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\DOI{10.5802/crchim.287}
\datereceived{2023-12-20}
\daterevised{2024-01-05}
\dateaccepted{2024-01-19}
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\dateposted{2024-02-07}
\begin{document}

\begin{noXML}

%\makeatletter
%\def\TITREspecial{\relax}
%\def\cdr@specialtitle@english{French Women in Chemistry in 2024}
%%\def\cdr@specialtitle@french{Les chimistes fran\c{c}aises en 2024}
%\makeatother

\title{Non-covalent interactions in supported asymmetric catalysis: 
a~brief account}

\alttitle{Interactions non covalentes en catalyse asym\'{e}trique
support\'{e}e : un bref aper\c{c}u}

\author{\firstname{L\'{e}a} \lastname{Ibos}}
\address{Universit\'{e} Paris-Saclay, CNRS, Institut de Chimie
Mol\'{e}culaire et des Mat\'{e}riaux d'Orsay, Site Henri Moissan, 17,
avenue des Sciences, 91400 Orsay, France}

\author{\firstname{Emmanuelle} \lastname{Schulz}\CDRorcid{0000-0002-0844-8825}\IsCorresp}
\addressSameAs{1}{Universit\'{e} Paris-Saclay, CNRS, Institut de Chimie
Mol\'{e}culaire et des Mat\'{e}riaux d'Orsay, Site Henri Moissan, 17,
avenue des Sciences, 91400 Orsay, France}
\email[E. Schulz]{emmanuelle.schulz@universite-paris-saclay.fr}

\keywords{\kwd{Asymmetric catalysis}
\kwd{Recycling}
\kwd{Heterogeneous catalysis}
\kwd{Electrostatic interactions}
\kwd{${\uppi}$-interactions}
\kwd{Donor--acceptor complexes}
\kwd{Metal organic frameworks}}

\altkeywords{\kwd{Catalyse asym\'{e}trique}
\kwd{Recyclage}
\kwd{Catalyse h\'{e}t\'{e}rog\`{e}ne}
\kwd{Interactions \'{e}lectrostatiques}
\kwd{Interactions ${\uppi}$}
\kwd{Complexes donneurs--accepteurs}
\kwd{R\'{e}seaux m\'{e}tallo-organiques}}

\thanks{We are grateful to the CNRS, the Universit\'e Paris-Saclay for
their support and to the Agence Nationale de la Recherche
(ANR-22-CE07-0A40-01, PhD financial support to LI)}

\begin{abstract}
Recent developments in asymmetric catalysis involve the
heterogeneization of chiral complexes so that they can be easily
immobilized on different supports. This account focuses on procedures
that lead to the formation of non-covalent interactions between the
chiral active sites and the chosen support, as they generally involve
less tedious synthetic modifications and can allow either the chiral
catalyst or the support to be easily recovered, at will. As a result,
electrostatic interactions between inorganic supports and chiral
organometallic complexes have been described to lead to efficient and
recoverable catalysts. More recently, other weak interactions, such as
${\uppi}$-interactions, but also donor--acceptor complexes, have been
implicated for implementation of robust immobilizing procedures. There
are also many examples of the use of coordination links, such as those
present in metal organic frameworks for supported asymmetric catalysis,
which pave the way for efficient cooperative or tandem asymmetric
catalysis.\vspace*{.3pc}
\end{abstract}

\begin{altabstract}
De nombreuses m\'{e}thodes d'h\'{e}t\'{e}rog\'{e}n\'{e}isation de
complexes chiraux, efficaces pour la catalyse asym\'{e}trique, sont
actuellement en cours de d\'{e}veloppement, et elles impliquent
l'utilisation de supports de structure vari\'{e}e. Cet article se
concentre sur les proc\'{e}dures qui conduisent \`{a} la formation
d'interactions non covalentes entre les sites actifs chiraux et le
support choisi, car celles-ci n\'{e}cessitent g\'{e}n\'{e}ralement des
modifications synth\'{e}tiques moins fastidieuses et peuvent permettre
de r\'{e}cup\'{e}rer facilement le catalyseur chiral ou le support,
\`{a} volont\'{e}. Ainsi, des interactions \'{e}lectrostatiques entre
des supports inorganiques et des complexes organom\'{e}talliques
chiraux ont \'{e}t\'{e} d\'{e}crites, conduisant \`{a} des catalyseurs
actifs, \'{e}nantios\'{e}lectifs et ais\'{e}ment r\'{e}cup\'{e}rables
et r\'{e}utilisables. Plus r\'{e}cemment, d'autres interactions
faibles, telles que les interactions
{${\uppi}$}, mais aussi les complexes
donneur-accepteur, ont \'{e}t\'{e} utilis\'{e}es dans la mise en
\oe{}uvre de proc\'{e}dures d'immobilisation \'{e}galement tr\`{e}s
robustes. Il existe \'{e}galement de nombreux exemples d'utilisation de
liens de coordination, tels que ceux pr\'{e}sents dans les r\'{e}seaux
m\'{e}tallo-organiques pour la catalyse asym\'{e}trique support\'{e}e,
qui permettent une catalyse asym\'{e}trique coop\'{e}rative ou tandem,
efficace.
\end{altabstract}

\maketitle

\twocolumngrid

\end{noXML}

\section{Introduction}\label{sec1}

Since its discovery over 50 years ago, asymmetric catalysis has enabled
the preparation of a wide variety of enantioenriched synthons with
different functionalities, with an efficiency in line with green
chemistry concepts. A step forward has been taken with the development
of heterogeneous asymmetric catalysis, aimed at separating the catalyst
from the substrates and reaction products in two different phases
(usually a solid and a liquid phase) for easy recovery and reuse of the
precious chiral active species. This process has made it possible both
to increase the turnover number of the catalysts by recycling them, and
to implement flow procedures to best meet industry needs. Kagan and his
group pioneered this field by describing the covalent attachment of a
chiral rhodium complex analogous to the DIOP ligand to oxidized
Merrifield resin and demonstrating its activity in asymmetric
hydrogenation and hydrosilylation reactions~\cite{1}. They already
highlighted the effect of the nature of the support on the activity and
enantioselectivity of these reactions, which were subsequently studied
and optimized by Stille group~\cite{2a,2b}.

In Kagan's seminal paper, the rhodium active sites were covalently
anchored to the support to prevent leaching of the metal and hence loss
of activity, or even contamination of the products. This type of
supported catalyst preparation may, however, require several synthesis
steps to modify at least the ligand, but sometimes also the support,
for strong grafting \textit{via} the formation of covalent chemical
bonds. Interest has therefore been focused on the immobilization of
chiral catalysts \textit{via} non covalent interactions on different
supports, with the aim of offering robust systems with simpler
preparation but also enabling both the catalyst and/or the released
support to be recovered at will, for another use.

Original and long-standing approaches to supported asymmetric catalysis
involving the modification of natural chiral supports by metal
catalysts should be mentioned here, as did Schwab and Rudolph who
studied metal-supported cleaved quartz surfaces~\cite{3} or Izumi
\etal, who used Pd dispersed on silk fibers~\cite{4}. This
has led to disappointing results in terms of activity and
enantioselectivity values, but nevertheless remains a fundamental proof
of concept. On the other hand, other procedures were examined in which
a conventional metal catalyst was modified by adsorption of natural
chiral molecules. This is the case, for example, with highly efficient
hydrogenation catalysts such as tartaric acid-modified Ni catalysts or
cinchona-modified Pt catalysts. In the presence of such metallic
surfaces modified by these chiral inducers, the asymmetric
transformation is due to the selective adsorption of the substrate onto
the chiral surface, leading to very convincing results, for the
hydrogenation of ${\upbeta}$-ketoesters or ${\upbeta}$-diketones for
the first catalyst, and for the hydrogenation of
${\upalpha}$-ketoesters for the second one. This field of research has
been the subject of numerous reports, including a comprehensive review
by Blaser~\cite{5}, and these methods have also been successfully
applied on a large scale, for example in the preparation of Benazepril,
an angiotensin-converting enzyme inhibitor intermediate~\cite{6}.

However, major difficulties have arisen in achieving reproducible
reaction rates and optical yields, as the selectivity of the
transformations is highly dependent on the catalyst preparation
procedure and/or its modification with the chiral inducer.
Enantioselectivity indeed results from specific interactions between
the substrate, the chiral modifier and the metal, the nature of which
remains largely unknown and uncontrolled. Work in this field has now
mostly shifted to the use of well-defined chiral active catalysts whose
activity is more predictable and reproducible thanks to their
immobilization on different supports~\cite{7a,7b,7c,7d,7e,7f,7g}.

Non-covalent immobilization of enantioselective catalysts was described
in exhaustive reviews nearly 15 years ago, concerning
organometallic~\cite{8} or organic catalysts~\cite{9}, organized
according to the immobilization method used. At that time, most of them
involved electrostatic, acid-base, hydrophobic or coordination
interactions, adsorption or some entrapment methods. Since then, new
strategies have emerged involving ${\uppi}$-stacking or charge-transfer
interactions, coming from our group and others. Accordingly, this
account will highlight some of the most recent results describing
non-covalent interactions for the easy recovery and reuse of
enantioselective catalysts, starting with a selection of articles
dealing with the use of ionic interactions with inorganic supports to
immobilize catalysts. Then asymmetric catalysis with active chiral
species immobilized by ${\uppi}$-stacking interactions will be
summarized, as well as examples implying the formation of charge
transfer complexes. Finally, we have chosen to present some of the most
recent examples of coordination interactions, such as those leading to
metal organic frameworks (MOFs), as they also enable recent, contextual
and valuable asymmetric multicatalysis. The vast majority of the
examples we have chosen to highlight here involve the use of the
well-known salen complexes, due to their ease of access and their high
efficiency in a very large number of asymmetric catalysis reactions.

