Chiral Source Research Articles

Corrigendum to ‘Absolute asymmetric polymerizations in solution needing no physical chiral source’ [Polymer 245 (2022) 124673

Corrigendum to ‘Absolute asymmetric polymerizations in solution needing no physical chiral source’ [Polymer 245 (2022) 124673

Metallo‐Supramolecular Octahedral Cages with Three Types of Chirality towards Spontaneous Resolution

Chirality is one of the most important intrinsic properties of (supra)molecules. In this study, we obtained enantiomeric metallo-supramolecular octahedra without using any chiral sources. Such cages were self-assembled by prochiral trispyridine ligand L based on a C3h truxene core and CuII salts. Crystallization of the cages with BF4 - as counterions afforded racemate crystals; while crystallizations of cages with ClO4 - and OTf- as counterions resulted in conglomerates with spontaneous resolution. Three types of chirality were observed in each cage, including planar chirality of the truxene core, axial chirality from the pyridyl and truxene moieties, and propeller chirality of the pyridyl-CuII coordination sites. The cages reported here are among the largest discrete synthetic metallo-supramolecules ever reported with chiral self-sorting behavior. Remarkably, the chiral cages exhibited very slow racemization even at low concentrations, suggesting their high stability in solution.

Metallo‐Supramolecular Octahedral Cages with Three Types of Chirality towards Spontaneous Resolution

AbstractChirality is one of the most important intrinsic properties of (supra)molecules. In this study, we obtained enantiomeric metallo‐supramolecular octahedra without using any chiral sources. Such cages were self‐assembled by prochiral trispyridine ligand L based on a C3h truxene core and CuII salts. Crystallization of the cages with BF4− as counterions afforded racemate crystals; while crystallizations of cages with ClO4− and OTf− as counterions resulted in conglomerates with spontaneous resolution. Three types of chirality were observed in each cage, including planar chirality of the truxene core, axial chirality from the pyridyl and truxene moieties, and propeller chirality of the pyridyl‐CuII coordination sites. The cages reported here are among the largest discrete synthetic metallo‐supramolecules ever reported with chiral self‐sorting behavior. Remarkably, the chiral cages exhibited very slow racemization even at low concentrations, suggesting their high stability in solution.

Diastereoselective Synthesis of Chiral Oxathiazine 2‐Oxide Scaffolds as Sulfinyl Transfer Agents

AbstractAn efficient diastereoselective route for the preparation of chiral oxathiazine 2‐oxide scaffolds as sulfinyl transfer agents, using tert‐butanesulfinamide (tBSA) both as the source of chirality and as the precursor to the required nitrogen electron withdrawing group on the scaffold, was developed. This methodology allows the introduction of different substituents on the chiral scaffold, using commercially available reagents and standard synthetic transformations. The synthesized scaffolds were tested in the preparation of enantioenriched sulfinamides, providing results comparable to the sulfinyl transfer agents so far proposed in the literature, and opening the possibility to further elaborate these scaffolds, with the aim to support them on solid phases so to facilitate their recovery and reuse.magnified image

Asymmetric Synthesis of Pyrrolidines via Oxetane Desymmetrization.

Asymmetric synthesis of chiral pyrrolidines bearing an all-carbon quaternary stereocenter in the 3-position remains challenging. Herein we report two efficient protocols by means of oxetane desymmetrization, featuring the use of a readily available tert-butylsulfinamide chiral auxiliary and a catalytic system with chiral phosphoric acid as the source of chirality, respectively.

A structural study into halogenated derivatives of mandelic acid as building blocks of chiral coordination polymers

Mandelic acid and its derivatives are an excellent source of chirality for the construction of chiral coordination polymers (CPs) and metal-organic frameworks (MOFs) for enantioselective applications. To date, limited reports exist for the incorporation of mandelic acid derivatives with halogen substituents such as fluorine and chlorine despite the extra intermolecular interactions possible. The extra sites for hydrogen and halogen bonding in these mandelic acid derivatives may afford interesting modes of coordination and packing in 3 D space. Six CPs containing mandelic acid and its halogenated analogues, (R)-2-chloromandelic acid, 3,5-difluoromandelic acid, 4-trifluoromethylmandelic acid, together with linear dipyridyl co-ligands are reported. These structures consist of three 2 D sql sheets and three 1 D chains with a range of packing motifs influenced by the differing intermolecular interactions present.

