Chiral Elements Research Articles

An Efficient Synthesis of Chiral Catalyst: Application in Enantioselective Michael Addition Reactions

Asymmetric synthesis, also called stereoselective synthesis, chiral synthesis or enantioselective synthesis, is a form of organic synthesis which presentes one or more new elements of chirality. Use of catalysts is one of the most effective methods preferred by the researchers in recent years. It causes to the preferential formation of a stereoisomer rather than a constitutional isomer. In this study, tetraoxocalix[2]arene[2]triazine was synthesized firstly by using resorcinol and cyanuric chloride and then this starting material was derivatized with (R)-(-)-2-phenylglycinol to obtain tetraoxocalix[2]arene[2]triazine based chiral compound. Characterization of tetraoxocalix[2]arene[2]triazine was done by 1H and 13C NMR spectroscopy which is depicted in literature. Then, new organocatalyst, which possess an amino and a hydroxyl group, was designed and synthesized. The structure of the receptor characterized by FTIR, 1H spectroscopy, 13C NMR spectroscopy, optical rotation and elemental analysis measurement was also included. The newly prepared tetraoxocalix[2]arene[2]triazine derivative was employed as a chiral ligand in the enantioselective Michael addition of dimethylmalonate to conjugated nitroalkenes and good to excellent enantioselectivities were obtained. Various factors, (solvent, temperature, catalyst %) were examined and the reactions were optimized. The best condition for the Michael addition reaction was determined as room temperature, toluene as solvent and 10 mol% of heteroatom-bridged calixaromatic based chiral catalyst as organocatalyst loading. The catalytic efficiency of the chiral catalyst was analyzed by HPLC using chiral columns. The corresponding adducts were generally obtained in (S)-forms with great yields (up to 93%) and enantioselectivities (up to 95% ee).

Scalable Syntheses of Methoxyaspartate and Preparation of the Antibiotic Cystobactamid 861-2 and Highly Potent Derivatives.

An improved scalable synthesis of orthogonally functionalized methoxyaspartate, the chiral hinge region element in cystobactamids, is reported. This improvement sets the stage for the total synthesis of four new cystobactamids along with cystobactamid 861-2, whose antibacterial properties are determined and compared. The cyano derivative of cystobactamide 861-2 shows superior antibacterial activity against Gram-negative bacteria to any natural cystobactamide tested so far.

Liquid-Crystal-Mediated Geometric Phase: From Transmissive to Broadband Reflective Planar Optics.

Planar optical elements that can manipulate the multidimensional physical parameters of light efficiently and compactly are highly sought after in modern optics and nanophotonics. In recent years, the geometric phase, induced by the photonic spin-orbit interaction, has attracted extensive attention for planar optics due to its powerful beam shaping capability. The geometric phase can usually be generated via inhomogeneous anisotropic materials, among which liquid crystals (LCs) have been a focus. Their pronounced optical properties and controllable and stimuli-responsive self-assembly behavior introduce new possibilities for LCs beyond traditional panel displays. Recent advances in LC-mediated geometric phase planar optics are briefly reviewed. First, several recently developed photopatterning techniques are presented, enabling the accurate fabrication of complicated LC microstructures. Subsequently, nematic LC-based transmissive planar optical elements and chiral LC-based broadband reflective elements are reviewed systematically. Versatile functionalities are revealed, from conventional beam steering and focusing, to advanced structuring. Combining the geometric phase with structured LC materials offers a satisfactory platform for planar optics with desired functionalities and drastically extends exceptional applications of ordered soft matter. Some prospects on this rapidly advancing field are also provided.

Central (S) to Central (M=Ir, Rh) to Planar (Metallocene, M=Fe, Ru) Chirality Transfer Using Sulfoxide‐Substituted Mesoionic Carbene Ligands: Synthesis of Bimetallic Planar Chiral Metallocenes

Enantiopure bimetallic systems containing three different elements of chirality, namely a main-group-based chiral center (sulfur), a transition-metal chiral center (rhodium or iridium), and a planar chiral element (ferrocene or ruthenocene), have been prepared by a sequence of diastereoselective reactions. The chirality of the chiral sulfur center attached to C-5 of a 1,2,3-triazolylidene mesoionic carbene (MIC) ligand coordinated to a metal (Ir, Rh) was transferred through the formation of bimetallic complexes having a chiral-at-metal center and a planar chiral metallocene by C-H activation of the sandwich moiety (M=Fe, Ru). The sense of the planar chirality formed in this sequence of reactions depended on the nature of the ligands at the metal center of the starting complex. The configurations of these species were assigned on the basis of a combination of X-ray diffraction and CD measurements. An electrochemical study of these bimetallic complexes in coordinating solvents showed an equilibrium between the cationic complexes and the neutral species. The effect of the half-sandwich moiety on the oxidation potentials of the system is remarkable, producing notable cathodic displacements. DFT calculations support these findings.

