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Citation: Sanchez-Fuente, M.;
Alonso-Gómez, J.L.; Salonen, L.M.;
Mas-Ballesté, R.; Moya, A. Chiral
Porous Organic Frameworks:
Synthesis, Chiroptical Properties, and
Asymmetric Organocatalytic
Applications. Catalysts 2023,13, 1042.
https://doi.org/10.3390/
catal13071042
Academic Editors: Victorio Cadierno
and Raffaella Mancuso
Received: 7 June 2023
Revised: 20 June 2023
Accepted: 21 June 2023
Published: 27 June 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
catalysts
Review
Chiral Porous Organic Frameworks: Synthesis, Chiroptical
Properties, and Asymmetric Organocatalytic Applications
Miguel Sanchez-Fuente 1, JoséLorenzo Alonso-Gómez 2, Laura M. Salonen 3, * , Ruben Mas-Ballesté1, 4, *
and Alicia Moya 1, *
1Department of Inorganic Chemistry (Module 7), Facultad de Ciencias, Universidad Autónoma de Madrid,
28049 Madrid, Spain; miguel.sanchezd@uam.es
2Department of Organic Chemistry, Universidade de Vigo, CINTECX, 36310 Vigo, Spain; lorenzo@uvigo.gal
3Department of Organic Chemistry, Universidade de Vigo, CINBIO, 36310 Vigo, Spain
4Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid,
28049 Madrid, Spain
*Correspondence: lauramaria.salonen@uvigo.es (L.M.S.); ruben.mas@uam.es (R.M.-B.);
alicia.moya@uam.es (A.M.)
Abstract:
Chiral porous organic frameworks have emerged in the last decade as candidates for
heterogeneous asymmetric organocatalysis. This review aims to provide a summary of the synthetic
strategies towards the design of chiral organic materials, the characterization techniques used to
evaluate their chirality, and their applications in asymmetric organocatalysis. We briefly describe
the types of porous organic frameworks, including crystalline (covalent organic frameworks, COFs)
and amorphous (conjugated microporous polymers, CMPs; covalent triazine frameworks, CTFs and
porous aromatic frameworks, PAFs) materials. Furthermore, the strategies reported to incorporate
chirality in porous organic materials are presented. We finally focus on the applications of chiral
porous organic frameworks in asymmetric organocatalytic reactions, summarizing and categorizing
all the available literature in the field.
Keywords:
covalent organic frameworks; covalent triazine frameworks; conjugated microporous
polymers; asymmetric organocatalysis; chirality
1. Introduction
Chirality has important implications for many biological processes and plays a crucial
role in the development of new drugs and materials [
1
,
2
]. For instance, more than half of
the commercial pharmaceuticals are chiral. Thus, in the recent years, a growing interest
in enantiomerically pure compounds has emerged in medicinal chemistry because of
the possible toxicity of inactive enantiomers [
3
,
4
]. In addition, chirality is relevant for a
wide variety of other fields, such as crop protection, flavors, fragrancies, and synthetic
chemistry [
5
–
8
]. Therefore, asymmetric catalysis, the use of chiral catalysts to selectively
produce a desired chiral product, is an important research field that includes several
strategies, such as the use of metal complexes or enzymes.
Organocatalysis, the use of chiral organic molecules as catalysts, has emerged as a
highly efficient alternative to traditional asymmetric catalysis methods. Chiral organocata-
lysts correspond to different kinds of molecules such as amines or amino acids, Brønsted
acids, phosphoric acids, or imidazolidinones [
9
]. Asymmetric organocatalysis offers several
advantages over traditional strategies. For instance, chiral organic molecules are generally
less toxic and more environmentally friendly than metal catalysts [
10
]. Furthermore, chiral
organic molecules can be readily synthesized and are often less expensive. Asymmetric
organocatalysis also offers high functional group compatibility, as the reactions can be
carried out under mild conditions, reducing the risk of unwanted side reactions. However,
Catalysts 2023,13, 1042. https://doi.org/10.3390/catal13071042 https://www.mdpi.com/journal/catalysts
Catalysts 2023,13, 1042 2 of 24
organocatalysis suffers from some general drawbacks, such as the need for high catalyst
loading, low catalyst stability, and the difficulty in catalyst recovery [11].
Owing to the inherent advantages of asymmetric organocatalysis, the research on
systems that allow to overcome their common drawbacks, described above, is a major
goal in modern chemistry. To this end, the incorporation of organocatalytic fragments
into porous materials is a strategy that has recently started to blossom [
12
]. A particularly
appealing family of porous frameworks with a great potential are those constructed by
the covalent assembly of exclusively organic building blocks. Such materials, covalent
organic frameworks and their amorphous analogs, offer several advantages over other
types of porous materials [
13
,
14
]. First, porous organic materials can present high stability
under a wide range of conditions, including high temperatures and acidic or basic envi-
ronments. Moreover, they possess an extraordinarily tailorable structures and, therefore,
their properties can be precisely tuned by modifying their molecular precursors, which can
include chiral moieties of different nature [
15
]. Thus, in the literature a growing number
of examples of covalent organic frameworks containing chiral fragments have started to
appear, as well as their non-crystalline counterparts.
The aim of this review is to compile in an organized manner the examples available
in the literature of porous organic frameworks that contain asymmetric fragments able to
act as organocatalysts. We start this manuscript by making a brief critical statement on
the current general categorization of porous organic materials. Then, we summarize the
strategies used to incorporate chirality in such structures and the techniques employed to
determine their chiroptical responses. Finally, applications in asymmetric organocatalysis
are briefly presented. This short overview offers a comprehensive compilation of the
principles that form the foundation of the many expected future developments in this
fast-growing field.
2. Critical Considerations on the Classification of Porous Organic Frameworks
Porous organic frameworks are materials designed according to the reticular strategy
by connecting predetermined building blocks to generate predictable structures and topolo-
gies. The term reticular refers to the structure of the materials obtained, which consists of
a network of nodes and linkers that form a three-dimensional framework, and can arise
from the expansion of a 3D geometry or from the ordered staking of layered structures [
16
].
Strictly, the definition reticular chemistry implies the isolation of crystalline materials,
which is not always the case for the extended structures included in this review. In fact, we
have included catalytic applications of crystalline and amorphous structures.
The goal of reticular design is to create materials with tailored properties, such as
specific pore sizes, shapes, and pore surface functionalities, which can be used for a
variety of applications, including catalysis. As a result of their potential advanced catalytic
applications, these materials could address some of the most urgent global social challenges,
such as energy and environmental sustainability, and are, therefore, the subject of intense
research worldwide [17].
A particular research playground is the synthetic design and application of porous
organic frameworks. One of the most attractive features of these materials is the fact
that they are constructed from interconnected networks of organic molecules and, as a
consequence, possess a high degree of tunability. Therefore, it is possible to design and
synthesize extended organic materials with a wide range of different properties, making
them suitable for use in a variety of different contexts.
The assembly of organic materials following reticular design has resulted in a plethora
of materials that correspond to different denominations. The first and most popular family
of reticular organic materials are the Covalent Organic Frameworks (COFs), which are
defined as follows: “Class of materials that form two- or three-dimensional structures through
reactions between organic precursors resulting in strong, covalent bonds to afford porous, stable, and
crystalline materials” [
18
]. Depending on the geometry of the selected building blocks, the
extended structures can adopt several laminar or 3D topologies. This structural design gives
Catalysts 2023,13, 1042 3 of 24
rise to engineered pores of predictable sizes and shapes, as shown in Figure 1. The most
common approaches for synthesizing COFs include solvothermal, solid-state, microwave-
assisted methods, and condensation reactions performed at room temperature [
19
]. In all
cases, the reactivity between the functional groups on the organic building blocks leads to
the formation of strong covalent bonds as links of the extended organic framework. The
types of linkages that have been used for the preparation of COFs include, among others,
boronic esters, boroxine, imine, hydrazone, phenazine, azine, imide, and triazine moieties
(Scheme 1) [20,21].
Catalysts 2023, 13, x FOR PEER REVIEW 3 of 26
blocks, the extended structures can adopt several laminar or 3D topologies. This structural
design gives rise to engineered pores of predictable sizes and shapes, as shown in Figure
1. The most common approaches for synthesizing COFs include solvothermal, solid-state,
microwave-assisted methods, and condensation reactions performed at room temperature
[19]. In all cases, the reactivity between the functional groups on the organic building
blocks leads to the formation of strong covalent bonds as links of the extended organic
framework. The types of linkages that have been used for the preparation of COFs include,
among others, boronic esters, boroxine, imine, hydrazone, phenazine, azine, imide, and
triazine moieties (Scheme 1) [20,21].
Figure 1. Representative topologies commonly obtained in the assembly COFs.
Scheme 1. Reactions commonly used in the assembly of COFs.
A key feature that is inherent to the COF definition is crystallinity, allowing to assign
these materials the tag of “reticular chemistry”. This feature is highly relevant for certain
applications, such as gas storage and separation, because it is associated with a highly
ordered structure with well-defined pores. However, achievement of this property is re-
stricted to condensation reactions with a high degree of reversibility (Scheme 1) that can
result, under specific reaction conditions, in the self-healing of structural defects and even-
tually to preserved long-range structural order.
Amorphous reticular organic designs have been classified in categories different
from COFs. One family of amorphous porous organic frameworks are the so-called
Figure 1. Representative topologies commonly obtained in the assembly COFs.
Catalysts 2023, 13, x FOR PEER REVIEW 3 of 26
blocks, the extended structures can adopt several laminar or 3D topologies. This structural
design gives rise to engineered pores of predictable sizes and shapes, as shown in Figure
1. The most common approaches for synthesizing COFs include solvothermal, solid-state,
microwave-assisted methods, and condensation reactions performed at room temperature
[19]. In all cases, the reactivity between the functional groups on the organic building
blocks leads to the formation of strong covalent bonds as links of the extended organic
framework. The types of linkages that have been used for the preparation of COFs include,
among others, boronic esters, boroxine, imine, hydrazone, phenazine, azine, imide, and
triazine moieties (Scheme 1) [20,21].
Figure 1. Representative topologies commonly obtained in the assembly COFs.
Scheme 1. Reactions commonly used in the assembly of COFs.
A key feature that is inherent to the COF definition is crystallinity, allowing to assign
these materials the tag of “reticular chemistry”. This feature is highly relevant for certain
applications, such as gas storage and separation, because it is associated with a highly
ordered structure with well-defined pores. However, achievement of this property is re-
stricted to condensation reactions with a high degree of reversibility (Scheme 1) that can
result, under specific reaction conditions, in the self-healing of structural defects and even-
tually to preserved long-range structural order.
