Chiral Catalysis Research Articles

Stereoselective synthesis of fissoldhimine alkaloid analogues via sequential electrooxidation and heterodimerization of ureas.

This study develops a biogenetic synthesis strategy using electrooxidation and heterodimerization of N-substituted pyrrolidine-1-carboxamides to create diverse analogues of the fissoldhimine alkaloid core. Under acidic conditions, 2-alkoxypyrrolidine-1-carboxamides from Shono oxidation formed endo-heterodimers with high yields and diastereoselectivity. Enantioselective heterodimerization using chiral phosphoric acid catalysis produced exo-heterodimers with high enantioselectivity.

Organocatalytic enantioselective (4+3) cyclization for the synthesis of spiro-fused heterocyclic compounds containing isoindolinone, oxepine and indole moieties.

A refined strategy has been developed to control the regioselective asymmetric (4+3) cyclization of α-(3-isoindolinonyl) propargylic alcohols with 2-indolylmethanols, utilizing chiral phosphoric acid catalysis. This innovative organocatalytic cyclization yields spiro isoindolinone-oxepine-fused indoles featuring a spiro-quaternary stereocenter in high yields and enantioselectivities, facilitated by the solvent of 1,1-dichloro-1-fluoroethane and the additive of hexafluoroisopropanol. Additionally, the photophysical properties of product 3k are examined, revealing bright fluorescence both in the solution and the solid state.

Tartaric acid-derived chiral carbon nanodots for catalytic enantioselective ring-opening reactions of styrene oxide.

Chiral carbon nanodots (CNDs) were fabricated through the hydrothermal processing of sulfanilic acid and chiral tartaric acid, exhibiting outstanding catalytic performance for the chiral catalysis of the ring-opening reaction. Furthermore, the catalytic mechanism was proposed to understand the link between the chiral structure and the performance of the catalyst.

Chiral Quantum Materials: When Chemistry Meets Physics.

Chirality is a fundamental property of nature with relevance in biochemistry and physics, particularly in the field of catalysis. Understanding the mechanisms underlying chirality transfer is crucial for advancing the knowledge of chiral-related catalysis. Chiral quantum materials with intriguing chirality-dependent electronic properties, such as spin-orbital coupling (SOC) and exotic spin/orbital angular momentum (SAM/OAM), open novel avenues for linking solid-state topologies with chiral catalysis. In this review, the growth of topological homochiral crystals (THCs) is described, and their applications in heterogeneous catalysis, including hydrogen evolution reaction (HER), oxygen electrocatalysis, and asymmetric catalysis are summarized. A possible link between chirality-dependent electronic properties and heterogeneous catalysis is discussed. Finally, existing challenges in this field are highlighted, and a brief outlook on the impact of THCs on the overarching chemical-physical research is presented.

Dual Chiral Catalysis Enabled Asymmetric Syntheses of Amines

Dual Chiral Catalysis Enabled Asymmetric Syntheses of Amines

Chiral Pool Meets Chiral Catalysis: Eight-Step Convergent Total Synthesis of Anticancer Natural Lipid Mycalol.

An exemplary blend of chiral pool with chiral catalysis is exhibited in an eight-step (longest) convergent asymmetric total synthesis of mycalol, which is a promising anticancer natural lipid from a marine source. The polyhydroxy lipid is constructed by using four blocks, and two of which are derived from the chiral pool (d-mannitol and d-gluconolactone) and the other two by chiral catalysis (Sharpless epoxidation and Keck allylation). Alkylation and metathesis were used to knit the blocks in an excellent display of a modular convergent eight-step synthesis. The modular excess will enable rapid analogue generation as revealed by the convenient synthesis of 4-epi-mycalol similarly in an eight-step sequence.

Chiral Carbon Dots and Chiral Carbon Dots with Circularly Polarized Luminescence: Synthesis, Mechanistic Investigation and Applications.

Chiral carbon dots (CCDs) can be widely used in various fields such as chiral recognition, chiral catalysis and biomedicine because of their unique optical properties, low toxicity and good biocompatibility. In addition, CCDs with circularly polarized luminescence (CPL) can be synthesized, thus broadening the prospects of CCDs applications. Since the research on CCDs is still in its infancy, this paper reviews the chiral origin, formation mechanism, chiral evolution, synthesis and emerging applications of CCDs, with a special focus on CCDs with CPL activity. It is hoped that it will provide some reference to solve the current problems faced by CCDs. Finally, the opportunities and challenges of the current research on CCDs are described, and their future development trends have also been prospected.