Chirality makes a move.

Interlocked molecules can exhibit chiral stereogenic elements that are not found in covalently bound systems. Now, the shuttling of the ring in a [2]rotaxane has been shown to result in enantiomeric co-conformations that selectively bind chiral guests.

Enantioselective Folding of Enynes by Gold(I) Catalysts with a Remote C2-Chiral Element.

Chiral gold(I) catalysts have been designed based on a modified JohnPhos ligand with a distal C2-2,5-diarylpyrrolidine that creates a tight binding cavity. The C2-chiral element is close to where the C-C bond formation takes place in cyclizations of 1,6-enynes. These chiral mononuclear catalysts have been applied for the enantioselective 5-exo-dig and 6-endo-dig cyclization of different 1,6-enynes as well as in the first enantioselective total synthesis of three members of the carexane family of natural products. Opposite enantioselectivities have been achieved in seemingly analogous reactions of 1,6-enynes, which result from different chiral folding of the substrates based on attractive aryl-aryl interactions.

Orchestrating Communications in a Three-Type Chirality Totem: Remote Control of the Chiroptical Response of a Möbius Aromatic System.

Among the various types of chirality (central, axial, helical, planar, etc.), that inherent to Möbius topology remains almost unexplored, partly due to the difficulty to access Möbius compounds. Over the past decade, [28]hexaphyrins have been revealed to be among the best candidates to build on Möbius aromaticity. Whereas their flexibility needs to be controlled to get P/M twist enantioselectivity, it could be of great interest to sustain dynamic chirality transfer. In this context, we report herein the first example of a Möbius aromatic ring capped by a cavity, consisting of a Möbius [28]hexaphyrin doubly linked to an α-cyclodextrin. This unique design affords a "totem" of three different chirality elements arising from the cyclodextrin (fix central chirality), the bridging pattern (dynamic planar chirality), and the hexaphyrin (dynamic topological chirality). Chirality transfers (as shown in the TOC graphic) are characterized by a stereospecific planar-to-topological communication (diastereomeric excess >95%; the highest asymmetric selectivity reported to date for a Möbius ring) combined to a stereoselective central-to-planar communication (up to 60% diastereomeric excess). Interestingly, the stereoselectivity is remotely controlled by coordination of an achiral effector to the hexaphyrin, increasing up to 5 times the chiroptical response of the Möbius aromatic π-system. These results highlight the advantageous use of dynamic chirality transfers to further incorporate Möbius chirality and aromaticity into all kinds of stimuli-responsive devices.

Molecular and supramolecular helicity induction in trityl group-containing compounds: The case of chiral 3,3,3-triphenylpropionic acid derivatives

The process of dynamic chirality transmission from permanent chirality element to stereodynamic triphenylmethyl group placed in the distance of 4 bonds, has been studied for series of optically active 3,3,3-triphenylpropionic acid derivatives. Structural analysis, carried out with the use of complementary methods and supported by theoretical calculations, enabled us to determine the mechanism of chirality transmission. The observed chirality transfer phenomenon, demonstrated unequivocally as raising of non-zero Cotton effects in the region of UV absorption of trityl group, is a cascade process driven by weak intramolecular interactions. Despite the much larger inductor-effector distance, the sensitivity in chirogenesis is comparable to other stereodynamic probes reported so far. In the crystalline phase, the combination of trityl group with amino acid moiety results in the formation of helical superstructures, where individual molecules are held together by hydrogen bonding cascades. The proper combination of functionalities in the molecule skeleton allows, to some extent, the control over the association process and authorizes determination of the trityl group as the supramolecular synthon.

