Catalysts by virtue of lowering the activation barrier helps in the completion of a chemical reaction in a lesser amount of time without being themselves consumed. Utilizing the diverse non-covalent interactions in the design and construction of catalysts, recently anion-π interactions were also introduced, giving rise to an emerging field of anion-π catalysis. In the newly constructed anion-π catalysts, significant lowering of activation energy occurs by virtue of anion-π interactions. Till now, several important reactions generating chiral centers have been carried out on the π-acidic surfaces of anion-π catalysts, thereby revealing the significance of anion-π catalysis in the domain of asymmetric synthesis. The motive of this chapter is to highlight the role of anion-π catalysis in asymmetric synthesis and we surely believe that it will offer new opportunities in supramolecular chemistry.
- anion-π catalysis
- anion-π interaction
- asymmetric synthesis
- cascade reaction
- enolate chemistry
- naphthalene diimide
From the past few decades, non-covalent interactions have gained the new heights in the domain of catalysis and supported to construct functional systems of fundamental significance. Infact, the application of non-covalent interactions in the field of catalysis are nowadays studied under a separate branch of science known as supramolecular catalysis . By virtue of non-covalent supramolecular interactions, not only the catalytic efficiency of the existed catalysts has been improved but the novel organocatalysts have also been developed . Amongst various supramolecular interactions, the cation-π and anion-π interactions are most promising in the field of catalysis. In cation-π interactions, the cation interacts with π-basic aromatic systems possessing negative quadrupole moment (Qzz < 0), whileas in case of recently recognized anion-π interactions, the anion interacts with π-acidic aromatic systems possessing positive quadrupole moment (Qzz > 0). For example, benzene (Qzz = -9B) is π-basic in nature which makes it suitable to interact with cations through cation-π interactions (Figure 1) . However, the interaction of anion with this system looks counterintuitive, as it will lead to repulsion between anion and π-electron cloud of benzene. For this purpose, researchers have inverted the intrinsic negative Qzz of aromatic systems into positive one (Qzz > 0) by attaching strong electron withdrawing substituents on aromatic systems. By virtue of this, they have generated various π-acidic aromatic scaffolds possessing strong positive quadrupole moment, which in turn interact with diverse anions through anion-π interactions (Figure 1) .
The recognition of anions is of paramount importance as anions are abundant in nature and play very essential biological role through participation in enzymatic reactions. The transport of anions across biomembranes during different biochemical events makes their recognition even more important . Scientists around the globe are constructing diverse artificial anion receptors, which mimic the function of biosystems and involve anion-π interactions besides other non-covalent interactions in the recognition phenomenon of anions . From the recent theoretical, computational, and experimental investigation, it has been observed that anion-π interactions have shown a promising role in supramolecular catalysis and has given rise to a new concept of anion-π catalysis. The emerging field of anion-π catalysis has not yet much explored in chemistry and until now only few reports are available in literature [7, 8, 9]. This is because of the fact that anion-π interactions have recently got experimental evidence, and also there is a dearth of π-acidic aromatic systems being the supreme prerequisite of these interactions . Theoretical and experimental studies have revealed that anion-π catalysis works on the fundamental principle of the stabilization of anionic transition state on π-acidic aromatic surfaces. This stabilization in turn lowers the activation barrier of a particular reaction and hence leads to the formation of a selective desired product quickly under normal reaction conditions [11, 12]. The first evidence of anion-π catalysis came from the Matile’s group after carrying out the transmembrane transport of anion by virtue of anion-π interactions . Researchers have developed various anion-π catalysts by adapting different synthetic methodologies [7, 8, 9]. It is not feasible herein to discuss such methodologies, but for the convenience of the readers, we have assembled a group of anion-π catalysts used in this chapter (Figure 2) [11, 12]. In this chapter, we will discuss the role of these anion-π catalysts in various chemical reactions like Kemp elimination, Michael-addition reactions, Diels-Alder reactions, and epoxide ring opening reactions followed by ether and polyether cascade cyclization reactions. Mostly these reactions involve the generation of chiral centers and hence are of prime importance in the arena of asymmetric synthesis.
