Chiral Organic Compounds Research Articles

Cobalt-Catalyzed Regio- and Enantioselective Hydroalkylation of 1,1-Disubstituted Styrenes

AbstractThe metal hydride catalyzed alkene hydroalkylation enables efficient alkyl–alkyl coupling, yielding structurally diverse chiral organic compounds. However, the control of stereochemical selectivity in alkene hydroalkylation still heavily relies on the assistance of substrate Lewis basic functional groups or polar heteroatom functional groups. We have recently developed a cobalt hydride catalytic system and established a paradigm of enantioselective control assisted by C–H···π noncovalent interactions. This approach enables the asymmetric hydroalkylation of 1,1-disubstituted styrenes, thereby circumventing the limitations imposed by substrate heteroatom functional groups.1 Introduction2 Reaction Development3 Synthetic Applications4 Mechanistic Investigation5 Conclusion and Future Outlook

A Chiral Hexa-amino Cyclotriphosphazene for Enantioselective Recognition of Small Organic Compounds.

Chiral recognition and separation studies are of paramount importance in research in view of their applications in asymmetric catalysis and substrate recognition in biological processes. The efficiencies of these processes are governed by the subtle differences in noncovalent interactions between the host and guest molecules. Hexakis(organoamino)phosphazenes are versatile building blocks for host-guest chemistry for their ability to act as both the donor and the acceptor of H-bonds. Herein, we report an enantiomeric pair of cyclotriphosphazenes [P3N3(NHR*)6], [R* = (R)-(CH(CH3)Ph)] (1-R) and [(S)-(CH(CH3)Ph)] (1-S), with chiral α-methylbenzylamino substituents. The chiral recognition capabilities of its R-enantiomer were further probed for several chiral organic compounds containing a range of functional groups. Among these, a remarkable guest selectivity (ξ) value of 2506 was observed for binol (BOL) in favor of its R-enantiomer. DFT-optimized structures of the host-guest pairs suggest that the multiple noncovalent interactions between the molecules in the two unique types of binding sites at the phosphazenes play a crucial role in the observed high binding selectivities.

Cellulose supported TiO2/Cu2O for highly asymmetric conjugate addition of α,β-unsaturated compounds in aqueous phase

A series of new kind green cellulose-supported bimetallic TiO2/Cu2O (Cell@TiO2/Cu2O) catalytic materials were obtained by in-situ reduction method employing cellulose as the carrier. The effects of metal percentage composition on the morphology and construction of the catalytic materials were systematically investigated. The Cell@TiO2/Cu2O were characterized by FT-IR, TG, XPS, SEM, TEM, EDS, and the element content was obtained by elemental analysis. Then, the achieved catalytic materials were applied to the chiral borylation reaction of α,β-unsaturated compounds, including nitrile compounds, esters, and α,β-unsaturated ketones. Remarkably, this approach provides an efficient strategy to gain an important class of chiral organic boron compounds with target chiral products in high yields as well as enantioselectivities. Besides, the Cell@TiO2/Cu2O could be easily recycled and effectively reused. This work constructed bimetallic TiO2/Cu2O on cellulose as a newly catalyst to obtain chiral boron compounds in aqueous phase.

Chiral Recognition of Chiral (Hetero)Cyclic Derivatives Probed by Tetraaza Macrocyclic Chiral Solvating Agents via 1H NMR Spectroscopy.

In the field of chiral recognition, chiral cyclic organic compounds, especially heterocyclic organic compounds, have attracted little attention and have been rarely studied as chiral substrates by means of 1H NMR spectroscopy. In this paper, enantiomers of thiohydantoin derivatives, representing typical five-membered N,N-heterocycles, have been synthesized and utilized for assignment of absolute configuration and analysis of enantiomeric excess. All enantiomers have been successfully differentiated with the assistance of novel tetraaza macrocyclic chiral solvating agents (TAMCSAs) by 1H NMR spectroscopy. Surprisingly, unprecedented nonequivalent chemical shift values (up to 2.052 ppm) of the NH proton of substrates have been observed, a new milestone in the evaluation of enantiomers. To better understand the intermolecular interactions between host and guest, Job plots and theoretical calculations of (S)-G1 and (R)-G1 with TAMCSA 1a were investigated and revealed significant geometric differentiation between the diastereomers. In order to evaluate practical applications of the present systems in analyzing optical purity of chiral substrates, enantiomeric excesses of a typical substrate (G1) with different optical compositions in the presence of a representative TAMCSA (1a) can be accurately calculated based on the integration of the NH proton's signal peaks. Importantly, this work provides a significant breakthrough in exploring and developing the chiral recognition of chiral heterocyclic organic compounds by 1H NMR spectroscopy.

