Planar Chirality Research Articles

Designing a Planar Chiral Rhodium Indenyl Catalyst for Regio- and Enantioselective Allylic C-H Amidation.

Chiral variants of group IX Cp and Cp* catalysts are well established and catalyze a broad range of reactions with high levels of enantioselectivity. Enantiocontrol in these systems results from ligand design that focuses on appropriate steric blocking. Herein we report the development of a new planar chiral indenyl rhodium complex for enantioselective C-H functionalization catalysis. The ligand design is based on establishing electronic asymmetry in the catalyst, to control enantioselectivity during the reactions. The complex is easily synthesized from commercially available starting materials and is capable of catalyzing the asymmetric allylic C-H amidation of unactivated olefins, delivering a wide range of high-value enantioenriched allylic amide products in good yields with excellent regio- and enantioselectivity. Computational studies suggest that C-H cleavage is rate- and enantio-determining, while reductive C-N coupling from the RhV-nitrenoid intermediate is regio-determining.

Design and Synthesis of a [2.2]Paracyclophane‐based Planar Chiral Dirhodium Catalyst and its Applications in Cyclopropanation Reaction of Vinylarenes with α‐Methyl‐α‐Diazo Esters

AbstractA planar chiral dirhodium paddlewheel complex Rh2(Sp−PCP)4 based on the [2.2]paracyclophane has been synthesized for the challenging cyclopropanation of venylarene derivatives with tert‐butyl α‐diazo propionates. The homobimetallic rhodium catalyst relies on the high steric demand and rigidity of [2.2]paracyclophane that favors the cyclopropanation of 1‐aryl substituted, 1,1‐disubstituted and benzannulated alkenes over β‐hydride migration at room temperature with high diastereoselectivity.magnified image

Development of Ferrocene-Based Planar Chiral Imidazopyridinium Salts for Catalysis

Imidazol-2-ylidenes and their N,N′-diaryl derivatives constitute an important class of N-heterocyclic carbenes (NHCs) which possess a unique level of versatility in both organocatalysis and transition-metal catalysis. However, there remain few examples of carbenes of this type that are chiral. Here we describe the development of a family of closely related imidazopyridine-based NHCs that derive their asymmetry purely from planar chirality through the incorporation of the classic metallocene framework. An NMR analysis of 77Se complexes of this family is used to assess their degrees of σ donicity and π acidity in comparison to a larger family of NHCs. Percent buried volume (%Vbur) calculations were performed to measure the steric bulk of this distinct class of NHCs. Additionally, these NHCs were employed in various enantioselective transformations to survey their use as organocatalysts as well as ligands for transition-metal-catalyzed processes.

Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells.

The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium-catalysed intramolecular direct C-H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. This bioactivity arises from two mechanisms: Fenton-type chemistry and the anti-estrogenic activity associated with the tamoxifen-like structure.

Synthesis and Chiroptical Properties of †- and ‡-Shaped Molecules Based on Planar Chiral [2.2]Paracyclophane

Abstract Two types of optically active molecules based on planar chiral 4,7,12,15-tetrasubstituted [2.2]paracyclophane were synthesized through chemoselective Sonogashira-Hagihara coupling. One is a †-shaped molecule consisting of two π-electron systems stacked, and the other is a ‡-shaped molecule consisting of three π-electron systems stacked. Their optical and chiroptical properties were investigated, which exhibited large molar absorption coefficient, excellent photoluminescence quantum efficiency, and intense circularly polarized luminescence (CPL).

Second harmonic generation as a probe of broken mirror symmetry

The notion of spontaneous symmetry breaking has been used to describe phase transitions in a variety of physical systems. In crystalline solids, the breaking of certain symmetries, such as mirror symmetry, is difficult to detect unambiguously. Using 1$T$-TaS$_2$, we demonstrate here that rotational-anisotropy second harmonic generation (RA-SHG) is not only a sensitive technique for the detection of broken mirror symmetry, but also that it can differentiate between mirror symmetry-broken structures of opposite planar chirality. We also show that our analysis is applicable to a wide class of different materials with mirror symmetry-breaking transitions. Lastly, we find evidence for bulk mirror symmetry-breaking in the incommensurate charge density wave phase of 1$T$-TaS$_2$. Our results pave the way for RA-SHG to probe candidate materials where broken mirror symmetry may play a pivotal role.

