Planar Chirality Research Articles

Enantioselective Synthesis of Planar Chiral Ferrocene Triflones

AbstractA multi‐gram scale synthesis of ferrocenetriflone was optimised from ferrocenesulfonyl fluoride and Me3SiCF3 (Ruppert reagent). Enantioselective deprotolithiations were then optimised using alkyllithiums in the presence of catalytic (+)‐sparteine to afford 2‐substituted ferrocene triflones in 79–84% ee. The use of chiral lithium amides in the presence of in situ traps was also optimised and was found to outperform alkyllithium⋅chiral diamine chelates for the first time in the ferrocene series, with 89–93% ee. Crystallisation of derivatives afforded enantiopure compounds that were engaged in deprotolithiation‐electrophilic trapping sequences, a halogen ‘dance’ reaction and transition metal‐promoted coupling to afford a wide range of variously polysubstituted ferrocene triflones.

Ansa–Ferrocene Derivatives as Potential Therapeutics

It has been known since the 1990s that the introduction of a ferrocenyl–type substituent into compounds with proven biological activity can improve their properties. More recently, it was also shown that a carbon bridge connecting the two cyclopentadienyl rings in ferrocene derivatives could enhance the biological properties of the new compounds compared to those without them. However, the synthesis of ferrocenes with this additional linker, known as ansa–ferrocenes, is more difficult due to advanced synthetic protocols and the phenomenon of planar chirality in ring–substituted compounds. As a result, research into the formation of hybrids, conjugates and other ansa–ferrocene derivatives has not been widely conducted. This review discusses the potential biological properties of these units, covering scientific articles published between 1980 and 2024.

Enantioselective Organozinc Addition to Aldehydes Using Planar Chiral [2.2]Paracyclophane-Imidazoline N,O-ligands.

We present an improved and convenient synthesis of [2.2]paracyclophane-imidazoline N,O-ligands with central and planar chirality in seven steps starting from [2.2]paracyclophane. The utility of these ligands in organozinc additions to aldehydes is described. The asymmetric ethylation of aldehydes proceeded with enantioselectivities of up to 97% ee, while the asymmetric arylation of aldehydes gave up to 95% ee (R) and 82% ee (S) using (S,S,SP)-UCD-Imphanol and (S,S,RP)-UCD-Imphanol, respectively.

Rhodium(III)-Catalyzed Atroposelective Indolization to Access Planar-Chiral Macrocycles.

Macrocycles incorporating conformationally defined indoles are widely found in bioactive natural products. However, the catalytic enantioselective synthesis of planar-chiral indoles via indolization involving macrocyclization remains elusive. Herein, we present the first rhodium(III)-catalyzed atroposelective macrocyclization, which involves the C-H activation of aniline, and a subsequent oxidation [3 + 2] annulation reaction with an intramolecular alkyne. This protocol achieves the construction of indoles, macrocyclization, and planar chirality control in a single step. Importantly, this strategy produces macrocyclic atropisomers bearing full-carbon ansa chains, which represent challenging targets in organic synthesis. Thermodynamic experiments revealed that the rotational barrier of the full-carbon ansa chain-linked macrocyclic atropisomer was lower than that of the atropisomer bearing an oxa-ansa chain. The reaction mechanism was elucidated by computational studies, which revealed that the C-H activation and intramolecular alkyne insertion steps collectively determined the enantioselectivity.

Planar Chiral Charge‐Transfer Cyclophanes: Convenient Synthesis, Circularly Polarized Light‐Responsive Photothermal Conversion and Supramolecular Chiral Assembly

We report herein a series of macrocycles in which the densely π‐stacked charge‐transfer (CT) donor/acceptor with naphthalenediimides (NDIs) or perylene diimide (PDI) as acceptor moiety pairing various donor moieties are locked by covalent bond. The X‐ray crystallography of C8BDT‐NDI reveals a short intramolecular π‐stacking distance around 3.4 Å and the existence of intermolecular donor/acceptor π‐stacking (3.7 Å). The intramolecular CT is highly dependent on the electron‐donating ability of donor moiety and replacing carbazole (C8KZ) with benzo[1,2‐b:4,5‐b']dithiophene (C8BDT) or dihydroindolo[3,2‐b]indole (C8DN) redshift CT absorption into NIR region. Notably, both C8BDT‐NDI and C8DN‐NDI demonstrate excellent photothermal performance, which is a result of the active non‐radiative pathways. Interestingly, the different molecular symmetry between donor and acceptor moiety endows C8BDT‐NDI and C8DN‐NDI with intrinsic planar chirality. The enantiomeric C8BDT‐NDI shows chiral selectivity for incident light, i.e., when irradiated by left‐circularly polarized light, (R)‐C8BDT‐NDI is more sensitive and a higher maximum stable temperature is achieved. While, enantiomeric C8DN‐NDI pack with different orientations forming M‐ and P‐handedness helix, respectively, demonstrating molecular planar chirality being transferred and amplified through molecular assembly. These results provide insight into the intramolecular charge transfer in enforced D/A π‐stacks in which CT interactions and planar chirality would be engineered through structural control.