Bridging of Cove Regions: A Strategy for Realizing Persistently Chiral Double Heterohelicenes with Attractive Luminescent Properties

AbstractThe racemization of chiral organic compounds is a common chemical phenomenon. However, it often poses configurational‐stability issues to the application of this class of compounds. Achieving chiral organic compounds without the risk of racemization is fascinating, but it is challenging due to a lack of strategies. Here, we reveal the cove‐regions bridging strategy for achieving persistently chiral multi‐helicenes (incapable of racemization), based on the synthesized proof‐of‐concept double hetero[4]helicenes featuring macrocycle structures with a small 3D cavity. Additionally, we demonstrate that the strategy is also effective in tuning the electronic structures of multi‐helicenes, resulting in a conversion from luminescence silence into thermally activated delayed fluorescence (TADF) for the present system. Furthermore, red circularly polarized TADF based on small double [4]helicene systems is achieved for the first time using this strategy. The disclosed cove‐regions bridging strategy provides an opportunity to modulate the electronic structures and luminescent properties of multi‐helicenes without concern for racemization, thus significantly enhancing the structural and property diversity of multi‐helicenes for various applications.

Bridging of Cove Regions: A Strategy for Realizing Persistently Chiral Double Heterohelicenes with Attractive Luminescent Properties.

The racemization of chiral organic compounds is a common chemical phenomenon. However, it often poses configurational-stability issues to the application of this class of compounds. Achieving chiral organic compounds without the risk of racemization is fascinating, but it is challenging due to a lack of strategies. Here, we reveal the cove-regions bridging strategy for achieving persistently chiral multi-helicenes (incapable of racemization), based on the synthesized proof-of-concept double hetero[4]helicenes featuring macrocycle structures with a small 3D cavity. Additionally, we demonstrate that the strategy is also effective in tuning the electronic structures of multi-helicenes, resulting in a conversion from luminescence silence into thermally activated delayed fluorescence (TADF) for the present system. Furthermore, red circularly polarized TADF based on small double [4]helicene systems is achieved for the first time using this strategy. The disclosed cove-regions bridging strategy provides an opportunity to modulate the electronic structures and luminescent properties of multi-helicenes without concern for racemization, thus significantly enhancing the structural and property diversity of multi-helicenes for various applications.

Recent advances in circularly polarized luminescence of planar chiral organic compounds.

Circularly polarized luminescence (CPL), as an important chiroptical phenomenon, can not only directly characterize excited-state structural information about chiroptical materials but also has great application prospects in 3D optical displays, information storage, biological probes, CPL lasers and so forth. Recently, chiral organic small molecules with CPL have attracted a lot of research interest because of their excellent luminescence efficiency, clear molecular structures, unique flexibility and easy functionalization. Planar chiral organic compounds make up an important class of chiral organic small molecular materials and often have rigid macrocyclic skeletons, which have important research value in the field of chiral supramolecular chemistry (e.g., chiral self-assembly and chiral host-guest chemistry). Therefore, research into planar chiral organic compounds has become a hotspot for CPL. It is time to summarize the recent developments in CPL-active compounds based on planar chirality. In this feature article, we summarize various types of CPL-active compounds based on planar chirality. Meanwhile, we overview recent research in the field of planar chiral CPL-active compounds in terms of optoelectronic devices, asymmetric catalysis, and chiroptical sensing. Finally, we discuss their future research prospects in the field of CPL-active materials. We hope that this review will be helpful to research work related to planar chiral luminescent materials and promote the development of chiral macrocyclic chemistry.

ENANTIOSELECTIVE AND CHEMOSELECTIVE OPTICAL DETECTION OF CHIRAL ORGANIC COMPOUNDS WITHOUT RESORTING TO CHROMATOGRAPHY.