\section{Electrostatic interactions with inorganic supports}\label{sec2}

As previously mentioned, the non-covalent immobilization of chiral
catalysts has already been widely developed and mainly involved
anchoring complexes on silica supports, modified accordingly to allow
predominantly ionic interactions \textit{via} sulfonic acid bonds. As
an example, Kim and coworkers have described the hydrothermal synthesis
of sulfonic acid-functionalized SBA-16 mesoporous silica~\cite{10}. The
incorporation of active Co-salen moieties was achieved by the addition
of Co(II) complexes in \mbox{solution} and subsequent oxidation in air leading
to a stable linkage in the form of ionic pairs with sulfonate anions on
the surface. The robustness of the solid catalyst was tested for the
Asymmetric Ring Opening (ARO) of \textit{rac}-epichlorohydrin by water
or phenol derivatives. The reactions even gave better results than
those carried out with analogous homogeneous catalysts, i.e. with lower
catalyst loading and shorter reaction time. The targeted products were
recovered, after simple solid filtration, with enantioselectivity
values exceeding 98\% in some cases and yields reaching 45\% 
(Scheme~\ref{sch1}). A slight drop in activity was observed when
recycling was attempted in the hydrolytic kinetic resolution of
\textit{rac}-epichlorohydrin, leading to a polar diol, which may
compromise ionic pairing on silica. In the case of the formation of
less polar compounds, using phenols as nucleophiles for example, no
loss of activity was observed and the catalyst could be reused. The
authors proved that the support could be recovered and reused after a
new Co-salen re-attachment; they also demonstrated that no reaction
occurred in the supernatant after catalyst removal before complete
conversion, as a proof of the effectiveness of the heterogeneous
procedure. 

\begin{scheme}
\includegraphics{sc01}
\vspace*{6pt}
\caption{\label{sch1}Immobilization by ion pair interactions for the
ARO of epoxides.}
\vspace*{-4pt}
\end{scheme}

New developments include the use of a different support, namely chiral
silica, in the hope of synergy for possible matching effects between
the two chiral elements, the support and the complex. In this context,
Sun and his group prepared a series of helical silica materials in a
sol--gel procedure doped with sodium lactate to affect chirality, and
carried out subsequent phenylsulfonylation before immobilizing Mn-salen
complexes in ionic pairs~\cite{11}. Comprehensive analytical studies
were performed to prove the immobilization of the chiral catalysts and
the integrity of the helical structure. These new structures were
tested as catalysts to promote the hetero-Diels--Alder reaction between
Danishefsky's diene and various aldehydes. Active and enantioselective
catalysts were obtained after immobilization of achiral Mn-complexes,
demonstrating the chiral induction induced by the support alone.
Immobilization of a chiral catalyst improved enantioselectivity values,
the molecular catalyst being responsible for product configuration and
the chiral environment for enantioselectivity enhancement. The authors
describe a series of four different aldehydes and the reaction with
acetophenone with varying success, which they attribute to restricted
conformational changes by hydrogen bond or other adsorptions on the
support, depending on the substrate structure. The transformation of
heptaldehyde, however, has been described with total conversion and
selectivity (Scheme~\ref{sch2}). A major influence of solvents was observed,
with ionic liquids influencing the product configuration and promoting
catalyst recyclability. Six cycles of the solid catalyst in
BMImBF$_4$ gave stable results in terms of product yield
(74\%) and enantioselectivity (${>}$99\%). These chiral
helical silica supports have also been studied for their ability to
promote asymmetric epoxidations of non-functionalized alkenes, in the
presence of PhIO or \textit{m}-CPBA~\cite{12}. In this case the silica
support has been modified with pendant ammonium groups and the Mn-salen
derivative was modified on the aryl moieties by a sulfonyl group,
remote from the catalytic center, to enable ion pair formation. Again,
an enantioselective transformation occurred in the presence of the
exclusive helical chirality, and synergistic effects were highlighted
between the mesoscopic and the molecular chirality, with match or
\textit{mis}-match properties.

\begin{scheme}
\includegraphics{sc02}
\vspace*{4pt}
\caption{\label{sch2}Immobilization by ion pair interactions on chiral
silica for the hetero Diels--Alder reaction.}
\end{scheme}

Other types of supports, namely layered zinc or Lanthanum Hydroxide
Nitrates (LHS, Layered Hydroxide Salts) have also been used as
ion-exchangeable supports to immobilize Mn-salen complexes modified
with sodium sulfonate groups~\cite{13}. The lower inter-layer forces
allowed indeed the intercalation of larger anions, even though FT-IR
analyses revealed only partial exchange of nitrates by the anionic
catalyst. The benchmark reaction involved the enantioselective
epoxidation of styrene derivatives and the Zn-LHS-supported Mn-salen
sandwich structure gave the best results in terms of activity and
selectivity, achieving 79\% conversion and 99\% ee for the epoxidation
of ${\upalpha}$-methylstyrene with iodosylbenzene (Scheme~\ref{sch3}).
Recycling can be achieved after simple filtration and the epoxidation
was successful for the following four cycles.

\begin{scheme}
\includegraphics{sc03}
\vspace*{4pt}
\caption{\label{sch3}Layered Hydroxide Salts as ion-exchangeable
supports for alkenes epoxidation.}
\end{scheme}

Ionic links of different nature have further been exploited towards
immobilization of metal-salen derivatives on silica supports. Bhaumik,
Islam \etal~prepared a chemically transformed carboxylic acid
functionalized mesoporous silica (AFS-1) by modification of the SBA-15
outer sphere~\cite{14}. A methylammonium-modified Co-salen complex was
then immobilized by ionic exchange interactions between the anionic
support and the cationic complex. Asymmetric aminolysis of racemic and
\textit{meso} epoxides (10 examples) has been achieved with excellent
results under solvent-free conditions, leading for example to the
formation of 2-(phenylamino)phenol in 97\% isolated yield and ${>}$99\%
ee. The high recyclability of the catalyst has been described, as it
can be engaged in successive transformations up to 5 times with almost
no loss of efficiency (Scheme~\ref{sch4}A). An analogous
catalytic material was also prepared with the corresponding Cu-complex
and found to promote the asymmetric nitroaldol reaction between various
aryl- or alkylaldehydes and nitromethane (11 examples) with high
enantioselectivity (up to 94\%) and TONs~\cite{15}. The recyclability
of the procedure was demonstrated by performing the multiple reaction
of \textit{p}-nitrobenzaldehyde with nitromethane with the same batch
of catalyst in dichloromethane, which proceeded successfully with only
a slight loss in activity (95\% to 84\% conversion) and an identical
enantioselectivity value (91\%) for eight consecutive cycles
(Scheme~\ref{sch4}B). Interestingly, this supported catalyst
has been used to prepare ($R$)-isoproterenol, a non-selective
${\upbeta}$-adrenoreceptor agonist.

\begin{scheme*}
\includegraphics{sc04}
\vspace*{4pt}
\caption{\label{sch4}Immobilization by ion pair interactions on
mesoporous silica for aminolysis of epoxides and nitroaldol reactions.}
\vspace*{8pt}
\end{scheme*}

The last example we have chosen to present concerns the preparation of
heterogeneous Mn-salen complexes anchored on mesoporous materials
functionalized with imidazole groups~\cite{16}. Modified silica
supports were obtained by co-condensation of tetraethyl orthosilicate
and \textit{N}-(3-triethoxysilylpropyl) imidazole, resulting in
functionalized MCM-41, favoring homogeneous distribution of organic
species. Immobilization of the Mn-salen complex was achieved in
refluxing toluene to form electrostatic bonds with the imidazole group,
resulting in a solid catalyst offering high activity and
enantioselectivity similar to that obtained with soluble catalysts, in
the epoxidation of olefins (3 examples, up to 99\% conversion and 85\%
ee for the oxidation of indene) (Scheme~\ref{sch5}). It should be noted
that very small quantities of catalyst could be used, due both to the
high electron-donating capacity of the imidazole ligand and the good
accessibility of the catalytic sites. Virtually no metal leaching was
detected by ICP-AES analysis (Inductively Coupled Plasma Atomic
Emission Spectrometry); nevertheless, the supported catalyst
progressively lost its efficiency when subjected to recycling
experiments (3~runs).

\begin{scheme*}
\includegraphics{sc05}
\vspace*{7pt}
\caption{\label{sch5}Immobilization by ion pair interactions on MCM-41
for alkenes epoxidation.}
\end{scheme*}

\begin{scheme*}
\includegraphics{sc06}
\vspace*{5pt}
\caption{\label{sch6}Immobilization by hydrogen bonding for nitroaldol
reactions and hydrolysis of epoxides.}
\end{scheme*}



Other types of electrostatic interaction than those reported previously
are existing, namely hydrogen bonding which has been used, however not
{specifically} for the immobilization of catalysts on a solid support,
but to bring two salen complexes together, with the aim of promoting
their cooperativity~\cite{17}. Hong and his group have prepared
unsymmetrical Co-salen complexes bearing complementary
2-pyridone/aminopyridine moieties on each phenolic group, capable of
creating self-assembled dimers in solution \textit{via} hydrogen
bonding. The reaction tested was the Henry reaction, in which both the
aldehyde and the nitronate ion are activated by the cobalt center so
that the asymmetric catalysis can take place in the presence of a
tertiary amine, as a base. Control experiments revealed significant
rate {acceleration} {using} this assembled catalyst, as well as kinetic
studies indicated a second order relative to the cobalt concentration,
with excellent enantioselectivity values for a range of aldehydes (8
examples, up to 96\% ee, Scheme~\ref{sch6}A). These authors
demonstrated that other functionalities, notably the urea unit, could
be used to create directional hydrogen-bonding interactions for
self-assembly~\cite{18}. Therefore, they prepared various symmetrical
Co-salen complexes functionalized with bis-urea units and studied their
efficiency in catalyzing the HKR {(Hydrolytic} Kinetic Resolution) of
\textit{rac}-epichlorohydrin; these dimeric species {(11 examples)} were
found to exhibit a significant rate acceleration compared with the
monomeric catalyst, both in solution (in THF, up to 92\% ee) and under
solvent-free conditions (up to 93\% ee), and this proved true for the
transformation of four different terminal epoxides
(Scheme~\ref{sch6}B).  In this case, kinetic studies also
showed that the rate laws were second-order in the cobalt concentration
and further mechanistic studies were carried out, consistent with the
fact that the observed rate enhancement was due to the self-assembly by
urea-urea hydrogen bonding.