Active Control and Sensing Application of Ultra-Narrowband Circular Dichroism in Multilayer Chiral Nanorod Arrays.

Narrowband circular dichroism (CD) has attracted wide attention for its high sensitivity in detecting chiral molecules and catalysis. However, designing a chiral metasurface with excellent sensing performance that can be dynamically tuned still poses challenges. This paper introduces lithium niobate, an electrically tunable material, and a distributed Bragg reflector into chiral nanorod structures to form multilayer chiral nanorod arrays (MCNAs). Simulation results show that MCNAs can generate four strong ultra-narrowband (UNB) CD signals in the visible light spectrum. The UNB CD signal intensity was up to 0.86, and the minimum full width at half-maximum (FWHM) was up to 0.21 nm. The surface electric field and current distribution of MCNAs indicate that the four UNB CD signals mainly originate from the x and y direction Tamm resonances in the chiral nanorod layer. The refractive index of lithium niobate can be tuned by changing the electric field, allowing the active tuning of UNB CD signals. In addition, the sensing performance of MCNAs in the SARS-CoV-2 solution was analyzed, and the figure of merit (FOM) can reach an astonishing 2092. These findings not only assist with the design of UNB chiral devices but also offer new possibilities for the environmental monitoring and ultrasensitive detection of chiral molecules.

Chiral SPINOL-Based Pt(II) Metallacycles For Immunogenic Cell Death.

The incorporation of chirality endows Pt(II)-based metal-organic complexes (MOCs) with unique potentials in several fields such as nonlinear optics and chiral catalysis. However, the exploration of chiral Pt(II) metallacycles in biological responses remains underdeveloped. Herein, we designed and synthesized two chiral Pt(II) metallacycles 1 and 2 via the coordination-driven self-assembly of chiral 1,1'-spirobiindane-7,7'-diol (SPINOL)-derived ligands and cis-Pt(PEt3)2(OTf)2 (90°Pt). Their structures were well characterized by 1H NMR, 31P{1H} NMR, ESI-TOF-MS, and X-ray crystallography, and their photophysical properties were investigated by UV-vis absorption, fluorescence, and circular dichroism (CD) spectroscopies. Then, the antitumor activity of the two chiral metallacycles in vitro was further tested. Complexes 1 and 2 exhibited strong cytotoxicity, especially toward the A549 cells. The destruction of the mitochondrial function, the inhibition of the glutathione (GSH)/glutathione disulfide (GSSG) level, and the inactivation of superoxide dismutase (SOD) induced by complexes 1 and 2 led to the massive accumulation of reactive oxygen species (ROS). The overloaded ROS then triggered apoptotic cell death, and the release of damage-associated molecular patterns (DAMPs) further induced immunogenic cell death (ICD). To the best of our knowledge, this is the first example of Pt(II)-based metallacycles that can induce immunogenic cell death, providing a new strategy for the future design and construction of immune-modulating platinum agents in cancer therapy.

Understanding how charge-charge interaction affects the stereochemistry of enamine fluorination by chiral primary amine catalysis

Understanding how charge-charge interaction affects the stereochemistry of enamine fluorination by chiral primary amine catalysis

Chirality-Induced Spin Selectivity in Supramolecular Chirally Functionalized Graphene.

Chiral graphene hybrid materials have attracted significant attention in recent years due to their various applications in the areas of chiral catalysis, chiral separation and recognition, enantioselective sensing, etc. On the other hand, chiral materials are also known to exhibit chirality-dependent spin transmission, commonly dubbed "chirality induced spin selectivity" or CISS. However, CISS properties of chiral graphene materials are largely unexplored. As such, it is not clear whether graphene is even a promising material for the CISS effect given its weak spin-orbit interaction. Here, we report the CISS effect in chiral graphene sheets, in which a graphene derivative (reduced graphene oxide or rGO) is noncovalently functionalized with chiral Fmoc-FF (Fmoc-diphenylalanine) supramolecular fibers. The graphene flakes acquire a "conformational chirality" postfunctionalization, which, combined with other factors, is presumably responsible for the CISS signal. The CISS signal correlates with the supramolecular chirality of the medium, which depends on the thickness of graphene used. Quite interestingly, the noncovalent supramolecular chiral functionalization of conductive materials offers a simple and straightforward methodology to induce chirality and CISS properties in a multitude of easily accessible advanced conductive materials.