Amorphous reticular organic designs have been classified in categories different
from COFs. One family of amorphous porous organic frameworks are the so-called
Scheme 1. Reactions commonly used in the assembly of COFs.
A key feature that is inherent to the COF definition is crystallinity, allowing to assign
these materials the tag of “reticular chemistry”. This feature is highly relevant for certain
applications, such as gas storage and separation, because it is associated with a highly
ordered structure with well-defined pores. However, achievement of this property is
restricted to condensation reactions with a high degree of reversibility (Scheme 1) that
can result, under specific reaction conditions, in the self-healing of structural defects and
eventually to preserved long-range structural order.
Amorphous reticular organic designs have been classified in categories different from
COFs. One family of amorphous porous organic frameworks are the so-called Conjugated
Microporous Polymers (CMPs), which are defined as a class of organic materials that
Catalysts 2023,13, 1042 4 of 24
combine extended
π
-conjugation with a permanently microporous layered structure. The
high degree of electron mobility in CMPs makes them very attractive for optoelectronic and
photocatalytic applications. The porous structure and electronic properties of CMPs can be
tailored by varying the monomer composition, degree of polymerization, and the reaction
conditions. CMPs can be synthesized using various polymerization techniques, such as
oxidative, Sonogashira, and palladium-catalyzed coupling reactions (Scheme 2) [22].
Catalysts 2023, 13, x FOR PEER REVIEW 5 of 26
Scheme 2. (A) Reactions commonly used in the assembly of CMPs and PAFs. (B) Representative
basic structural motifs in CMPs and PAFs.
Analysis of the available literature reveals a striking ambiguity on which structures
could be considered CMPs or a laminar PAFs. For instance, the exactly same chemical
structure can be found in literature as CTF-3 or PAF-56 [28,29]. Although the synthetic
routes are significantly different, assigning different classifications to identical structures
may lead to confusion. Another example of very similar structures consists of porphyrin
units assembled through biphenyl (PAF-40) or terphenyl (FeP-CMP) fragments [30,31].
Despite their similarity, the structures are assigned to PAF and CMP families, respectively.
Many other examples of laminar designs denominated as PAFs but undistinguishable
from CMPs can be found in the literature. For instance, assembly via Sonogashira–Hagi-
hara coupling reaction of 1,3,6,8-tetrabromopyrene with 1,4-diethynylbenzene or 1,3,5-tri-
ethynylbenzene resulted in conjugated structures with permanent porosities—therefore
qualifying them as CMPs—albeit being denominated as PAF-19 and PAF-20, respectively
[32].
Overall, considering the lack of clarity in the classification of amorphous COF coun-
terparts (Figure 2), we urge the researchers in the field to establish unified criteria. Other-
wise, further confusion will be added to the literature, increasing the difficulty in the
search for published information. As a suitable guideline we propose to make a clear dif-
ference between CMP and PAF materials (Figure 2). In this respect, considering the semi-
nal works that reported such structures, it seems reasonable to restrict the PAF definition
to non-conjugated structures, such as the 3D architectures that were initially reported un-
der the PAF denomination. Otherwise, it appears logical to propose that conjugated ma-
terials should be exclusively denominated as CMPs. In a more general view, a common
name should be found for all COFs and their amorphous analogs that are also designed
Scheme 2.
(
A
) Reactions commonly used in the assembly of CMPs and PAFs. (
B
) Representative
basic structural motifs in CMPs and PAFs.
A specific design of conjugated microporous materials is the one that corresponds
to Covalent Triazine Frameworks (CTFs), which can be defined as a class of extended
porous organic materials that are composed of triazine-based moieties linked by covalent
bonds [
23
]. Triazine fragments in CTFs provide a flat (layered) structure with high stability.
The aromatic carbon–nitrogen bond is very stable and irreversible under standard condi-
tions, and thus, CTFs are generally highly chemically and thermally stable and amorphous
in nature. The general synthetic methods to obtain CTFs consist of the cyclotrimerization
reaction of the nitrile functional group using Brønsted acids, or Suzuki cross-coupling,
Friedel–Crafts reaction, or amidine-mediated procedures [
23
]. Thus, although amorphous
CTFs can be considered a subclass of CMPs because they are microporous and have
extended
π
-conjugation, they are usually denominated according to their specific nomen-
clature because they were developed separately, and the chemistry of their formation
was initially quite different. However, in some limited cases, CTFs synthesized through
ionothermal or microwave-assisted methods present partially crystalline structures, which
opens the door of the COF realm to CTFs [24,25].
A further twist in the field of reticular designs for organic materials was the appearance
of materials known as Porous Aromatic Frameworks (PAFs), which are commonly defined
as porous organic polymer formed exclusively by aromatic rigid linkers assembled through
strong covalent bonds [
26
]. Interestingly, first PAF, PAF-1, resulted from the assembly of the
Catalysts 2023,13, 1042 5 of 24
tetrakis(4-bromophenyl)methane building block by means of Yamamoto-type Ullman cross-
coupling reaction (Scheme 2) [
27
]. The resulting material was a 3D network containing
biphenyl fragments held together by sp
3
-carbon atoms. Thereafter, many 3D PAFs were
developed based on building blocks containing sp
3
-C atoms. Therefore, PAFs that do
not possess extended
π
-conjugation (which is broken by tetrahedral sp
3
-C) should be
considered as a class of porous organic frameworks different from that of CMPs. However,
the definition of PAFs does not exclude laminar designs, which could result in an overlap
with the CMP denomination.
Analysis of the available literature reveals a striking ambiguity on which structures
could be considered CMPs or a laminar PAFs. For instance, the exactly same chemical struc-
ture can be found in literature as CTF-3 or PAF-56 [
28
,
29
]. Although the synthetic routes
are significantly different, assigning different classifications to identical structures may
lead to confusion. Another example of very similar structures consists of porphyrin units
assembled through biphenyl (PAF-40) or terphenyl (FeP-CMP) fragments [30,31]. Despite
their similarity, the structures are assigned to PAF and CMP families, respectively. Many
other examples of laminar designs denominated as PAFs but undistinguishable from CMPs
can be found in the literature. For instance, assembly via Sonogashira–Hagihara coupling
reaction of 1,3,6,8-tetrabromopyrene with 1,4-diethynylbenzene or 1,3,5-triethynylbenzene
resulted in conjugated structures with permanent porosities—therefore qualifying them as
CMPs—albeit being denominated as PAF-19 and PAF-20, respectively [32].
Overall, considering the lack of clarity in the classification of amorphous COF counter-
parts (Figure 2), we urge the researchers in the field to establish unified criteria. Otherwise,
further confusion will be added to the literature, increasing the difficulty in the search
for published information. As a suitable guideline we propose to make a clear difference
between CMP and PAF materials (Figure 2). In this respect, considering the seminal works
that reported such structures, it seems reasonable to restrict the PAF definition to non-
conjugated structures, such as the 3D architectures that were initially reported under the
PAF denomination. Otherwise, it appears logical to propose that conjugated materials
should be exclusively denominated as CMPs. In a more general view, a common name
should be found for all COFs and their amorphous analogs that are also designed using a
reticular approach. Using terminology found in the literature, this comprehensive group of
materials could be known as porous organic frameworks (POFs).
Catalysts 2023, 13, x FOR PEER REVIEW 6 of 26
using a reticular approach. Using terminology found in the literature, this comprehensive
group of materials could be known as porous organic frameworks (POFs).
Figure 2. Current classification of extended organic materials. The representative examples of amor-
phous materials are shown.
3. Introduction of Chirality into Porous Organic Frameworks
There are four main strategies to incorporate chirality into porous organic frame-
works (Figure 3):
(i) Synthesis using chiral building blocks;
(ii) Post-synthetic modification;
(iii) Asymmetric synthesis;
(iv) External chiral induction.
The most straightforward approach is (i) using chiral building blocks as the starting
materials, as this approach ensures the full incorporation of the chiral moieties into the
material [33–38]. Typically, only one of the building blocks contains the chiral moiety.
However, care needs to be taken that racemization of the building block does not occur
under the chosen synthesis conditions. In addition, the reaction conditions need to be op-
timized separately for each building block. Furthermore, the use of bulky building blocks
may prevent stacking interactions, which could hinder the formation of COF structures.
This could potentially be mitigated using a mixed-linker strategy, where the building
block bearing the chiral information is mixed with a less bulky non-chiral compound, alt-
hough in such a case determining the number of chiral groups incorporated into the ma-
terial may be challenging.
In (ii) post-synthetic modification (PSM), chiral moieties are incorporated to an al-
ready synthesized material [39–42]. This strategy is advantageous to obtain derivatives of
a material in one step, and typically high-yielding reactions are employed, such as az-
ide−alkyne and thiol−ene click reactions. The PSM conditions need to be carefully chosen
not to jeopardize the integrity of the material and to prevent racemization of the chiral
moiety being incorporated. The disadvantages of this strategy include the difficulties in
determining the yield of the functionalization reactions, especially in the case of materials
of high stability that cannot be digested to the respective building blocks for analysis. In
Figure 2.
Current classification of extended organic materials. The representative examples of
amorphous materials are shown.
Catalysts 2023,13, 1042 6 of 24
3. Introduction of Chirality into Porous Organic Frameworks
There are four main strategies to incorporate chirality into porous organic
frameworks (Figure 3):
(i)
Synthesis using chiral building blocks;
(ii)
Post-synthetic modification;
(iii)
Asymmetric synthesis;
(iv)
External chiral induction.
Catalysts 2023, 13, x FOR PEER REVIEW 7 of 26
addition, the spatial distribution of the chiral functionalities can be difficult to control in
the case of non-quantitative reactions.
Although (iii) asymmetric synthesis is well established in organic synthesis [43], it
has not been widely employed to date in the preparation of chiral porous organic frame-
works. The aractive feature of this approach is that chirality is imparted by the catalyst
material, and thus achiral starting materials can be used. However, determination of the
degree of transfer of chiral information may not be trivial. In addition, finding the appro-
priate reaction conditions to ensure sufficient reversibility to yield reticular materials with
long-range order could pose a challenge.
Another less commonly explored approach to chiral porous organic frameworks is
(iv) chiral induction [44,45]. In this strategy, the chiral information is imparted by a com-
pound that is present in the reaction medium but that does not become part of the final
product, such as a chiral solvent or a chiral modulator, i.e., a compound that reversibly
reacts with the building blocks. Although achiral compounds can be used as starting ma-
terials, the requirement for the building blocks is that they must have the ability to arrange
in a chiral manner. Additionally, in this strategy, determining the degree to which chiral
information has been incorporated into the resulting material is not trivial.
Figure 3. The reported approaches to incorporate chirality into reticular organic materials and re-
lated advantages and disadvantages (ticks denote advantages and X denotes disadvantages).