\begin{scheme*}
\includegraphics{sc07}
\vspace*{5pt}
\caption{\label{sch7}${\uppi}$-stacking interactions on CNTs for
Rh-catalyzed asymmetric hydrogenation.}
\vspace*{-2pt}
\end{scheme*}

\begin{scheme*}
\includegraphics{sc08}
\vspace*{5pt}
\caption{\label{sch8}${\uppi}$-stacking interactions on CNTs for
Rh-catalyzed asymmetric hydrogenation of norbornene.}
\vspace*{-2pt}
\end{scheme*}

\section{$\uppi$-stacking interactions with carbon supports}\label{sec3}

In 2008, Zhou \etal~reported an example of enantioselective
hydrogenation of ${\upalpha}$-dehydroamino esters catalysed by a Rh(I)
complex immobilized \textit{via} a pyrene-modified PyrPhos ligand on
Carbon Nanotubes (CNTs)~\cite{19}. This ligand is readily accessible by
simple amide coupling, and both the activity and enantioselectivity of
the corresponding catalyst are unaffected by the presence of the
pyrene-tag. Various examples of substrates containing electron-donating
or electron-withdrawing \textit{para}-substituted aromatic groups have
led to the targeted products in excellent yields (${>}$99\%)
and very good enantiomeric excess values (92--96\% ee). The main
advantage of these modified catalysts remains their solvent-dependent
adsorption capacity. As such, reactions can be carried out under
homogeneous conditions, and the catalyst recovered by filtration after
a simple change of solvent for precipitation. The authors showed that
the lowest adsorption rate on CNTs was obtained when using
dichloromethane (50\%), which was considered the best solvent because
the catalyst was fairly mobile and the active sites easily accessible.
On the contrary, the use of a solvent with a high adsorption rate on
CNT, as ethyl acetate, led to the precipitation of the complex, making
it suitable for catalyst recovery and recycling by filtration. By
playing on this difference of adsorption, easy catalysts recycling was
performed by a simple solvent change and 9 cycles were realized without
affecting either the conversion or the enantioselectivity
(Scheme~\ref{sch7}A). A similar transformation was reported
by Fern\'{a}ndez, Khiar and their group in 2017, for which they
proposed a pyrene-tagged carbohydrate-based phosphorus/sulfur ligand
for Rh(I) catalysis immobilized on Single-Walled Carbon Nanotubes
(SWCNTs)~\cite{20}. Here, the effect of carbon linker length on
catalytic activity was investigated for the hydrogenation of methyl
${\upalpha}$-acetoamido-cinnamate. Notably, they demonstrated low
activity using a one-carbon linker, whereas a three-carbon linker
achieved the same conversion and enantioselectivity as with a
traditional Rh complex in dichloromethane (${>}$99\%
conversion, 90\% ee). In addition, they also showed that the presence
of this pyrene-tag made the reaction efficiency more solvent-dependent,
probably due to possible competitive complexation of Rh(I) with the
aromatic rings to form Rh(I)-${\upeta}^{6}$-arene
complexes. As mentioned previously~\cite{19}, the solvent also
influenced the catalyst adsorption on CNTs, allowing reactions to be
carried out under homogeneous conditions and the catalyst to be
recovered by \mbox{changing} the solvent. Here also, dichloromethane was the
solvent of choice to carry out the reaction. On the other hand, while
the reaction went poorly in ethyl acetate, the use of this solvent
enabled almost complete adsorption onto the CNTs after one hour of
sonication, which allowed to switch to heterogeneous conditions for
easy catalyst recovery. Based on these results, four successive runs
were carried out with the same batch of catalyst, starting with
excellent conversion (${>}$99\%) and enantiomeric excess (96\%) to
dramatically decreased values at the end (${<}$10\% conversion, 40\% ee),
probably due to the intrinsic instability of the catalyst
(Scheme~\ref{sch7}B). Later, in 2020, Shi \etal~described a
method for the {asymmetric} {hydrogenation} of dehydroamino acid esters
under heterogeneous conditions~\cite{21}. They employed pyrene-modified
MonoPhos-Rh(I) complexes immobilized on graphene, demonstrating both
high catalytic activity and enantioselectivity. The use of ethyl
acetate enabled the achievement of comparable catalytic performance to
classical homogeneous conditions, coupled with high adsorption on
graphene. The study encompassed eight examples of substrates featuring
variously \mbox{substituted} aromatic groups. This resulted quantitative
yields and enantiomeric excess values ranging from 91 to 96\% for the
{targeted} {products} (Scheme~\ref{sch7}C). Notably, diverse
analytical methods were employed to confirm well-defined
immobilisation. $^{31}\mathrm{P}$ Cross-polarization
magic-angle spinning (CP-MAS) NMR spectra demonstrated that the Rh
complexation pattern remained unchanged after adsorption on graphene
surfaces with a  $3\times10^{-4}$~mmol${\cdot}$mg$^{-1}$ loading on graphene.
Additionally, EDS TEM analyses (Energy Dispersive Spectroscopy for
elemental mapping in Transmission Electron Microscopy) illustrated a
homogeneous distribution of the Rh complex on the surface. BET
(Brunauer--Emmett--Teller) measurements indicated a surface area for the
immobilized catalyst reduced by half compared to the raw graphene. The
catalyst exhibited reusability for up to 13 cycles without compromising
the conversion of the starting material or enantiomeric excess values.
However, it is worth mentioning that the reaction time had to be
extended from 2~h to 10~h after seven cycles, likely due to the
instability of the filtrated intermediate in the absence of a hydrogen
atmosphere.\looseness=-1

Another example of immobilised Rh(I)-catalysed reaction on carbon
surfaces has been developed by Godard and his group in 2019~\cite{22}.
The authors focused on the asymmetric hydroformylation of norbornene to
preferentially obtain the \textit{exo}-product, utilizing new
pyrene-tagged diphosphite ligands supported on various carbon materials
and adapted for continuous flow conditions (Scheme~\ref{sch8}).
Initially, the authors designed new sugar-based ligands to achieve good
\textit{exo}-product yields (${>}$99\%) and enantiomeric excess values
(62\%) under homogeneous conditions. Optimization efforts revealed that
glucofuranose-diphosphite ligands exhibited 
\mbox{better} \mbox{enantioselectivity}
than xylofuranose-derivatives, especially when introducing substituents
on the biphenyl moiety. Moreover, the \textit{O}-alkylation at the
{glucofuranose-C5-position} played a crucial role in catalyst activity.
Subsequently, the heterogenization of the reaction was undertaken by
adding a pyrene-tag to the effective ligand, ensuring no modification
of the {catalyst} activity. The immobilization of the tagged
Rh(I)-complexes was studied on different carbon materials (Multi-Walled
Carbon NanoTubes (MWCNTs), Reduced Graphene Oxide (rGO) and Carbon
Black (CB)). The results were consistent when using MWCNTs or rGO but
significantly increased on CBs, likely due to the entrapment of the
complexes in the material structure. The effect of carbon-linker length
was highlighted, with the four-carbon linker on MWCNT showing the best
results being selected for the rest of the study. However,
heterogeneous catalysis resulted in significantly lower
enantioselectivity values, and in terms of the recycling ability of the
immobilized catalyst in batch conditions, no conversion of the starting
material was observed after three runs. ICP-MS (Inductively Coupled
Plasma Mass Spectrometry) analysis demonstrated high Rh leaching during
the reaction. Nevertheless, with the most optimized conditions in hand,
the authors have tested continuous flow conditions. Injecting the
syngas mixture \textit{via} a mass flow controller, they optimized the
reaction at 10 bar pressure to achieve higher {enantioselectivity} in the
flow mode (72\%) than in batch (62\%). This improvement was attributed
to more efficient gas-mass transfer which increased gas solubility, and
better exposure of substrates to the catalyst, resulting in a higher
local catalyst concentration. Subsequently, the support was changed for
rGO or CBs, and similar enantioselectivity was obtained with
approximately the same substrate conversion and lower decay. This was
explained by a larger surface area of rGO
(450~$\mathrm{m}^{2}{\cdot}\mathrm{g}^{-1}$) and CBs 
(211~$\mathrm{m}^{2}{\cdot}\mathrm{g}^{-1}$) compared to MWCNTs
(80~$\mathrm{m}^{2}{\cdot}\mathrm{g}^{-1}$) and improved ligand
interactions with those supports, facilitated by the presence of
functional groups on rGO or entrapment in mesoporous CBs. Although
increasing the catalyst loading in CBs support allowed to increase the
conversion up to 35\% with the same enantiomeric excess value, Rh
leaching remained a significant drawback for this {reaction}.
\looseness=-1

\begin{scheme*}
\includegraphics{sc09}
\vspace*{10pt}
\caption{\label{sch9}$\uppi$-stacking interactions on carbon supports
for Cu-catalyzed nitroaldol and ene reactions.}
\vspace*{-2pt}
\end{scheme*}