Catalytic access to ferrocenyl phosphines bearing both planar and central chirality – A kinetic resolution approach via catalytic asymmetric P(III)–C bond formation

A series of enantioenriched ferrocenyl monophosphines imbued with both central and planar chirality were obtained catalytically (80–99% ee) via the kinetic resolution of 1,2-disubstituted planar chiral ferrocenyl enone racemates. The synthetic approach utilized a chiral palladacycle to facilitate the asymmetric hydrophosphination (AHP) as a means to achieve high stereoselectivity. The enantioenriched ferrocenylphosphine products could be protected and further recrystallized to obtain ees up to 99%. The modularity of the phosphine framework obtained was demonstrated via derivatization of its functional handles via a simple nucleophilic substitution to yield optically pure bisphosphines.

Rhodium-Catalyzed Pyridine-Assisted C–H Arylation for the Synthesis of Planar Chiral Ferrocenes

Planar chiral ferrocenes are widely applied in organic synthesis, materials science, and medicinal chemistry, but their synthesis is not trivial. Herein, a highly efficient synthesis of planar chir...

Planar Chiral Organoboranes with Thermoresponsive Emission and Circularly Polarized Luminescence: Integration of Pillar[5]arenes with Boron Chemistry

AbstractEnantiopure molecules based on macrocyclic architecture are unique for applications in enantioselective host‐guest recognition, chiral sensing and asymmetric catalysis. Taking advantage of the chiral transfer from the intrinsically planar chirality of pillar[5]arenes, we herein present an efficient and straightforward approach to achieve early examples of highly luminescent chiral systems (P5NN and P5BN). The optical resolution of their enantiomers has been carried out via preparative chiral HPLC, which was ascribed to the molecular functionalization of pillar[5]arenes with π‐conjugated, sterically bulky triarylamine (Ar3N) as an electron donor and triarylborane (Ar3B) as an acceptor. This crucial design enabled investigations of the chiroptical properties, including circular dichroism (CD) and circularly polarized luminescence (CPL) in the solid state. The intramolecular charge transfer (ICT) nature in P5BN afforded an interesting thermochromic shift of the emission over a wide temperature range.

Planar Chiral Organoboranes with Thermoresponsive Emission and Circularly Polarized Luminescence: Integration of Pillar[5]arenes with Boron Chemistry.

Enantiopure molecules based on macrocyclic architecture are unique for applications in enantioselective host-guest recognition, chiral sensing and asymmetric catalysis. Taking advantage of the chiral transfer from the intrinsically planar chirality of pillar[5]arenes, we herein present an efficient and straightforward approach to achieve early examples of highly luminescent chiral systems (P5NN and P5BN). The optical resolution of their enantiomers has been carried out via preparative chiral HPLC, which was ascribed to the molecular functionalization of pillar[5]arenes with π-conjugated, sterically bulky triarylamine (Ar3 N) as an electron donor and triarylborane (Ar3 B) as an acceptor. This crucial design enabled investigations of the chiroptical properties, including circular dichroism (CD) and circularly polarized luminescence (CPL) in the solid state. The intramolecular charge transfer (ICT) nature in P5BN afforded an interesting thermochromic shift of the emission over a wide temperature range.

Reversible Circular Dichroism Induced by Energy Losses without Changing Chirality of Structure

AbstractTunable circular dichroism (CD) is widely used in biology signal detection and chemical analysis. Researchers usually tune CD by changing the chirality and symmetry of nanostructures either directly or indirectly. Changes to a planar nanostructure's chirality are resisted by its structural reciprocity, which also constrains its CD tuning. However, the distribution of finite non‐radiative (ohmic) losses on a planar nanostructure will not be constrained by the reciprocity of structure. Here, a nanostructure is designed to tune the intensity of energy losses rather than change the chirality and symmetry of the whole structure. The results show that not only are the position and intensity of CD affected, but also the sign of the CD signal changes. These methods and results can help in utilizing the new approach to tune the modes and sign of a CD signal.

Enantioselective Synthesis of Planar Chiral Zigzag-Type Cyclophenylene Belts by Rhodium-Catalyzed Alkyne Cyclotrimerization.