Chiral Symmetry Breaking of Monoacylated Anhydroerythritols and meso‐1,2‐Diols through Crystallization‐Induced Deracemization

AbstractWe developed a chiral symmetry breaking method for monoacylated meso diols. The X‐ray crystal structure analysis of monoacylated 1,4‐anhydroerythritols, meso cyclic diols with a cis configuration, revealed that the O‐(p‐anisoyl) derivative crystallized as a racemic conglomerate of the P212121 crystal system. It was confirmed that the substrate racemized by intramolecular transfer of the acyl group in the presence of a catalytic amount of base. Evaporating the solvent gradually from the solution or Viedma ripening to promote crystallization‐induced deracemization efficiently led to enantiomer crystals. These results provide the first successful example of asymmetric expression and amplification by deracemization of sugar derivatives without an external chemical chiral source. Furthermore, we applied this methodology to acyclic meso‐1,2‐diols. Three O‐monoacylated substrates were successfully deracemized to 99 % ee by Viedma ripening. We also developed asymmetric desymmetrization of meso‐1,2‐diols by combining acylation and crystallization‐induced deracemization.

Chiral Symmetry Breaking of Monoacylated Anhydroerythritols and meso-1,2-Diols through Crystallization-Induced Deracemization.

We developed a chiral symmetry breaking method for monoacylated meso diols. The X-ray crystal structure analysis of monoacylated 1,4-anhydroerythritols, meso cyclic diols with a cis configuration, revealed that the O-(p-anisoyl) derivative crystallized as a racemic conglomerate of the P21 21 21 crystal system. It was confirmed that the substrate racemized by intramolecular transfer of the acyl group in the presence of a catalytic amount of base. Evaporating the solvent gradually from the solution or Viedma ripening to promote crystallization-induced deracemization efficiently led to enantiomer crystals. These results provide the first successful example of asymmetric expression and amplification by deracemization of sugar derivatives without an external chemical chiral source. Furthermore, we applied this methodology to acyclic meso-1,2-diols. Three O-monoacylated substrates were successfully deracemized to 99 % ee by Viedma ripening. We also developed asymmetric desymmetrization of meso-1,2-diols by combining acylation and crystallization-induced deracemization.

Use of Non‐Aromatic Hydrophobic α‐Amino Acids (α‐AA) and Non‐Amino Acid Derived Synthons: Comparative Studies Towards Total Syntheses of Selected Bioactive Natural Alkaloids

AbstractEnantiomerically pure non‐aromatic α‐amino acids having hydrophobic side chains (Isoleucine, Valine, Leucine, Methionine and Alanine) have been acknowledged as an important chiral pool. The wide range of chemical and biological applications associated with these α‐amino acids has encouraged organic chemists to develop new synthetic methodologies for the total synthesis of bioactive molecules. In this review, the synthetic routes of 10 bioactive natural alkaloids have been covered. The present article is an attempt to discuss various synthetic approaches of therapeutically active natural alkaloids and related diversity from non‐aromatic hydrophobic α‐amino acids and non‐amino acid derived synthetic approaches to present a comparative study between the methods. The synthetic steps and the key strategies involved in the total synthesis of selected natural alkaloids have been compared based on atom economy, overall chemical yield, stereoselectivity and sustainability with cost effective manner by using inexpensive commercially available starting materials but the source of chiral pool mainly α‐amino acids to target natural alkaloids in chiral synthesis will be playing an important role. In selected cases of alkaloids synthesized from non‐amino acid route, an external chiral source of induction like metal and organometallic catalysts to generate chirality in the molecule are used.

Absolute asymmetric polymerizations in solution needing no physical chiral source

Absolute asymmetric polymerizations, which do not need chiral compounds, are very limited. In addition, they involve spontaneously formed supramolecular compounds, or they need circularly polarized light, and the resulting polymers are often insoluble showing no chiral information at the molecular level. Here we have achieved five kinds of real absolute asymmetric polymerizations of achiral acetylene monomers showing no CD in solution to yield soluble high MW chiral polymers showing CD peaks in solution. These polymerizations did not contain spontaneously formed chiral crystals of monomers or did not use circularly polarized light. A new mechanism we propose here for this new unusual polymerization will give us clues to a better understanding of the reason for the homochirality of our world.