In 2013, Schulz \etal~described the use of immobilized
bis(oxazoline)-ligands for both copper-catalyzed Henry and ene
reactions (Scheme~\ref{sch9})~\cite{23}. The use of anthracene-tagged
ligands was favored to optimize the reaction conditions and study the
recyclability of the supported catalysts. First, the Henry reaction
between benzaldehyde and nitromethane was carried out using an
anthracene-bis(oxazoline)-tagged Cu(OAc)$_{2}$ complex in ethanol under
{homogeneous} conditions, which furnished excellent yield (89\%) and
enantiomeric excess (90\%). However, after immobilization on activated
carbon, the yield and enantioselective excess value slightly decreased
(68\% isolated yield, 69\% ee), indicating that the support interferes
with the reaction, leading to less accessible active sites. Moreover,
formation of traces of elimination by-products was observed, probably
due to the non-negligible acidity of the support, explaining the loss
of yield. Then, recycling of the catalyst was achieved after
centrifugation of the reaction medium to recover the catalyst. After 6
runs, the reaction time increased from 24 to 120~h for moderate
yields and enantiomeric excesses. A test reaction performed with the
supernatant after a recycling cycle gave comparable results, showing
that a non-negligible amount of catalyst had been solubilized during
the washing. Then, the reaction scope was extended to the ene reaction
between ethyl glyoxylate and ${\alpha}$-methyl-styrene with the
anthracene-bis(oxazoline)-tagged Cu(OTf)$_{2}$ catalyst in
dichloromethane. In this case, the same activity and enantioselectivity
were obtained compared with homogeneous conditions (89\% yield, 67\%
ee). However, throughout the runs, a slight decrease in activity and
enantiomeric excesses was observed, as in the previous case. The
catalyst immobilization on charcoal was then experimented and gave
similar good results (85\% yield, 70\% ee). {Attempts} to recover and
reuse the free ligand, exempt of the anthracene-tag, gave poor results
during the recycling, indicating that those tags are really necessary
for the catalyst recovery, without affecting its activity. Finally, to
diversify supports, studies using a pyrene-tag instead of an anthracene
one has been conducted to compare the effect of various carbon
surfaces: charcoal, fullerene and SWCNT. After one run, some
differences were already observable: all supported
Cu(OTf)$_{2}$-supported catalysts allowed to obtain the desired product
of the ene reaction with excellent yields (89\%) but with variable
enantioselectivity. The best enantiomeric excess was obtained with the
catalyst supported on charcoal (69\% ee), \mbox{followed} by SWNCT-supported
reaction (64\% ee) and then fullerene (56\% ee). Pyrene- or
{anthracene-tags} showed no change in recyclability, despite a stronger
${\uppi}$--${\uppi}$ interaction in the former case. After seven runs,
the charcoal-supported catalyst showed a slight decrease in yield and
enantiomeric excesses. For the fullerene-based catalyst, the values
remained more stable due to strong stacking with the pyrene-tag, which
allowed easy recyclability throughout the cycles, but with lower
enantioselectivity. On the other hand, the SWCNT-supported
Cu(OTf)$_{2}$ complex gave better results in terms of activity, and
values remained constant. This support seemed to be the best
immobilization method, avoiding leaching, and promoting strong
interactions with the pyrene-tag to ensure a good anchoring of the
catalyst for recycling.

\begin{scheme*}
\includegraphics{sc10}
\vspace*{7pt}
\caption{\label{sch10}${\uppi}$-stacking interactions on rGO for
epoxides aminolysis and hetero Diels--Alder reaction.}
\end{scheme*}

Later, in 2021, Schulz \etal~described the immobilization of another
type of organometallic complex \textit{via} a pyrene-tagged salen
ligand for both the Asymmetric Ring-Opening (ARO) of a
\textit{meso}-epoxide and the hetero-Diels--Alder reaction (HDA)
(Scheme~\ref{sch10})~\cite{24}. Herein, different types of chromium
salen complexes have been designed and their activity studied for the
cyclohexene oxide ARO. Indeed, \textit{one}- and \textit{four}-carbon
linkers have been synthesized and then, both respective symmetric and
unsymmetric ligands have been accessed to finally compare the four
ligand-tagged activity. First, in homogeneous conditions, those
new-designed catalysts have shown a better activity with improved
conversion rates of starting materials compared to the classical
Jacobsen ligand, probably explained by possible ${\uppi}$-stacking
interactions between two catalysts to form bi-metallic more active
complexes. However, symmetric catalysts seemed to be considerably less
enantioselective than unsymmetric ones. Then, the immobilization of
unsymmetric complexes on rGO as a suspension with a 4:1 mass ratio,
characterised by UV--Vis and XPS (X-Ray Photoelectron Spectroscopy)
analyses, has been performed to switch to heterogeneous conditions.
Interestingly, in this case, the catalyst activity was not affected by
the heterogenization although the \mbox{enantioselectivity} slightly decreased
after the first run. Nevertheless, as the recycling progressed, the
enantiomeric excesses increased to reach the same values as the ones
obtained under homogeneous conditions. Next, HDA of different aldehydes
with Danishefsky's diene has been then performed to extend the
application scope of this new-designed unsymmetrical salen chromium
complex immobilized on rGO. Again, the catalyst efficiency was not
affected in terms of yields and enantioselectivity with benzaldehyde
compared to the use of the classic salen {complex}. Concerning the
immobilization procedure, the nature of the washing solvent which
allowed the supported catalyst recovery after one run proved to be very
important. Indeed, both cold dichloromethane and acetone afforded a
non-negligible leaching of the catalyst which affected the conversion
of the starting materials. Diethyl ether finally allowed to perform
seven cycles without any impact on either the conversion or the
enantioselectivity. Moreover, the authors studied the ability of using
the same immobilized-catalyst batch for the transformation of three
different aldehydes, successively. Interestingly, the reactivity, with
the three different substrates, remained stable even after two runs,
showing the robustness of the recovery procedure.

\begin{scheme*}
\includegraphics{sc11}
\vspace*{6pt}
\caption{\label{sch11}${\uppi}$-stacking interactions on rGO for the
enantioselective synthesis of oxaziridine derivatives.\vspace*{5pt}}
\end{scheme*}

In the same year, Schulz and her group developed heterogeneous
conditions to perform the enantioselective 
formal~[$3+2$]-cycloaddition of oxaziridine with ammonium enolates
described by Smith group~\cite{25}. This reaction was promoted by an
IsoThioUrea (ITU) catalyst on phenyl acetic anhydrides allowing to
study the heterogenization of the organocatalytic transformation by
${\uppi}$-stacking interactions (Scheme~\ref{sch11}). Indeed, the
organic catalyst has been tagged with a pyrene group on the
benzotetramisole phenyl ring and the activity of this newly designed
species has been first evaluated {under} {homogeneous} conditions.
Fortunately, the same high activity as described with the unmodified
ITU was recorded and it was shown that using the soluble H\"{u}nig base
instead of inorganic Cs$_{2}$CO$_{3}$ {resulted} in improving the yields
(92\%) despite a slight decrease in selectivity (55/45\%
dr$_{({\mathrm{anti}}/{\mathrm{syn}})}$, 89/89\%
ee$_{({\mathrm{anti}}/{\mathrm{syn}})}$) and the formation of a small
amount of \textit{N}-tosylbenzylimine by-product. With those results in
hands, the immobilised catalyst on rGO has been engaged and both
organic and inorganic bases have been tested allowing to maintain quite
the same activity, a stable good activity along three runs (60\% yield,
dr$_{({\mathrm{anti}}/{\mathrm{syn}})}$ about 50:50, and ee values for
both products varying between 85 and 93\%). Using dichloromethane was
preferred as both reaction and washing solvent. Finally, an extended
scope was developed, using four different substituted homoanhydrides,
and the same batch of reused catalyst enabled the four different
product mixtures to be obtained successively in good yields, with
moderate diastereoselectivity and high enantioselectivity values.
\looseness=-1

\begin{scheme*}
\includegraphics{sc12}
\vspace*{6pt}
\caption{\label{sch12}Immobilization by CTC interactions for the
Diels--Alder reaction.}
\vspace*{2pt}
\end{scheme*}