Planar chiral zigzag-type [8]- and [12]cyclophenylene (CP) belts have been synthesized in good yields with high ee values of 98% and 83%, respectively, by the rhodium-catalyzed enantioselective intramolecular sequential cyclotrimerizations of the corresponding cyclic polyynes. The observed high enantioselectivity arises from the regioselective formation of a rhodacycle intermediate from an unsymmetric triyne unit. The X-ray crystal structural analysis of the racemic planar chiral zigzag-type [8]CP belt revealed that the uneven molecules mesh with each other to form a one-dimensional columnar packing structure, in which one column contains single enantiomers, giving two types of chiral columns [(S)- and (R)-form columns] arranged alternately. The ring strain of the zigzag-type [8]CP belt was smaller than that of the armchair-type [8]CPP belt despite its smaller ring size, due to the presence of the strain-relieving m-terphenyl moieties. The effect of the number of the benzene rings of the zigzag-type CP belts on absorption and emission peaks was small due to interruption of π-conjugation at the m-phenylene moieties. However, the bending effect on the absolute fluorescence quantum yield as well as absorption and emission peaks was significant. Concerning chiroptical properties, the modest anisotropy dissymmetry factors of ECD and CPL were observed in the [8]CP belt.

Pseudoasymmetry paradox: A suggestion to introduce the term pseudostereogenicity and address reflection issues

The confusion about the nomenclature of a tetrahedral carbon attached to a pair of enantiomorphic ligands (AR and AS) with the other two ligands different from each other as well as from A has been critically reexamined. Until now, this carbon has been known as a pseudoasymmetric center. However, according to Mislow, since asymmetry is the property of a molecule as a whole, it seems appropriate to replace ‘pseudoasymmetry’ with the term ‘pseudostereogenicity’. This is more relevant, particularly for molecules where different achiral ligands other than the enantiomorphic ones are attached to the pseudoasymmetric center. The molecule is not asymmetric as it has a S1 or σ plane. Another contentious issue is whether chiral molecules can be included in the domain of “pseudostereogenicity” and the related reflection invariance of the configuration (rectus remains rectus or sinister remains sinister). For chiral molecules containing such centers, the expectation is that the absolute configuration of the pseudoasymmetric center should invert upon reflection which is not the case as per the existing system. This article addresses all these issues like inclusion of chiral molecules bearing pseudoasymmetric center and making the center reflection variant by a simple introduction of a pilot atom based approach, which is already used in CIP system for planar chirality.

Pillararene Host-Guest Complexation Induced Chirality Amplification: A New Way to Detect Cryptochiral Compounds.

The contradiction between the rising demands of optical chirality sensing and the failure in chiral detection of cryptochiral compounds encourages researchers to find new methods for chirality amplification. Inspired by planar chirality and the host-guest recognition of pillararenes, we establish a new concept for amplifying CD signals of cryptochiral molecules by pillararene host-guest complexation induced chirality amplification. The planar chirality of pillararenes is induced and stabilized in the presence of the chiral guest, which makes the cryptochiral molecule detectable by CD spectroscopy. Several chiral guests are selected in these experiments and the mechanism of chiral amplification is studied with a non-rotatable pillararene derivative and density functional theory calculations. We believe this work affords deeper understanding of chirality and provides a new perspective for chiral sensing.

Pillararene Host–Guest Complexation Induced Chirality Amplification: A New Way to Detect Cryptochiral Compounds

AbstractThe contradiction between the rising demands of optical chirality sensing and the failure in chiral detection of cryptochiral compounds encourages researchers to find new methods for chirality amplification. Inspired by planar chirality and the host–guest recognition of pillararenes, we establish a new concept for amplifying CD signals of cryptochiral molecules by pillararene host–guest complexation induced chirality amplification. The planar chirality of pillararenes is induced and stabilized in the presence of the chiral guest, which makes the cryptochiral molecule detectable by CD spectroscopy. Several chiral guests are selected in these experiments and the mechanism of chiral amplification is studied with a non‐rotatable pillararene derivative and density functional theory calculations. We believe this work affords deeper understanding of chirality and provides a new perspective for chiral sensing.

Pagoda[4]arene and i-Pagoda[4]arene.