In the following, selected examples of each of these four strategies employed to the
preparation of chiral porous organic frameworks are presented.
3.1. Chiral Building Blocks
The strategy of preparing chiral porous organic frameworks from chiral building
blocks was employed to incorporate a diarylprolinol silyl ether Jørgensen–Hayashi cata-
lyst through Co
2
(CO)
8
-mediated trimerization of ethyne-containing building blocks [46],
giving access to a high surface area material with both micro- and mesoporosity (Scheme
3A). Sonogashira coupling was used to incorporate chiral tetraaryl-1,3-dioxolane-4,5-di-
methanol (TADDOL) building block (Scheme 3B) [47,48], a pyrrolidine compound
(Scheme 3C) [49], and an imidazolidinone MacMillan catalyst (Scheme 3C) [50]. BINAP-
containing POFs were prepared using copper-catalyzed alkyne−azide click reaction start-
ing from diethynyl 2,2′-bis(diphenylphosphino)-1,1′-binaphthlyl (BINAP) compound
(Scheme 3D) [51]. POFs composed of BINOL building blocks have been prepared using
various couplings [52], such as FeCl
3
-induced oxidative homocoupling polymerization
(Scheme 3E) [53] or Suzuki coupling (Scheme 3E) [54]. Proline-functionalized building
Figure 3.
The reported approaches to incorporate chirality into reticular organic materials and related
advantages and disadvantages (ticks denote advantages and X denotes disadvantages).
The most straightforward approach is (i) using chiral building blocks as the starting
materials, as this approach ensures the full incorporation of the chiral moieties into the
material [
33
–
38
]. Typically, only one of the building blocks contains the chiral moiety.
However, care needs to be taken that racemization of the building block does not occur
under the chosen synthesis conditions. In addition, the reaction conditions need to be
optimized separately for each building block. Furthermore, the use of bulky building blocks
may prevent stacking interactions, which could hinder the formation of COF structures.
This could potentially be mitigated using a mixed-linker strategy, where the building block
bearing the chiral information is mixed with a less bulky non-chiral compound, although
in such a case determining the number of chiral groups incorporated into the material may
be challenging.
In (ii) post-synthetic modification (PSM), chiral moieties are incorporated to an already
synthesized material [
39
–
42
]. This strategy is advantageous to obtain derivatives of a
material in one step, and typically high-yielding reactions are employed, such as azide–
alkyne and thiol–ene click reactions. The PSM conditions need to be carefully chosen
not to jeopardize the integrity of the material and to prevent racemization of the chiral
moiety being incorporated. The disadvantages of this strategy include the difficulties in
determining the yield of the functionalization reactions, especially in the case of materials
of high stability that cannot be digested to the respective building blocks for analysis. In
addition, the spatial distribution of the chiral functionalities can be difficult to control in
the case of non-quantitative reactions.
Although (iii) asymmetric synthesis is well established in organic synthesis [
43
], it has
not been widely employed to date in the preparation of chiral porous organic frameworks.
The attractive feature of this approach is that chirality is imparted by the catalyst material,
and thus achiral starting materials can be used. However, determination of the degree
of transfer of chiral information may not be trivial. In addition, finding the appropriate
Catalysts 2023,13, 1042 7 of 24
reaction conditions to ensure sufficient reversibility to yield reticular materials with long-
range order could pose a challenge.
Another less commonly explored approach to chiral porous organic frameworks is (iv)
chiral induction [
44
,
45
]. In this strategy, the chiral information is imparted by a compound
that is present in the reaction medium but that does not become part of the final product,
such as a chiral solvent or a chiral modulator, i.e., a compound that reversibly reacts with
the building blocks. Although achiral compounds can be used as starting materials, the
requirement for the building blocks is that they must have the ability to arrange in a chiral
manner. Additionally, in this strategy, determining the degree to which chiral information
has been incorporated into the resulting material is not trivial.
In the following, selected examples of each of these four strategies employed to the
preparation of chiral porous organic frameworks are presented.
3.1. Chiral Building Blocks
The strategy of preparing chiral porous organic frameworks from chiral building
blocks was employed to incorporate a diarylprolinol silyl ether Jørgensen–Hayashi catalyst
through Co
2
(CO)
8
-mediated trimerization of ethyne-containing building blocks [
46
], giving
access to a high surface area material with both micro- and mesoporosity (Scheme 3A).
Sonogashira coupling was used to incorporate chiral tetraaryl-1,3-dioxolane-4,5-dimethanol
(TADDOL) building block (Scheme 3B) [
47
,
48
], a pyrrolidine compound (Scheme 3C) [
49
],
and an imidazolidinone MacMillan catalyst (Scheme 3C) [
50
]. BINAP-containing POFs
were prepared using copper-catalyzed alkyne–azide click reaction starting from diethynyl
2,2
0
-bis(diphenylphosphino)-1,1
0
-binaphthlyl (BINAP) compound (Scheme 3D) [
51
]. POFs
composed of BINOL building blocks have been prepared using various couplings [
52
],
such as FeCl
3
-induced oxidative homocoupling polymerization (Scheme 3E) [
53
] or Suzuki
coupling (Scheme 3E) [
54
]. Proline-functionalized building blocks were used to build
defects into a porous framework prepared by Ni-catalyzed Yamamoto-type Ullmann cross-
coupling reaction (Scheme 3F) [55].
The first COF using chiral building blocks was prepared using an imidazole scaffold
on a 4,4
0
-diamino-p-terphenyl building block, which featured a chiral pyrrolidine moi-
ety [
37
]. The strategy was shown to yield both chiral imine and
β
-ketoenamine-linked
COFs with high crystallinity. Since then, various chiral building blocks have been used
as linkers in COF synthesis (Scheme 3G,I) [
56
], such as enantiopure 1,1
0
-bi-2-naphthol
(BINOL) (Scheme 3H) [
57
] and TADDOL (Scheme 3I) [
58
] derivatives to gain access to 3D
COFs. 1,3,5-Triformylphloroglucinol (Tp) functionalized with chiral (+)-diacetyl-L-tartaric
anhydride was employed to obtain a chiral carboxylic-acid-bearing Tp derivative (CTp)
(Scheme 3J) [
36
]. Tetracarbaldehyde diphospine MeO-BIPHEP ligand reacted with linear
diamines to form ABC-stacked COFs (Scheme 3J) [59].
Homochiral organic frameworks have been prepared from metalated tetrakis(4-
bromophenyl)porphyrin and S-(+)-2-methylpiperazine through Pd coupling (Scheme 4A) [
60
].
A similar synthesis strategy was used to obtain chiral frameworks from cyanuric chloride
and (2S,5S)-2,5-dimethylpiperazine (Scheme 4B) [61].
Recently, in an interesting cascade reaction, a pyrrolidine-containing dihydrazine
building block was condensed with a trialdehyde compound to give a hydrazone COF.
(Scheme 4C) [
62
]. By scanning electron microscopy, these COFs were found to assemble
as double helical structures, whereas no such arrangement was found for the racemic
control compound.
3.2. Post-Synthetic Modification with Chiral Moieties
For COFs, the first introduction of chirality through PSM was carried out using
azide–alkyne cycloaddition (Scheme 5A) [
63
]. Using a multivariant strategy, the COF was
assembled from tetrakis(4-aminophenyl)porphyrin with mixed ratios of dihydroxytereph-
thalaldehyde and a propargylated derivative thereof. The surface area and crystallinity of
the materials decreased with increasing propargyl content, and after the click reaction with
Catalysts 2023,13, 1042 8 of 24
chiral pyrrolidine azide, the materials were found to be crystalline up to 50% propargyl con-
tent. After this seminal work, further examples on the use of click reactions to obtain chiral
COFs have emerged, both using azide–alkyne (Scheme 5A) [
40
] and thiol–ene chemistry
(Scheme 5B) [64–66].
Catalysts 2023, 13, x FOR PEER REVIEW 8 of 26
blocks were used to build defects into a porous framework prepared by Ni-catalyzed
Yamamoto-type Ullmann cross-coupling reaction (Scheme 3F) [55].
The first COF using chiral building blocks was prepared using an imidazole scaffold
on a 4,4′-diamino-p-terphenyl building block, which featured a chiral pyrrolidine moiety
[37]. The strategy was shown to yield both chiral imine and β-ketoenamine-linked COFs
with high crystallinity. Since then, various chiral building blocks have been used as linkers
in COF synthesis (Scheme 3G,I) [56], such as enantiopure 1,1′-bi-2-naphthol (BINOL)
(Scheme 3H) [57] and TADDOL (Scheme 3I) [58] derivatives to gain access to 3D COFs.
1,3,5-Triformylphloroglucinol (Tp) functionalized with chiral (+)-diacetyl-L-tartaric anhy-
dride was employed to obtain a chiral carboxylic-acid-bearing Tp derivative (CTp)
(Scheme 3J) [36]. Tetracarbaldehyde diphospine MeO-BIPHEP ligand reacted with linear
diamines to form ABC-stacked COFs (Scheme 3J) [59].
Scheme 3. (A–J) Examples of chiral porous organic materials using chiral building blocks. Refer-
ences are included in the brackets.
Homochiral organic frameworks have been prepared from metalated tetrakis(4-bro-
mophenyl)porphyrin and S-(+)-2-methylpiperazine through Pd coupling (Scheme 4A)
[60]. A similar synthesis strategy was used to obtain chiral frameworks from cyanuric
chloride and (2S,5S)-2,5-dimethylpiperazine (Scheme 4B) [61].
Recently, in an interesting cascade reaction, a pyrrolidine-containing dihydrazine
building block was condensed with a trialdehyde compound to give a hydrazone COF.
(Scheme 4C) [62]. By scanning electron microscopy, these COFs were found to assemble
as double helical structures, whereas no such arrangement was found for the racemic con-
trol compound.
Scheme 3.
(
A
–
J
) Examples of chiral porous organic materials using chiral building blocks. References
are included in the brackets.
Catalysts 2023, 13, x FOR PEER REVIEW 9 of 26
Scheme 4. (A–C) Examples of triazine-containing chiral frameworks using asymmetric building
blocks. References are included in the brackets.
3.2. Post-Synthetic Modification with Chiral Moieties
For COFs, the first introduction of chirality through PSM was carried out using az-
ide−alkyne cycloaddition (Scheme 5A) [63]. Using a multivariant strategy, the COF was
assembled from tetrakis(4-aminophenyl)porphyrin with mixed ratios of dihydroxyter-
ephthalaldehyde and a propargylated derivative thereof. The surface area and crystallin-
ity of the materials decreased with increasing propargyl content, and after the click reac-
tion with chiral pyrrolidine azide, the materials were found to be crystalline up to 50%
propargyl content. After this seminal work, further examples on the use of click reactions
to obtain chiral COFs have emerged, both using azide−alkyne (Scheme 5A) [40] and
thiol−ene chemistry (Scheme 5B) [64–66].