\section{Formation of charge-transfer complexes}\label{sec4}

Schulz and collaborators, using Atomic Force Microscopy (AFM), were
able to visualize the formation of weak bonds between two
acceptor--donor aromatic molecules, forming Charge-Transfer Complexes
(CTC). They indeed successfully functionalized a tip and a probe with
electron-deficient TriNitroFluorenone (TNF, (acceptor)) and
electron-rich 1-methanolanthracene siloxane (donor), respectively, to
quantify the reversible pull-off force between the two
species~\cite{26}. Furthermore, they showed that CTC interactions could
be influenced by the presence of competitive species. For instance,
employing an apolar dodecane solvent revealed stronger interactions
($6.6\pm3.5$~nN) than using aromatic apolar 1-methylnaphthalene
($1.7\pm0.5$~nN), which engaged in competitive ${\uppi}$-stacking
interactions and saturated the tip-accessible sites, leading to
decreased measurements. Various factors, such as time of contact
between the species, medium concentration, \mbox{viscosity,} sweep time, and
tip geometry, played crucial roles in measuring bonding
forces~\cite{27}. Building on these results, Schulz  \etal~exploited 
CTC interactions for asymmetric catalysis. They developed an
innovative recycling method by creating solid CTC between a
donor-tagged catalyst and a good acceptor additive, facilitating simple
recovery through filtration at the end of the reaction. The first
described example involved the design of new anthracene-tagged
bis(oxazoline) ligands complexed with Cu(II) to proceed
enantioselective Diels--Alder reaction~\cite{28}. First, the activity of
the new designed complex was evaluated under homogeneous conditions in
dichloromethane and showed no impact on both conversion (${>}$99\%) and
selectivity (93\% de, 84\% ee) after the first run, for the reaction
between cyclopentadiene and 3-acryloyl-oxazolidin-2-one. CTC formation
was then achieved by adding TNF, and the resulting complex precipitated
thanks to pentane addition, enabling easy catalyst recovery for
subsequent runs without compromising activity. Switching to another
dienophile with the same recovered catalyst allowed for five more
cycles at 20~\textdegree C. Eleven runs were successfully processed with
the same batch, recovered by precipitation, and washing with pentane,
without impacting yields and enantioselectivity 
(Scheme~\ref{sch12}A). 
The following year, in 2007, the method was extended to
three newly designed bis(oxazoline) ligands in the Cu(II) promoted
Diels--Alder reaction~\cite{29}, involving one (\textit{R})-valinol and
two \textit{tert}-leucinol bis(oxazoline) derivatives, each tagged with
anthracene. At first, the reaction was conducted under homogeneous
conditions to assess the impact of ligand modification on catalyst
activity. Concerning the ($\mathrm{R}$)-valinol derivative, there was a
significant decrease on selectivity (22\% ee), mainly explained by the
partial loss of the $\mathrm{C}_{2}$ symmetry of the ligand after
functionalization on the \textit{gem}-dimethyl group compared to
classical bis(oxazoline). Then, regarding the catalyst recovery, CTC
were prior prepared \textit{ex-situ} before being introduced to the
reaction solvent with substrates. Fortunately, over six runs, the
recovered catalyst was re-engaged with new substrates without
compromising the enantioselectivity. In parallel, similar study was
conducted with the two \textit{tert}-leucinol derivatives as ligand
(three- and five-carbon linker) which appeared to have a lesser impact
on enantioselectivity than the first one (97\% ee after one run under
homogeneous conditions). However, initial tests in the presence of the
corresponding CTC-based catalysts were much less effective (15 and 33\%
ee). The reuse for a second attempt with the same CTCs and new
substrates surprisingly resulted in significantly improved enantiomeric
excesses in both cases. Notably, the addition of molecular sieves was
mandatory to prevent the detrimental effect of water on copper complex.
PM3 calculations also revealed that in these latter complexes, the
distortion degree between \textit{tert}-leucinol-derivative ligands and
the catalytic site was larger than with ($\mathrm{R}$)-valinol one,
involving more steric hindrance around the copper center. To overcome
this activity loss, it was demonstrated that the first run needed to
proceed without the electron-deficient precursor to achieve better
results (89\% yield, 87\% ee), and the formation of the CTC must be
executed only at the end of the first transformation. By adopting this
approach, improved yields (89\%) and \mbox{enantiomeric} excesses (87\% ee)
were achieved after the second run with the same catalyst batch and
remained stable along two additional cycles. Finally, three more cycles
were conducted by switching from previously used
3-(but-2-enoyl)-oxazolidin-2-one to 3-acryloyloxazolidin-2-one,
sustaining satisfactory activity (Scheme~\ref{sch12}B). In
2008, our group proposed to use CTC interactions to prepare mimic
bidentate complexes from anthracene- and TNF-tagged monodentate
bis(oxazoline)~\cite{30}. We focused on the design of reversible
copper(II) catalysts from copper triflate for use in asymmetric
Diels--Alder cycloaddition. Initially, unsymmetrical modified
bis(oxazoline) was prepared by deriving from \textit{(S)-}valinol,
($\mathrm{R}$)-phenylglycinol and \textit{(S)}-\textit{tert}-leucinol.
These three ligands were respectively tagged with both anthracene as a
donor and TNF as an acceptor. With these six ligands in hand, catalytic
tests were attempted under homogeneous conditions to evaluate the tag
impact on reactivity. Fortunately, good conversion and
enantioselectivities were achieved using monodentates species
independently, resulting in major formation of the
\textit{endo}-product with the anthracene-tagged electron-rich ligand
and \textit{exo}-product with the TNF-tagged electron-deficient one.
This phenomenon was particularly evident with \textit{tert}-leucinol
derivatives and was explained by likely ${\uppi}$-stacking interactions
between the tags, favoring the formation of homodimeric copper
complexes well known to efficiently catalyze asymmetric
transformations. Subsequently, mixtures of one electron-rich and one
electron-deficient ligand equivalent (1:1) afforded heterodimeric CTC.
Unfortunately, as previously demonstrated~\cite{26,27}, competitive
${\uppi}$-stacking could occur between aromatic moieties, leading to
the formation of homo-and hetero-dimeric bidentate complexes, resulting
in poor yields and enantiomeric excesses for the \textit{endo} and
\textit{exo} products. Nevertheless, a method has been developed for
easily recovering the catalyst by precipitating the CTCs, facilitated
by a simple pentane addition. The reuse of those CTC complexes did not
affect conversion and enantioselectivity in two runs, demonstrating the
efficiency of the procedure for recycling
(Scheme~\ref{sch12}C).

In the same year, Gennari \etal~also reported the
formation of bidentate complexes \textit{via} CTC interactions between
modified ligands, applied to Rh-catalysed hydrogenation~\cite{31}. They
first prepared a library of tagged-ligands, consisting in eight
electron-rich (six BINOL-and two octahydro-BINOL-based) and two
electron-deficient pentafluorobenzyl phosphites (\textit{R} and
\textit{S}). After isolating these compounds, they engaged them
separately into a solution with the Rh(cod)BF$_4$ pre-catalyst 
\mbox{(L/Rh ${=}$ 2:1)} to form homodimeric complexes, characterized by $^{31}\mathrm{P}$
NMR. In parallel, they applied the same method to obtain heterodimeric
CTC by mixing an equimolar ratio of electron-rich, electron-poor, and
Rh pre-catalyst. In these cases, they observed the formation of the
desired hetero-CTC (50\%), but unfortunately, also the formation of
homo-complexes (50\%) due to competitive interactions. Consequently,
they decided to conduct attempts with homodimeric and heterodimeric
complexes in the enantioselective hydrogenation of dimethyl itaconate
(Scheme~\ref{sch13}). The best outcome was achieved with the mixture of
($\mathrm{R}$)-electron-poor phosphite and
($\mathrm{R}$)-\textit{meta}-dimethoxybenzylalcohol-modified
electron-rich ligand (99\% ee). Other heterodimeric derivatives yielded
moderate to excellent enantioselectivities, generally exhibiting higher
activity with ($\mathrm{R}$)/(R) mixtures compared to
($\mathrm{R}$)/(S) ones. Additionally, concerning homodimeric species,
methoxyphenol derivatives led to improved enantioselectivities
(92--99\% ee) compared to methoxybenzylalcohol ones, which delivered
poor enantiomeric excesses (70--84\% ee) and octahydro-BINOL ones,
which provided moderate values (50--54\% ee). Finally, they applied
their library of bidentate complexes to the same reaction on methyl
acetamido acrylate and, again, heterodimeric
($\mathrm{R}$)-dimethoxybenzylalcohol
derivative/($\mathrm{R}$)-pentafluorobenzyl one was the most successful
trial (93\% ee). Despite the heterodimeric catalyst not being pure, the
corresponding heterodimeric/homodimeric mixture turned out to be the
most active catalytic species.

\begin{scheme}
\includegraphics{sc13}
\vspace*{4pt}
\caption{\label{sch13}CTC interactions for hydrogenation reactions.}
\end{scheme}

In 2010, the Schulz group described a new immobilization method based
on the same CTC interactions but involving the use of a modified-resin
solid support~\cite{32}. In this case, they thought to functionalize a
Merrifield resin with a TNF moiety as an acceptor for immobilizing
anthracene-tagged ligands. The advantage of this method is that it
facilitates catalyst recovery and allows one catalyst to be replaced by
another to carry out different reactions in sequence, while using the
same support. The reaction chosen to highlight this strategy was the
Cu(II) enantioselective Diels--Alder reaction between
\mbox{3-but-2-enoyl-oxazolidin-2-one} and cyclopentadiene. Initially, the
efficiency of the newly designed tagged ligand was evaluated under
homogeneous conditions without any detrimental effect on activity (83\%
ee, 78\% de). Subsequently, the newly formed Cu(II)-catalyst was
engaged under the same reaction conditions after its immobilization was
conducted \textit{ex situ} by CTC formation with the modified resin
(0.5 mmol/g TNF loading, ${<}$50 mesh particle size). Once again, the
same activity was achieved, leading to the desired \textit{endo}
product as the major compound (91\% yield, 76\% ee). Five additional
runs were achieved using the same immobilized catalyst batch, recovered
by simple{\unskip\break} filtration, and washing with pentane. During the first two
reuses, the activity seemed stable, but from the fourth recycling, the
yield and selectivity began to decrease, reaching very low values after
the sixth reuse (28\% yield, 39\% ee). Test reactions indicated a
partial leaching of the catalyst and weak CTC interactions
(Scheme~\ref{sch14}A). Finally, the same support was tested
for different reactions; to this end, the first attempts were run with
a single anthracene-tagged catalyst over four successive runs,
revealing a loss of activity during the last two runs. To change the
catalyst, toluene was introduced as a competitive solvent for CTC
interactions, facilitating the removal of the catalyst from the solid
support. The \textit{ent}-catalyst was then easily added in
dichloromethane to bind it to the recovered TNF-tagged solid support,
and the same antagonistic reaction was conducted. Four additional runs
were carried out using the same conditions, furnishing the opposite
enantiomer of the target product with the same enantiomeric excesses as
before. This method has proved to be an effective approach for the
recycle of the catalysts and conducting multiple reactions using the
same support, which could prove particularly useful in flow chemistry,
for example. The same group also described another multi-reaction
approach facilitated by CTC assistance for Cu(II)-catalyst
recycling~\cite{33}. In this context, the aim was to use the same
catalyst batch for the asymmetric Henry nitroaldolization, applied to
multiple substrates. The study focused on an anthracene-tagged
bis(oxazoline) ligand, as previously described, complexed with
Cu(OAc)$_{2}{\cdot}\mathrm{H}_{2}$O. The presence of the anthracene moiety was
proven to be not detrimental to the reaction activity (89\% yield, 90\%
ee). Conveniently, catalyst recovery was achieved by adding TNF for CTC
formation and subsequent precipitation in pentane at the end of the
first run. After one recycling, the enantioselectivity remained stable,
indicating that the CTC formation had no negative impact on the
catalyst activity. Notably, the reaction time increased over the other
runs, probably due to a leaching of the catalyst, but six reuses were
successfully conducted while maintaining good results. This method was
then applied to various substrates, including five aldehydes and two
nitroalkane derivatives, resulting in seven different products with
good yields and enantiomeric excesses. Especially, reactions involving
nitroethane yielded a diastereoisomer mixture, with the
\textit{anti}-isomer as the major product. With these results in hands,
they accomplished the recycling of one catalyst batch for nine
different transformations, demonstrating that no impact on selectivity
was observed over the runs. Despite a slight increase in reaction time
during the subsequent runs, it is important to note that no traces of
the previous product were observed during the next run, indicating that
the recycling and washing procedures had been well optimized. Finally,
they switched to heterogeneous conditions by grafting TNF moieties onto
activated silica and immobilizing an anthracene-tagged Cu(II) catalyst
\textit{via} CTC interactions. The Henry reaction could be performed
five successive times with the same catalyst batch, without additional
precipitation in pentane, affording the desired product with the same
yields and enantioselectivity values as under homogeneous conditions
(Scheme~\ref{sch14}B). This method represents another
original example of \mbox{immobilization} and recovery of catalysts on a solid
support by non-covalent CTC\break interactions.\looseness=1

\begin{scheme*}
\includegraphics{sc14}
\vspace*{4pt}
\caption{\label{sch14}Immobilization by formation of CTC with organic
and inorganic supports.}
\vspace*{2pt}
\end{scheme*}

