Mid-IR and CH stretching vibrational circular dichroism spectroscopy to distinguish various sources of chirality: The case of quinophaneoxazoline based ruthenium(II) complexes.

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid-IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced-dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region.

Enhancing the Efficacy of Chiral Ligands and Catalysts: Siloxane-Substituted Oxazoline Ferrocenes as Next-Generation Candidates.

Since the discovery of classical chiral oxazoline ferrocene ligands in 1995, they have become pivotal in transition metal-catalyzed asymmetric transformations. Over the past decade, a notable evolution has been observed with the emergence of siloxane-substituted oxazoline ferrocenes, demonstrating significant potential as chiral ligands and catalysts. These compounds have consistently delivered exceptional results in diverse and mechanistically distinct transformations, surpassing the capabilities of classical oxazoline ferrocene ligands. This review meticulously delineates the research progress on siloxane-substituted oxazoline ferrocene compounds. It encompasses the synthesis of crucial precursors and desired products, highlights their achievements in asymmetric catalysis reactions, and delves into the exploration of the derivatization of these compounds, emphasizing the introduction of ionophilic groups and their impact on the recovery of transition metal catalysts. In addition to presenting the current state of knowledge, this review propels future research directions by identifying potential topics for further investigation concerning the siloxane-tagged derivatives. These derivatives are poised to be promising candidates for the next generation of highly efficient ligands and catalysts.

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field.

With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon centered chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This review summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

Self-Assembled Pure Covalent Tubes Exhibiting Circularly Polarized Luminescence.

Here, we successfully synthesized four structurally analogous, self-assembled chiral molecular tubes with relatively high yields. This achievement involved the condensation of six equivalents of enantiomerically pure trans-cyclohexane-1,2-diamine (trans-CHDA) and three equivalents of the corresponding tetraformyl precursor. Each precursor was equipped with a luminescent linker terminated by two m-phthalaldehyde units. Even though these tetraformyl precursors are barely soluble in almost all organic solvents, the molecular tubes are highly soluble in nonpolar solvents such as chloroform, allowing us to fully characterize them in solution. The stereo-chirality of the chiral bisamino building blocks endows the frameworks of molecular tubes with planar chirality. As a consequence, all of these molecular tubes exhibit circularly polarized luminescence (CPL) with relatively large dissymmetry values |glum| up to 7×10-3, providing an efficient method for synthesizing CPL-active materials.

Ferrocene derivatives with planar chirality and their enantioseparation by liquid-phase techniques.

In the last decade, planar chiral ferrocenes have attracted a growing interest in several fields, particularly in asymmetric catalysis, medicinal chemistry, chiroptical spectroscopy and electrochemistry. In this frame, the access to pure or enriched enantiomers of planar chiral ferrocenes has become essential, relying on the availability of efficient asymmetric synthesis procedures and enantioseparation methods. Despite this, in enantioseparation science, these metallocenes were not comprehensively explored, and very few systematic analytical studies were reported in this field so far. On the other hand, enantioselective high-performance liquid chromatography has been frequently used by organic and organometallic chemists in order to measure the enantiomeric purity of planar chiral ferrocenes prepared by asymmetric synthesis. On these bases, this review aims to provide the reader with a comprehensive overview on the enantioseparation of planar chiral ferrocenes by discussing liquid-phase enantioseparation methods developed over time, integrating this main topic with the most relevant aspects of ferrocene chemistry. Thus, the main structural features of ferrocenes and the methods to model this class of metallocenes will be briefly summarized. In addition, planar chiral ferrocenes of applicative interest as well as the limits of asymmetric synthesis for the preparation of some classes of planar chiral ferrocenes will also be discussed with the aim to orient analytical scientists towards 'hot topics' and issues which are still open for accessing enantiomers of ferrocenes featured by planar chirality.

Synthesis of Two Novel Optically Active #-Shaped Cyclic Tetramers Based on Planar Chiral [2.2]Paracyclophanes.

This study reports the synthesis of optically active cyclic tetramers comprising four stacked π-electron systems from two enantiomerically pure [2.2]paracyclophane compounds (bis-(para)-pseudo-ortho- and bis-(para)-pseudo-meta-tetrasubstituted [2.2]paracyclophane compounds). Depending on the combination of the absolute configurations of the planar chiral pseudo-ortho- and pseudo-meta-[2.2]paracyclophane units, the cyclic tetramers formed either parallel-#- or weave-#-structures. The optical and chiroptical properties of both structures were investigated experimentally and theoretically. In particular, the weave-#-shaped cyclic tetramer exhibited good chiroptical properties and emitted circularly polarized luminescence (CPL) with a high anisotropy factor (|glum | value of the order of 10-3 ) and a CPL brightness (BCPL ) higher than 100.