Enantiorecognition and resolution are of essential importance in many diverse areas of science. Whenever there arises a need to analyze/investigate enantiomers in different situations chromatography stands up in our minds immediately. Nevertheless, chemoselective and enantioselective recognition/discrimination (without going for separation) constitutes a different perception and requirement. The techniques using chiroptical sensing cause detection based on molecular interactions induced in different manners. Enantioselective sensing of monosaccharides in γ-cyclodextrin assembly and by diboronic acid based fluorescent sensors, application of bi-naphthol and H8BINOL based sensors and dendrimers, metal-to-ligand charge transfer transitions in CD, exciton-coupled circular dichroism, surface enhanced Raman spectroscopy, and enantioselective indicator displacement sensor arrays for enantioselective recognition/detection of chiral organic compounds, such as amines, amino acids/alcohols, and hydroxycarboxylic acids have been discussed in progressive manner with mechanistic explanations, wherever available. Besides, the chiroptical vs LC approach has been discussed. The present paper is focused on certain different non-chromatographic optical techniques and aims to extend an understanding and a view to consider such techniques which have been successful in selective detection, and determination of absolute configuration and enantiomeric excess, (without resorting to separation vis-à-vis LC) and that have potential use in high-throughput chiral assay and combinatorial search for asymmetric catalysts and reagents.

Stereogenic π-Conjugated Macrocycles: Synthesis, Structure, and Chiroptical Properties Including Circularly Polarized Luminescence

AbstractHighly symmetrical and aesthetically pleasing molecules have attracted the attention of organic chemists. We synthesized new highly symmetric stereogenic π-conjugated macrocycles with planar or axial chirality. Macrocyclic oligomers synthesized by Yamamoto coupling or Suzuki–Miyaura cross-coupling from the π-unit containing chirality. These cyclization reactions gave multiple oligomers in relatively high yields. We then elucidated their structures and investigated their chiroptical properties, including circular dichroism (CD) and circularly polarized luminescence (CPL). Because of the selection rule for rigid and symmetric structures, these macrocycles exhibit a high dissymmetry factor (g abs or g lum) for circularly polarized light in CD or CPL. Several rigid cyclic compounds retain a highly symmetric structure in the excited state and exhibit higher g lum values than common chiral organic compounds. This Account provides a brief background regarding chiroptical properties, followed by a summary of the various macrocycles synthesized in this study. We are glad if this Account will be a source of ideas not only for chemists working with π-conjugated compounds, but also for synthetic chemists working with chiral compounds, especially those engaged in asymmetric synthesis.1 Introduction2 Brief Description of Chiroptical Properties3 Stereogenic Macrocycle Based on [2.2]Paracyclophane3.1 Stereogenic Double-decker Oligothiophene3.2 Stereogenic Biselenophene Macrocycle3.3 Helical Oligophenylene Linked with [2.2]Paracyclophane4 Stereogenic Macrocycle Based on Binaphthyl4.1 Cyclic Oligomer of Chiral Binaphthyl4.2 Doubly Twisted Binaphthyl Dimer4.3 Cyclic Oligomer of Binaphthyl Extended with Paraphenylene4.4 Curved Helical Paraphenylene Anchoring Chiral Binaphthyl4.5 Binaphthyl-Hinged [5]-Helicene5 Summary

Spin-induced nanomaterials for detection of chiral volatile organic compounds

The capacity to recognize chiral Volatile Organic Compounds (VOCs) is a noteworthy element in many areas, for example, chemistry, pharmacology, and ecological observing. This review centers around the recent advancements in the field of spin-based chiral recognition, with the potential to improve the detection and classification of chiral VOCs in wearable, convenient, low-power, and with least human contribution. It will present and discuss the utilization of chiral molecules and helical structures to impact the spin course of electrons going through them, offering another way for chiral recognition of VOCs. Different dimensionalities of nano materials and related hypothetical leaps forward will be presented and discussed, which could pave the way for smart and miniaturized chiral recognition devices. These devices would empower quicker and more precise location of chiral VOCs in different settings, making them advantageous for a scope of applications later on.

Nanomaterials may offer smaller, low-power alternative to detecting chiral volatile organic compounds

Harnessing spin selection in chiral molecules miniaturizes sensors and expands applications for VOC detection.

Asymmetric Access to Boryl-Substituted Vicinal Aminoalcohols through Cu-Catalyzed Reductive Coupling.

Herein, we report the development of a Cu-catalyzed enantioselective borylative aminoallylation of aldehydes using a N-substituted allene to access boryl-substituted 1,2-aminoalcohol synthons for diversification to chiral heteroatom-rich organic compounds. The reported reaction provides access to several different substitution patterns of chiral 1,2-aminoalcohol products from the same readily available starting materials with high diastereo- and enantioselectivity.

