Chirality in the Absence of Rigid Stereogenic Elements: The Absolute Configuration of Residual Enantiomers of C3‐Symmetric Propellers

Two new tris(aryl)phosphane oxides existing as configurationally stable residual enantiomers have been synthesised and their racemates resolved by semipreparative HPLC on a chiral stationary phase (CSP HPLC). One of them, recognised as a conglomerate, could be resolved by fractional crystallisation at a preparative scale level. In this case, the absolute configuration of the propeller‐shaped molecule was determined by anomalous X‐ray scattering. The problem of the correlative assignment of the absolute configuration to all known C₃‐symmetric three‐bladed propeller‐shaped molecules existing as stable residual enantiomers is discussed. The configurational stability of the new chiral phosphane oxides and of the corresponding phosphanes was evaluated by CD signal decay kinetics and dynamic ¹H NMR spectroscopy. The racemisation barriers in phosphanes were found about 10 kcal mol^?1 lower than those found for the corresponding oxides, though geometry and inter‐ring gearing would be very similar in the two series. Configurational stability of residual tris(aryl)phosphanes was found to be influenced by the electronic availability of the phosphorus centre, as evaluated by electrochemical CV experiments.     

Chirality in the Absence of Rigid Stereogenic Elements: The Design of Configurationally Stable C3‐Symmetric Propellers

Residual stereoisomerism is a form of stereoisomerism scarcely considered so far for applicative purposes, though extremely interesting, since the production of stereoisomers does not involve classical rigid stereogenic elements. In three‐bladed propeller‐shaped molecules, a preferred stereomerization mechanism, related to the correlated rotation of the rings, allows the free interconversion of stereoisomers inside separated sets (the residual stereoisomers) that can interconvert through higher energy pathways. In light of possible future applications as chiral ligands for transition metals in stereoselective processes, some C₃‐symmetric phosphorus‐centered propellers, which could exist as residual enantiomers, are synthesized and the possibility of resolving their racemates into residual antipodes is explored. While the tris(aryl)methanes are configurationally stable at room temperature, only selected tris(aryl)phosphane oxides display a configurational stability high enough to allow resolution by HPLC on a chiral stationary phase (CSP HPLC) at a semipreparative level at room temperature. Stability was evaluated through different techniques (circular dichroism (CD) signal decay, dynamic CSP HPLC (CSP DHPLC), dynamic NMR analysis (DNMR)) and the results compared and discussed. Phosphanes were found much less stable than the corresponding phosphane oxides, for which preliminary calculations suggest that the three‐ring‐flip enantiomerization mechanism (M₀) would be easier than phosphorus pyramidal inversion. The parameters affecting the configurational stability of the residual enantiomers of C₃‐symmetric propellers are discussed.     

Stereocontrolled Synthesis of Chiral Heteroaromatic Propellers with Small Optical Bandgaps

Chiral heteroaromatic propellers based on radially π‐extended hexapyrrolohexaazacoronenes were obtained in a concise synthesis from suitably functionalized donor–acceptor monopyrroles. To overcome steric hindrance, a new cyclodehydrogenation method was developed, and it uses bromine electrophiles as oxidative coupling agents instead of the commonly employed high‐potential oxidants. The new reaction offers high yields of propeller‐shaped targets, even for electron‐deficient precursors, and shows electrophile‐dependent stereoselectivity, with N‐bromosuccinimide and dibromine yielding, respectively D₆‐ and C₂‐symmetric products. The propeller azacoronenes are chiral and can be separated into configurationally stable enantiomers. In addition to providing steric bulk, peripheral functionalization considerably affects the electronic properties of the propellers, which exhibit reduced optical and electrochemical band gaps, and a more clearly defined electroreduction behavior.     