Molecular Chirality and Morphological Structural Chirality of Exogenous Chirality-Induced Liquid Crystalline Block Copolymers

Chiral expression from the molecular to macromolecular level, as well as aggregates, plays an important role in natural physiological activity. Therefore, understanding the chirality transfer mechanism will provide guidance for the design of new functional chiral materials. Herein, we have systematically investigated the chiral assembly and transfer from the molecular to morphological level in liquid crystalline block copolymers (LC-BCPs) induced by enantiopure tartaric acid (TA) as a chiral source. Both the experimental and theoretical results indicate that the self-organization of the liquid crystal side chains and H-bonding interactions formed between the chiral additive and LC-BCPs are key factors for chiral expression in the self-assembly of LC-BCPs doped with TA. Furthermore, the various morphologies, including particles, spheres, worms, helical cylinders, and spirals, were observed in the LC-BCPs using transmission electron microscopy. The strength of the liquid crystal related to the azobenzene side chain structure has a crucial effect on the morphological transition. This work provides guidance for the design of diverse chiral nanostructures in a chiral molecule-induced achiral polymer system and may establish a fabrication platform for chiral cryptography, optical metamaterials, and other potential applications.

Planar Chirality and Optical Spin-Orbit Coupling for Chiral Fabry-Perot Cavities.

We design, in a most simple way, Fabry–Perot cavities with longitudinal chiral modes by sandwiching between two smooth metallic silver mirrors a layer of polystyrene made planar chiral by torsional shear stress. We demonstrate that the helicity-preserving features of our cavities stem from a spin–orbit coupling mechanism seeded inside the cavities by the specific chiroptical features of planar chirality. Planar chirality gives rise to an extrinsic source of three-dimensional chirality under oblique illumination that endows the cavities with enantiomorphic signatures measured experimentally and simulated with excellent agreement. The simplicity of our scheme is particularly promising in the context of chiral cavity QED and polaritonic asymmetric chemistry.

Ru-catalyzed mechanochemical asymmetric transfer hydrogenations in aqueous media using chitosan as chirality source

As the demand for sustainable methods increases, synthetic chemistry is focusing on the application of environmentally benign methods, such as fast reactions induced by alternative energy transmission. Chitosan is a chiral biopolymer of natural origin, which can be used in asymmetric catalysis. The application of Ru-chitosan complexes along with the mechanochemical activation may open great opportunities for sustainable preparation of optically pure alcohols. In the present study, we optimized the mechanochemical asymmetric transfer hydrogenation of 4-chromanone, carried out in a mixing mill. The reaction was catalyzed by the in situ formed Ru-chitosan complex, applying HCOONa as the hydrogen donor in aqueous media. We examined the mechanical effects of different grinding media sizes, then explored the scope of the system using 24 prochiral ketones, which ranged from hetero- and carbocyclic ketones to acetophenone derivatives. In most of the cases, the reactions were successfully scaled up to 1 mmol and the products were isolated in good yields and outstanding enantioselectivities. Our present study is a significant step forward to the development of environmentally benign and sustainable enantioselective processes, as the alternative activation method provided optically enriched alcohols using a biodegradable chirality source in aqueous media.

Natural deep eutectic solvent assisted synthesis and applications of chiral carbon dots

Novel N, Cl-doped chiral carbon dots (CCDs) were prepared for the first time through a one-step hydrothermal method using vine tea as the precursor, and natural deep eutectic solvents as the eco-friendly solvent, doping agent, and chiral source.

Building permanently optically active particles from an absolutely achiral polymer

A novel strategy has developed for constructing polymer particles with permanent chirality by partially cross-linking the azobenzene units to allow perfect recovery of the destroyed helical superstructure without any chiral sources.

