek, Angew. Chem. Int. Ed. 2014,
[36] I. Jacobs, Insights In Rhodium-Catalyzed Hydroformylation In
Supramolecular Cages
A Combined Experimental and Theoretical
53, 13380–13384.
Approach, 2015.
[
[
[
[
[
[
[
25] L. J. Jongkind, X. Caumes, A. P. T. Hartendorp, J. N. H. Reek, Acc.
Chem. Res. 2018, 51, 2115–2128.
[37] Y. Chen, K. B. Fields, X. P. Zhang, J. Am. Chem. Soc. 2004, 126, 14718–
14719.
26] V. F. Slagt, J. N. H. Reek, P. C. J. Kamer, P. W. N. M. Van Leeuwen,
Angew. Chem. Int. Ed. 2001, 40, 4271–4274.
[38] T. Jongsma, G. Challa, P. W. N. M. van Leeuwen, J. Organomet. Chem.
1991, 421, 121–128.
27] V. F. Slagt, P. C. J. Kamer, P. W. N. M. Van Leeuwen, J. N. H. Reek, J.
Am. Chem. Soc. 2004, 126, 1526–1536.
[39] X. Wang, S. S. Nurttila, W. I. Dzik, R. Becker, J. Rodgers, J. N. H. Reek,
Chem. Eur. J. 2017, 23, 14769–14777.
28] V. Bocokić, A. Kalkan, M. Lutz, A. L. Spek, D. T. Gryko, J. N. H. Reek,
Nat. Commun. 2013, 4, 1–9.
[40] T. Gadzikwa, R. Bellini, H. L. Dekker, J. N. H. Reek, J. Am. Chem. Soc.
2012, 134, 2860–2863.
29] T. Besset, D. W. Norman, J. N. H. Reek, Adv. Synth. Catal. 2013, 355,
[41] A. M. Kluwer, I. Ahmad, J. N. H. Reek, Tetrahedron Lett. 2007, DOI
10.1016/j.tetlet.2007.02.127.
348–352.
30] V. Bocokić, Supramolecular Encapsulation of
Hydroformylation Catalyst: A Mechanistic Study, 2011.
a
Rhodium
[42] P. C. J. Kamer, A. van Rooy, G. C. Schoemaker, P. W. N. M. van
Leeuwen, Coord. Chem. Rev. 2004, 248, 2409–2424.
31] R. Bellini, J. N. H. Reek, Eur. J. Inorg. Chem. 2012, 2012, 4684–4693.
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901771
Full paper
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
L.J.Jongkind, J.N.H.Reek*
Page No. – Page No.
Encapsulation in chiral capsules:
Encapsulation of a hydroformylation
catalyst in a chiral capsule, consisting of
an achiral ligand and chiral capsule
building blocks leads to enantioselective
hydroformylation
This article is protected by copyright. All rights reserved.