A New Chiral Binaphthalene‐Based Fluorescence Polymer Sensor for the Highly Enantioselective Recognition of Phenylalaninol

A new (S)‐binaphthalene‐based polymer ( P ‐ 1 ) was synthesized by the polymerization of 5,5′‐((2,5‐dibutoxy‐1,4‐phenylene)bis(ethyne‐2,1‐diyl))bis(2‐hydroxy‐3‐(piperidin‐1‐ylmethyl) benzaldehyde ( M ‐ 1 ) with (S)‐2,2′‐dimethoxy‐(1,1′‐binaphthalene)‐3,3′‐diamine ( M ‐ 2 ) through the formation of a Schiff base; the corresponding chiral polymer ( P ‐ 2 ) could be obtained by the reduction of polymer P ‐ 1 with NaBH₄. Chiral polymer P ‐ 1 exhibited a remarkable “turn‐on” fluorescence‐enhancement response towards (D )‐phenylalaninol and excellent enantioselective recognition behavior with enantiomeric fluorescence difference ratios (ef) as high as 8.99. More importantly, chiral polymer P ‐ 1 displays a bright blue fluorescence color change upon the addition of (D )‐phenylalaninol under a commercially available UV lamp, which can be clearly observed by the naked eye. On the contrary, chiral polymer P ‐ 2 showed weaker enantioselective fluorescence ability towards the enantiomers of phenylalaninol.     

Natural terpene derivatives as new structural task‐specific ionic liquids to enhance the enantiorecognition of acidic enantiomers on teicoplanin‐based stationary phase by high‐performance liquid chromatography

We present the specific cooperative effect of a semisynthetic glycopeptide antibiotic teicoplanin and chiral ionic liquids containing the (1R ,2S ,5R )‐(–)‐menthol moiety on the chiral recognition of enantiomers of mandelic acid, vanilmandelic acid, and phenyllactic acid. Experiments were performed chromatographically on an Astec Chirobiotic T chiral stationary phase applying the mobile phase with the addition of the chiral ionic liquids. The stereoselective binding of enantiomers to teicoplanin in presence of new chiral ionic liquids were evaluated applying thermodynamic measurements and the docking simulations. Both the experimental and theoretical methods revealed that the chiral recognition of enantiomers in the presence of new chiral ionic liquids was enthalpy driven. The changes of the teicoplanin conformation occurring upon binding of the chiral ionic liquids are responsible for the differences in the standard changes in Gibbs energy (ΔG ⁰) values obtained for complexes formed by the R and S enantiomers and teicoplanin. Docking simulations revealed the steric adjustment between the chiral ionic liquids cyclohexane ring (chair conformation) and the β‐d ‐glucosamine ring of teicoplanin and additionally hydrophobic interactions between the decanoic aliphatic chain of teicoplanin and the alkyl group of the tested salts. The obtained terpene derivatives can be considered as “structural task‐specific ionic liquids” responsible for enhancing the chiral resolution in synergistic systems with two chiral selectors.     

Stable Enantiomers Displaying Thermally Activated Delayed Fluorescence: Efficient OLEDs with Circularly Polarized Electroluminescence

Aromatic‐imide‐based thermally activated delayed fluorescent (TADF) enantiomers, (+)‐(S,S)‐ CAI‐Cz and (?)‐(R,R)‐ CAI‐Cz , were efficiently synthesized by introducing a chiral 1,2‐diaminocyclohexane to the achiral TADF unit. The TADF enantiomers exhibited high PLQYs of up to 98 %, small ΔE_ST values of 0.06 eV, as well as obvious temperature‐dependent transient PL spectra, thus demonstrating their excellent TADF properties. Moreover, the TADF enantiomers showed mirror‐image CD and CPL activities. Notably, the CP‐OLEDs with CPEL properties based on the TADF enantiomers not only achieved high EQE values of up to 19.7 and 19.8 %, but also displayed opposite CPEL signals with g_EL values of ?1.7×10^?3 and 2.3×10^?3, which represents the first CP‐OLEDs, based on the enantiomerically pure TADF materials, having both high efficiencies and intense CPEL.     