PlanarChiral Charge-Transfer Cyclophanes: Convenient Synthesis, Circularly Polarized Light-Responsive Photothermal Conversion and Supramolecular Chiral Assembly.

We report herein a series of macrocycles in which the densely π-stacked charge-transfer (CT) donor/acceptor with naphthalenediimides (NDIs) or perylene diimide (PDI) as acceptor moiety pairing various donor moieties are locked by covalent bond. The X-ray crystallography of C8BDT-NDI reveals a short intramolecular π-stacking distance around 3.4 Å and the existence of intermolecular donor/acceptor π-stacking (3.7 Å). The intramolecular CT is highly dependent on the electron-donating ability of donor moiety and replacing carbazole (C8KZ) with benzo[1,2-b:4,5-b']dithiophene (C8BDT) or dihydroindolo[3,2-b]indole (C8DN) redshift CT absorption into NIR region. Notably, both C8BDT-NDI and C8DN-NDI demonstrate excellent photothermal performance, which is a result of the active non-radiative pathways. Interestingly, the different molecular symmetry between donor and acceptor moiety endows C8BDT-NDI and C8DN-NDI with intrinsic planar chirality. The enantiomeric C8BDT-NDI shows chiral selectivity for incident light, i.e., when irradiated by left-circularly polarized light, (R)-C8BDT-NDI is more sensitive and a higher maximum stable temperature is achieved. While, enantiomeric C8DN-NDI pack with different orientations forming M- and P-handedness helix, respectively, demonstrating molecular planar chirality being transferred and amplified through molecularassembly. These results provide insight into the intramolecular charge transfer in enforced D/A π-stacks in which CT interactions and planar chirality would be engineered through structural control.

Synthesis, Characterization, and Catalysis of Planar Chiral Ferrocene‐based N‐Heterocyclic Carbene Ligands and Its Metal Complexes

This study presents the development of a novel planar chiral ferrocene‐based NHC ligand and its corresponding metal complexes. The key unit of the imidazolium backbone, planar chiral ortho‐isopropyl ferrocenyl amine, was synthesized starting from (R)‐Ugi's amine. Imidazolium was obtained through the sequential condensation of glyoxal with ferrocenyl amine, followed by the ring‐closure of 1,3‐diferrocenyldiimine with chloromethylethyl ether. Chiral imidazolylidene NHC (IFcPr) metal complexes were prepared by treating imidazolium with silver oxide or base followed by transmetalation with appropriate metal salts. The steric and electronic properties of the IFcPr ligand were assessed using %Vbur and TEP, respectively. These assessments indicated that the ligand was as bulky as the adamantyl NHC ligand and exhibited strong donor ability similar to that of a triazolylidene NHC ligand. The catalytic performance of the copper and palladium complexes was evaluated in the asymmetric borylation of ethyl cinnamate and Suzuki–Miyaura coupling reactions, respectively. The IFcPr‐Cu complex catalyzed the borylation of ethyl cinnamate with bis(pinacolato) diboron, followed by oxidation to yield the hydroxy ester with 58% yield and 30% ee. In contrast, the IFcPr‐Pd‐PEPPSI complex provided the axial chiral binaphthyl compound with 59% yield and 51% ee at a low catalyst loading (0.1 mol%, TON = 590).

Recent Advances on Catalytic Atroposelective Synthesis of Planar‐Chiral Macrocycles

AbstractPlanar‐chiral skeletons widely exist in natural products, bioactive compounds, and other functional molecules. Although significant progress has been made in the field of asymmetric synthesis of centrally or axially chiral molecules over the past years, enantioselective constructing of planar chirality is still a big obstacle and numerous efforts have been made in this field. Previous works have mainly focused on the assembly of planar‐chiral [2,2]‐paracyclophanes and metallocenes. This Minireview describes recent advancements in asymmetric catalytic synthesis of planar‐chiral macrocycles, including ansa chain construction, plane formation and asymmetric transformation strategies. It is anticipated that this Minireview will sever as a source of inspiration for developing new unconventional procedures for access to planar‐chiral skeletons.

