Chiral Anion Research Articles

Chiral and racemic BINOL spiroborate anions and radical-cation salt with BEDT-TTF

Sodium salts of the spiroborate anion bis[(1,1′-binaphthalene)-2,2′-diolato-O,O’]borate in enantiopure and racemic forms have been obtained through reaction of BORAX (sodium tetraborate hexahydrate) with the corresponding stereoisomers of BINOL [(1,1′-binaphthalene)-2,2′-diol]. Electrocrystallisationof these saltswith BEDT-TTF produces single crystals of a 1:1 radical-cation salt, (BEDT-TTF){B[1,1′-bis(BINOL)]2}•THF, with the racemic spiroborate anion whilst no crystals were obtained with the enantiopure forms.

Synergistic Photoredox/Palladium Catalyzed Enantioconvergent Carboxylation of Racemic Heterobiaryl (Pseudo)Halides with CO2.

Herein, we report a synergistic photoredox/palladium catalytic system for the efficient enantioconvergent synthesis of axially chiral esters from racemic heterobiaryl (pseudo)halides (bromides/triflates) with CO2 and alkyl bromides under mild conditions. A wide range of axially chiral esters were obtained in good to high yields with excellent enantioselectivities. Detailed mechanistic studies unveiled that the ratio of photocatalyst and palladium catalyst exhibited significant impact on the chemo- and enantioselectivities of the reaction. Kinetic studies and control experiments supported the proposed mechanism involving cascade asymmetric carboxylation followed by SN2 substitution. The achievement of high enantioselectivity relies not only on the choice of synergistic metallaphotoredox catalysts but also on the utilization of alkyl bromides, which trap the generated chiral carboxylic anions in situ, thus preventing their immediate racemization.

Endowing Metal-Organic Coordination Materials with Chiroptical Activity by a Chiral Anion Strategy.

Recently, chiral metal-organic coordination materials have emerged as promising candidates for a wide range of applications in chiroptoelectronics, chiral catalysis, and information encryption, etc. Notably, the chiroptical effect of coordination chromophores makes them appealing for applications such as photodetectors, OLEDs, 3D displays, and bioimaging. The direct synthesis of chiral coordination materials using chiral organic ligands or complexes with metal-centered chirality is very often tedious and costly. In the case of ionic coordination materials, the combination of chiral anions with cationic, achiral coordination compounds through noncovalent interactions may endow molecular materials with desirable chiroptical properties. The use of such a simple chiral strategy has been proven effective in inducing promising circular dichroism and/or circularly polarized luminescence signals. This concept article mainly delves into the latest advances in exploring the efficacy of such a chiral anion strategy for transforming achiral coordination materials into chromophores with superb photo- or electro-chiroptical properties. In particular, ionic small-molecular metal complexes, metal clusters, coordination supramolecular assemblies, and metal-organic frameworks containing chiral anions are discussed. A perspective on the future opportunities on the preparation of chiroptical materials with the chiral anion strategy is also presented.

Asymmetric Ion-Pairing Photoredox Catalysis for Stereoselective Cationic Polymerization under Light Control.

By virtue of noninvasive regulations by light, photocontrolled polymerizations have attracted considerable attention for the precision synthesis of macromolecules. However, a cationic polymerization with simultaneous photocontrol and tacticity-regulation remains elusive so far. Herein, we introduce an asymmetric ion-pairing photoredox catalysis strategy that allows for the development of a stereoselective cationic polymerization with concurrent light regulation for the first time. By employing an ion pair catalyst (PC+/*A-) consisting of a photoredox active cation (PC+) and a sterically confined chiral anion (*A-) to deliver the stereochemical control, the cationic polymerization of vinyl ethers can be achieved with photocontrol and high isotactic selectivity (up to 91% m) at a remarkable low catalyst loading (50 ppm).