A chiral cationic COF was obtained through PSM of a COF self-assembled from
2,4,6-(4′-triaminophenyl)pyridine and 2-hydroxy-1,3,5-tribenzaldehyde (Scheme 5C) [42],
where the reaction of the pyridine N atom with prolinol bromoacetate at room tempera-
ture gave access to cationic chiral material without loss of crystallinity. In another study,
Banerjee and co-workers developed a sequential PSM to incorporate folic acid to their
β-ketoenamine COF materials, consisting of a reaction between the hydroxy groups on
the COF with epoxypropyl alcohol, followed by the incorporation of an amino group
through reaction with 3-aminopropyltriethoxysilane, and finally amide coupling to aach
folic acid (Scheme 5D) [67]. Using this synthetic strategy, Qu and co-workers gained ac-
cess to L-histidine-functionalized COF nanozyme with different amino acid loadings [68].
Amide coupling has also been used in surface functionalization of COFs with biomole-
cules (Scheme 5E) [69]. Taking advantage of residual carboxylic acid groups from the con-
densation anhydrides and amines, lysozyme, a tripeptide, and lysine were bound to the
COF surface. As compared to non-covalent adsorption, the covalent method provided
higher loading amounts of the biomolecules and less leaching.
Scheme 4.
(
A
–
C
) Examples of triazine-containing chiral frameworks using asymmetric building
blocks. References are included in the brackets.
Catalysts 2023,13, 1042 9 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 10 of 26
Scheme 5. (A–E) Chiral porous organic frameworks obtained through post-synthetic modifications.
References are included in the brackets.
3.3. Asymmetric Catalysis
Asymmetric catalysis is an established method to introduce chirality during organic
synthesis. In 2020, this method was employed in COF synthesis for the first time, when
chiral materials were obtained by means of A3 coupling (Scheme 6A) [70]. Under ambient
conditions using a chiral PYBOX ligand with copper(I) triflate as catalyst, the coupling of
dimethoxyterephthalaldehyde, tris(4-aminophenyl)benzene, and phenylacetylene gave
access to chiral, crystalline propargylamine-linked DTP-COF. The method was extended
in a following study by employing tetrakis(4-aminophenyl)porphyrin and ammonium-
bromide-decorated phenylacetylene as building blocks (Scheme 6B) [71].
Scheme 5.
(
A
–
E
) Chiral porous organic frameworks obtained through post-synthetic modifications.
References are included in the brackets.
A chiral cationic COF was obtained through PSM of a COF self-assembled from
2,4,6-(4
0
-triaminophenyl)pyridine and 2-hydroxy-1,3,5-tribenzaldehyde (Scheme 5C) [
42
],
where the reaction of the pyridine N atom with prolinol bromoacetate at room tempera-
ture gave access to cationic chiral material without loss of crystallinity. In another study,
Banerjee and co-workers developed a sequential PSM to incorporate folic acid to their
β
-ketoenamine COF materials, consisting of a reaction between the hydroxy groups on
the COF with epoxypropyl alcohol, followed by the incorporation of an amino group
through reaction with 3-aminopropyltriethoxysilane, and finally amide coupling to attach
folic acid (Scheme 5D) [
67
]. Using this synthetic strategy, Qu and co-workers gained ac-
cess to L-histidine-functionalized COF nanozyme with different amino acid loadings [
68
].
Amide coupling has also been used in surface functionalization of COFs with biomolecules
(Scheme 5E) [
69
]. Taking advantage of residual carboxylic acid groups from the condensa-
tion anhydrides and amines, lysozyme, a tripeptide, and lysine were bound to the COF
surface. As compared to non-covalent adsorption, the covalent method provided higher
loading amounts of the biomolecules and less leaching.
Catalysts 2023,13, 1042 10 of 24
3.3. Asymmetric Catalysis
Asymmetric catalysis is an established method to introduce chirality during organic
synthesis. In 2020, this method was employed in COF synthesis for the first time, when
chiral materials were obtained by means of A
3
coupling (Scheme 6A) [
70
]. Under ambient
conditions using a chiral PYBOX ligand with copper(I) triflate as catalyst, the coupling
of dimethoxyterephthalaldehyde, tris(4-aminophenyl)benzene, and phenylacetylene gave
access to chiral, crystalline propargylamine-linked DTP-COF. The method was extended
in a following study by employing tetrakis(4-aminophenyl)porphyrin and ammonium-
bromide-decorated phenylacetylene as building blocks (Scheme 6B) [71].
Catalysts 2023, 13, x FOR PEER REVIEW 11 of 26
Scheme 6. (A,B) Chiral COFs obtained through asymmetric catalysis. References are included in the
brackets.
3.4. Chiral Induction
The ordered nature of COFs gives the possibility of arranging achiral building blocks
in an asymmetric manner in space, which requires external chiral input.. To date, reports
using chiral induction to gain access to chiral COFs remain scarce and are to the best of
our knowledge restricted to β-ketoenamine-linked COFs. The first example was reported
in 2018 [45], where a catalytic amount of an enantiomerically pure phenylethylamine was
employed during COF synthesis under solvothermal conditions to induce chiral arrange-
ment of the three-fold-symmetric tris(N-salicylideneamine) core (Scheme 7A). While the
use of triformylbenzene as a building block resulted in achiral materials, 1,3,5-tri-
formylphloroglucinol (Tp) gave access to a series of chiral COFs. This was aributed to
the keto−enol tautomerization of the building block upon imine formation, giving rise to
propeller-like arrangement of the salicylideneamine core, which, upon reversible reaction
with chiral phenylethylamine modulator, acquired a chiral arrangement. Following this
study, chiral induction in β-ketoenamine COFs has also been achieved using (1-naph-
thyl)ethylamine (Scheme 7B) [44] and even under ambient conditions using 2-methylpyr-
rolidine (Scheme 7C) [72].
Scheme 6.
(
A
,
B
) Chiral COFs obtained through asymmetric catalysis. References are included in
the brackets.
3.4. Chiral Induction
The ordered nature of COFs gives the possibility of arranging achiral building blocks
in an asymmetric manner in space, which requires external chiral input. To date, re-
ports using chiral induction to gain access to chiral COFs remain scarce and are to the
best of our knowledge restricted to
β
-ketoenamine-linked COFs. The first example was
reported in 2018 [
45
], where a catalytic amount of an enantiomerically pure phenylethy-
lamine was employed during COF synthesis under solvothermal conditions to induce
chiral arrangement of the three-fold-symmetric tris(N-salicylideneamine) core (Scheme 7A).
While the use of triformylbenzene as a building block resulted in achiral materials, 1,3,5-
triformylphloroglucinol (Tp) gave access to a series of chiral COFs. This was attributed
to the keto–enol tautomerization of the building block upon imine formation, giving
rise to propeller-like arrangement of the salicylideneamine core, which, upon reversible
reaction with chiral phenylethylamine modulator, acquired a chiral arrangement. Fol-
lowing this study, chiral induction in
β
-ketoenamine COFs has also been achieved using
(1-naphthyl)ethylamine (Scheme 7B) [
44
] and even under ambient conditions using 2-
methylpyrrolidine (Scheme 7C) [72].
Catalysts 2023,13, 1042 11 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 12 of 26
Scheme 7. (A–C) Chiral COFs obtained through chiral induction. References are included in the
brackets.
4. Chiroptical Responses
Chiroptical responses, those employing right and left circularly polarized light, have
been extensively used in the last half a century for the structural characterization of chiral
systems [73]. These spectroscopies feature larger sensitivity to the geometry of the system
under study compared to the non-chiral spectroscopy counterparts, i.e., electronic circular
dichroism (ECD) vs. ultraviolet/visible spectroscopy (UV/Vis). While UV/Vis is only pro-
portional to the transition electric dipole moment, ECD is proportional to the dot product
of the transition electric dipole moment and transition magnetic dipole moment (Figure
4). In the illustrated example, while the electron density displacement along the three
chromophores present in the system (black arrows) features an overall transition electric
dipole moment perpendicular to the macrocycle (gray arrow), this circulation of electron
density around the cycle generates a transition magnetic dipole moment perpendicular to
the cycle (orange arrow). However, the antiparallel or antiparallel alignment of transition
electric and magnetic dipole moments depends on the chirality of the system (antiparal-
lel/parallel in the illustrated (M,M,M)/(P,P,P)-enantiomer) [74]. This particularity enables
not only the determination of the absolute configuration [75], the handedness of a system,
but also the determination of the conformation [76] and even the characterization of
host−guest complexes [77] and self-assembled systems [78].
Scheme 7.
(
A
–
C
) Chiral COFs obtained through chiral induction. References are included in
the brackets.
4. Chiroptical Responses
Chiroptical responses, those employing right and left circularly polarized light, have
been extensively used in the last half a century for the structural characterization of chiral
systems [
73
]. These spectroscopies feature larger sensitivity to the geometry of the system
under study compared to the non-chiral spectroscopy counterparts, i.e., electronic circular
dichroism (ECD) vs. ultraviolet/visible spectroscopy (UV/Vis). While UV/Vis is only pro-
portional to the transition electric dipole moment, ECD is proportional to the dot product
of the transition electric dipole moment and transition magnetic dipole moment (Figure 4).
In the illustrated example, while the electron density displacement along the three chro-
mophores present in the system (black arrows) features an overall transition electric dipole
moment perpendicular to the macrocycle (gray arrow), this circulation of electron density
around the cycle generates a transition magnetic dipole moment perpendicular to the cycle
(orange arrow). However, the antiparallel or antiparallel alignment of transition electric
and magnetic dipole moments depends on the chirality of the system (antiparallel/parallel
in the illustrated (M,M,M)/(P,P,P)-enantiomer) [
74
]. This particularity enables not only
the determination of the absolute configuration [75], the handedness of a system, but also
the determination of the conformation [
76
] and even the characterization of host–guest
complexes [77] and self-assembled systems [78].
Catalysts 2023, 13, x FOR PEER REVIEW 12 of 26
Scheme 7. (A–C) Chiral COFs obtained through chiral induction. References are included in the
brackets.