Synthesis, structural characterization, and chiroptical properties of planarly and axially chiral boranils.

2-Amino[2.2]paracyclophane reacts with salicylaldehyde or 2-hydroxyacetophenone to yield imines that then give access to a new series of boranils (8b-d) upon complexation with BF2 . These novel boron-containing compounds display both planar and axial chiralities and were examined experimentally and computationally. In particular, their photophysical and chiroptical properties were studied and compared to newly prepared, simpler boranils (9a-d) exhibiting axial chirality only. Less sophisticated chiral architectures were shown to demonstrate overall stronger circularly polarized luminescence (CPL) activity.

Nitrenoid from Oxime: A Practical Synthesis of Planar Chiral Ferrocenyl Phenanthridines via Nitrene-Involved Ring-Expansion Reaction.

Nitrenes and nitrenoids are highly reactive species and the proposed key intermediates in nitrogen-containing heterocyclic compound synthesis. In this work, we developed a practical method for the synthesis of phenanthridines by the reaction of oximes and Grignard reagents (with or without diethylzinc) via ring-expansion of magnesium coordinated nitrenoid complex as the key step. The method has been used to synthesize optically active planar chiral ferrocenyl phenanthridines.

Planar Chiral Multiple Resonance Thermally Activated Delayed Fluorescence Materials for Efficient Circularly Polarized Electroluminescence.

Chiral boron/nitrogen doped multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters are promising for highly efficient and color-pure circularly polarized organic light-emitting diodes (CP-OLEDs). Herein, we report two pairs of MR-TADF materials (Czp-tBuCzB, Czp-POAB) based on planar chiral paracyclophane with photoluminescence quantum yields of up to 98 %. The enantiomers showed symmetric circularly polarized photoluminescence spectra with dissymmetry factors |gPL | of up to 1.6×10-3 in doped films. Meanwhile, the sky-blue CP-OLEDs with (R/S)-Czp-tBuCzB showed an external quantum efficiency of 32.1 % with the narrowest full-width at half-maximum of 24 nm among the reported CP-OLEDs, while the devices with (R/S)-Czp-POAB displayed the first nearly pure green CP electroluminescence with |gEL | factors at the 10-3 level. These results demonstrate the incorporation of planar chirality into MR-TADF emitter is a reliable strategy for constructing of efficient CP-OLEDs.

Acetylene Derivatives of Cationic Diazaoxatriangulenes and Diaza [4]Helicenes - Access to Red Emitters and Planar Chiral Stereochemical Traits.

Cationic triangulenes, and related helicenes, constitute a rich class of dyes and fluorophores, usually absorbing and emitting light at low energy, in the orange to red domains. Recently, to broaden the scope of applications, regioselective late-stage functionalizations on these core moieties have been developed. For instance, with the introduction of electron-donating groups (EDGs), important bathochromic shifts are observed pushing absorptions towards or in the near-infrared (NIR) spectral domain while emissive properties disappear essentially completely. Herein, to upset this drawback, acetylene derivatives of cationic diazaoxa triangulenes (DAOTA) and [4]helicenes are prepared (16 examples). Contrary to other EDG-functionalized derivatives, C≡C- functionalized products remain broadly fluorescent, with red-shifted absorptions (Δλabs up to 25 nm) and emissions (Δλem up to 73 nm, ΦPL up to 51 %). Quite interestingly, a general dynamic stereoisomerism phenomenon is evidenced for the compounds derived from achiral DAOTA cores. At low temperature in 1 H NMR spectroscopy (218 K), N-CH2 protons become diastereotopic with chemical shifts differences (Δδ) as high as +1.64 ppm. The signal coalescence occurs around 273 K with a barrier of ∼12 kcal mol-1 . This phenomenon is due to planar chiral conformations (Sp and Rp configurations), induced by the geometry of the alkyl (n-propyl) side-chains next to the acetylenic substituents. Ion pairing studies with Δ-TRISPHAT anion not only confirm the occurrence of the chiral conformations but evidence a moderate but definite asymmetric induction from the chiral anion onto the cations. Finally, DFT calculations offer a valuable insight on the geometries, the corresponding stereodynamics and also on the very large difference in NMR for some of the diastereotopic protons.