Transition metal-catalyzed construction of C-X bonds via cleavage of C-N bond of quaternary ammonium salts

<abstract> <p>Amines are abundant in natural product chemistry and are readily available chemical raw materials. The C-N bonds of amines are difficult to break due to the large C-N bond energy. In recent years, chemists have developed a variety of activation methods for amino groups of amines. Among these reported methods, to convert amines into quaternary ammonium salts is preferred, for quaternary ammonium salts are readily available and stable. In recent years, great progress has been achieved in the study of transition metal-catalyzed construction of various C-X bonds involving aromatic amines and benzyl amines-derived quaternary ammonium salts by cleavage of C-N bonds. This review describes the transition metal-catalyzed reaction of quaternary ammonium salts to construct C-X bonds by cleavage of C-N bond. Moreover, if chiral benzylamines-derived quaternary ammonium salts are used, a variety of highly enantiomeric pure chiral organic compounds can also be obtained. The chirality of quaternary ammonium salts remained good in the products and all reactions underwent S<sub>N</sub>2-type configuration inversion.</p> </abstract>

Redox Biocatalysis: Quantitative Comparisons of Nicotinamide Cofactor Regeneration Methods.

Enzymatic processes, particularly those capable of performing redox reactions, have recently been of growing research interest. Substrate specificity, optimal activity at mild temperatures, high selectivity, and yield are among the desirable characteristics of these oxidoreductase catalyzed reactions. Nicotinamide adenine dinucleotide (phosphate) or NAD(P)H-dependent oxidoreductases have been extensively studied for their potential applications like biosynthesis of chiral organic compounds, construction of biosensors, and pollutant degradation. One of the main challenges associated with making these processes commercially viable is the regeneration of the expensive cofactors required by the enzymes. Numerous efforts have pursued enzymatic regeneration of NAD(P)H by coupling a substrate reduction with a complementary enzyme catalyzed oxidation of a co-substrate. While offering excellent selectivity and high total turnover numbers, such processes involve complicated downstream product separation of a primary product from the coproducts and impurities. Alternative methods comprising chemical, electrochemical, and photochemical regeneration have been developed with the goal of enhanced efficiency and operational simplicity compared to enzymatic regeneration. Despite the goal, however, the literature rarely offers a meaningful comparison of the total turnover numbers for various regeneration methodologies. This comprehensive Review systematically discusses various methods of NAD(P)H cofactor regeneration and quantitatively compares performance across the numerous methods. Further, fundamental barriers to enhanced cofactor regeneration in the various methods are identified, and future opportunities are highlighted for improving the efficiency and sustainability of commercially viable oxidoreductase processes for practical implementation.

Covalent Organic Frameworks-Based Membranes as Promising Modalities from Preparation to Separation Applications: An Overview.

Covalent organic frameworks (COFs) are a promising class of porous crystalline materials made up of covalently connected and periodically protracted network topologies through organic linkers. The tailorability of organic linker and intrinsic structures endow COFs with a tunable porosity and structure, low density, facilely-tailored functionality, and large surface area, attracting increasing amount of interests in variety of research areas of membrane separations. COF-based membranes have spawned a slew of new research projects, ranging from fabrication methodologies to separation applications. Herein, we tried to emphasis the major developments in the synthetic approaches of COFs based membranes for a variety of separation applications such as, separation of gaseous mixtures, water treatment as well as separation of isomeric and chiral organic compounds. The proposed methods for fabricating COF-based continuous membranes and columns for real world applications are also thoroughly explored. Finally, a viewpoint on the future directions and remaining challenges for COF research in the area of separation is provided.

Chirality Induced Crystal Structural Difference in Metal Halide Composites

AbstractIncorporating chiral organic compounds into metal halide frames is a common and useful method to introduce chirality in metal halide composites. The structures of resulting racemic and chiral composites are usually considered to be nearly identical owing to similar chemical bonding. In this work, by incorporating chiral MBABr (bromide methylbenzylamine) into an inorganic frame, a significant crystallization difference between the resulting racemic and chiral metal halide composites is observed, as confirmed by both structural and spectroscopic measurements. In addition, the structural transformation in the chiral composites can also be induced by moisture, ascribed to the asymmetric hydrogen bonding in chiral materials. These results provide new insights for the future synthesis of chiral materials and open up new possibilities to advance the materials functionalities.

Stereodivergent Desymmetrization of Simple Dicarboxylates via Branch-Selective Pd/Cu Catalyzed Allylic Substitution.