Recent Advances on Catalytic Atroposelective Synthesis of Planar-Chiral Macrocycles.

Planar-chiral skeletons widely exist in natural products, bioactive compounds, and other functional molecules. Although significant progress has been made in the field of asymmetric synthesis of centrally or axially chiral molecules over the past years, enantioselective constructing of planar chirality is still a big obstacle and numerous efforts have been made in this field. Previous works have mainly focused on the assembly of planar-chiral [2,2]-paracyclophanes and metallocenes. This Minireview describes recent advancements in asymmetric catalytic synthesis of planar-chiral macrocycles, including ansa chain construction, plane formation and asymmetric transformation strategies. It is anticipated that this Minireview will sever as a source of inspiration for developing new unconventional procedures for access to planar-chiral skeletons.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling.

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling

Enantioselective Construction of Planar‐Chiral Molecules by Catalytic Asymmetric Late‐Stage Functionalizations

Planar chirality, as one of the most important manifestations of chirality, is frequently employed to constrain three‐dimensional chiral configurations. Recent advancements in the study of planar chirality by chemists have opened up innovative possibilities for designing new catalysts, developing novel drugs, and creating new optical materials. However, the flexible ansa chains present a challenge during the synthesis process of these unique planar‐chiral macrocycles, hindering chemists from achieving high enantioselectivity. In this mini review, we primarily introduce the catalytic asymmetric synthesis methods that have been reported for late‐stage functionalization of planar macrocycles to generate planar chirality. Additionally, we present several recent examples of catalytic enantioselective synthesis of mechanically planar‐chiral rotaxanes through late‐stage functionalization methods. The sources of stereoselectivity are also discussed in this mini review. We aim to inform more researchers about this field and attract chemists to engage in this important and scientifically significant area of research.

One‐Step Synthesis of Chiral 9,10‐Dihydrophenanthrenes via Ligand‐Enabled Enantioselective Cascade β,γ‐Diarylation of Acids

AbstractPd(II)‐catalyzed enantioselective C−H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd‐catalyzed enantioselective cascade β,γ‐methylene C(sp3)−H diarylation of free carboxylic acids using bidentate chiral mono‐protected amino thioether ligands (MPAThio), enabling one‐step synthesis of a complex chiral 9,10‐dihydrophenanthrene scaffolds with high enantioselectivity. In this process, two methylene C(sp3)−H bonds and three C(sp2)−H bonds were activated, leading to the formation of four C−C bonds and three chiral centers in one pot. A plausible catalytic pathway starts with enantioselective β,γ‐dehydrogenation to form chiral β,γ‐cyclohexene. Intriguingly, this olefin serves as a norbornene‐type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C−H arylation reaction to furnish chiral 9,10‐dihydrophenanthrenes along with meta‐selective homocoupling products of iodoarene.

One-Step Synthesis of Chiral 9,10-Dihydrophenanthrenes via Ligand-Enabled Enantioselective Cascade β,γ-Diarylation of Acids.

Pd(II)-catalyzed enantioselective C-H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd-catalyzed enantioselective cascade β,γ-methylene C(sp3)-H diarylation of free carboxylic acids using bidentate chiral mono-protected amino thioether ligands (MPAThio), enabling one-step synthesis of a complex chiral 9,10-dihydrophenanthrene scaffolds with high enantioselectivity. In this process, two methylene C(sp3)-H bonds and three C(sp2)-H bonds were activated, leading to the formation of four C-C bonds and three chiral centers in one pot. A plausible catalytic pathway starts with enantioselective β,γ-dehydrogenation to form chiral β,γ-cyclohexene. Intriguingly, this olefin serves as a norbornene-type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C-H arylation reaction to furnish chiral 9,10-dihydrophenanthrenes along with meta-selective homocoupling products of iodoarene.

Controllable perfect chiral optical response in planar metasurfaces empowered by quasi-bound states in the continuum

Chiral metasurfaces with strong chirality and high quality factors (Q-factors) have become essential components for achieving strong light-matter interactions and have a wide range of applications in chiral lasers, detectors, etc. However, current schemes primarily focus on enhancing the chiral response and Q-factor, with limited consideration of their modulability and flexibility. In this paper, we present a chiral a-Si metasurface that can support multiple symmetry-protected bound states in the continuum (BIC). The perfect extrinsic and intrinsic chiral responses (circular dichroism exceeding 0.99), with ultra-high Q-factors, are achieved by utilizing quasi-BICs induced by illumination symmetry and in-plane symmetry breaking. The circular dichroism value and the transmittance of the two circular polarization states can be arbitrarily controlled by adjusting the structural parameters. Furthermore, the feasibility of achieving dynamic modulation of chiral response is demonstrated based on the a-Si-graphene hybrid metasurface. Our research offers an approach to the design of controllable planar optical chirality, which also provides promising avenues for applications in spin-selective bio-detection, electrically tunable chiral switching, and chiral lasers.