In 2011, our group proposed a new asymmetric multi-reaction method
facilitating the promotion of additional Cu-catalyzed transformations,
namely ene and cyclopropanation reactions~\cite{34}. These
transformations were already known to process by bis(oxazoline) ligands
with Cu(OTf)$_{2}$. This study reported the use of anthracene-modified
bis(oxazoline) for the easy recovery and recycling of the catalyst. The
ene reaction was firstly carried out under homogeneous conditions
between ${\upalpha}$-methylstyrene and ethyl glyoxylate, resulting in a
similar yield (89\%) and enantiomeric excess (67\% ee) as with the
parent symmetrical ligands. Secondly, after the first run and TNF
addition, a further nine cycles of catalyst recycling were carried out
with no effect on catalyst activity. CTC Precipitation in pentane was
employed to ensure effective recovery and similar results were achieved
on the analogous 3,3,3-trifluoro-2-oxo-propionic acid methylester over
seven reuses using the same method. Likewise, the cyclopropanation of
styrene with ethyl diazoacetate was investigated with the same
Cu-complex. The initial trial also showed a good yield (69\%) with a
mixture of diastereoisomers (2:3 ratio) and good enantiomeric excesses
(72\% and 69\% ee for each diastereoisomers), in agreement with the
results obtained using conventional homogeneous catalysts. These
results were replicated over five cycles, with a slight loss in
activity observed from the sixth run (41\% yield, 67 and 69\% ee). The
main objective of this work was therefore to execute these different
reactions using a single catalyst batch, thanks to the precipitation of
CTC for catalyst recycling (Scheme~\ref{sch15}). As previously
reported~\cite{28,29}, Diels--Alder cycloaddition was also achieved
\textit{via} this procedure and was consequently considered. The
reaction was first carried out twice between 3-acryloyloxazolidin-2-one
and cyclopentadiene, then twice more times between
3-(but-2-enoyl)-oxazolidin-2-one and the same diene to yield another
derivative. Subsequently, the ene reaction was conducted three times
with ${\upalpha}$-methylstyrene and ethyl glyoxylate, yielding good
results. Finally, the same batch of catalyst was again used for
cyclopropanation, giving results in line with those described above.
This unprecedented multi-reaction approach enabled the same catalyst
batch to be reused nine times without any loss of activity in
successive reactions with different substrates.

\begin{scheme*}
\includegraphics{sc15}
\vspace*{4pt}
\caption{\label{sch15}CTC interactions for an asymmetric multi-reaction
procedure.}
\end{scheme*}


\begin{scheme*}
\includegraphics{sc16}
\vspace*{4pt}
\caption{\label{sch16}CTC formation for ARO of epoxides.}
\end{scheme*}

On another hand, in 2012, Schulz and Didier described the
immobilization of the same bis(oxazoline) structures but tagged with an
electron-deficient TNF moiety~\cite{35}. Immobilization \textit{via}
CTC interactions was therefore considered by adding anthracene after
the first reaction and introducing apolar pentane to precipitate the
formed CTC, facilitating a good catalyst recovery. The first attempt
involved the TNF-modified ligand and Cu(OTf)$_{2}$ in the well-known
Diels--Alder cycloaddition between cyclopentadiene and
3-but-2-enoyloxazolidin-2-one. At the end of the reaction, a
precipitation procedure and filtration were conducted to recover the
solid. Surprisingly, all the anthracene was recovered in solution,
indicating that the interactions with the CTC were not sufficiently
strong. In fact, regarding the solubility of the TNF-tagged Cu-complex
in different solvents, it precipitated on its own when the solvent was
changed, and the addition of anthracene for the CTC formation was not
necessary for the catalyst recovery. Subsequently, the solid
TNF-complex was reused with new substrates and proved effective in
fourteen runs with the same reactant, followed by a further six runs
with analogous 3-acryloyloxazolidin-2-one. A lower temperature was
required with this latter substrate to inhibit competitive racemic
transformation. More recently, in 2019, Liang and collaborators
described the use of CTC in the Hydrolytic Kinetic Resolution (HKR) of
epichlorohydrin, catalyzed by Co(III)-salen complexes~\cite{36}. Since
this transformation involves a bimetallic system, where one metal acts
as a Lewis acid to activate the epoxide and the other to activate the
hydroxide, the formation of donor--acceptor complexes to bring two salen
molecules together was found to be highly beneficial. Modification of
the symmetrical salen-ligands with two electron-poor diimide tags
facilitated interactions with additional polyaromatic species, allowing
the formation of acceptor--donor--acceptor CTC sandwiches at an ideal
distance of around 7--8~\AA{}, optimal for enhancing HKR reactions. The
group synthesized three generations of modified salen ligands to
explore various parameters. Their results revealed that flexible alkyl
ester linkers between the acceptor and the salen core were more
efficient than rigid conjugated phenyl linkers, enabling favorable
orientation and geometrical arrangement of the \mbox{bimetallic} system. In
addition, the choice of polyaromatic donor species played a crucial
role, improving the catalyst activity when used in the proper quantity.
In this case, the best results were obtained with the symmetrical
di-Pyromellitic DiImide (PDI) acceptor in the presence of pyrene or
perylene (conversion rates of 52\% and 54\%, ${>}$99\% ee, respectively),
outperforming the classical Jacobsen salen (10 h vs. 42 h). The
face-to-face stacking of the bimetallic CTC probably optimally aligned
the Co(III)-salen cores, optimizing the interactions between both
substrates. This was supported by $^1\mathrm{H}$ NMR and UV--Vis
studies, highlighting donor--acceptor interactions between PDI and
pyrene moieties (Scheme~\ref{sch16}{A}). In addition to this,
the same group reported another CTC-immobilized bimetallic system for
the same reaction, expanding the scope to other epoxides and
nucleophiles~\cite{37}. They designed new modified salen ligands,
including unsymmetrical Naphtalene DiImide (NDI)/pyrene-bi-tagged,
mono-NDI or mono-pyrene, and symmetrical bi-NDI or bi-pyrene-tagged
ligands, comparing their activity with the non-substituted Jacobsen
complex. In the epichlorohydrin HKR, all catalysts led to improved
yields (50\%--59\%) and enantioselectivity (${>}$99\%) compared to the
classical salen, with particularly decreased reaction rates obtained in
the presence of the unsymmetrical acceptor--donor tagged ligand (3.5 h).
Another noteworthy attempt, involving a mixture of both
mono-substituted acceptor and donor (1:1 ratio), yielded similar
results (59\% yield, ${>}$99\% ee). Further experiments involved
\mbox{committing} both CTCs to other terminal epoxides HKR, which gave
satisfactory results, with slightly better activity observed with the
mixture of two differently tagged complexes, particularly on aliphatic
and hindered substrates. It also allowed to reduce reaction time for
the transformation of 1,2-epoxybutane and 1,2-epoxyhexane epoxide
without affecting the selectivity. The higher activity was attributed
to a more flexible bi-complex between two mono-tagged than two
bi-tagged ones, allowing an optimized arrangement in the space between
the two salen catalytic moieties (Scheme~\ref{sch16}{B}).
Overall, these results were also observed on more complex substrates,
demonstrating good solvent adaptability, high catalytic activity, and
enantioselectivity in the asymmetric ring opening of epoxides.


\section{Coordination links---Metal Organic Frameworks (MOF)}\label{sec5}

Another strategy has been developed for the immobilization of chiral
organometallic catalysts involving the heterocombination or
homocombination of different mutitopic ligands with metal ions, leading
to self-supported catalysts, active as heterogeneous species, or to
self-supported dynamic catalysts, mainly effective as homogeneous
species~\cite{38}. To illustrate the first case, Ding and coworkers
prepared two different ligands both possessing ditopic sites in the
form of a bridged BINAP and a bridged diphenyldiamine
(Scheme~\ref{sch17})~\cite{39}. After coordination of ruthenium in the
presence of the two ligands, a one-dimensional structure is formed as a
self-supported Noyori-type catalyst, in the form of an
\textit{iso}-propanol-insoluble light-brown solid. The selectivity of
this catalyst proved superior to that of its homogeneous counterpart,
promoting the hydrogenation of acetophenone and seven other arylketones
with enantioselectivities in excess of 94.5\% ee, thus demonstrating
the synergistic impact of the supramolecular self-supported assembly on
the catalytic behavior. The insoluble catalyst was recovered by
filtration and reused seven consecutive times without losing its
efficiency.

\begin{scheme*}
\includegraphics{sc17}
\vspace*{5pt}
\caption{\label{sch17}Immobilization by heterocombination of mutitopic
ligands for asymmetric hydrogenation.}
\vspace*{4pt}
\end{scheme*}

Another related approach involves the homo-assembly of multitopic
ligands by metal coordination leading to a polymeric structure. What is
looked for in this case, is a catalyst that remains heterogeneous in
its resting state at the end of catalysis, yet capable of undergoing a
reversible partial de-coordination process in the reaction mixture to
become the active species. This concept was demonstrated by Garc\'{i}a
\etal, who prepared a new chiral ditopic ligand bearing two
azabis(oxazoline) groups (Scheme~\ref{sch18})~\cite{40}. Using copper
salts of weakly coordinating anions with an equimolar amount of the
ditopic ligand in a non-coordinating solvent, formation of the desired
coordination polymer occurred. The reaction tested involved the
cyclopropanation of styrene with ethyldiazoacetate, as a strongly
coordinating species, leading to a de-coordination process upon its
addition and a reaction taking place in the homogeneous phase with even
higher enantioselectivity values for both cyclopropane isomers (ee up
to 97\% for the \textit{trans} product). After completion of the
reaction, the coordination polymer is formed again, and can be easily
recovered by filtration for its efficient recycling (14 cycles).