Chiral zwitterionic stationary phases based on Cinchona alkaloids and dipeptides – design, synthesis and application in chiral separation

Chiral resolution of polar organic compounds such as amino acids and peptides represents an important chromatographic task due to increasing significance of natural species, which play important signaling and regulatory roles in the living organisms. Despite the number of available chiral stationary phases, this task remains challenging, since not many of the commercially available systems are capable to resolve non-derivatized zwitterionic species. In this study, we present a target-oriented design of a new class of chiral selectors. Pursuing the goal to separate amino acids, and especially short peptides, we have combined Cinchona alkaloids – quinine and quinidine – with three different biogenic dipeptides. We have synthesized six different chiral stationary phases, with selector loading of ∼200 μmol g−1, and tested their chiral recognition capabilities for acidic, basic and zwitterionic analytes using various mobile phases. We have observed that all chiral stationary phases retain the chiral anion exchange capability known for commercially available Cinchona-based columns leading to baseline or partial resolution of six out of ten analytes. The performance in chiral resolution of basic analytes is not optimum due to the weak cation exchange character of the peptidic residue. However, we report on encouraging results in the chiral resolution of short peptides, for which, depending on their structure, we see the chiral resolution of up to three stereoisomers (from four possible) in a preliminary screening.

Catalytic Enantioselective Nucleophilic α-Chlorination of Ketones with NaCl.

Catalytic enantioselective α-chlorination of ketones is a highly desirable process. Different from the conventional approaches that employ corrosive electrophilic chlorination reagents, the process disclosed here employs nucleophilic chloride, aqueous NaCl solution, and even seawater, as green inexpensive chlorine sources. This mechanistically distinct and electronically opposite approach provides facile access to diverse highly enantioenriched acyclic α-chloro ketones that are less straightforward by conventional approaches. With a chiral thiourea catalyst, a range of racemic α-keto sulfonium salts underwent enantioconvergent carbon-chlorine bond formation with high efficiency and excellent enantioselectivity under mild conditions. The sulfonium motif plays a crucial triple role by permitting smooth dynamic kinetic resolution to take place via a chiral anion binding mechanism in a well-designed phase-transfer system. This protocol represents a new general platform for the asymmetric nucleophilic α-functionalization of carbonyl compounds.

Organocatalytic enantio- and diastereoselective assembly of cyclopropane-incorporated polycyclic molecules via isobenzopyrylium ions.

A highly enantio- and diastereoselective organocatalytic formation of cyclopropanes embedded in a complex bridged polycyclic architecture is disclosed. In the presence of a chiral phosphoric acid catalyst, this reaction generates four new stereogenic centers and three new C-C bonds efficiently from isochromene acetals and vinylboronic acids under mild conditions. Different from conventional asymmetric cyclopropanation strategies, this process does not involve carbenes or carbenoids. The complex products can serve as precursors to useful homoenolate equivalents. Mechanistically, DFT studies provided insights into the key transition states of the enantiodetermining [4 + 2] cycloaddition, in which the enantioselectivity is induced by the chiral phosphate counter anion of the isobenzopyrylium intermediate.

Redox-Mediated Enantioselective Interactions in Chiral Metallopolymers Possessing Supramolecular Chirality

Synthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox-mediated electrochemical processes. Redox metallopolymers represent a distinct class of versatile functional materials and have been extensively studied for a wide scope of applications such as membranes, self-assembly, hydrogels, and redox-mediated ion separation. However, many studies have focused on molecularly-selective binding and release of achiral molecules, with limited studies on chirality strategies for enantioselective interactions. Chiral organic anions comprise an important class of biologically-relevant molecules, and their separation and sensing have received intense attention. Here, we introduce new chiral redox-polymers with chiral ferrocene (Fc) building blocks, that can serve as an electro-responsive enantioselective platform for a variety of amino acids and pharmaceutical carboxylates, taking advantage of supramolecular chirality for enhancing electrochemical recognition. Two chiral redox-metallopolymers were designed and synthesized based on Ugi’s amine-inspired chiral monomers containing an amide (poly-1) or amine group (poly-2), and their enantioselective recognitions toward amino acids and pharmaceutical carboxylates were investigated by redox potential shifts using square wave voltammetry. The half potential shift of both poly-(S)-1 and poly-(S)-2 increased more with increasing D-tryptophan concentration than the other enantiomer, L-tryptophan, while the half potential of poly-(R)-1 and poly-(R)-2 shifted more with L-tryptophan than with D-tryptophan, proving the enantioselective interaction of both redox-metallopolymers. Nuclear Overhauser Effect spectroscopy (2D NOESY) and solid-state circular dichroism revealed the emergence of supramolecular chirality of the polymers resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone, and the steric hindrance of the ferrocene within the polymer. The half-peak potential shift demonstrated the remarkable enhancement of enantioselective recognition with tryptophan (Trp) and naproxen, provided by the chiral polymers possessing the supramolecular chirality over the single-site, chiral building block itself. For instance, the two (S) polymers showed the potential shift difference 2.4-2.8 times higher than the corresponding monomers upon the binding of Trp enantiomers. The enantioselective potential shift of the chiral metallopolymer electrodes could determine enantiomeric excess (%ee) of Trp over the range of 0–100%ee. Investigation on solvent polarity and pH effect revealed that the enantioselective mechanism of the chiral redox polymers was attributed to the subtle balance between hydrogen bonding and π-π interaction. We also identified the importance of aromatic groups on the analytes for increasing enantioselectivity of the chiral redox polymers. This work highlights the potential of chiral redox-metallopolymers as platforms for electrochemically-modulated enantioselective processes toward a variety of amino acids and pharmaceutical carboxylates. Figure 1

Chiral Benzene Triimide (BTI) Radical Anions for Probing the Interplay of Unpaired Electron Spin and Chirality.

Herein a series of chiral BTI radical anions bearing different chiral substituents were efficiently prepared by chemical reduction. X-ray crystallography revealed finely-tuned packing and helix assemblies of the radicals by the size of chiral substituents in crystalline state. In accordance with the crystalline-state packing, the powder ESR spectra indicate that 4 a- ⋅CoCp2 + and 4 c- ⋅CoCp2 + π-dimers exhibit thermally excited triplet states arising from strong spin-spin interactions, while discrete 4 b- ⋅CoCp2 + shows a broad doublet-state signal reflecting weak spin-spin interactions. The interplay between the unpaired electron spin and chiral substituents was studied by UV-Vis-NIR spectra, electronic circular dichroism (ECD) and TD DFT calculations. Different NIR absorptions of the radicals attributing to isolated SOMO→LUMO+1 (~889 nm) transitions were recorded. The emergence of Cotton effects (CEs) at the NIR region for 4 c- ⋅CoCp2 + radical enantiomers suggest the interplay between chirality and unpaired electron spin. The origin of the different circularly polarized light absorptions regarding SOMO derived transitions (around 880 nm) was attributed to chiral substitutes regulated electric and magnetic transition dipole moments of the unpaired electron participated transition.

Manipulation of Hierarchical Chiral Self-assembly and Anion Recognition by Supramolecular Systems of β-Glucopyranoside, Pillar[5]arenes, and Polyoxometalates.