A Theoretical Analysis of the Differential Chemical Reaction Results Caused by Chirality Induction.

The theory of electron spin has been proposed for a century, but the study of quantum effects in biological molecules is still in its infancy. Chirality-induced spin selectivity (CISS) is a very modern theory that can explain many biochemical phenomena. In this paper, we propose a new theoretical model based on CISS theory and quantum chemistry theory, which can well explain the theoretical explanation of the chiral selectivity of chiral proteins. Moreover, this theory can predict the spin state of corresponding chiral molecules. Taking the L-DOPA and AADC enzymes as examples, this theoretical model elucidates the AADC enzyme's chiral catalysis selectivity and successfully predicts the spin state of L-DOPA and D-DOPA's valence electrons.

Turning on Asymmetric Catalysis of Achiral Metal-Organic Frameworks by Imparting Chiral Microenvironment.

The development of heterogeneous asymmetric catalysts has attracted increasing interest in synthetic chemistry but mostly relies on the immobilization of homogeneous chiral catalysts. Herein, a series of chiral metal-organic frameworks (MOFs) have been fabricated by anchoring similar chiral hydroxylated molecules (catalytically inactive) with different lengths onto Zr-oxo clusters in achiral PCN-222(Cu). The resulting chiral MOFs exhibit regulated enantioselectivity up to 83 % ee in the asymmetric ring-opening of cyclohexene oxide. The chiral molecules furnished onto the catalytic Lewis sites in the MOF create multilevel microenvironment, including the hydrogen interaction between the substrate and the chiral -OH group, the steric hindrance endowed by the benzene ring on the chiral molecules, and the proximity between the catalytic sites and chiral molecules confined in the MOF pores, which play crucial roles and synergistically promote chiral catalysis. This work nicely achieves heterogeneous enantioselective catalysis by chiral microenvironment modulation around Lewis acid sites.

Turning on Asymmetric Catalysis of Achiral Metal‐Organic Frameworks by Imparting Chiral Microenvironment

AbstractThe development of heterogeneous asymmetric catalysts has attracted increasing interest in synthetic chemistry but mostly relies on the immobilization of homogeneous chiral catalysts. Herein, a series of chiral metal–organic frameworks (MOFs) have been fabricated by anchoring similar chiral hydroxylated molecules (catalytically inactive) with different lengths onto Zr‐oxo clusters in achiral PCN‐222(Cu). The resulting chiral MOFs exhibit regulated enantioselectivity up to 83 % ee in the asymmetric ring‐opening of cyclohexene oxide. The chiral molecules furnished onto the catalytic Lewis sites in the MOF create multilevel microenvironment, including the hydrogen interaction between the substrate and the chiral −OH group, the steric hindrance endowed by the benzene ring on the chiral molecules, and the proximity between the catalytic sites and chiral molecules confined in the MOF pores, which play crucial roles and synergistically promote chiral catalysis. This work nicely achieves heterogeneous enantioselective catalysis by chiral microenvironment modulation around Lewis acid sites.

The separation of the enantiomers of diquats by capillary electrophoresis using randomly sulfated cyclodextrins as chiral selectors.

Diquats, derivatives of the widely used herbicide diquat, represent a new class of functional organic molecules. A combination of their special electrochemical properties and axial chirality could potentially result in their important applications in supramolecular chemistry, chiral catalysis, and chiral analysis. However, prior to their practical applications, the diquats have to be prepared in enantiomerically pure forms and the enantiomeric purity of their P- and M-isomers has to be checked. Hence, a chiral capillary electrophoresis (CE) method has been developed and applied for separation of P- and M-enantiomers of 11 new diquats. Fast and better than baseline CE separations of enantiomers of all 11 diquats within a short time 5-7min were achieved using acidic buffer, 22mM NaOH, 35mM H3 PO4 , pH 2.5, as a background electrolyte, and 6mM randomly sulfated α-, β-, and γ-cyclodextrins as chiral selectors. The most successful selector was sulfated γ-cyclodextrin, which baseline separated the enantiomers of all 11 diquats, followed by sulfated β-cyclodextrin and sulfated α-cyclodextrin, which baseline separated enantiomers of 10 and nine diquats, respectively. Using this method, a high enantiopurity degree of the isolated P- and M-enantiomers of three diquats with a defined absolute configuration was confirmed and their migration order was identified.

Catalytic Desymmetrizing Baeyer-Villiger Oxidation of Quaternary Carbon-Containing Cyclobutane-1,3-diones.