Nanosized Carbon Macrocycles Based on a Planar Chiral Pseudo Meta-[2.2]Paracyclophane.

Structural designs combining cycloparaphenylenes (CPPs) backbone with planar chiral [2.2]paracyclophane ([2.2]PCP) lead to optical-active chiral macrocycles with intriguing properties. X-ray crystal analysis revealed aesthetic necklace-shaped structures and size-dependent packages with long-range channels. The macrocycles exhibit unique photophysical properties with high fluorescence quantum yield of up to 82 %, and the fluorescent color varies with ring size. In addition, size-dependent chiroptical properties with moderately large CPL dissymmetry factor of 10-3 and CPL brightness in the range of 30-40 M-1 cm-1 were observed.

Eight new arnebinol B-based meroterpenoids with planar chirality in the constrained 6/10/5 tricyclic skeleton from Arnebia euchroma and their cytotoxicities.

Eight new arnebinol B-based meroterpenoids ((-)-1, 2, 3, (-)-5, and 7-10) with a constrained 6/10/5 tricyclic backbone were isolated from the roots of Arnebia euchroma. The planar and steric structures of these new compounds were unambiguously elucidated by extensive spectroscopic analyses, X-ray diffraction crystallography, and ECD calculations. The predominant relative orientation between H-7 and the Z double bond with a methyl substituent in the rigid 10-membered carbocycle, along with the planar chirality of the Z double bond was analyzed and discussed for the first time. The illustration of the planar chirality derived from the Z double bond should be paid great importance during the structure elucidation on these homologous meroterpenoids. All the isolated meroterpenoids were screened for their cytotoxicities against the HCT-8, PANC-1, HGC-27, HepG2, and PC9 cell lines, and compounds (+)-5 and (-)-5 exhibited the most potent cytotoxicity.

Stereochemical study on planar-chiral cyclic molecules using polysaccharide-based column chromatography.

The presence of planar chirality of a variety of medium-sized heterocycles, along with nine-membered cyclic ketone and its enol ester, was revealed by observation of isolable enantiomers by analytical high-performance liquid chromatography (HPLC) using a chiral stationary phase with a polysaccharide-based chiral selector. Several tens of milligrams of enantiomers of the planar-chiral molecules were successfully separated by preparative-scale HPLC, leading to the preparation of an enantioenriched sample. This in turn enabled detailed stereochemical studies, including measurement of half-lives of the optical activity and X-ray crystallography for elucidation of stereochemistry.

Comparative enantioseparation of planar chiral ferrocenes on polysaccharide-based chiral stationary phases.

Planar chiral ferrocenes are well-known compounds that have attracted interest for application in synthesis, catalysis, material science, and medicinal chemistry for several decades. In spite of the fact that asymmetric synthesis procedures for obtaining enantiomerically enriched ferrocenes are available, sometimes, the accessible enantiomeric excess of the chiral products is unsatisfactory. In such cases and for resolution of racemic planar chiral ferrocenes, enantioselective high-performance liquid chromatography (HPLC) on polysaccharide-based chiral stationary phases (CSPs) has been used in quite a few literature articles. However, although moderate/high enantioselectivities have been obtained for planar chiral ferrocenes bearing polar substituents, the enantioseparation of derivatives containing halogens, or exclusively alkyl groups, remains rather challenging. In this study, the enantioseparation of ten planar chiral 1,2- and 1,3-disubstituted ferrocenes was explored by using five polysaccharide-based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.20 to 2.92. The presence of π-extended systems in the analyte structure was shown to impact affinity of the most retained enantiomer toward amylose-based selectors, observing retention times higher than 80 min with methanol-containing mobile phases (MPs). Electrostatic potential (V) analysis and molecular dynamics (MD) simulations were used in order to study interaction modes at the molecular level.

Planar Chirality: A Mine for Catalysis and Structure Discovery.

Planar chirality is one of the most fascinating expressions of chirality, which is exploited by nature to lock three-dimensional chiral conformations and, more recently, by chemists to create new chiral reagents, catalysts, and functional organic materials. Nevertheless, the shortage of procedures able to induce and secure asymmetry during the generation of these unique chiral entities has dissuaded chemists from exploiting their structural properties. This Minireview intends to illustrate the limited but remarkable catalytic methods that have been reported for the production of planar chirality in strained molecules and serve as a source of inspiration for the development of new unconventional procedures, which are expected to appear in the near future.

Synthesis of Cyclophenacene- and Chiral-Type Cyclophenylene-Naphthylene Belts.