4. Chiroptical Responses
Chiroptical responses, those employing right and left circularly polarized light, have
been extensively used in the last half a century for the structural characterization of chiral
systems [73]. These spectroscopies feature larger sensitivity to the geometry of the system
under study compared to the non-chiral spectroscopy counterparts, i.e., electronic circular
dichroism (ECD) vs. ultraviolet/visible spectroscopy (UV/Vis). While UV/Vis is only pro-
portional to the transition electric dipole moment, ECD is proportional to the dot product
of the transition electric dipole moment and transition magnetic dipole moment (Figure
4). In the illustrated example, while the electron density displacement along the three
chromophores present in the system (black arrows) features an overall transition electric
dipole moment perpendicular to the macrocycle (gray arrow), this circulation of electron
density around the cycle generates a transition magnetic dipole moment perpendicular to
the cycle (orange arrow). However, the antiparallel or antiparallel alignment of transition
electric and magnetic dipole moments depends on the chirality of the system (antiparal-
lel/parallel in the illustrated (M,M,M)/(P,P,P)-enantiomer) [74]. This particularity enables
not only the determination of the absolute configuration [75], the handedness of a system,
but also the determination of the conformation [76] and even the characterization of
host−guest complexes [77] and self-assembled systems [78].
Figure 4.
Representation of transition electric dipole moment (gray arrows: total transition electric
dipole moment; black arrows: the contribution from the different chromophores in the molecule)
and transition magnetic dipole moment (red arrows) of the lowest electronic transition of a (M,M,M)-
configured (left) and (P,P,P)-configured (right) cyclic spirobifluorene oligomer [74].
Catalysts 2023,13, 1042 12 of 24
The dissymmetry factor, also referred to as the g-factor, is typically used to evaluate the
chiroptical power of a system. In ECD, for instance, the g-factor is calculated as
∆ε
/
ε
. For
chiroptical responses arising from isolated systems such as discrete molecules in solution,
the typical values of g-factor are in the range of 10
−4
–10
−2
, whereas for aggregated systems
where the neighboring fragments are ordered in a chiral manner, the values can be 10
−1
or
higher [
79
]. While the chiroptical responses of most discrete molecules are evaluated in
solution in transmittance mode, this approach can also be applied to insoluble systems by
dispersing them in a solvent. An alternative for insoluble materials is the diffuse-reflectance
mode on a suitable substrate.
4.1. Sample Preparation and Measurement Modes for Determining Chiroptical Responses of
Solid Samples
Chiroptical measurements of solid samples in the transmittance mode (Figure 5, left)
can be measured using a dispersion of a powder in Nujol, refined mineral oil, or a liquid
with a refractive index similar to that of the chiral material, placed between two optical
windows. While the systems are considered isotropic, scattering may provide significant
noise in the recorded spectra that can be partially attenuated [
80
]. For samples that react
with mineral oil, the sample can be measured as a pellet with KBr, CsI, or KCl. In this
methodology, the presence of scattering may hamper the measurements. On the other
hand, measurements in diffuse-reflectance mode can be made using a pellet, as mentioned
above, or directly on a powder sample. To carry out these measurements, an integrating
sphere is needed (Figure 5, right).
Catalysts 2023, 13, x FOR PEER REVIEW 13 of 26
Figure 4. Representation of transition electric dipole moment (gray arrows: total transition electric
dipole moment; black arrows: the contribution from the different chromophores in the molecule)
and transition magnetic dipole moment (red arrows) of the lowest electronic transition of a
(M,M,M)-configured (left) and (P,P,P)-configured (right) cyclic spirobifluorene oligomer [74].
The dissymmetry factor, also referred to as the g-factor, is typically used to evaluate
the chiroptical power of a system. In ECD, for instance, the g-factor is calculated as Δε/ε.
For chiroptical responses arising from isolated systems such as discrete molecules in so-
lution, the typical values of g-factor are in the range of 10−4–10−2, whereas for aggregated
systems where the neighboring fragments are ordered in a chiral manner, the values can
be 10−1 or higher [79]. While the chiroptical responses of most discrete molecules are eval-
uated in solution in transmiance mode, this approach can also be applied to insoluble
systems by dispersing them in a solvent. An alternative for insoluble materials is the dif-
fuse-reflectance mode on a suitable substrate.
4.1. Sample Preparation and Measurement Modes for Determining Chiroptical Responses of
Solid Samples
Chiroptical measurements of solid samples in the transmiance mode (Figure 5, left)
can be measured using a dispersion of a powder in Nujol, refined mineral oil, or a liquid
with a refractive index similar to that of the chiral material, placed between two optical
windows. While the systems are considered isotropic, scaering may provide significant
noise in the recorded spectra that can be partially aenuated [80]. For samples that react
with mineral oil, the sample can be measured as a pellet with KBr, CsI, or KCl. In this
methodology, the presence of scaering may hamper the measurements. On the other
hand, measurements in diffuse-reflectance mode can be made using a pellet, as mentioned
above, or directly on a powder sample. To carry out these measurements, an integrating
sphere is needed (Figure 5, right).
Figure 5. Representation of transmiance and diffuse-reflectance modes for spectroscopy measure-
ments.
In general, for measurements of solid samples the evaluation of the UV/Vis spectra
of the sample is recommended to exclude the presence of artifacts in the chiroptical spec-
tra [81] and the use of homogeneous particle distribution in the sample to minimize ab-
sorption flaening.
4.2. Chiroptical Responses in Porous Organic Frameworks
Axially chiral binaphthyl moieties have been employed to develop a chiral COF pre-
senting g-factors of 0.02 and 0.04 by ECD and circularly polarized luminescence (CPL),
respectively [82]. The high g-value for CPL was concluded to stem from confined chirality
transfer within the COF structure based on the lack of such a response in a discrete model
compound. The samples were prepared as suspensions in ethylene glycol and measured
Figure 5.
Representation of transmittance and diffuse-reflectance modes for spectroscopy
measurements.
In general, for measurements of solid samples the evaluation of the UV/Vis spec-
tra of the sample is recommended to exclude the presence of artifacts in the chiroptical
spectra [
81
] and the use of homogeneous particle distribution in the sample to minimize
absorption flattening.
4.2. Chiroptical Responses in Porous Organic Frameworks
Axially chiral binaphthyl moieties have been employed to develop a chiral COF
presenting g-factors of 0.02 and 0.04 by ECD and circularly polarized luminescence (CPL),
respectively [
82
]. The high g-value for CPL was concluded to stem from confined chirality
transfer within the COF structure based on the lack of such a response in a discrete model
compound. The samples were prepared as suspensions in ethylene glycol and measured
in transmission mode. To demonstrate the lack of artifacts in the chiroptical spectra, the
authors showed the linear dichroism spectra with no significant features. This work is a
good example of how chiroptical responses can be used not only to verify the presence of
chirality in a material, but also to understand the nature of such chirality (Scheme 8).
Catalysts 2023,13, 1042 13 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 14 of 26
in transmission mode. To demonstrate the lack of artifacts in the chiroptical spectra, the
authors showed the linear dichroism spectra with no significant features. This work is a
good example of how chiroptical responses can be used not only to verify the presence of
chirality in a material, but also to understand the nature of such chirality (Scheme 8).
Scheme 8. Comparison between the chiroptical responses of a model system and a COF from a
chiral building block gives valuable information about the chirality of the developed chiral material.
[82].
A chiral tris(N-salicylideneamine) COF was synthesized via external chiral induction
(Scheme 7), and the mirror image spectra measured in the solid state of the two enantio-
meric COFs was used to certify the incorporation of chirality in the material. The authors
propose a propeller-shaped configuration based on geometry simulations [45].
Chiroptical responses may be useful not only for the characterization of developed
materials, but also for several applications. For instance, systems presenting CPL can be
applied to, e.g., optical displays, bioimaging, or sensing. With the aim of developing ma-
terials with tunable CPL properties, ultrathin chiral COF nanosheets were developed by
chiral induced synthesis. The characterization via ECD and CPL was performed in COF
samples dispersed in ethanol to confirm their chirality. The different features of the chiral
COF compared to model systems indicated that the chirality in the developed materials
originates from their asymmetrical microstructure. In order to take advantage of the CPL
responses of these materials for applications, the chiral COFs were implemented into
transparent films also showing intense CPL intensities. Furthermore, the g-factor was in-
creased from 0.02 to 0.1 by a combination of the chiral COF with dyes [44]. Finally, chi-
roptical responses have also been employed for the stability evaluation of chiral COFs [83].
5. Applications in Asymmetric Organocatalysis
In this section, we review the performance of porous organic frameworks in asym-
metric organocatalysis. In general, the use of such materials in organocatalytic processes
has gained remarkable industrial interest because of their many advantages, such as the
avoidance of expensive or toxic metals, their environmentally benign nature, and highly
recyclability. However, the design of chiral porous organic frameworks for heterogeneous
asymmetric catalytic reactions is in its infancy. Below we summarize the literature exam-
ples of organocatalytic processes categorized by the type of catalytic reaction.
5.1. Covalent Catalysis
Chiral covalent organocatalysis relies on the formation of reversible covalent bonds
between the catalyst and the substrate. The catalyst transfers the chiral information to the
substrate and the organocatalyst is then released to close the catalytic cycle. In this section,
we provide a summary of porous organic frameworks that incorporate commonly used
organocatalysts, such as pyrrolidine or imidazolidine moieties. These frameworks have
been employed for various asymmetric organocatalytic reactions, such as Michael addi-
tion, aldol condensation, and Diels−Alder reactions.
Scheme 8.
Comparison between the chiroptical responses of a model system and a COF from a chiral
building block gives valuable information about the chirality of the developed chiral material [82].
A chiral tris(N-salicylideneamine) COF was synthesized via external chiral induction
(Scheme 7), and the mirror image spectra measured in the solid state of the two enantiomeric
COFs was used to certify the incorporation of chirality in the material. The authors propose
a propeller-shaped configuration based on geometry simulations [45].
Chiroptical responses may be useful not only for the characterization of developed
materials, but also for several applications. For instance, systems presenting CPL can
be applied to, e.g., optical displays, bioimaging, or sensing. With the aim of developing
materials with tunable CPL properties, ultrathin chiral COF nanosheets were developed by
chiral induced synthesis. The characterization via ECD and CPL was performed in COF
samples dispersed in ethanol to confirm their chirality. The different features of the chiral
COF compared to model systems indicated that the chirality in the developed materials
originates from their asymmetrical microstructure. In order to take advantage of the CPL
responses of these materials for applications, the chiral COFs were implemented into trans-
parent films also showing intense CPL intensities. Furthermore, the g-factor was increased
from 0.02 to 0.1 by a combination of the chiral COF with dyes [
44
]. Finally, chiroptical
responses have also been employed for the stability evaluation of chiral COFs [83].
5. Applications in Asymmetric Organocatalysis
In this section, we review the performance of porous organic frameworks in asym-
metric organocatalysis. In general, the use of such materials in organocatalytic processes
has gained remarkable industrial interest because of their many advantages, such as the
avoidance of expensive or toxic metals, their environmentally benign nature, and highly
recyclability. However, the design of chiral porous organic frameworks for heterogeneous
asymmetric catalytic reactions is in its infancy. Below we summarize the literature examples
of organocatalytic processes categorized by the type of catalytic reaction.