The first highly enantioselective Baeyer-Villiger oxidation of quaternary carbon-containing cyclobutane-1,3-diones using chiral phosphoric acid catalysis and commercially available oxidants was reported. According to the structure of the substrates, two optimized reaction conditions were developed to afford the corresponding chiral tetronic acid products in ≤93% and ≤95% ee values. This reaction offers the first catalytic asymmetric approach to chiral 5,5-disubstituted tetronic acid derivatives. The synthetic potential of this method has been demonstrated by the formal asymmetric synthesis of (-)-vertinolide and the first catalytic asymmetric total synthesis of plakinidone B.

Enantioselectivity of discretized helical supramolecule consisting of achiral cobalt phthalocyanines via chiral-induced spin selectivity effect

Enantioselectivity of helical aggregation is conventionally directed either by its homochiral ingredients or by introduction of chiral catalysis. The fundamental question, then, is whether helical aggregation that consists only of achiral components can obtain enantioselectivity in the absence of chiral catalysis. Here, by exploiting enantiospecific interaction due to chiral-induced spin selectivity (CISS) that has been known to work to enantio-separate a racemic mixture of chiral molecules, we demonstrate the enantioselectivity in the assembly of mesoscale helical supramolecules consisting of achiral cobalt phthalocyanines. The helical nature in our supramolecules is revealed to be mesoscopically incorporated by dislocation-induced discretized twists, unlike the case of chiral molecules whose chirality are determined microscopically by chemical bond. The relevance of CISS effect in the discretized helical supramolecules is further confirmed by the appearance of spin-polarized current through the system. These observations mean that the application of CISS-based enantioselectivity is no longer limited to systems with microscopic chirality but is expanded to the one with mesoscopic chirality.

Design and Application of Peptide-Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis.

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer catalysis, has proven to be a powerful strategy for the stereoselective preparation of diverse optically active molecules. However, there still remain numerous forbidding issues of reactivity and selectivity in such well-known organocatalysis system. Accordingly, the development of new and high-performance phosphonium salt catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes the prominent endeavours in the development of a new family of chiral peptide-mimic phosphonium salt catalysts with multiple hydrogen-bonding donors and their applications in a plethora of enantioselective synthesis during the past few years. Hopefully, this minireview will pave a way for further developing much more efficient and privileged chiral ligands/catalysts featuring exclusively catalytic ability in asymmetric synthesis.

Enantioselective inorganic nanomaterials with near-infrared circular-polarized-activated photothermal response

Chiral inorganic semiconductor materials have great potential in chiral catalysis, biomedicine and chiroptical devices. However, the narrow chiroptical response and weak chiroptical intensity limit their development. Herein, chiral CuS (D-/L-CuS) were prepared by a facile ligand exchange method using alanine (Ala) and penicillamine (Pen), respectively. The properties and stereostructures of chiral ligands resulted in enantioselectivity and chiroptical activity from ultraviolet to near-infrared (NIR) of chiral CuS. And the maximum of asymmetry factor |g| was up to 1.02 × 10-2, which is far higher than those of most chiral ligand-modified inorganic semiconductor nanomaterials. The NIR chiroptical activity facilitated photothermal performance, which could be tuned by circularly polarized light (CPL). D-CuS showed higher photothermal efficiency under right CPL radiation, while L-CuS showed higher photothermal efficiency under left CPL radiation. L-Pen-CuS exhibited the highest photothermal conversion efficiency of 22.18% under left CPL radiation. Moreover, the underlying mechanism of chirality in CuS was revealed for the first time. The coupling of amino acid ligands and CuS through Coulomb interactions allowed chiral transfer, and the orbital hybridization of chiral ligand orbitals with CuS molecular orbitals transferred chiral information. This work will further promote the understanding of induced chirality in inorganic semiconductor materials and the application of chiroptical-active inorganic semiconductor materials.

Catalytic Asymmetric Visible-Light de Mayo Reaction by ZrCl4-Chiral Phosphoric Acid Complex.

Catalytic asymmetric de Mayo reaction was achieved for the first time under visible light using asymmetric binary acid catalysis (ABC) involving zirconium chloride and chiral phosphoric acid (CPA). The chiral zirconium catalysis enables effective reactions over a broad range of 1,3-diketones and alkenes with up to >99% yield and 98% ee. The key chiral zirconium enolate was isolated and characterized to account for the observed catalysis and stereoselectivity.