Hierarchical chiral structures have broad applications in optical devices, asymmetric catalysis, and biological systems. The delicate balance of various interactions are key to the self-assembly of chiral structures. Herein, a ternary co-assembly consisting of cationic pillar[5]arenes (P5As), anionic β-glucopyranoside (βGlcD/βGlcL), and Anderson-type polyoxometalates (POMs) were constructed. Through adjusting the stoichiometry of βGlcD, the assemblies were effectively controlled to form hierarchical nano-leaf assemblies with twisted nanoribbons in a homochiral direction. The co-assemblies exhibit strong Cotton effects, and successfully induced the chirality of Anderson-type POMs. More interestingly, by changing the central metal in Anderson-type POMs (XMo6 O24 3- (X=Cr, Al, and Ga)), even though the three clusters have the same numbers of charge and size, the hierarchical chirality of the related assemblies varied in the morphology of the assemblies and the Cotton effect in the CD spectra. Results in theoretical calculations and ITC titration indicates that the tiny difference in long-range electrostatic interaction would result in the anion recognition of POMs, modulated by βGlcD through host-guest inclusion and hydrogen bonding in the assembly process.

Stereospecific synthesis of silicon-stereogenic optically active silylboranes and general synthesis of chiral silyl Anions

Silicon-stereogenic optically active silylboranes could potentially allow the formation of chiral silyl nucleophiles as well as the synthesis of various chiral silicon compounds. However, the synthesis of such silicon-stereogenic silylboranes has not been achieved so far. Here, we report the synthesis of silicon-stereogenic optically active silylboranes via a stereospecific Pt(PPh3)4-catalyzed Si–H borylation of chiral hydrosilanes, which are synthesized by stoichiometric and catalytic asymmetric synthesis, in high yield and very high or perfect enantiospecificity (99% es in one case, and >99% es in the others) with retention of the configuration. Furthermore, we report a practical approach to generate silicon-stereogenic silyl nucleophiles with high enantiopurity and configurational stability using MeLi activation. This protocol is suitable for the stereospecific and general synthesis of silicon-stereogenic trialkyl-, dialkylbenzyl-, dialkylaryl-, diarylalkyl-, and alkylary benzyloxy-substituted silylboranes and their corresponding silyl nucleophiles with excellent enantiospecificity (>99% es except one case of 99% es). Transition-metal-catalyzed C–Si bond-forming cross-coupling reactions and conjugate-addition reactions are also demonstrated. The mechanisms underlying the stability and reactivity of such chiral silyl anion were investigated by combining NMR spectroscopy and DFT calculations.

Circularly polarized phosphorescence and photon transport of micro/nanocrystals of ruthenium and iridium complexes with chiral anions

Circularly polarized phosphorescence and photon transport of micro/nanocrystals of ruthenium and iridium complexes with chiral anions

Enhancing Circularly Polarized Phosphorescence via Integrated Top‐Down and Bottom‐Up Approach

AbstractIn the dynamic domain of chiroptical technologies, it is imperative to engineer emitters endowed with circularly polarized luminescence (CPL) properties. This research demonstrates an advancement by employing a combined top‐down and bottom‐up strategy for the simultaneous amplification of photoluminescence quantum yield (Φ) and the luminescence dissymmetry factor (glum). Square‐planar Pt(II) complexes form helical assemblies, driven by torsional strain induced by bis(nonyl) chains. Integration of chiral anions leads these assemblies to prefer distinct helical sense. This arrangement activates the metal‐metal‐to‐ligand charge transfer (MMLCT) transition that is CPL‐active, with Φ and |glum| observing an upswing contingent on the charge number and aryl substituents in chiral anions. Utilizing the soft‐lithographic micromolding in capillaries technique, we could fabricate exquisitely‐ordered, one‐dimensional co‐assemblies to achieve the metrics to Φ of 0.32 and |glum| of 0.13. Finally, our spectroscopic research elucidates the underlying mechanism for the dual amplification, making a significant stride in the advancement of CPL‐active emitters.

Enhancing Circularly Polarized Phosphorescence via Integrated Top-Down and Bottom-Up Approach.