Catalytic Enantioselective Macrocyclization for the Synthesis of Planar‐Chiral Cyclophanes: Recent Updates

The planar chirality of macrocycles is a fascinating research topic. Locking the configurational flip between the benzene ring and macrocycle leads to planar chirality, which can significantly enhance the biological activity of cyclophanes. Planar‐chiral cyclophanes are widely used in pharmaceuticals, chiral catalysts, and functional materials. However, accessing planar‐chiral cyclophanes via asymmetric catalysis has remained challenging. Among the various strategies, asymmetric macrocyclization provides a powerful tool for accessing planar‐chiral cyclophanes. This method allows for control of the planar chirality when constructing the macrocycle and greatly improves the efficiency. There are three types of macrocyclization reactions: transition metal‐catalyzed, organocatalyzed, and biocatalyzed. In addition, the chiral confinement strategy breaks through conservative synthetic approaches. This review summarizes these achievements, aiming to highlight the catalytic asymmetric synthesis of cyclophanes and inspire interested researchers.

Terpenoid Cyclophanes with Planar Chirality.

The strain-induced chirality of cyclophanes has attracted interest within the synthetic community. Herein, we report the synthesis of anilinocyclophanes derived from naturally occurring terpenes, such as citronellol, geraniol, and farnesol. The resulting cyclic oligoprenyl molecules exhibit considerable ring strain (up to 31 kcal/mol), as evident from their bent aniline planes, and possess chirality across the planes of an aryl ring and double bonds. Unexpected outcomes, such as the formation of isomerized neraniline, highlight the influence of ring strain on the stability and reactivity of terpenoid para-cyclophanes.

Unravelling dispersion forces in liquid-phase enantioseparation. Part II: Planar chiral 1-(iodoethynyl)-3-arylferrocenes

BackgroundIn the first part of our study on possible contribution of dispersion forces in liquid-phase enantioseparations, the enantioseparation of the axially chiral 3,3′-dibromo-5,5′-bis-ferrocenylethynyl-4,4′-bipyridine with an amylose tris(3,5-dimethylphenylcarbamate)-based chiral column appeared reasonably consistent with a picture of the enantioselective recognition based on the interplay between hydrogen bond (HB), π-π stacking and dispersion interactions. ResultsIn the second part of this study, we evaluated the impact of analyte and chiral stationary phase (CSP) structure, mobile phase and temperature on the enantioseparations of planar chiral 1-(iodoethynyl)-3-arylferrocenes (3-aryl = phenyl, 2-naphthyl, 4-methylphenyl, 4-t-butylphenyl) with polysaccharide-based chiral columns. The main aim of the present study was to understand the molecular bases of the high affinity observed for the second eluted (Rp)-enantiomer of some of these analytes toward amylose phenylcarbamate-based selectors when methanol-containing mixtures were used as mobile phases. Significantly, higher affinity of the second eluted (Rp)-enantiomer toward the selector could be also observed for the sterically hindered 1-(iodoethynyl)-3-(4-t-butylphenyl)ferrocene (k2 = 6.21) compared to the smaller 1-(iodoethynyl)-3-(4-methylphenyl)ferrocenes (k2 = 4.07) as 2.5% methanol was added to the n-hexane-based mobile phase. SignificanceThis study reasonably showed that the contribution of dispersion forces may explain the unusually large retention of the second eluted enantiomers observed for the enantioseparation of some planar chiral 1-(iodoethynyl)-3-arylferrocenes with amylose-based selectors. Based on the obtained results, we can conclude that in liquid-phase enantioseparation steric repulsion can be turned into attraction depending on the features of analyte, selector, and mobile phase.

Synthesis of terminus-decorated aza[9]helicenes: control of interlayer interaction

Abstract Azahelicenes are intriguing luminescent materials with a planar chirality. The properties of aza[9]helicene can be perturbed by attaching substituent at the termini. The impact of the terminal decoration has been investigated in view of structural and electronic aspects, leading to the control of interlayer interaction.

Symmetry and planar chirality measured with a log-polar transformation in a transmission electron microscope

Symmetry and planar chirality measured with a log-polar transformation in a transmission electron microscope