Inherently Chiral Spider‐Like Oligothiophenes

The racemate of an inherently chiral “spider‐like” octathiophene monomer T8₃ , in which chirality is generated by torsion in its backbone, was synthesized. The racemate was resolved into configurationally stable antipodes by HPLC on a chiral stationary phase. Electrooxidation of the enantiomers resulted in materials displaying high enantiorecognition ability towards the antipodes of some chiral probes. Moreover, the T8₃ racemate demonstrated great aptitude to stimulate formation of 3D rigid architectures if used as a cross‐linking monomer for molecular imprinting. This feature was exploited to devise a molecularly imprinted polymer‐based chemosensor selective for a thymine–adenine oligonucleotide.     

Tribenzotriquinacenes Based on Regioselective Bis‐formylation: Optical Resolution and Absolute Configuration of Inherently Chiral Derivatives and Synthesis of the First Cyclophane‐Type Tribenzotriquinacene Dimers

Enantiomerically pure tribenzotriquinacenes (TBTQs) bearing two monofunctionalized aromatic nuclei were synthesized for the first time and their optical properties and absolute configuration determined. A remarkably regioselective bis‐formylation of the fully bridgehead methylated parent TBTQ hydrocarbon with MeOCHCl₂/TiCl₄ afforded a mixture of two C_s‐symmetrical (achiral) difunctionalized derivatives together with one C₁‐symmetrical (chiral) isomer. Reduction and subsequent column chromatography furnished the three respective benzylic TBTQ dialcohols. Optical resolution of the racemic 2,6‐bis(hydroxymethyl) derivative was achieved via the diastereomeric (R)‐1,1′‐bi‐2‐naphthol ethers and the absolute configuration of the enantiomers was determined by CD exciton model analysis. The electronic circular dichroism (ECD) spectra and the specific rotation of the enantiomers were found to agree with the results of DFT calculations. Among the C_s‐symmetrical isomers, the “proximal” 2,11‐dialdehyde and the corresponding benzylic dialcohol were identified by 2D NMR spectroscopy and X‐ray crystallographic analysis, respectively, and used as the starting point for the synthesis of several novel dithiametacyclophanes. These include the first “dimeric” tribenzotriquinacene‐based cyclophanes bearing the bowls of the two TBTQ units attached to each other in a syn (concave–concave) or anti (convex–concave) configuration. The usefulness of such thiacyclophanes as fluorescent chemosensors for different metal ions is also demonstrated.     

Hg2+‐Induced In Situ Generated Radical Cation of (S)‐BINOL‐Based Polymer for Highly Enantioselective Recognition of Phenylalaninol

Phenylalaninol enantiomers are one of the most important chiral compounds due to its presence in biologically active molecules and pharmaceutical products. In this paper, a novel chiral fluorescence polymer sensor incorporating (S)‐BINOL and oligomeric aniline via a nucleophilic addition–elimination reaction is designed and synthesized. Polymer sensor exhibits “turn‐off” fluorescence quenching response upon the addition of Hg²⁺, and “turn‐on” moderate fluorescence enhancement behavior towards phenylalaninol enantiomers. Meanwhile, this kind of (S)‐BINOL‐based polymer sensor can exhibit highly selective enantioselective recognition response towards (L)‐phenylalaninol upon the addition of Hg²⁺ and the value of ef can reach as high as 5.4, which can be attributed to the formation of in situ generated radical cation arisen from oligomeric aniline moiety by Hg²⁺ induction.

     

Magnetic Coupling in Enantiomerically Pure Trinuclear Helicate‐Type Complexes Formed by Hierarchical Self‐Assembly

Based on chiral, enantiomerically pure 7‐[(S)‐phenylethylurea]‐8‐hydroxyquinoline ( 1 ‐H), trinuclear helicate‐type complexes 2 – 5 are formed with divalent transition‐metal cations. X‐ray structural analyses reveal the connection of two monomeric complex units [M( 1 )₃]^? (M=Zn, Mn, Co, Ni) by a central metal ion to form a “dimer”. Due to the enantiopurity of the ligand, the complexes are obtained as pure enantiomers, resulting in pronounced circular dichroism (CD) spectra. Single‐ion effects and intra‐ and intermolecular coupling are observed with dominating ferromagnetic coupling in the case of the cobalt(II) and nickel(II) and dominating antiferromagnetic coupling in the case of the manganese(II) complex.     