Development of Atroposelective Antibodies by Immunization with a Racemic Mixture of Binaphthyl Derivatives

Abstract The design and creation of chiral recognition elements are important for the synthesis, separation, and detection of chiral molecules. We prepare monoclonal antibodies (mAbs), which are chemically homogeneous antibodies, as tailored chiral recognition elements by immunizing mice with a racemic mixture of a binaphthyl derivative (BN (rac)) conjugated to keyhole limpet hemocyanin (KLH). Immunization with BN (rac) induces an immunoresponse that is as strong as that with enantiomerically pure antigens and yields mAbs for each enantiomer of BN, simultaneously. Notably, one of the mAbs prepared by immunization with BN (rac) recognizes the axial chirality of the BN enantiomer with a 14000-fold difference in affinity. These findings provide a strategy to obtain atroposelective antibodies for each enantiomer of BN with a single immunization. mAbs also recognize the axial chirality of 1,1′-bi-2-naphthol (BINOL) and 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BNPA), which are an important chiral building block and a chiral organic catalyst, respectively. The cross reactivity of mAbs for the partial structure of BN is significantly low. Therefore, mAbs recognize the axial chirality of BN, BINOL, and BNPA by binding their binaphthyl moiety.

Ancistrobreveines A-D and related dehydrogenated naphthylisoquinoline alkaloids with antiproliferative activities against leukemia cells, from the West African liana Ancistrocladus abbreviatus.

A unique series of six biaryl natural products displaying four different coupling types (5,1′, 7,1′, 7,8′, and 5,8′) were isolated from the roots of the West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Although at first sight structurally diverse, these secondary metabolites all have in common that they belong to the rare group of naphthylisoquinoline alkaloids with a fully dehydrogenated isoquinoline portion. Among the African Ancistrocladus species, A. abbreviatus is so far only the second one that was found to produce compounds with such a molecular entity. Here, we report on four new representatives, named ancistrobreveines A–D (12–14, and 6). They were identified along with the two known alkaloids 6-O-methylhamateine (4) and ent-dioncophylleine A (10). The two latter naphthylisoquinolines had so far only been detected in Ancistrocladus species from Southeast Asia. All of these fully dehydrogenated alkaloids have in common being optically active despite the absence of stereogenic centers, due to the presence of the rotationally hindered biaryl axis as the only element of chirality. Except for ent-dioncophylleine A (10), which lacks an oxygen function at C-6, the ancistrobreveines A–D (12–14, and 6) and 6-O-methylhamateine (4) are 6-oxygenated alkaloids, and are, thus, typical ‘Ancistrocladaceae-type’ compounds. Ancistrobreveine C (14), is the first – and so far only – example of a 7,8′-linked fully dehydrogenated naphthylisoquinoline discovered in nature that is configurationally stable at the biaryl axis. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR) and chiroptical (electronic circular dichroism) methods. Ancistrobreveine C (14) and 6-O-methylhamateine (4) exhibited strong antiproliferative activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000.

Antiprotozoal dimeric naphthylisoquinolines, mbandakamines B3 and B4, and related 5,8'-coupled monomeric alkaloids, ikelacongolines A-D, from a Congolese Ancistrocladus liana.

From the leaves of a botanically and phytochemically as yet unexplored Ancistrocladus liana discovered in the rainforests of the Central region of the Democratic Republic of the Congo in the vicinity of the town of Ikela, six new naphthylisoquinoline alkaloids were isolated, viz., two constitutionally unsymmetric dimers, the mbandakamines B3 (3) and B4 (4), and four related 5,8′-linked monomeric alkaloids, named ikelacongolines A–D (5a, 5b, 6, and 7). The dimers 3 and 4 are structurally unusual quateraryls comprising two 5,8′-coupled monomers linked via a sterically strongly constrained 6′,1′′-connection between their naphthalene units. These compounds contain seven elements of chirality, four stereogenic centers and three consecutive chiral axes. They were identified along with two known related compounds, the mbandakamines A (1) and B2 (2), which had so far only been detected in two Ancistrocladus species indigenous to the Northwestern Congo Basin. In addition, five known monomeric alkaloids, previously found in related Central African Ancistrocladus species, were isolated from the here investigated Congolese liana, three of them belonging to the subclass of 5,8′-coupled naphthylisoquinoline alkaloids, whereas two compounds exhibited a less frequently occurring 7,8′-biaryl linkage. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR), chemical (oxidative degradation), and chiroptical (electronic circular dichroism) methods. The mbandakamines B3 (3) and B4 (4) displayed pronounced activities in vitro against the malaria parasite Plasmodium falciparum and the pathogen of African sleeping sickness, Trypanosoma brucei rhodesiense.

Central-to-Helical-to-Axial-to-Central Transfer of Chirality with a Photoresponsive Catalyst.