2. Kemp elimination: a classical tool for anion-π catalysis
The Kemp elimination is a well-known reaction, which involves the abstraction of a proton from the carbon of the benzisoxazole substrate with the help of a catalytic amount of base. This reaction plays an essential biological role and has been documented as an ideal conventional tool for anion-π catalysis by Matile’s group. They have carried out this reaction by virtue of the NDI-based anion-π catalysts possessing covalently linked carboxylate base and a solubilizer (alkyl tail) on the π-acidic surface . There occurs the formation of phenolate in the anionic transition-state
3. Michael-addition reactions through anion-π catalysis
Michael-addition, a powerful tool in organic synthesis is a nucleophilic addition reaction which involves the addition of a nucleophile to an
On the other hand, experimental studies have revealed that Michael-addition between malonic acid half thioester (
By virtue of positive molecular electrostatic potential (MEP), the fullerene (C60) is considered as a potential candidate for anion-
Currently, catalysis by means of an electric field has gained a significant interest in molecular transformations, stereoselectivities, and multistep organic synthesis . Electric fields and potentials besides accelerating the reactions have also been shown to activate the conventional catalysts, enzymes, and catalytic pores . Recent studies have revealed that electric fields can just function as a remote control for anion-π catalysts. It has been observed that immobilization of anion-
In another event, Matile and teammates have used foldamers (
Moreover, quite recently Matile’s group has stapled short peptides to NDI-based anion-π catalysts (
Anion-π catalysis play a significant role in the asymmetric synthesis and leads to the generation of chiral isomers selectively. In this regard, the same group has also incorporated NDI moiety in between a carboxylate base and a proline unit for the construction of an anion-π catalyst (
On the other occasion, the same group has also carried out asymmetric synthesis on anion-π catalytic surfaces of perylenediimides (PDIs). It has been observed that twist in the π-acidic surface determines the catalytic activity of these PDI-based anion-π catalysts in case of Michael addition reactions of enolates and enamines. This is in contrary to the catalytic activity of NDIs, where reducibility of π-surfaces plays a prominent role. Experimental studies have revealed asymmetric addition of
In another event, Matile’s group has also observed anion-π interactions in anion-π enzymes after preparing anion-π enzyme artificially. They have equipped a range of anion-π catalysts with a water-soluble vitamin known as biotin in order to determine the selectivity of Michael addition product (
More interestingly, the same group has reported innovative anion-π catalysis on the surfaces of carbon nanotubes and synthesized selective addition products on their π-acidic surfaces (Figure 13). Studies have revealed that tertiary amine based multi-walled carbon-nanotubes (MWCNT) display much higher efficiency as compared to single-walled carbon nanotubes (SWCNT). This is by virtue of the fact that between and along the nanotubes of MWCNT, there exists a polarizibility induced π-acidic surfaces .
4. Anion-π catalysis in action for Diels-Alder reactions
The Diels-Alder reaction discovered in 1928 (Noble prize 1950), a pericyclic [4 + 2] cycloaddition reaction unites diene and dienophile in an atom economic way to yield corresponding Diels-Alder adducts in a regio- and stereoselective manner. Interestingly, this reaction has been used for the synthesis of a plethora of medicinal as well as other compounds. With these thoughts in mind, Matile’s group in recent years has successfully carried out Diels-Alder reactions by means of anion-π catalysts based on fullerenes . During the experimental studies, they have got thermodynamically more stable
There is no doubt that the main objective of anion-π catalysis is to discover the reactions of indefinite reactivities and the Diels-Alder reactions of anionic nature offers a first indication in this direction. Matile’s group has revealed that that the reaction between
5. Cascade reactions through anion-π catalysis
Cascade reactions are also known as domino or tandem reactions and comprises of at least two simultaneous consecutive reactions. Herein, the preceding reaction develops a chemical functionality on which a subsequent reaction occurs. Such reactions are of vital importance in the synthesis of complex natural products possessing various chiral centers . During these cascade cyclization reactions, charge displacements are stretched over longer distances. Matile’s group has revealed that anion-π catalysis in terms of anion-π interactions is highly capable in the stabilization of these charge displacements. With the help of anion-π catalysis, the cascade reactions on the π-acidic catalytic surface leads to generation of bicyclic asymmetric products possessing four chiral centers (Figure 16). Moreover, cascade cyclization reactions through anion-π catalysis are also in action in the generation of asymmetric cyclohexane moieties containing five chiral centers generated in a single step on π-acidic catalytic surface (Figure 17). The concept of anion-π catalysis also play a central role in other cascade reactions on the π-acidic aromatic surface. For instance, the reaction of
Epoxide ring opening followed by ether and polyether cascade cyclic reactions are considered as conventional reactions in chemical and biological sciences. Nowadays, these reactions are also considered as attractive tools for anion-π catalysis. To this context, Matile’s group has reported some functional systems which operate through anion-π interactions and show autocatalysis. Studies have revealed that aromatic π-acidic surfaces involve epoxide ring opening followed by ether cyclization without any activating group (Figure 19) . Quite recently, they have also observed exceptional high autocatalysis on the π-acidic surfaces of hexafluorobenzene and substituted NDI’s as far as epoxide ring opening followed by cyclisation reactions are concerned. This unique characteristic of autocatalysis not only adds complexity to reaction mechanisms but also offers intriguing perspectives towards future developments [38, 39].
Besides the above-mentioned catalytic relevances of anion-π interactions in the domain of catalysis, amidation reactions driven by light have also been carried out by means of these interactions. It has been observed that anion-π interactions helps in the stabilization of transient complex formed between electron deficient moiety
6. Conclusions and outlook
Anion-π catalysis in general operates on the fundamental principle of anionic transition state stabilization on π-acidic aromatic surfaces and offers a novel approach towards diverse molecular transformations. Over the past seven years, steady advancement has been made in the domain of anion-π catalysis with regard to the design of catalyst and the scope of the reaction. Considering the significance of polarizability, it is believed that there will be the emergence of more hidden occurrences of immature anion-π catalysis in the near future. The unconventional anion-π catalysis gains an optimistic outlook from the immense impact of current developments made with conventional cation-π and ion-pairing interactions. It is thus expected that anion-π catalysis will eventually offer new mechanisms and access to new reactivities. However so far, anion-π catalysis fails in the general expectation to produce novel products. Nevertheless, efforts are being carried out all across the globe to meet the general expectations of anion-π catalysis to offer access to novel products with exceptional features, which are far outside the scope of conventional catalysis.
We are grateful to DST-SERB New Delhi for financial support (Project File no. ECR/2017/000821). I. A. R. thanks CSIR, New Delhi for the award of the JRF and SRF. R. A. thanks Jamia Millia Islamia, New Delhi for providing the necessary research facilities.
Conflicts of interest
The authors declare no conflicts of interest.