5.1. Covalent Catalysis
Chiral covalent organocatalysis relies on the formation of reversible covalent bonds
between the catalyst and the substrate. The catalyst transfers the chiral information to the
substrate and the organocatalyst is then released to close the catalytic cycle. In this section,
we provide a summary of porous organic frameworks that incorporate commonly used
organocatalysts, such as pyrrolidine or imidazolidine moieties. These frameworks have
been employed for various asymmetric organocatalytic reactions, such as Michael addition,
aldol condensation, and Diels–Alder reactions.
The first example of a robust chiral porous material with an embedded organocata-
lysts was reported in 2012 using the Jorgensen–Hayashi catalyst (JH). Xu and co-workers
developed a highly efficient heterogeneous organocatalysis called JH-CPP towards the
asymmetric Michael addition of aldehydes to nitroalkenes (Scheme 9A) [
46
] They obtained
the desired products with yields of 67–99%, high enantioselectivity (93–99% ee) and high
diastereoselectivity (dr of 74:26 to 97:3). The reuse of JH-CPP was successful during four
cycles without loss of enantioselectivity (97–99% ee) and diastereoselectivity (dr 92:8 to
88:12). Another example of the incorporation of pyrrolidine derivatives into a porous
Catalysts 2023,13, 1042 14 of 24
structure by post-functionalization methods was reported by Xu et al. (Scheme 9B) [
63
].
They tested imine-based COFs with different densities of pyrrolidine units for the Michael
addition reaction of trans-4-chloro-
β
-nitrostyrene and propionaldehyde. Their results con-
firm the effectiveness of the pore surface engineering strategy to functionalize the COF pore
structure with organocatalytic fragments. The 25% pyrrolidine loading was the optimum
for high activity and good recyclability, with 86–93% yields while retaining diastereos-
electivity (dr of 70/30). In addition, these materials have a high capability to perform
transformations under batch and flow conditions. In another study, Xu and co-workers
reported an imine-based TPB-DMTP-COF that was post-synthetically functionalized by
anchoring chiral (S)-pyrrolidine centers onto the channel walls of the COF. The resulting
material was used as a heterogeneous organocatalyst for the Michael addition reaction of
cyclohexanone and
β
-nitrostyrene, achieving 100% conversion in water solutions with ee
of 90–96% and dr values more than 90/10 (Scheme 9C) [40].
Catalysts 2023, 13, x FOR PEER REVIEW 15 of 26
The first example of a robust chiral porous material with an embedded organocata-
lysts was reported in 2012 using the Jorgensen–Hayashi catalyst (JH). Xu and co-workers
developed a highly efficient heterogeneous organocatalysis called JH-CPP towards the
asymmetric Michael addition of aldehydes to nitroalkenes (Scheme 9A) [46] They ob-
tained the desired products with yields of 67–99%, high enantioselectivity (93–99% ee)
and high diastereoselectivity (dr of 74:26 to 97:3). The reuse of JH-CPP was successful
during four cycles without loss of enantioselectivity (97–99% ee) and diastereoselectivity
(dr 92:8 to 88:12). Another example of the incorporation of pyrrolidine derivatives into a
porous structure by post-functionalization methods was reported by Xu et al. (Scheme 9B)
[63]. They tested imine-based COFs with different densities of pyrrolidine units for the
Michael addition reaction of trans-4-chloro-β-nitrostyrene and propionaldehyde. Their re-
sults confirm the effectiveness of the pore surface engineering strategy to functionalize the
COF pore structure with organocatalytic fragments. The 25% pyrrolidine loading was the
optimum for high activity and good recyclability, with 86–93% yields while retaining di-
astereoselectivity (dr of 70/30). In addition, these materials have a high capability to per-
form transformations under batch and flow conditions. In another study, Xu and co-work-
ers reported an imine-based TPB-DMTP-COF that was post-synthetically functionalized
by anchoring chiral (S)-pyrrolidine centers onto the channel walls of the COF. The result-
ing material was used as a heterogeneous organocatalyst for the Michael addition reaction
of cyclohexanone and β-nitrostyrene, achieving 100% conversion in water solutions with
ee of 90–96% and dr values more than 90/10 (Scheme 9C) [40].
More recently, pyrrolidine fragments have been used as building units for the incor-
poration of chiral fragments into the COF structure, which are referred to as chiral COFs
(CCOFs). For example, in 2019 Zhang et al. developed the chiral Tfp2-COF containing
pyrrolidine derivatives (Scheme 9D) [84]. This material was used as a heterogeneous or-
ganocatalyst for asymmetric Michael addition reactions of cyclohexanone with β-nitrosty-
rene, resulting in products with 85–95% yields and a 17:1 anti/syn ratio. Moreover, Tfp2-
COF showed comparable enantioselectivities and higher distereoselectivities than the ho-
mogeneous control. Another example of a CCOF formed via catalytic polymerization of
prochiral monomers used propargylamine fragments to construct DTP-COF, which were
also used to catalyze Michael addition reactions (Scheme 9E) [70]. Thus, they used both
(S)- and (R)-propargylamine-linked CCOFs for Michael addition of cyclohexanone with
β-nitrostyrene derivatives with substituents at different positions. Under the optimal con-
ditions, they achieved 82−99% yields with dr = 68:32−88:12 and 90−99% ee values, respec-
tively.
Scheme 9. (A–E) Chiral porous organic frameworks used for asymmetric Michael addition reac-
tions. References are included in the brackets.
Scheme 9.
(
A
–
E
) Chiral porous organic frameworks used for asymmetric Michael addition reactions.
References are included in the brackets.
More recently, pyrrolidine fragments have been used as building units for the in-
corporation of chiral fragments into the COF structure, which are referred to as chiral
COFs (CCOFs). For example, in 2019 Zhang et al. developed the chiral Tfp2-COF con-
taining pyrrolidine derivatives (Scheme 9D) [
84
]. This material was used as a heteroge-
neous organocatalyst for asymmetric Michael addition reactions of cyclohexanone with
β
-nitrostyrene, resulting in products with 85–95% yields and a 17:1 anti/syn ratio. More-
over, Tfp2-COF showed comparable enantioselectivities and higher distereoselectivities
than the homogeneous control. Another example of a CCOF formed via catalytic poly-
merization of prochiral monomers used propargylamine fragments to construct DTP-COF,
which were also used to catalyze Michael addition reactions (Scheme 9E) [
70
]. Thus, they
used both (S)- and (R)-propargylamine-linked CCOFs for Michael addition of cyclohex-
anone with
β
-nitrostyrene derivatives with substituents at different positions. Under the
optimal conditions, they achieved 82–99% yields with dr = 68:32–88:12 and 90–99% ee
values, respectively.
Porous organic frameworks post-modified by pyrrolidine units have further been used
as heterogeneous catalyst for the asymmetric aldol reaction, one of the most important
routes for asymmetric C–C bond formation. For example, Xu et al. constructed two new
chiral COFs, LZU-72 and LZU-76, from chiral pyrrolidine fragments. Interestingly, the
presence of
β
-ketoenamine linkages in the structure of LZU-76 made its catalytic perfor-
mance in the aldol reaction under acidic conditions. However, the low stability of the imine
linkages in LZU-72 under acidic conditions were a limiting characteristic for its application
Catalysts 2023,13, 1042 15 of 24
as heterogeneous catalyst for this type of reaction. The LZU-76 material was used for
the asymmetric aldol reaction between aromatic aldehydes and acetone, achieving high
enantioselectivity (up to 94:6 er), comparable to the corresponding homogeneous system.
Importantly, the new material has enabled their reutilization up to three times without
loss of enantioselectivity (Scheme 10A) [
37
]. Another attractive strategy was developed
by Lin et al. who built four defective porous organic frameworks (dPOFs) that were used
as supports for the immobilization of proline-based organocatalysts. The materials were
tested towards direct asymmetric aldol reaction between p-nitrobenzaldehyde and ace-
tone as a model reaction. Remarkably, the dPOFs showed higher catalytic activities and
enantioselectivities than homogeneous L-proline catalysts with yields of 71–83% and ee of
66–85%. Furthermore, the dPOFs did not present leaching and could be reused at least five
times without significant loss of activity and merely a small decrease of enantioselectivity
(Scheme 10B) [55].
Catalysts 2023, 13, x FOR PEER REVIEW 16 of 26
Porous organic frameworks post-modified by pyrrolidine units have further been
used as heterogeneous catalyst for the asymmetric aldol reaction, one of the most im-
portant routes for asymmetric C−C bond formation. For example, Xu et al. constructed
two new chiral COFs, LZU-72 and LZU-76, from chiral pyrrolidine fragments. Interest-
ingly, the presence of β-ketoenamine linkages in the structure of LZU-76 made its catalytic
performance in the aldol reaction under acidic conditions. However, the low stability of
the imine linkages in LZU-72 under acidic conditions were a limiting characteristic for its
application as heterogeneous catalyst for this type of reaction. The LZU-76 material was
used for the asymmetric aldol reaction between aromatic aldehydes and acetone, achiev-
ing high enantioselectivity (up to 94:6 er), comparable to the corresponding homogeneous
system. Importantly, the new material has enabled their reutilization up to three times
without loss of enantioselectivity (Scheme 10A) [37]. Another aractive strategy was de-
veloped by Lin et al. who built four defective porous organic frameworks (dPOFs) that
were used as supports for the immobilization of proline-based organocatalysts. The ma-
terials were tested towards direct asymmetric aldol reaction between p-nitrobenzaldehyde
and acetone as a model reaction. Remarkably, the dPOFs showed higher catalytic activi-
ties and enantioselectivities than homogeneous L-proline catalysts with yields of 71–83%
and ee of 66–85%. Furthermore, the dPOFs did not present leaching and could be reused
at least five times without significant loss of activity and merely a small decrease of enan-
tioselectivity (Scheme 10B) [55].
Scheme 10. (A,B) Chiral porous organic frameworks used for asymmetric aldol addition reactions.
References are included in the brackets.
In addition to pyrrolidine, imidazolidine compounds, also known as MacMillan cat-
alysts, have been incorporated into CCOFs to perform heterogeneous asymmetric organo-
catalytic reactions. Zhang et al. prepared a series of CCOFs containing the MacMillan cat-
alysts, which enabled the α-aminooxylation reaction between aldehydes and nitrosoben-
zene, forming a product with 76% isolated yield and 94% ee. The catalytic aldol reaction
of cyclohexanone with 4-nitrobenzaldehyde and 3-nitrobenzaldehyde afforded 92% and
86% ee, 95% and 94% yield, and 90:10 and 90:10 anti/syn ratio, respectively. Finally, asym-
metric Diels−Alder cycloaddition reaction with cyclopentadiene and (E)-cinnamaldehyde
formed the cycloadduct in 83% isolated yield and excellent selectivity (13:1 endo/exo, 90%
ee for the endo isomer). In all studied reactions, the stereoselectivity and diastereoselectiv-
ity was comparable and even superior to the homogeneous analogs (Scheme 11) [85].