A Quintuple [6]Helicene with a Corannulene Core as a C5‐Symmetric Propeller‐Shaped π‐System

The synthesis and structural analysis of a quintuple [6]helicene with a corannulene core is reported. The compound was synthesized from corannulene in three steps including a five‐fold intramolecular direct arylation. X‐ray crystallographic analysis revealed a C₅‐symmetric propeller‐shaped structure and one‐dimensional alignment in the solid state. The enantiomers of the quintuple [6]helicene were successfully separated by HPLC, and the chirality of the two fractions was identified by CD spectroscopy. A kinetic study yielded a racemization barrier of 34.2 kcal mol^?1, which is slightly lower than that of pristine [6]helicene. DFT calculations indicate a rapid bowl‐to‐bowl inversion of the corannulene moiety and a step‐by‐step chiral inversion pathway for the five [6]helicene moieties.     

The Dual‐Stereocontrol Mechanism: Heteroselective Polymerization of rac‐Lactide and Syndioselective Polymerization of meso‐Lactide by Chiral Aluminum Salan Catalysts

We describe alkoxo‐aluminum catalysts of chiral bipyrrolidine‐based salan ligands that follow the dual‐stereocontrol mechanism wherein a given combination of stereogeneities at the metal site and the proximal center of the last inserted lactidyl (“match”) is active towards lactide having a proximal stereogenic center of the opposite configuration, while the diastereomeric combination of stereogeneities (“mismatch”) is inactive towards any lactide. Polymerization of rac‐LA by the enantiomerically pure catalysts was sluggish and gave stereoirregular poly(lactic acid) (PLA) because selective insertion to a match diastereomer gives a mismatch diastereomer. The racemic catalysts showed higher activity and led to highly heterotactic PLA following polymeryl exchange between two mismatched catalyst enantiomers. A succession of match diastereomers in selective meso‐LA insertions led to syndiotactic PLAs reaching a syndiotacticity degree of α=0.96. This polymer featured a T_m of 153 °C matching the highest reported value, and the highest crystallinity (ΔH_m=56 J g^?1) ever reported for syndiotactic PLA.     

Gas Chromatographic Separation of Enantiomers on Optically Active Metal-Complex-Free Stationary Phases. New Analytical Methods (24)

If a stationary phase A employed in gas chromatography possesses a chemical affinity for substance B, which is to be separated, then the retention behavior is not only determined by the normal physical equilibrium between the gas and liquid phases but also by the chemical equilibrium A + B ? AB. If A and B are chiral and A is present in optically active form while B is a racemic mixture, then it is possible to achieve a gas chromatographic enantiomer resolution without the isolation of diastereomers: the energetically different diastereomeric associates A_R B_R and A_R B_S are formed rapidly and reversibly. This enantiospecific resolution principle was first demonstrated in 1966 by the quantitative resolution of racemic amino acid derivatives on optically active peptide phases in analogy to the well-known stereospecificity of enzymes. The anchoring of the chiral resolving agent to thermally stable polysiloxanes together with the employment of high resolution capillary columns and the use of appropriate derivatization strategies has led to the development of enantiomer resolution into a routine modern method for many classes of substances. The demonstration of enantiospecificity in the gas chromatographic separation process is of fundamental interest, and its systematic study can result in a significant contribution to the understanding of the molecular mechanism of “chiral recognition”. The gas chromatographic separation of enantiomers has also proven to be an accurate and sensitive method for the determination of the enantiomeric composition of natural products and products of enantioselective transformations (asymmetric syntheses, “chiral pool” transformations, kinetic resolutions, biomimetic reactions) and for the quantification of racemization, e.g. in the synthesis and hydrolysis of peptides. In any research program devoted to the phenomenon of chirality, the gas chromatographic separation of the enantiomers of volatile compounds constitutes an indispensable modern instrumental technique.     