A new type of macrocyclic arenes, named pagoda[4]arene (P4) and i-pagoda[4]arene (i-P4), were conveniently synthesized by the TFA-catalyzed one-pot condensation of 2,6-dimethoxylanthracene and paraformaldehyde in dichloromethane at room temperature. P4 and i-P4 showed unique square pagoda structures and fixed conformations in solution and also exhibited strong blue fluorescence. Moreover, P4 and i-P4 with deep and rich-electron cavities could not only encapsulate n-hexane and one or two dichloromethane molecules in the solid state but also showed strong binding abilities toward neutral dinitriles with different chain lengths and various nitrogen-containing heterocyclic salts to form 1:1 stable host-guest complexes in both solution and the solid state. In particular, it was also found that with the increase in the alkyl chain length of the dinitriles, the association constants for their complexes with both P4 and i-P4 were markedly increased from glutaronitrile to octanedinitrile as a result of the deep cavities of the macrocycles and multiple intermolecular interactions. Since P4 and i-P4 had stable planar chirality, their efficient resolutions were further achieved by HPLC with a chiral column. Interestingly, the two enantiomers showed mirror-imaged CD signals and excellent CPL properties, which could allow them to have potential applications in chiral luminescent materials.

Tricyclic Sulfoxide–Alkene Hybrid Ligands for Chiral Rh(I) Complexes: The “Matched” Diastereomer Catalyzes Asymmetric C–C Bond Formations

Deprotonation of phenyldibenzo[b,f]tropylidene (8) with LDA/t-BuOK followed by quenching with either diastereomer of inexpensive glucose-based t-Bu-sulfinate (R)- or (S)-11 affords a sulfoxide–alkene hybrid ligand as the diastereomeric pairs (SS,SC)-9/(SS,RC)-10 and (RS,RC)-9/(RS,SC)-10, respectively, which via chromatographic/recrystallization may be separated into the four isomers. The optically pure diastereomeric ligands (SS,SC)-9 and (SS,RC)-10 react with [RhCl(coe)2]2 to form the dinuclear complexes (RS,SC)-11 and (RS,RC)-12, respectively, in which the bidentate ligands coordinate the metal centers through the sulfur and alkene donor functions. These complexes catalyze the conjugate addition of arylboronic acids to cyclic Michael acceptors with enantioselectivities of up to 99% ee. DFT calculations show the preponderant influence of planar chirality of the ligand alkene function. The enantioselectivity switch observed between (RS,SC)-11 and (RS,RC)-12 is explained by the inverted cis–trans coordinations of the substrate molecules in catalytic steps.

Combined Experimental and Theoretical Studies on Planar Chirality of Partially Overlapped C2-Symmetric [3.3](3,9)Dicarbazolophanes.

Partially overlapped dicarbazolophanes exhibit a planar chirality. In this study, C2-symmetrical [3.3](3,9)dicarbazolophane derivatives (CZ1-CZ3) have been optically resolved by preparative chiral high-performance liquid chromatography for the first time. In their circular dichroism (CD) spectra, moderate Cotton effects (CEs) were observed for their 1Lb and 1La transitions (|Δε| = 10-12 and 51-57 M-1 cm-1, respectively), while intense CEs were notified in their 1B transitions (|Δε| = 156-216 M-1 cm-1), absorption dissymmetry (gabs) factors being in orders of 10-2. Circularly polarized luminescence spectrum was also obtained for cyanamide derivative CZ1, with a comparative luminescence dissymmetry (glum) factor of 0.013. A computational investigation was applied to address the factors for such remarkable chiroptical responses in these dicarbazolophanes of planar chirality. Absolute configurations were unambiguously determined by the comparison of experimental and theoretical CD spectra, which was affirmed by the X-ray crystal structural analysis of enantiomerically pure sulfonamide derivative CZ2.

Enzymes lock in planar chirality

Biocatalysis Molecules with very large rings—macrocycles—are often conformationally constrained, and some exhibit planar chirality when substituents of the ring cannot rotate freely. Restricted rotation is generally valued in macrocycles because it can hold the molecule in functional conformations. Using a well-established lipase enzyme, Gagnon et al. developed a synthesis of planar chiral macrocycles with handles that can be easily functionalized. Computational docking suggests how using an enzyme as the catalyst for sequential acylation reactions can impart the observed stereochemistry. Science , this issue p. [917][1] [1]: /lookup/doi/10.1126/science.aaz7381

Biocatalytic synthesis of planar chiral macrocycles.

Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.