Scheme 10.
(
A
,
B
) Chiral porous organic frameworks used for asymmetric aldol addition reactions.
References are included in the brackets.
In addition to pyrrolidine, imidazolidine compounds, also known as MacMillan cata-
lysts, have been incorporated into CCOFs to perform heterogeneous asymmetric organocat-
alytic reactions. Zhang et al. prepared a series of CCOFs containing the MacMillan
catalysts, which enabled the
α
-aminooxylation reaction between aldehydes and nitrosoben-
zene, forming a product with 76% isolated yield and 94% ee. The catalytic aldol reaction of
cyclohexanone with 4-nitrobenzaldehyde and 3-nitrobenzaldehyde afforded 92% and 86%
ee, 95% and 94% yield, and 90:10 and 90:10 anti/syn ratio, respectively. Finally, asymmetric
Diels–Alder cycloaddition reaction with cyclopentadiene and (E)-cinnamaldehyde formed
the cycloadduct in 83% isolated yield and excellent selectivity (13:1 endo/exo, 90% ee for
the endo isomer). In all studied reactions, the stereoselectivity and diastereoselectivity was
comparable and even superior to the homogeneous analogs (Scheme 11) [85].
Finally, in a similar work, Wang et al. embedded MacMillan catalysts into a porous or-
ganic framework, forming a family of materials referred to as Mac-CPOPs (Scheme 12) [
50
].
These materials were successfully applied as highly efficient and recoverable heteroge-
neous organocatalysts in the asymmetric Diels–Alder reaction of 1,3-cyclopentadiene with
(E)-cinnamaldehyde with high activity (90–95% yields) and enantioselectivity (75–81% ee
for endo, 71–75% ee for exo).
Catalysts 2023,13, 1042 16 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 17 of 26
Scheme 11. DMTA-TPB1 COF derivatives used for a variety of asymmetric organocatalytic reac-
tions. The reference is included in the brackets.
Finally, in a similar work, Wang et al. embedded MacMillan catalysts into a porous
organic framework, forming a family of materials referred to as Mac-CPOPs (Scheme 12)
[50]. These materials were successfully applied as highly efficient and recoverable hetero-
geneous organocatalysts in the asymmetric Diels−Alder reaction of 1,3-cyclopentadiene
with (E)-cinnamaldehyde with high activity (90–95% yields) and enantioselectivity (75–
81% ee for endo, 71–75% ee for exo).
Scheme 12. Mac-CPOPs used for asymmetric Diels−Alder reaction. The reference is included in the
brackets.
5.2. Hydrogen-Bond Catalysis
Hydrogen-bond catalysis relies on the formation of hydrogen-bond interactions be-
tween catalyst and the substrate. Although the hydrogen-bond organocatalysis is well-
known in homogeneous systems, it has been scarcely studied using porous organic frame-
works as heterogeneous organocatalysts. Merely two reports have emerged, where
Scheme 11.
DMTA-TPB1 COF derivatives used for a variety of asymmetric organocatalytic reactions.
The reference is included in the brackets.
Catalysts 2023, 13, x FOR PEER REVIEW 17 of 26
Scheme 11. DMTA-TPB1 COF derivatives used for a variety of asymmetric organocatalytic reac-
tions. The reference is included in the brackets.
Finally, in a similar work, Wang et al. embedded MacMillan catalysts into a porous
organic framework, forming a family of materials referred to as Mac-CPOPs (Scheme 12)
[50]. These materials were successfully applied as highly efficient and recoverable hetero-
geneous organocatalysts in the asymmetric Diels−Alder reaction of 1,3-cyclopentadiene
with (E)-cinnamaldehyde with high activity (90–95% yields) and enantioselectivity (75–
81% ee for endo, 71–75% ee for exo).
Scheme 12. Mac-CPOPs used for asymmetric Diels−Alder reaction. The reference is included in the
brackets.
5.2. Hydrogen-Bond Catalysis
Hydrogen-bond catalysis relies on the formation of hydrogen-bond interactions be-
tween catalyst and the substrate. Although the hydrogen-bond organocatalysis is well-
known in homogeneous systems, it has been scarcely studied using porous organic frame-
works as heterogeneous organocatalysts. Merely two reports have emerged, where
Scheme 12.
Mac-CPOPs used for asymmetric Diels–Alder reaction. The reference is included in
the brackets.
5.2. Hydrogen-Bond Catalysis
Hydrogen-bond catalysis relies on the formation of hydrogen-bond interactions be-
tween catalyst and the substrate. Although the hydrogen-bond organocatalysis is well-
known in homogeneous systems, it has been scarcely studied using porous organic frame-
works as heterogeneous organocatalysts. Merely two reports have emerged, where CCOFs
have been used for asymmetric amination catalyzed by benzimidazole-derived secondary
amines and asymmetric acetalization catalyzed by BINOL moieties.
In 2019, four structures of chiral COFs were published by Wang et al. based on
benzimidazoles as building blocks for the integration of hydrogen-bond-donor, Brønsted-
acidic, and Brønsted-basic sites. The resulting CCOF materials contain multiple hydrogen-
bonding sites and/or tertiary and secondary amines. These moieties can perform hydrogen-
bond catalysis in a similar manner to other frequently used homogeneous catalysts, such as
Catalysts 2023,13, 1042 17 of 24
(thio)urea and squaramide derivatives. In this work, they performed asymmetric amination
of
β
-keto esters obtaining high yields of up to 98% and enantioselectivities up to 91% ee,
superior to those obtained with homogeneous catalysts (Scheme 13) [86].
Catalysts 2023, 13, x FOR PEER REVIEW 18 of 26
CCOFs have been used for asymmetric amination catalyzed by benzimidazole-derived
secondary amines and asymmetric acetalization catalyzed by BINOL moieties.
In 2019, four structures of chiral COFs were published by Wang et al. based on ben-
zimidazoles as building blocks for the integration of hydrogen-bond-donor, Brønsted-
acidic, and Brønsted-basic sites. The resulting CCOF materials contain multiple hydrogen-
bonding sites and/or tertiary and secondary amines. These moieties can perform hydro-
gen-bond catalysis in a similar manner to other frequently used homogeneous catalysts,
such as (thio)urea and squaramide derivatives. In this work, they performed asymmetric
amination of β-keto esters obtaining high yields of up to 98% and enantioselectivities up
to 91% ee, superior to those obtained with homogeneous catalysts (Scheme 13) [86].
Scheme 13. Series of chiral COFs used for asymmetric amination reaction of β-keto esters. The ref-
erence is included in the brackets.
A recent article reported by Hou et al. presents another example of chiral porous
organic frameworks used for Brønsted acid catalysis. Specifically, they prepared two chi-
ral 3D COFs by condensation of a tetrahedral tetraamine and two linear dialdehydes de-
rived from enantiomerically pure BINOL. Such molecules are moderate Brønsted acids
and induce the acetalization of 2-aminobenzamides with aldehydes to produce dihydro-
quinazolinones (DHQZs) with high enantioselectivity. Supported by DFT calculations,
the 3D porous framework offers a chiral confined microenvironment that is essential for
enantioselective generation of chiral DHQZ products. Interestingly, the heterogeneous or-
ganocatalysts led to beer enantioselectivity (up to 97% ee) than the homogeneous coun-
terparts, which showed null enantioselectivity (Scheme 14) [87].
Scheme 13.
Series of chiral COFs used for asymmetric amination reaction of
β
-keto esters. The
reference is included in the brackets.
A recent article reported by Hou et al. presents another example of chiral porous or-
ganic frameworks used for Brønsted acid catalysis. Specifically, they prepared two chiral 3D
COFs by condensation of a tetrahedral tetraamine and two linear dialdehydes derived from
enantiomerically pure BINOL. Such molecules are moderate Brønsted acids and induce the
acetalization of 2-aminobenzamides with aldehydes to produce dihydroquinazolinones
(DHQZs) with high enantioselectivity. Supported by DFT calculations, the 3D porous
framework offers a chiral confined microenvironment that is essential for enantioselective
generation of chiral DHQZ products. Interestingly, the heterogeneous organocatalysts
led to better enantioselectivity (up to 97% ee) than the homogeneous counterparts, which
showed null enantioselectivity (Scheme 14) [87].
5.3. Other Types of Organocatalysis
Further strategies using chiral heterogeneous organocatalytic materials include a Lewis
base catalyst developed for asymmetric Steglich reaction. In particular, chiral TPB2-COF
material containing 2,3-dihydroimidazo[1,2-a]pyridine (DHIP). The material catalyzed the
asymmetric Steglich rearrangement to oxindole derivatives through the imidazole frag-
ments of TPB2-COF, resulting in yields of 83–95% and 61–84% ee. Importantly, TPB2-COF
showed comparable enantioselectivities and higher distereoselectivities to the homoge-
neous control compound (Scheme 15) [
84
]. To the best of our knowledge, this is the only
reported example of enantioselective basic catalysts using porous organic frameworks.
Catalysts 2023,13, 1042 18 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 19 of 26
Scheme 14. BINOL-derived chiral COFs used in asymmetric synthesis of DHQZs. The reference is
included in the brackets.
5.3. Other Types of Organocatalysis
Further strategies using chiral heterogeneous organocatalytic materials include a
Lewis base catalyst developed for asymmetric Steglich reaction. In particular, chiral
TPB2-COF material containing 2,3-dihydroimidazo[1,2-a]pyridine (DHIP). The material
catalyzed the asymmetric Steglich rearrangement to oxindole derivatives through the im-
idazole fragments of TPB2-COF, resulting in yields of 83–95% and 61–84% ee. Im-
portantly, TPB2-COF showed comparable enantioselectivities and higher distereoselectiv-
ities to the homogeneous control compound (Scheme 15) [84]. To the best of our
knowledge, this is the only reported example of enantioselective basic catalysts using po-
rous organic frameworks.
Scheme 15. Chiral COF used for asymmetric Steglich rearrangement reaction. The reference is in-
cluded in the brackets.
Scheme 14.
BINOL-derived chiral COFs used in asymmetric synthesis of DHQZs. The reference is
included in the brackets.
Catalysts 2023, 13, x FOR PEER REVIEW 19 of 26
Scheme 14. BINOL-derived chiral COFs used in asymmetric synthesis of DHQZs. The reference is
included in the brackets.