Chiral Recognition of Tryptophan Enantiomers Based on β‐Cyclodextrin‐platinum Nanoparticles/Graphene Nanohybrids Modified Electrode

The nanohybrids which based on β‐cyclodextrin, platinum nanoparticles and graphene (β‐CD‐PtNPs/GNs) were successfully synthesized and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT‐IR) and electrochemical impedance spectroscopy (EIS). Then they were used to construct a simple and reliable chiral sensing platform to interact with tryptophan (Trp) enantiomers. Differential pulse voltammetry (DPV) was used to investigate the stereo selectivity of β‐CD‐PtNPs/GNs to Trp enantiomers. After interaction, the obvious difference of peak currents of L‐Trp and D‐Trp was obtained, indicating this strategy could be employed to chiral recognition of Trp enantiomers. Under the optimum conditions, the chiral sensor exhibited a good linear response to Trp enantiomers in a linear range of 5.0×10^?5 to 5.0×10^?3 M with a low limit of detection of 1.7×10^?5 M (S/N=3). This approach provided a new available platform to recognize and determine Trp enantiomers.     

Tunneling and Parity Violation in Trisulfane (HSSSH): An Almost Ideal Molecule for Detecting Parity Violation in Chiral Molecules

Measuring the parity‐violating energy difference Δ_pvE between the enantiomers of chiral molecules is a major challenge of current physical‐chemical stereochemistry. An important step towards this goal is to identify suitable molecules for such experiments by means of theory. This step has been made by calculations for the complex dynamics of tunneling and electroweak quantum chemistry of parity violation in the “classic” molecule trisulfane, HSSSH, which satisfies the relevant conditions for experiments almost ideally, as the molecule is comparatively simple and parity violation clearly dominates over tunneling in the ground state. At the same time, the barrier for stereomutation is easily overcome by the S?H infrared chromophore.     

NMR Diffusion Measurements as a Simple Method to Examine Solvent–Solvent and Solvent–Solute Interactions in Mixtures of the Ionic Liquid [Bmim][N(SO2CF3)2] and Acetonitrile

The self‐diffusion coefficients of each component in mixtures of 1‐butyl‐3‐methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][N(SO₂CF₃)₂]) and acetonitrile were determined. The results suggest that the hydrodynamic boundary conditions change from “stick” to “slip” as the solvent composition transitions from “ionic liquid dissolved in acetonitrile” (χ_IL<0.4) to “acetonitrile dissolved in ionic liquid” (χ_IL>0.4). At higher χ_IL, the acetonitrile species are affected by “cage” and “jump” events, as the acetonitrile molecules reside nearer to the charged centre on the ions than in the “non‐polar” regions. The self‐diffusion coefficients of hexan‐1‐amine, dipropylamine, 1‐hexanol and dipropylether in mixtures of [Bmim][N(SO₂CF₃)₂] and acetonitrile were determined. In general, the nitrogen‐containing solutes were found to diffuse slower than the oxygen‐containing solutes; this indicates that there are greater ionic liquid–N interactions than ionic liquid–O interactions. This work demonstrates that the self‐diffusion coefficients of species can provide valuable information about solvent–solvent and solvent–solute interactions in mixtures containing an ionic liquid.     

One Stone for Three Birds‐Rhodium‐Catalyzed Highly Diastereoselective Intramolecular [4+2] Cycloaddition of Optically Active Allene‐1,3‐dienes

RhCl(PPh₃)₃‐catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene‐dienes afforded cis‐fused [3.4.0]‐bicyclic products with three chiral centers in good yields with an excellent chemo‐ and diastereoselectivity. A pair of enantiomers of such products was generated highly selectively from both enantiomers of starting allene‐dienes, indicating that the axial chirality dictated the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.     