In the dynamic domain of chiroptical technologies, it is imperative to engineer emitters endowed with circularly polarized luminescence (CPL) properties. This research demonstrates an advancement by employing a combined top-down and bottom-up strategy for the simultaneous amplification of photoluminescence quantum yield (Φ) and the luminescence dissymmetry factor (glum). Square-planar Pt(II) complexes form helical assemblies, driven by torsional strain induced by bis(nonyl) chains. Integration of chiral anions leads these assemblies to prefer distinct helical sense. This arrangement activates the metal-metal-to-ligand charge transfer (MMLCT) transition that is CPL-active, with Φ and |glum| observing an upswing contingent on the charge number and aryl substituents in chiral anions. Utilizing the soft-lithographic micromolding in capillaries technique, we could fabricate exquisitely-ordered, one-dimensional co-assemblies to achieve the metrics to Φ of 0.32 and |glum| of 0.13. Finally, our spectroscopic research elucidates the underlying mechanism for the dual amplification, making a significant stride in the advancement of CPL-active emitters.

Anion-Regulated Hierarchical Self-Assembly and Chiral Induction of Metallo-Tetrahedra.

The precise control over hierarchical self-assembly of superstructures relying on the elaboration of multiple noncovalent interactions between basic building blocks is both elusive and highly desirable. We herein report a terpyridine-based metallo-cage T with a tetrahedral motif and utilized it as an efficient building block for the controlled hierarchical self-assembly of superstructures in response to different halide ions. Initially, the hierarchical superstructure of metallo-cage T adopted a hexagonal close-packed structure. By adding Cl- /Br- or I- , drastically different hierarchical superstructures with highly-tight hexagonal packing or graphite-like packing arrangements, respectively, have been achieved. These unusual halide-ion-triggered hierarchical structural changes resulted in quite distinct intermolecular channels, which provided new insights into the mechanism of three-dimensional supramolecular aggregation and crystal growth based on macromolecular construction. In addition, the chiral induction of the metallo-cage T can be realized with the addition of chiral anions, which stereoselectively generated either PPPP- or MMMM-type enantiomers.

Anion‐Regulated Hierarchical Self‐Assembly and Chiral Induction of Metallo‐Tetrahedra

AbstractThe precise control over hierarchical self‐assembly of superstructures relying on the elaboration of multiple noncovalent interactions between basic building blocks is both elusive and highly desirable. We herein report a terpyridine‐based metallo‐cage T with a tetrahedral motif and utilized it as an efficient building block for the controlled hierarchical self‐assembly of superstructures in response to different halide ions. Initially, the hierarchical superstructure of metallo‐cage T adopted a hexagonal close‐packed structure. By adding Cl−/Br− or I−, drastically different hierarchical superstructures with highly‐tight hexagonal packing or graphite‐like packing arrangements, respectively, have been achieved. These unusual halide‐ion‐triggered hierarchical structural changes resulted in quite distinct intermolecular channels, which provided new insights into the mechanism of three‐dimensional supramolecular aggregation and crystal growth based on macromolecular construction. In addition, the chiral induction of the metallo‐cage T can be realized with the addition of chiral anions, which stereoselectively generated either PPPP‐ or MMMM‐type enantiomers.

Hydrogen-Bonded Matched Ion Pair Gold(I) Catalysis.

The enantioselective reaction of 1,6-enynes with O-, N-, and C-nucleophiles has been developed by matched ion pair gold(I) catalysis in which the chiral gold(I) cation and anion are H-bonded through a urea group. Very high levels of enantiocontrol are achieved (up to >99:1 er) for a broad scope of substrates. DFT studies demonstrate the importance of the H-bond donor group in anchoring the matched chiral cation- and anion-favoring additional noncovalent interactions.

Discovery and Development of the Enantioselective Minisci Reaction.