We report the synthesis of a [20]cyclophenacene-type cyclophenylene-naphthylene (CPN) belt and the enantioselective synthesis of chiral-type CPN belts (up to >99 % ee) by the cationic rhodium(I)-catalyzed intramolecular [2+2+2] cycloaddition of naphthalene-embedded cyclic polyynes. The synthesis of a depth-expanded CPN belt was also attempted, but the final intramolecular [2+2+2] cycloaddition was unsuccessful. Theoretical calculations clarified that the reactivity depends on the stability of the transition state in the initial oxidative cycloaddition step which is subject to molecular strain. The cylindrical structures of these CPN belts were confirmed by X-ray crystallographic analyses. As a result of π-extension through the introduction of naphthalenes in the chiral-type CPN belts, the anisotropy dissymmetry factors of electronic circular dichroism and circularly polarized luminescence are amplified compared with the corresponding zigzag-type chiral cyclophenylene belts.

Self-Assembly of Macrocyclic Triangles into Helicity-Opposite Nanotwists by Competitive Planar over Point Chirality.

While helix has elegant biomimetic structures and functionalities, it still remains a big question how the nanoscale helicity evolved from the molecular chiral building blocks across length scales. Herein, macrocyclic triangles composed of achiral edges and chiral vertices were rationally designed, in which the planar chirality emerged due to the restriction of edge rotation by intermolecular stackings and led to a unique chiral self-assembly. In contrast to the solution systems where the chiroptical property is exclusively dominated by the point chiral vertices, the emerged planar chirality was found to control the chiral self-assembly, resulting the nanotwist with the handedness determined by the planar chirality. Our work unveiled the self-assembly behaviors of macrocyclic conformers for the first time and provided a deep understanding on the macrocyclic chirality evolution including the excited-state chirality.

[2]Catenane Synthesis via Covalent Templating.

After earlier unsuccessful attempts, this work reports the application of covalent templating for the synthesis of mechanically interlocked molecules (MiMs) bearing no supramolecular recognition sites. Two linear strands were covalently connected in a perpendicular fashion by a central ketal linkage. After subsequent attachment of the first strand to a template via temporary benzylic linkages, the second was linked to the template in a backfolding macrocyclization. The resulting pseudo[1]rotaxane structure was successfully converted to a [2]catenane via a second macrocyclization and cleavage of the ketal and temporary linkages.

Enantioselective Preparation of Planar-Chiral Transition Metal Complexes by Asymmetric Olefin-Metathesis Reactions in Metal Coordination Spheres.

Planar-chiral transition metal complexes are useful chiral auxiliaries in organic and organometallic chemistry, and they have been utilized as chiral ligands, chiral catalysts, or chiral building blocks, etc. Despite the importance of such planar-chiral species in asymmetric synthesis, their preparation in optically active forms is still a challenging problem. Indeed, reported examples of catalytic enantioselective synthesis of planar-chiral complexes have been rare, and this has been a developing area in this field. In this personal account, recent results from our research group on the catalytic asymmetric synthesis of various planar-chiral transition metal complexes are summarized. The asymmetric ring-closing metathesis reactions catalyzed by the well-defined molybdenum-alkylidene species are powerful methods to control the planar chirality in ferrocenes, ruthenocenes, (η6 -arene)chromium complexes, and (η5 -cyclopentadienyl)manganese(I) complexes. Application of the enantiomerically enriched complexes obtained by our methods is described as well.

Enantiopure planar chiral [2.2]paracyclophanes: Synthesis and applications in asymmetric organocatalysis.

This short review focuses on enantiopure planar chiral [2.2]paracyclophanes (pCps), a fascinating class of molecules that possess an unusual three-dimensional core and intriguing physicochemical properties. In the first part of the review, different synthetic strategies for preparing optically active pCps are described. Although classical resolution methods based on the synthesis and separation of diastereoisomeric products still dominate the field, recent advances involving the kinetic resolution of racemic compounds and the desymmetrization of meso derivatives open up new possibilities to access enantiopure key intermediates on synthetically useful scales. Due to their advantageous properties including high configurational and chemical stability, [2.2]paracyclophanes are increasingly employed in various research fields, ranging from stereoselective synthesis to material sciences. The applications of [2.2]paracyclophanes in asymmetric organocatalysis are described in the second part of the review. While historically enantiopure pCps have been mainly employed by organic chemists as chiral ligands in transition-metal catalysis, these compounds can also be used as efficient catalysts in metal-free reactions and may inspire the development of new transformations in the near future.