CPL on/off control of an assembled system by water soluble macrocyclic chiral sources with planar chirality

Herein, we report the synthesis and planar chiral properties of a pair of water-soluble cationic pillar[5]arenes with stereogenic carbons. Interestingly, although units of the molecules were rotatable, only one planar chiral diastereomer existed in water in both cases. As a new type of chiral source, these molecules transmitted chiral information from the planar chiral cavities to the assembly of a water-soluble extended π-conjugated compound, affording circularly polarized luminescence (CPL). The chirality transfer process and resulting CPL were extremely sensitive to the feed ratio of the chiral pillar[5]arenes owing to the combined action of their planar chirality, bulkiness, and strong binding properties. When a limited amount of chiral source was added, further assembly of the extended π-conjugated compound into helical fibers with CPL was triggered. Unexpectedly, larger amounts of chiral source destroyed the helical fiber assemblies, resulting in elimination of the chirality and CPL properties from the assembled structures.

Pd(II)-Catalyzed Azine-Assisted Enantioselective Oxidative C-H/C-H Cross-Coupling of Ferrocenes with Various Heteroarenes.

A palladium(II)-catalyzed enantioselective oxidative cross-coupling of ferrocenes with heteroarenes is described. Mono-N-protected amino acids can be used as sources of chirality. With azine as an efficient directing group, various substituted planar chiral ferrocenes were obtained via a dual C-H bond activation pathway in medium yields (up to 72%) with good enantioselectivity (up to 89.4:10.6 er) under mild conditions.

Controlling the polarization of chiral dipolar emission with a spherical dielectric nanoantenna.

Circularly polarized light (CPL) carrying spin angular momentum is crucial to many applications, such as quantum computing, optical communication, novel displays, and biosensing. Nonetheless, the emission from chiral molecules contains comparable CPL components with opposite handedness, resulting in low levels of CPL overall with a small dissymmetry factor and fixed handedness consistent with the handedness of the molecules. Nanoantennas have proved to be useful tools for controlling the emission properties of quantum emitters. In particular, dielectric resonators support electric and magnetic modes, which implies unparalleled opportunities to interact with chiral molecules whose emission originates from both electric and magnetic dipole transitions. In this work, we theoretically study the effects of a spherical dielectric nanoantenna on the directionality and polarization of emission from a chiral molecule. With exact analytical solutions based on generalized Mie theory, we show that directional chiral light emission and nontrivial polarization modulation, such as handedness reversal or chirality enhancement, can be achieved simultaneously for a chiral dipole tangentially coupled with a silicon nanosphere. The influence of the relative strength and orientation between the electric and magnetic dipole moments is also discussed. Our results suggest a new approach to controlling chiral dipolar emission and could benefit the development of chiral light sources.

Recent Development of Bis-Cyclometalated Chiral-at-Iridium and Rhodium Complexes for Asymmetric Catalysis.

The field of asymmetric catalysis has been developing to access synthetically efficacious chiral molecules from the last century. Although there are many sustainable ways to produce nonracemic molecules, simplified and unique methodologies are always appreciated. In the recent developments of asymmetric catalysis, chiral-at-metal Lewis acid catalysis has been recognized as an attractive strategy. The catalysts coordinatively activate a substrate while serving the sole source of chirality by virtue of its helical environment. These configurationally stable complexes were utilized in a large number of asymmetric transformations, ranging from asymmetric Lewis acid catalysis to photoredox and electrocatalysis. Here we provide a comprehensive review of the current advancements in asymmetric catalysis utilizing iridium and rhodium-based chiral-at-metal complexes as catalysts. First, the asymmetric transformations via LUMO and HOMO activation assisted by a chiral Lewis acid catalyst are reviewed. In the second part, visible-light-induced asymmetric catalysis is summarized. The asymmetric transformation via the electricity-driven method is discussed in the final section.

Enantiodivergent Reaction of Ketimines with Malononitriles Using Single Cinchona Alkaloid Sulfonamide Catalysts

AbstractWe report the enantiodivergent reaction of ketimines derived from α‐ketoesters with malononitriles using a single chiral source. The reactions using an 8‐quinolinesulfonyl cinchona alkaloid catalyst in the presence and absence of Et2Zn gave both enantiomers in high yields with high enantioselectivities (53∼99% yield, 99:1∼3:97 er). The obtained malononitrile‐derived α‐amino acids were converted into various optically active compounds. A reaction mechanism is proposed to explain the observed enantiodivergency.magnified image