ConspectusThe class of reactions now known as Minisci reactions is broadly defined as the addition of nucleophilic carbon-based radicals to basic heteroarenes with subsequent rearomatization to form a new carbon-carbon bond. Since the pioneering work of Minisci in the 1960s and 1970s, these reactions are now widely used in medicinal chemistry due to the ubiquity of basic heterocycles in druglike molecules. One of the long-standing challenges of Minisci chemistry has been that of regioselectivity due to the mixtures of positional isomers commonly obtained on many substrates if there is a choice between similarly activated sites. At the outset of the work described herein, we hypothesized that it may be possible to tackle this using a catalytic strategy whereby a bifunctional Brønsted acid catalyst simultaneously activates the heteroarene and engages attractive non-covalent interactions with the incoming nucleophile, resulting in a proximal attack. Using chiral BINOL-derived phosphoric acids, we not only were able to achieve this goal of regiocontrol but also discovered that we could control the absolute stereochemistry at the new stereocenter formed when prochiral α-amino radicals were employed. At the time, this discovery was unprecedented in the context of Minisci reactions.This Account details the discovery of this protocol and the further development, expansion, and investigations into the mechanism that we have carried out since then, several in collaboration with other research groups. Collaborative efforts have involved an expansion of the scope to diazines guided by multivariate statistical analysis through the development of a predictive model (collaboration with Sigman). Also, a mechanistic study involving detailed DFT analysis (collaboration with Goodman and Ermanis) unveiled the selectivity-determining step as being the deprotonation of a key cationic radical intermediate by the associated chiral phosphate anion. We have additionally carried out a number of synthetic developments of the protocol such as removing the need to prefunctionalize the radical nucleophile; hydrogen-atom transfer can be used to enable a formal coupling of two C-H bonds to form a C-C bond while retaining high enantio- and regioselectivity. Most recently, we have been able to expand the protocol so that α-hydroxy radicals can be used: until this point, all examples had concerned α-amino radicals. Again, HAT was used to generate the α-hydroxy radicals, and DFT studies carried out in collaboration (Ermanis) provided mechanistic insights.Since our original report, there have appeared a number of exciting developments from other research groups whereby the protocol has been applied to new substrates or using different precursors to generate the requisite α-amino radical. There have also been several examples in which alternative photocatalyst systems have been used to reduce the redox-active esters in the original enantioselective Minisci protocol. While primarily an Account, these contributions from other research groups will be covered briefly for context toward the end of the article.

Highly Enantioselective Radical Cation [2 + 2] and [4 + 2] Cycloadditions by Chiral Iron(III) Photoredox Catalysis.

Radical cations show a unique reactivity that is fundamentally different from that of conventional cations and have thus attracted considerable attention as alternative cationic intermediates for novel types of organic reactions. However, asymmetric catalysis to promote enantioselective radical cation reactions remains a major challenge in contemporary organic synthesis. Here, we report that the judicious design of an ion pair consisting of a radical cation and a chiral counteranion induces an excellent level of enantioselectivity. This strategy was applied to enantio-, diastereo-, and regioselective [2 + 2] cycloadditions, as well as enantio-, diastereo-, and regioselective [4 + 2] cycloadditions, by using chiral iron(III) photoredox catalysis. We anticipate that this strategy has the potential to expand the use of several mature chiral anions to develop numerous unprecedented enantioselective radical cation reactions.

New Chemistry of Chiral 1,3-Dioxolan-4-Ones.

(2S,5S)-5-Phenyl-2-t-butyl-1,3-dioxolan-4-one, readily derived from mandelic acid, undergoes the Michael addition to butenolide and 4-methoxy-β-nitrostyrene with the absolute configuration of the products confirmed by X-ray diffraction in each case. In the former case, thermal fragmentation gives the phenyl ketone, thus illustrating use of the dioxolanone as a chiral benzoyl anion equivalent. The Diels-Alder cycloaddition chemistry of (2S)-5-methylene-2-t-butyl-1,3-dioxolan-4-one, derived from lactic acid, has been further examined with the X-ray structures of four adducts determined. In one case, thermal fragmentation of the adduct gives a chiral epoxy ketone resulting from the dioxolanone acting as a chiral ketene equivalent, while in others the products give insight into the mechanism of the dioxolanone fragmentation process.