Axially Chiral TADF‐Active Enantiomers Designed for Efficient Blue Circularly Polarized Electroluminescence

The use of a chiral, emitting skeleton for axially chiral enantiomers showing activity in thermally activated delayed fluorescence (TADF) with circularly polarized electroluminescence (CPEL) is proposed. A pair of chiral stable enantiomers, (?)‐(S)‐Cz‐Ax‐CN and (+)‐(R)‐Cz‐Ax‐CN, was designed and synthesized. The enantiomers, both exhibiting intramolecular π‐conjugated charge transfer (CT) and spatial CT, show TADF activities with a small singlet–triplet energy difference (ΔE_ST) of 0.029 eV and mirror‐image circularly polarized luminescence (CPL) activities with large g_lum values. Notably, CP‐OLEDs based on the enantiomers feature blue electroluminescence centered at 468 nm with external quantum efficiencies (EQEs) of 12.5 and 12.7 %, and also show intense CPEL with g_EL values of ?1.2×10^?2 and +1.4×10^?2, respectively. These are the first CP‐OLEDs based on TADF‐active enantiomers with efficient blue CPEL.     

A novel C2 symmetric chiral stationary phase with N‐[(4‐Methylphenyl)sulfonyl]‐l‐leucine as chiral side chains

In this study, a series of chiral stationary phases based on N‐[(4‐methylphenyl)sulfonyl]‐l ‐leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N‐[(4‐methylphenyl)sulfonyl]‐l ‐leucine showed much better enantioselectivities than that based on N‐(4‐methylbenzoyl)‐l ‐leucine amide. The construction of C₂ symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C₂ symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C₂ symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π–π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans‐N,N′‐(1,2‐diphenyl‐1,2‐ethanediyl)bis‐acetamide, which had an excellent separation factor on the C₂ symmetric chiral stationary phase, was investigated by ¹H‐NMR spectroscopy and 2D ¹H‐¹H nuclear overhauser enhancement spectroscopy.     

Optically Biaxial,Re‐entrant and Frustrated Mesophases in Chiral,Non‐symmetric Liquid Crystal Dimers and Binary Mixtures

Sixteen optically active, non‐symmetric dimers, in which cyanobiphenyl and salicylaldimine mesogens are interlinked by a flexible spacer, were synthesized and characterized. While the terminal chiral tail, in the form of either (R)‐2‐octyloxy or (S)‐2‐octyloxy chain attached to salicylaldimine core, was held constant, the number of methylene units in the spacer was varied from 3 to 10 affording eight pairs of (R & S) enantiomers. They were probed for their thermal properties with the aid of orthoscopy, conoscopy, differential scanning calorimetry and X‐ray powder diffraction. In addition, the binary mixture study was carried out using chiral and achiral dimers with the intensions of stabilizing optically biaxial phase/s, re‐entrant phases and important phase sequences. Notably, one of the chiral dimers as well as some mixtures exhibited a biaxial smectic A (SmA_b) phase appearing between a uniaxial SmA and a re‐entrant uniaxial SmA phases. The mesophases such as chiral nematic (N*) and frustrated phases viz., blue phases (BPs) and twist grain boundary (TGB) phases, were also found to occur in most of the dimers and mixtures. X‐ray diffraction studies revealed that the dimers possessing oxybutoxy and oxypentoxy spacers show interdigitated (SmA_d) phase where smectic periodicity is over 1.4 times the molecular length; whereas in the intercalated SmA (SmA_c) phase formed by a dimer having oxydecoxy spacer the periodicity was found to be approximately half the molecular length. The handedness of the helical structure of the N* phases formed by two enantiomers was examined with the aid of CD measurements; as expected, these enantiomers showed optical activities of equal magnitudes but with opposite signs. Overall, it appears that the chiral dimers and mixtures presented herein may serve as model systems in design and developing novel materials exhibiting the apolar SmA_b phase possessing D_2h symmetry and nematic‐type biaxiality.