Asymmetric desymmetrization has been demonstrated to be a powerful strategy for building stereocenters in asymmetric synthesis. Herein, a Pd/Cu catalyzed asymmetric desymmetrization reaction with a simple geminal dicarboxylate is reported. A wide scope of imino esters bearing an aryl or heteroaromatic group were compatible with this bimetallic catalytic system. The reactions proceeded smoothly, giving the desired products in good yields with high to excellent regio-, diastereo-, and enantioselectivity (up to 20 : 1 branched:linear, >20 : 1 dr, >99 % ee). Notably, the reaction favored branched selectivity, which is unusual for the Pd-catalyzed allylic alkylation reaction. In addition, the standard product could be easily transformed to other valuable molecules such as chiral allylic alcohols, carbamates, and organic boron compounds. Furthermore, DFT calculations were conducted to explain the origin of the branched selectivity.

ECD exciton chirality method today: a modern tool for determining absolute configurations.

The application of the exciton chirality method (ECM) to interpret electronic circular dichroism (ECD) spectra is a well‐established and still popular approach to assign the absolute configuration (AC) of natural products, chiral organic compounds, and organometallic species. The method applies to compounds containing at least two chromophores with electric dipole allowed transitions (e.g., π–π* transitions). The exciton chirality rule correlates the sign of an exciton couplet (two ECD bands with opposite sign and similar intensity) with the overall molecular stereochemistry, including the AC. A correct application of the ECM requires three main prerequisites: (a) the knowledge of the molecular conformation, (b) the knowledge of the directions of the electric transition moments (TDMs), and (c) the assumption that the exciton coupling mechanism must be the major source of the observed ECD signals. All these prerequisites can be easily verified by means of quantum‐mechanical (QM) calculations. In the present review, we shortly introduce the general principles that underpin the use of the ECM for configurational assignments and survey its applications, both classic ones and some reported in the recent literature. Based on these examples, we will stress the advantages of the ECM but also the key requisites for its correct application. Additionally, we will discuss the dependence of the couplet sign on geometrical parameters (angles α,β,γ between TDMs), which can be helpful for discerning the sign of exciton chirality in ambiguous situations. Finally, we will present a molecular orbital (MO) description of the exciton coupling phenomenon.

Thiourea Organocatalysts as Emerging Chiral Pollutants: En Route to Porphyrin-Based (Chir)Optical Sensing

Environmental pollution with chiral organic compounds is an emerging problem requiring innovative sensing methods. Amino-functionalized thioureas, such as 2-(dimethylamino)cyclohexyl-(3,5-bis(trifluoromethyl)phenyl)thiourea (Takemoto’s catalyst), are widely used organocatalysts with virtually unknown environmental safety data. Ecotoxicity studies based on the Vibrio fischeri luminescence inhibition test reveal significant toxicity of Takemoto’s catalyst (EC50 = 7.9 mg/L) and its NH2-substituted analog (EC50 = 7.2–7.4 mg/L). The observed toxic effect was pronounced by the influence of the trifluoromethyl moiety. En route to the porphyrin-based chemosensing of Takemoto-type thioureas, their supramolecular binding to a series of zinc porphyrins was studied with UV-Vis and circular dichroism (CD) spectroscopy, computational analysis and single crystal X-ray diffraction. The association constant values generally increased with the increasing electron-withdrawing properties of the porphyrins and electron-donating ability of the thioureas, a result of the predominant Zn⋯N cation–dipole (Lewis acid–base) interaction. The binding event induced a CD signal in the Soret band region of the porphyrin hosts—a crucial property for chirality sensing of Takemoto-type thioureas.

Asymmetric Autocatalysis as a Link Between Crystal Chirality and Highly Enantioenriched Organic Compounds

AbstractThe origin of biological homochirality has attracted much attention. Pyrimidyl alkanols exhibit asymmetric autocatalysis with significant amplification of enantiomeric excess in the reaction between pyrimidine‐5‐carbaldehyde and diisopropyl zinc (the Soai reaction). Chiral inorganic crystals such as quartz, cinnabar and sodium chlorate act as chiral triggers of asymmetric autocatalysis to afford highly enantioenriched pyrimidyl alkanol, with the absolute configurations corresponding to those of the chiral crystals. Chiral organic crystals composed of achiral organic compounds such as cytosine, adenine dinitrate, and γ‐glycine act as the chiral triggers of the Soai reaction to afford pyrimidyl alkanol with high ee that corresponds to the absolute configuration of the chiral trigger. This review describes that chiral minerals and chiral organic crystals act as the chiral triggers of the Soai reaction and that these chiral crystals are correlated to near‐enantiopure chiral organic compounds.