\begin{scheme*}
\includegraphics{sc18}
\vspace*{6pt}
\caption{\label{sch18}Self-supported dynamic copper catalysts for
cyclopropanation reactions.}
\vspace*{4pt}
\end{scheme*}

This procedure was subsequently studied by the Bellemin-Laponnaz group
for the enantioselective ${\upalpha}$-hydrazination of
${\upbeta}$-ketoesters with polytopic (\mbox{bis-,} tris- and tetratopic)
bisoxazoline as ligands~\cite{41}. The use of the ditopic ligand in
combination with Cu(OTf)$_{2}$ led to a highly efficient
self-supporting catalyst for reacting with acyclic and cyclic
${\upbeta}$-ketoesters (5 examples) delivering the desired products
with almost complete conversion and enantioselectivity values of 99\%.
Depending on the substrate structure, six to ten runs could be
performed without loss of efficiency. Interestingly, increasing the
topicity of the ligand led to a worse recycling and more catalyst
leaching. The authors also studied NonLinear Effects (NLE) to better
understand the aggregation state of the active species, conducting
experiments in which the optical purity of the ligand varied. Negative
NLE was observed, consistent with the preferential formation of a
homochiral metallopolymer, in equilibrium with the active monomeric
species. These authors applied further this concept for the preparation
of air- and moisture-stable nickel metallopolymers efficient as
enantioselective catalysts for the Michael addition of diester
malonates to nitroalkenes~\cite{42}. A chiral ditopic
cyclohexyldiamine-based ligand was prepared generating a self-supported
catalyst in the presence of nickel salts (Scheme~\ref{sch19}). The
substrate displaces a diamine ligand and generates an active catalyst
that contains only a single diamine ligand, giving an efficient
catalyst with greater activity than the corresponding monomer and
similar enantioselectivity. Five examples were described (complete
conversion and up to 93\% ee), along with a procedure for efficient
recovery of the catalytic species. It involves the addition of
diethylether for \mbox{catalyst} \mbox{precipitation,} filtration, washing and
subsequent reuse in up to 13 cycles with stable enantioselectivity and
a slight decrease in substrate conversion.

\begin{scheme*}
\includegraphics{sc19}
\vspace*{6pt}
\caption{\label{sch19}Ditopic cyclohexyldiamine-based ligand as
self-supported nickel catalyst.}
\vspace*{2pt}
\end{scheme*}

For over fifteen years now, metal organic frameworks (MOFs) have also
been studied as a response to certain challenges in supported
asymmetric catalysis~\cite{43,44}. The activity of these heterogeneous
catalysts comes either from unsaturated metal coordination sites, or
from active linkers between metals, or both, particularly if these
linkers are chiral organometallic complexes. In addition, the wide
choice of porous structures available allows selective limitations in
terms of size and shape through well-defined channels and pores. Thus,
MOFs have been reported fairly recently as effective heterogeneous
catalysts for a number of transformations, including enantioselective
reactions. A relatively early example was described by the Lin's group
for the preparation of homochiral porous MOFs from BINOL derivatives as
chiral bridging ligands containing bipyridyl units as orthogonal
functional groups (Scheme~\ref{sch20})~\cite{45}. They were able to
produce colorless crystals in the presence of CdCl$_{2}$ while the
chiral dihydroxy groups were accessible for reaction with
Ti(O\textit{i}-Pr)$_4$, enabling the formation of an active
heterogeneous catalyst for the addition of Et$_{2}$Zn to aromatic
aldehydes. The authors showed activity and enantioselectivity
equivalent to those obtained when homogeneous BINOL was used as a
ligand (8 examples compared), except for some substrates bearing
Frechet-type dendrons, which were probably unable to access the
catalytic sites because they were too large. This result proved that
catalysis occurred inside the MOF pores, and control experiments were
also carried out to confirm the heterogeneous nature of the reaction.

\begin{scheme*}
\includegraphics{sc20}
\vspace*{4pt}
\caption{\label{sch20}BINOL-based homochiral porous MOF for the
ZnEt$_2$ addition on aldehydes.}
\end{scheme*}

One year later, Nguyen and Hupp prepared another microporous MOF with
Mn-salen struts for asymmetric epoxidation~\cite{46}. The Mn-salen was
modified with two pyridine units, and a robust structure, in the form
of a pair of interpenetrating networks, was obtained from zinc salts
associated with biphenyldicarboxylate as the second ligand. For the
asymmetric epoxidation of chromene derivatives and
2-(\textit{tert}-butylsulfonyl)iodosylbenzene as oxidant, the
heterogeneous catalyst proved to be almost four times more active than
the corresponding homogeneous catalyst, with only a slight decrease in
enantioselectivity (from 88 to 82\% ee). Simple recovery of the MOF
catalyst by filtration enabled it to be reused for three cycles without
any decrease in enantioselectivity and with a slight loss of activity,
probably due to partial fragmentation of the particles.

Since these early examples, a great deal of work has been devoted to
the precise optimization of the MOF structure in order to enhance its
reactivity and selectivity according to the target. For instance, a
family of isoreticular chiral MOFs has been prepared under solvothermal
conditions from Mn-salen derivatives bearing dicarboxylic acids
functions attached by spacer bonds of different sizes~\cite{47}. The
corresponding materials therefore had different structures depending on
the solvent used to synthesize them and adjustable open channel sizes,
which in some cases led to heterogeneous catalysts that were as
effective as homogeneous ones for the \mbox{asymmetric} epoxidation of
alkenes, while at the same time being recoverable and reusable after
simple\break filtration.

The versatility of these crystalline structures for asymmetric
heterogeneous catalysis was demonstrated by Liu and Cui, who prepared a
porous Cr-salen MOF (Scheme~\ref{sch21}) and subjected it to a series of
four catalytic transformations involving different
mechanisms~\cite{48}. The crystalline catalyst was obtained by heating
the corresponding salen complex with CdI$_{2}$ and NaOAc and was tested
in the Nazarov reaction of alkoxydienones, affording functionalized
cyclopentenones with high selectivity. Although the enantioselectivity
remained slightly lower than the value obtained with the homogeneous
analog, a higher diastereoselectivity was observed, which was
attributed to the steric constraints of the confined network. Used in
other reactions such as the asymmetric aminolysis of
\textit{trans}-stilbene oxide, the Diels--Alder and hetero-Diels--Alder
reactions, it has led to increased enantioselectivity values compared
with homogeneous cases, with confinement effects allowing ideal
location of the active sites. Size selectivity was also demonstrated as
a bulky benzaldehyde derivative could not undergo an hetero-Diels--Alder
reaction, indicating a unique catalytic activity within the MOF pores.
The catalyst was reused in four aminolysis cycles, showing good
stability.

\begin{scheme*}
\includegraphics{sc21}
\vspace*{6pt}
\caption{\label{sch21}Porous Cr-salen MOF efficient for four catalytic
transformations.}
\end{scheme*}

Other advances involving the manipulation of such heterogeneous
catalysts concern their post-synthesis modification. Ren and Jiang, for
instance, synthesized and fully characterized a 3D Cu-salen MOF
possessing a 1D open channel~\cite{49}. They then carried out a
reduction step in the presence of NaBH$_4$, leading to the reduction of
the salen imine groups to a more basic and flexible skeleton, while
retaining its structural integrity. Although the Cu-salen MOF proved to
be a poor catalyst in the Henry reaction, the corresponding salan
derivative afforded the expected products with higher activity and
enantioselectivity (15 examples and ee up to 98\%) and was successfully
recovered and reused for five successive runs. Another
post-modification of an existing MOF was described by Liu and Cui, when
they heated a VO-salen MOF in the presence of a Cr-salen complex with
exactly the same structure; this solvent-assisted linker exchange
resulted in the partial replacement of certain VO-salen units by
Cr-ones as shown by Inductively Coupled Plasma -- Optical Emission
Spectrometry (ICP-OES analyses)~\cite{50}. While the first catalyst was
active in the cyanosilylation of aldehydes (with up to 95\% ee, 11
examples), the MOF exchanged by Cr-salen was engaged in asymmetric
kinetic resolution with aniline, a reaction that is not catalyzed by
VO-salen complexes. \textit{Cis}-stilbene oxide was efficiently
converted (87\%) to aminoalcohol (76\% ee), demonstrating the
introduction, by exchange, of chiral Cr-salen species leading to mixed
MOF, promising for cooperative or tandem catalysis. To illustrate
cooperative catalysis, the authors demonstrated the presence of a
synergistic pathway resulting from the close location of two V-salen
units in the open channels of a MOF~\cite{51}. They prepared two
different heterogeneous MOFs catalysts resulting from
Cd(NO$_{3}$)$_{2}$ and a VO-salen complex or a mixture of a Cu- and a
VO-salen complex. Once the two networks had been fully characterized,
they were used in the test reaction involving the asymmetric cyanation
of aldehydes. The homometallic heterogeneous catalyst was very active
and selective, particularly at low loadings, highlighting the positive
effect of confinement. As a result, the bimetallic Cu- and V-containing
MOF was far less active, as the synergistic VO--VO pathway was blocked
by the presence of the copper sites, resulting in less efficient
unimolecular activation of the substrates. In the context of tandem
catalysis, they proposed a similar strategy for the post-synthetic
exchange of achiral ligands from Zr-based UiO-68 MOF with chiral salen
complexes, bearing the same or different metal centers~\cite{52}.
Consequently, a Mn-salen derived UiO-68 was obtained, which cannot be
achieved by direct solvothermal synthesis. Then, from Mn-salen derived
UiO-68, mixed salen-containing MOFs were obtained (Mn/Cr and Mn/V) by
another solvent-assisted linker exchange procedure. These highly stable
platforms were precisely characterized using NMR spectroscopy, ICP-OES,
and Powder X-Ray Diffraction (PXRD). Excellent heterogeneous asymmetric
activity of the newly formed UiO-68-(monometallic salen) MOFs was
achieved depending on the nature of the trapped metal, such as
epoxidation for the Mn-containing material and epoxide ring opening for
Cr-one, for example. Finally, in the presence of the MOF
UiO-68-(bimetallic Mn/Cr salen), a sequential tandem transformation
(i.e. epoxidation followed by ring opening with anilines) was
carried out to give the targeted amino alcohol in very high yield and
almost complete enantioselectivity, with a low catalyst loading (0.5
mol\%). This bimetallic catalyst was recycled after extraction of the
products for at least 10 cycles without any loss of efficiency. 