Recent advances in molecular design have displayed striking examples of dynamic chirality transfer between various elements of chirality, e.g., from central to either helical or axial chirality and vice versa. While considerable progress in atroposelective synthesis has been made, it is intriguing to design chiral molecular switches able to provide selective and dynamic control of axial chirality with an external stimulus to modulate stereochemical functions. Here, we report the synthesis and characterization of a photoresponsive bis(2-phenol)-substituted molecular switch 1. The unique design exhibits a dynamic hybrid central-helical-axial transfer of chirality. The change of preferential axial chirality in the biaryl motif is coupled to the reversible switching of helicity of the overcrowded alkene core, dictated by the fixed stereogenic center. The potential for dynamic control of axial chirality was demonstrated by using (R)-1 as switchable catalyst to direct the stereochemical outcome of the catalytic enantioselective addition of diethylzinc to aromatic aldehydes, with successful reversal of enantioselectivity for several substrates.

Unidirectional light emission in PT-symmetric microring lasers.

The synergetic use of gain and loss in parity-time symmetric coupled resonators has been shown to lead to single-mode lasing operation. However, at the corresponding resonance frequency, an ideal ring resonator tends to support two degenerate eigenmodes, traveling along the cavity in opposite directions. Here, we show a unidirectional single-moded parity-time symmetric laser by incorporating active S-bend structures with opposite chirality in the respective ring resonators. Such chiral elements break the rotation symmetry of the ring cavities by providing an asymmetric coupling between the clockwise (CW) and the counterclockwise (CCW) traveling modes, hence creating a new type of exceptional point. This property, consequently, leads to the suppression of one of the counter-propagating modes. In this paper, we first measure the extinction ratio between the CW and CCW modes in a single ring resonator in the presence of an S-bend waveguide. We then experimentally investigate the unidirectional emission in PT-symmetric systems below and above the exceptional point. Finally, unidirectional emission will be shown in systems of two S-bend ring resonators coupled through a link structure.

Stereochemical Stability and Absolute Configuration of Atropisomeric Alkylthioporphyrazines by Dynamic NMR and HPLC Studies and Computational Analysis of HPLC‐ECD Recorded Spectra

The conformational and stereodynamic properties of a pyrene‐substituted ethylthioporphyrazine (PzPy), promising as a dye for organic optoelectronic applications and light‐harvesting systems, have been investigated by DFT computations and variable‐temperature NMR and HPLC. In PzPy, rotation around the pyrene–macrocycle bond is hindered and the molecule displays atropisomerism, existing as a pair of enantiomers, thus representing the first chiral alkyl‐porphyrazine to be reported in the literature. The rotational barrier (ΔG‡ ≈ 22.0 kcal mol–1), measured by variable‐temperature HPLC experiments, allows chromatographic separation of the enantiomers on a chiral stationary phase below 0 °C, whereas racemization spontaneously occurs at room temperature. The absolute configurations of the eluted enantiomers were also determined by computational analysis of their electronic circular dichroism spectra. The influence of alkyl chain length and metal complexation on the molecular stereodynamic properties have also been investigated by studying its novel octylthio derivative (PzPy‐octyl) and PdII complex (PdPzPy), respectively. The latter also is the first example of a PdII–alkylthioporphyrazine complex. Given that PzPy has been used in the preparation of hybrid materials with nanocarbons for optoelectronic applications, the presence of an axial chirality element may play a key role in its interaction with semiconducting chiral nanotubes.

Chiral Induction in [2+2+2] Cycloaddition Reactions

AbstractChiral compounds containing six‐membered rings, whether aromatic or not, are of interest in a wide range of disciplines, including material science, medicinal chemistry, and agrochemistry. As transition‐metal‐catalyzed [2+2+2] cycloaddition reactions are one of the most elegant routes for the construction of six‐membered rings, significant effort has been given to developing asymmetric variants. In this focus review, we bring together the work that has been done in optimizing diastereoselective [2+2+2] cycloaddition reactions of enantiomerically pure substrates. Two different approaches—chirality induction and chirality transfer—are considered in a review organized by the type of chiral element being constructed (central, axial, or helical). The general challenges that are involved are highlighted and possible future directions in the field are discussed.

Electrically and Optically Controlled Wideband Matching of Radio-Absorbing Composites to the Ambient Space

Microwave radio-absorbing metastructures are proposed that possess controlled broadband matching to the ambient space by virtue of an array of varactor-loaded chiral and annular elements in which magnetic resonance are excited. Experimentally in a rectangular waveguide and numerically in free space, it is shown that the tuning of the magnetic resonance frequency leads to a shift in the matching frequency region. The electric control of the magnetic resonance and, accordingly, the matching (25% relative tuning) is achieved by the variation in the reverse bias voltage at the varactor, and the optical control is achieved by directing a red laser pointer to a photodiode connected to the varactor in the photodiode mode.