5.3. Other Types of Organocatalysis
Further strategies using chiral heterogeneous organocatalytic materials include a
Lewis base catalyst developed for asymmetric Steglich reaction. In particular, chiral
TPB2-COF material containing 2,3-dihydroimidazo[1,2-a]pyridine (DHIP). The material
catalyzed the asymmetric Steglich rearrangement to oxindole derivatives through the im-
idazole fragments of TPB2-COF, resulting in yields of 83–95% and 61–84% ee. Im-
portantly, TPB2-COF showed comparable enantioselectivities and higher distereoselectiv-
ities to the homogeneous control compound (Scheme 15) [84]. To the best of our
knowledge, this is the only reported example of enantioselective basic catalysts using po-
rous organic frameworks.
Scheme 15. Chiral COF used for asymmetric Steglich rearrangement reaction. The reference is in-
cluded in the brackets.
Scheme 15.
Chiral COF used for asymmetric Steglich rearrangement reaction. The reference is
included in the brackets.
The use of light as an excitation source in catalytic reactions is a green and sustainable
alternative for typical organocatalytic reactions. However, its use produces highly reactive
radical species, which hamper the selectivity in catalytic reactions. In fact, we have only
found one recently published article using porous organic frameworks in light-mediated
asymmetric organocatalytic reactions. In 2022, Kan et al. presented a chiral COF for
enantioselective photooxidation of methylphenylsulfide (Scheme 16) [
71
]. They reported a
propargylamine-linked CCOF, (R)-DTP-COF-QA photocatalyst, that displayed the best cat-
alytic activity under 660 nm LED excitation with 94% yield and excellent enantioselectivity
(99% ee) for photooxidation of sulfides to sulfoxides in air and water.
Catalysts 2023,13, 1042 19 of 24
Catalysts 2023, 13, x FOR PEER REVIEW 20 of 26
The use of light as an excitation source in catalytic reactions is a green and sustainable
alternative for typical organocatalytic reactions. However, its use produces highly reactive
radical species, which hamper the selectivity in catalytic reactions. In fact, we have only
found one recently published article using porous organic frameworks in light-mediated
asymmetric organocatalytic reactions. In 2022, Kan et al. presented a chiral COF for enan-
tioselective photooxidation of methylphenylsulfide (Scheme 16) [71]. They reported a pro-
pargylamine-linked CCOF, (R)-DTP-COF-QA photocatalyst, that displayed the best cata-
lytic activity under 660 nm LED excitation with 94% yield and excellent enantioselectivity
(99% ee) for photooxidation of sulfides to sulfoxides in air and water.
Scheme 16. Propargylamine-linked CCOF for asymmetric photocatalytic sulfoxidation reactions.
The reference is included in the brackets.
Phosphine oxides offer an additional organocatalytic platform for asymmetric catal-
ysis as a result of their high nucleophilicity, which enables their function as Lewis bases.
As an example of the application of this concept in heterogeneous asymmetric organoca-
talysis, Mas-Ballesté and coworkers have recently designed a chiral organic material
(COM) based on (R)-BINAP Oxide [88]. This material was successfully applied in the al-
lylation reaction of aromatic aldehydes with allyltrichlorosilane (Scheme 17), leading to
yields and enantiomeric excesses competing with those reported previously in literature
for the molecular (R)-BINAP Oxide catalyst (54% yield and 42% ee for benzaldehyde al-
lylation).
Scheme 16.
Propargylamine-linked CCOF for asymmetric photocatalytic sulfoxidation reactions. The
reference is included in the brackets.
Phosphine oxides offer an additional organocatalytic platform for asymmetric catalysis
as a result of their high nucleophilicity, which enables their function as Lewis bases. As an
example of the application of this concept in heterogeneous asymmetric organocatalysis,
Mas-Ballestéand coworkers have recently designed a chiral organic material (COM) based
on (R)-BINAP Oxide [
88
]. This material was successfully applied in the allylation reaction
of aromatic aldehydes with allyltrichlorosilane (Scheme 17), leading to yields and enan-
tiomeric excesses competing with those reported previously in literature for the molecular
(R)-BINAP Oxide catalyst (54% yield and 42% ee for benzaldehyde allylation).
Catalysts 2023, 13, x FOR PEER REVIEW 21 of 26
Scheme 17. BINAP Oxide-based COM for the asymmetric allylation of aromatic aldehydes.
6. Conclusions
The design of chiral materials through the incorporation of asymmetric moieties into
porous organic frameworks is an emergent research topic. Chiral porous organic frame-
works have been typically explored for chiral separation, and their use in asymmetric or-
ganocatalysis is an emerging field that is gaining relevance.
Porous organic frameworks constitute a broad family of materials that can be subdi-
vided into different types. Typically, crystalline materials are categorized as COFs
whereas, amorphous structures are usually divided in a mixture of different denomina-
tions, such as CMPs, CTFs, and PAFs. As stated in this review, we urge the researchers in
the field to employ unified criteria for the denomination of materials, in order to clearly
distinguish between the different kinds of porous organic frameworks.
Independently of their classification, porous organic frameworks offer a very versa-
tile platform to introduce chiral fragments for different applications. The strategies used
for their synthesis are summarized in this review: (1) use of chiral building blocks; (2)
post-synthetic modification; (3) asymmetric synthesis, and (4) external chiral induction.
Although this research field seems mature, there are many asymmetric structures that re-
main to be explored in this area. In addition, the vast majority of reported structures have
been prepared from chiral building blocks or by post-synthetic modification, and there-
fore, new, exciting materials can be expected to emerge using the lile explored asymmet-
ric synthesis and chiral induction strategies. We therefore envisage future developments
with many other chiral motifs with different degrees of complexity immobilized on po-
rous organic frameworks.
Concerning the chiroptical characterization of COFs, in view of the challenges asso-
ciated with the analysis of solid samples, we encourage the community to give detailed
information concerning aspects such as sample preparation, measurement mode, and
sample holder. Furthermore, comparison of the experimental and theoretical chiroptical
responses, as has been done for other chiral materials [89], could shed more light on the
origin of the chiroptical responses of porous organic frameworks.
As an important application of chiral porous organic frameworks, asymmetric catal-
ysis plays a prominent role. In particular, a modern tendency in catalysis is the avoidance
of metal centers to achieve organocatalytic processes. This field is an ideal research play-
ground for porous organic frameworks. As a consequence, in recent years, examples have
appeared in the literature exploring this idea. In this review, we have compiled this infor-
mation and classified the asymmetric organocatalytic reactions performed by POFs into
Scheme 17. BINAP Oxide-based COM for the asymmetric allylation of aromatic aldehydes.
6. Conclusions
The design of chiral materials through the incorporation of asymmetric moieties
into porous organic frameworks is an emergent research topic. Chiral porous organic
Catalysts 2023,13, 1042 20 of 24
frameworks have been typically explored for chiral separation, and their use in asymmetric
organocatalysis is an emerging field that is gaining relevance.
Porous organic frameworks constitute a broad family of materials that can be subdi-
vided into different types. Typically, crystalline materials are categorized as COFs whereas,
amorphous structures are usually divided in a mixture of different denominations, such
as CMPs, CTFs, and PAFs. As stated in this review, we urge the researchers in the field to
employ unified criteria for the denomination of materials, in order to clearly distinguish
between the different kinds of porous organic frameworks.
Independently of their classification, porous organic frameworks offer a very ver-
satile platform to introduce chiral fragments for different applications. The strategies
used for their synthesis are summarized in this review: (1) use of chiral building blocks;
(2) post-synthetic
modification; (3) asymmetric synthesis, and (4) external chiral induction.
Although this research field seems mature, there are many asymmetric structures that
remain to be explored in this area. In addition, the vast majority of reported structures have
been prepared from chiral building blocks or by post-synthetic modification, and therefore,
new, exciting materials can be expected to emerge using the little explored asymmetric
synthesis and chiral induction strategies. We therefore envisage future developments with
many other chiral motifs with different degrees of complexity immobilized on porous
organic frameworks.
Concerning the chiroptical characterization of COFs, in view of the challenges asso-
ciated with the analysis of solid samples, we encourage the community to give detailed
information concerning aspects such as sample preparation, measurement mode, and
sample holder. Furthermore, comparison of the experimental and theoretical chiroptical
responses, as has been done for other chiral materials [
89
], could shed more light on the
origin of the chiroptical responses of porous organic frameworks.
As an important application of chiral porous organic frameworks, asymmetric cataly-
sis plays a prominent role. In particular, a modern tendency in catalysis is the avoidance
of metal centers to achieve organocatalytic processes. This field is an ideal research play-
ground for porous organic frameworks. As a consequence, in recent years, examples
have appeared in the literature exploring this idea. In this review, we have compiled
this information and classified the asymmetric organocatalytic reactions performed by
POFs into general types of organocatalytic activations. The achieved reactions are Michael
addition, aldol condensation, Diels–Alder, acetalization and amination reactions, Steglich
rearrangement, and light-mediated sulfoxidation. These model reactions offer a limited
scope of the overall possibilities of chiral organocatalytic transformations. Thus, the syn-
thetic potential of POFs is still waiting to be fully developed. With regard to material
design, there are possibilities remaining completely unexplored. One possibility is the
engineering of composite materials using chiral POFs and other polymeric nanometric
materials. This approach could open the door to scale-up the catalytic processes, thus
bringing these materials closer to industrial applicability. Overall, this review offers a
starting point to encourage researchers to move forward to new developments that will
widen the applicability of porous organic frameworks to overcome the common drawbacks
of traditional organocatalytic processes.
Author Contributions:
M.S.-F., J.L.A.-G., L.M.S., R.M.-B. and A.M. have contributed to the search
of literature, conceptualization, and writing of this review. All authors have read and agreed to the
published version of the manuscript.
Funding:
Financial support was provided by the Spanish Government (PID2019–110637RB-I00).
M.S.-F.
thanks Ministerio de Ciencia e Innovación for a FPI contract (PRE2020-092295). A.M. acknowl-
edges the Spanish Government and the European Union through the Funds Next Generation through
grant Maria Zambrano-UAM (CA3/RSUE/2021-00648). L.M.S. acknowledges financial support
from the Spanish Ministry of Science and Innovation through the Ramón y Cajal grant RYC2020-
030414-I. J.L.A.-G. acknowledges the financial support by Ministerio de Ciencia e Innovación through
TED2021-131760B-I00, and Xunta de Galicia through ED431C 2017/51.
Catalysts 2023,13, 1042 21 of 24
Data Availability Statement:
No new data are reported with respect to those published in the
original manuscripts cited in this review paper.
Conflicts of Interest: The authors declare no conflict of interest.
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