\begin{scheme*}
\includegraphics{sc22}
\vspace*{8pt}
\caption{\label{sch22}Immobilization of a Spinol-based chiral
phosphoric acid in Zr-MOFs for multi-component tandem reactions.}
\end{scheme*}

A variation in the structure of MOFs was also proposed by Ren, Jiang
and their group when they heated a mixture of
tetracarboxyphenyl-porphyrin and a Ni-salen complex in the presence of
Cd(NO$_{3}$)$_{2}$~\cite{53}. They obtained a porphyrin-salen based
chiral MOF, with two different interpenetrated networks, one in which
the porphyrin core contains $\mathrm{Cd}^{2+}$, the other being
metal-free. Efficient cooperativity could be demonstrated using this
MOF in catalytic asymmetric cyanosilylation (8 examples), due to the
presence of the high Lewis acidic sites of the $\mathrm{Cd}^{2+}$
ion in the porphyrin ring. The close location to the enantiopure
Ni-salen complex led to high values in terms of activity (up to 96\%
conversion) and enantioselectivity (up to 98\% ee). Finally, we chose
to highlight the immobilization of bulky Spinol-based chiral phosphoric
acids in stable Zr-MOFs, and their use as asymmetric Br\o{}nsted acid
catalysts to promote enantioselective multi-component tandem
reactions~\cite{54}. The structure of the chiral organocatalysts was
designed to protect them from coordinating with metal ions and to allow
the formation of MOFs with different channel sizes. The corresponding
heterogeneous catalysts were found to be more active than analogous
homogeneous catalysts, with increased acidity in the two-component
acetalization/Friedel--Crafts tandem reaction for the synthesis of
enantioenriched 2,3-dihydroquinazolinones (11 examples, up to full
conversion and enantioselectivity) or \mbox{\textit{iso}-Pictet--Spengler}
reaction of \textit{o}-aminobenzylindole with trifluoromethylated
ketones (7 examples, up to 98\% yield and 96\% ee). The catalyst was
reused 10 times for the first transformation without losing its
activity or enantioselectivity. A successful three-component tandem
reaction using indole, aldehydes and \textit{p}-toluenesulfonalide as
substrates (Scheme~\ref{sch22}) demonstrated interesting synergistic
effects with the Lewis acid Zr(IV) sites.



Similarly, the recent description of supramolecular coordination cages
has also produced excellent results for asymmetric catalysis~\cite{55}.
For example, various tetrahedral cages were prepared by mixing four
clusters of Cp$_{3}$Zr$_{3}$ with six dicarboxylate ligands derived
from metal-salen complexes. These new nanoreactors were described in
detail and the authors succeeded in obtaining cages containing
identical or different active catalytic sites~\cite{56}. Cages
containing Mn-salen were used for the epoxidation of chromene
derivatives with iodosylbenzene derivatives with enantioselectivity
values higher than those obtained with the monomer. On the other hand,
Cr-salen cages have been used successfully for the ring-opening of
epoxides with aniline or trimethylsilylazide. Consequently, the mixed
Cr/Mn-salen cage was tested in the sequential asymmetric
epoxidation/ring-opening reaction of alkenes with TMSN$_{3}$ (3
examples) or anilines (9 examples) and gave excellent results in terms
of activity and enantioselectivity, outperforming those obtained using
a 1/1 mixture of each cage containing either Cr-salen or Mn-salen as
the active species, demonstrating the positive confining effect of a
mixed cage. These few examples are only representative of a growing
\mbox{number} of articles in this field, which show the value of these
crystalline objects, which are perfectly defined and whose structure
has been precisely targeted to carry out extremely varied asymmetric
catalysis and asymmetric multicatalysis reactions, in highly efficient
recycling procedures.

\section{Ship in a bottle procedure}\label{sec6}

Finally, a last strategy based on non-covalent interactions to
immobilize chiral catalysts is worth mentioning, namely the ``ship in a
bottle'' strategy, which consists of trapping a homogeneous catalyst in
a solid porous matrix, leaving the space for the entry of substrates
and the exit of products. This procedure proved effective in
immobilizing a chiral Co-salen complex inside the mesoporous cage of
SBA-16, by controlling the size of the pore entrance, adapting the
autoclaving time and the silylation process~\cite{57}. The
corresponding heterogeneous chiral catalyst was successfully used for
the asymmetric hydrolytic ring-opening of epichlorohydrin and propylene
oxide with, in each case, values corresponding those obtained with the
homogeneous counterpart. Furthermore, this catalyst was reused after
simple filtration in ten recycles with propylene oxide as substrate,
showing almost no loss in activity or selectivity, as a proof of the
stability of the material and its ability to effectively trap active
salen species. Another more recent example concerns the encapsulation
of Mn-salen complexes in a one-step procedure for the synthesis of a
highly porous MOF, namely NH$_{2}$-MIL-101(Al), implying the linker,
the Mn-salen complex and $\mathrm{AlCl}_{3}$~\cite{58}. The
corresponding crystalline material was characterized indicating the
presence of a salen complex in one cage out of six. Although a lower
conversion was obtained compared to the homogeneous catalyst, the
enantioselectivity for the epoxidation of dihydronaphthalene remained
unchanged at 70\% ee, probably due to the soft encapsulation strategy
where the catalyst structure remained unchanged, without influence of
the MOFs walls. The MOF-cage thus assembled around the Mn-salen complex
was tested for four recycles with a slight decrease in activity and no
loss of selectivity. Further analytical studies of the solid catalyst
and filtrate were carried out, showing an unchanged structure and no
leaching, demonstrating the stability and truly heterogeneous nature of
the catalyst. A final example involves the entrapment of a chiral
Co-salen catalyst in IRMOF-3 nanocages by adsorption. As this support
is derived from tetranuclear Zn$_4$O clusters linked to
1,4-dicarboxylic benzene linkers with a functional amino group,
subsequent acylation of the free amino groups \textit{via} the
post-synthetic modification technique enabled the catalytic sites to be
trapped by reducing pores size and, therefore, access~\cite{59}. The
synthesis of enantioenriched cyclic carbonates from epoxides and
$\mathrm{CO}_{2}$ was used as a test reaction resulting in a product
with slightly reduced activity compared with the homogeneous case,
probably due to reduced diffusion. The control experiments nevertheless
proved the existence of heterogeneous activity inside the pores, with
the catalyst easily recovered and effectively reused over four repeated
runs.

\section{Conclusion and outlook}\label{sec7}

The immobilization of enantiopure catalysts, whether organic species or
organometallic complexes, \textit{via} non-covalent interactions on
various support is constantly evolving. The use of weak and reversible
interactions could lead to leaching of the catalyst and hinder, for
example, efficient recycling or promote metal contamination of the
target product. While this may still be true for certain methods of
immobilization by electrostatic interactions on silica-type supports,
partly because of their polar nature, many other solutions have been
found, for example by adapting the solvent so that the effective
recycling number reaches very high values. More recently,
${\uppi}$-interactions with carbon supports have also been exploited in
the field of asymmetric catalysis, enabling simple procedures to be
implemented since no modification of the support is required. The
conservation of the activity and enantioselectivity of the immobilized
catalyst was described, as well as numerous effective recycles, right
up to implementation in flow procedures as proof of the robustness of
this heterogenization process. Future developments of this method
should involve the co-immobilization of different (chiral) active
species on the same support in order to promote ambitious asymmetric
multicatalytic reactions. The formation of charge transfer complexes
for the recycling of chiral catalysts is rarer, but has also proved its
worth, either by acting in the homogeneous phase and being easily
recovered by the addition of an apolar solvent before filtration, or by
direct filtration when the CTC is formed directly with a species
anchored on a support. Examples of numerous recycling processes are
also described here as an interesting method for recovering and
reusing, not only the catalyst but also the support, through easy
exchanges of active species thanks to non-covalent interactions. These
immobilization procedures have also been used in multi-substrates
reactions, as well as in multi-reaction procedures proving both their
applicability and their robustness. The use of MOFs for supported
asymmetric catalysis is growing rapidly; in fact, today's perfect
mastery of the synthesis of these crystalline materials, whose
structure and porosity are controlled, means that we can decide on the
exact location of the catalytic sites, spacing them out or bringing
them closer together as required, depending on the desired reactivity,
whether individual or cooperative. These perfectly designed
nanoreactors offer size selectivity, multiple recycling without metal
contamination and asymmetric multicatalysis. The field of supported
asymmetric catalysis, involving the use of non-covalent bonds, is still
wide open to creativity, to easily carry out numerous transformations
using the support, not only for the purposes of economy and recycling,
but also to control the placement of numerous active catalytic sites
for the discovery of increasingly complex reactivities.

\section*{Declaration of interests}
The authors do not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and have
declared no affiliations other than their research organizations.

\section*{Acknowledgments} 
We are grateful to the CNRS, the Universit\'{e} Paris-Saclay for their
support and to the Agence Nationale de la Recherche
(ANR-22-CE07-0A40-01, PhD financial support to LI). For the purpose
of Open Access, a CC-BY public copyright licence has been applied by
the authors to the present document and will be applied to all
subsequent versions up to the Author Accepted Manuscript arising from
this submission.

\CDRGrant[ANR]{ANR-22-CE07-0A40-01}

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