α-Alkylation of N–C Axially Chiral Quinazolinone Derivatives Bearing Various ortho-Substituted Phenyl Groups: Relation between Diastereoselectivity and the ortho-Substituent

2-Ethylquinazolin-4-one derivatives bearing various ortho-substituted phenyl groups were revealed to possess a stable C–N axially chiral structure at ambient temperature. The reactions of alkyl halides with the anionic species prepared from these quinazolinones were systematically explored. The α-alkylation reactions proceeded with diastereoselectivities ranging from 1:1 to >50:1, depending upon the steric bulk of the ortho-substituent, to afford products having the elements of axial and central chirality in high yields (85–98%).

Divergent Control of Point and Axial Stereogenicity: Catalytic Enantioselective C-N Bond-Forming Cross-Coupling and Catalyst-Controlled Atroposelective Cyclodehydration.

Catalyst control over reactions that produce multiple stereoisomers is a challenge in synthesis. Control over reactions that involve stereogenic elements remote from one another is particularly uncommon. Additionally, catalytic reactions that address both stereogenic carbon centers and an element of axial chirality are also rare. Reported herein is a catalytic approach to each stereoisomer of a scaffold containing a stereogenic center remote from an axis of chirality. Newly developed peptidyl copper complexes catalyze an unprecedented remote desymmetrization involving enantioselective C-N bond-forming cross-coupling. Then, chiral phosphoric acid catalysts set an axis of chirality through an unprecedented atroposelective cyclodehydration to form a heterocycle with high diastereoselectivity. The application of chiral copper complexes and phosphoric acids provides access to each stereoisomer of a framework with two different elements of stereogenicity.

Divergent Control of Point and Axial Stereogenicity: Catalytic Enantioselective C−N Bond‐Forming Cross‐Coupling and Catalyst‐Controlled Atroposelective Cyclodehydration

AbstractCatalyst control over reactions that produce multiple stereoisomers is a challenge in synthesis. Control over reactions that involve stereogenic elements remote from one another is particularly uncommon. Additionally, catalytic reactions that address both stereogenic carbon centers and an element of axial chirality are also rare. Reported herein is a catalytic approach to each stereoisomer of a scaffold containing a stereogenic center remote from an axis of chirality. Newly developed peptidyl copper complexes catalyze an unprecedented remote desymmetrization involving enantioselective C−N bond‐forming cross‐coupling. Then, chiral phosphoric acid catalysts set an axis of chirality through an unprecedented atroposelective cyclodehydration to form a heterocycle with high diastereoselectivity. The application of chiral copper complexes and phosphoric acids provides access to each stereoisomer of a framework with two different elements of stereogenicity.

Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles

Understanding chirality, or handedness, in molecules is important because of the enantioselectivity that is observed in many biochemical reactions 1 , and because of the recent development of chiral metamaterials with exceptional light-manipulating capabilities, such as polarization control2-4, a negative refractive index 5 and chiral sensing 6 . Chiral nanostructures have been produced using nanofabrication techniques such as lithography 7 and molecular self-assembly8-11, but large-scale and simple fabrication methods for three-dimensional chiral structures remain a challenge. In this regard, chirality transfer represents a simpler and more efficient method for controlling chiral morphology12-18. Although a few studies18,19 have described the transfer of molecular chirality into micrometre-sized helical ceramic crystals, this technique has yet to be implemented for metal nanoparticles with sizes of hundreds of nanometres. Here we develop a strategy for synthesizing chiral gold nanoparticles that involves using amino acids and peptides to control the optical activity, handedness and chiral plasmonic resonance of the nanoparticles. The key requirement for achieving such chiral structures is the formation of high-Miller-index surfaces ({hkl}, h ≠ k ≠ l ≠ 0) that are intrinsically chiral, owing to the presence of 'kink' sites20-22 in the nanoparticles during growth. The presence of chiral components at the inorganic surface of the nanoparticles and in the amino acids and peptides results in enantioselective interactions at the interface between these elements; these interactions lead to asymmetric evolution of the nanoparticles and the formation of helicoid morphologies that consist of highly twisted chiral elements. The gold nanoparticles that we grow display strong chiral plasmonic optical activity (a dis-symmetry factor of 0.2), even when dispersed randomly in solution; this observation is supported by theoretical calculations and direct visualizations of macroscopic colour transformations. We anticipate that our strategy will aid in the rational design and fabrication of three-dimensional chiral nanostructures for use in plasmonic metamaterial applications.