Synthesis of Chiral Biphenyl Monophosphines as Ligands in Enantioselective Suzuki-Miyaura Coupling.

Herein, we describe our design and synthesis of novel chiral monophosphine ligands by the short-step addition of chiral lactates as side chains to the well-known ligand SPhos/RuPhos. The new chiral ligands were shown to be highly efficient in palladium-catalyzed Suzuki-Miyaura coupling, providing a series of axially chiral biphenyl products in high yield and high enantioselectivity. Furthermore, the gram-scale reaction and the diverse conversions of the products demonstrated the potential utility of the approach.

Induced Red Circularly Polarized Luminescence Emission Promoted by Intermolecular Förster Resonance Energy Transfer through a Cholesteric Liquid Crystal Medium.

In this paper, planar chiral helicenes based on [2.2]paracyclophane PCPH5 acted as both chiral inducers and energy donors to construct the circularly polarized luminescence (CPL)-active ternary cholesteric liquid crystals (T-N*-LCs) in a commercial nematic liquid crystal (SLC1717, N-LCs) medium. Induced red CPL emission based on the energy acceptor of the achiral polymer DTBTF8 could be successfully promoted by the intermolecular Förster resonance energy transfer mechanism. The resulting T-N*-LCs can generate intensive CPL signals with glum up to +0.70/-0.67. Interestingly, this kind of "on-off" CPL switching of T-N*-LCs can be manipulated by the applied direct current electric field.

Synthesis of a C2-Symmetric Chiral Borinic Acid and Its Application in Catalytic Desymmetrization of 2,2-Disubstituted-1,3-Propanediols.

Notwithstanding the common use of boronic acids in catalysis, the design and synthesis of efficient chiral boronic acids remains a formidable challenge. Herein we disclose a rational design and a concise synthesis of a series of novel C2-symmetric disubstituted boronic acids, or borinic acids. Chiral borinic acids have been found to be excellent agents that can achieve highly enantioselective desymmetrization of 2,2-disubstituted-1,3-propanediols, providing chiral diols with a quaternary stereocenter, which has been regarded in recent years as challenging. A wide range of substrates are tolerated in this reaction, providing a series of chiral diols with high enantioselectivity. The presence of the tetracoordinate borinate in the catalytic cycle has been proven by 11B NMR studies, and a stereocontrol model has been proposed.

Mechanism and Molecular Targets of a Water-Soluble Extract of Artemisia annua on the Treatment of Alzheimer's Disease Based on Network Pharmacology and Experimental Validation.

Oxidative stress is an important contributor to the pathogenesis of Alzheimer's disease (AD). The overproduction of reactive oxygen species observed in AD patients results in the loss of mitochondrial function, altered metal ion homeostasis, lipopolysaccharide metabolism disorder, reduced anti-oxidant defense, increased release of inflammatory factors, and the aggravation and accumulation of amyloid-beta and tau hyper-phosphorylation, which directly cause synaptic and neuronal loss and lead to cognitive dysfunction. Thus, oxidative stress proves to be a fundamental part of AD development and progression, suggesting the potential benefits of anti-oxidant-based therapies for AD. In this study, we found that a water-soluble extract of Artemisia annua (WSEAA), a traditional Chinese herbal medicine, has a strong anti-oxidant function. We also found that WSEAA is able to improve the cognitive function of 3xTg AD mice. However, the mechanisms and molecular targets underlying WSEAA action are still not known. In order to uncover the potential molecular mechanisms involved, we used a combination of network pharmacology and different experimental approaches. Obtained results revealed key genes (such as AKT1, BCL2, IL-6, TNF-[Formula: see text] and BAX) and signaling pathways (like PI3K-AKT and BCL2/BAX) are closely associated with the biological processes responding to oxidative stress. Further verification of the survival/anti-oxidant effects of WSEAA in vitro and in vivo showed that the extract has anti-oxidatant/neuronal survival action against H2O2-induced damage, and is thus able to prevent the cognitive decline and pathological changes of 3xTg transgenic (3xTg) mice via the regulation of key target-genes and pathways, such as PI3K-AKT and BCL2/BAX, related to survival/apoptosis. Our findings strongly indicate the potential of WSEAA for the prevention and treatment of AD.

Planar Chiral Multiple Resonance Thermally Activated Delayed Fluorescence Materials for Efficient Circularly Polarized Electroluminescence.

Chiral boron/nitrogen doped multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters are promising for highly efficient and color-pure circularly polarized organic light-emitting diodes (CP-OLEDs). Herein, we report two pairs of MR-TADF materials (Czp-tBuCzB, Czp-POAB) based on planar chiral paracyclophane with photoluminescence quantum yields of up to 98 %. The enantiomers showed symmetric circularly polarized photoluminescence spectra with dissymmetry factors |gPL | of up to 1.6×10-3 in doped films. Meanwhile, the sky-blue CP-OLEDs with (R/S)-Czp-tBuCzB showed an external quantum efficiency of 32.1 % with the narrowest full-width at half-maximum of 24 nm among the reported CP-OLEDs, while the devices with (R/S)-Czp-POAB displayed the first nearly pure green CP electroluminescence with |gEL | factors at the 10-3 level. These results demonstrate the incorporation of planar chirality into MR-TADF emitter is a reliable strategy for constructing of efficient CP-OLEDs.

A highly enantioselective approach towards optically active γ-amino alcohols by tin-catalyzed kinetic resolution of 1,3-amino alcohols.

A highly enantioselective kinetic resolution of racemic 1,3-amino alcohols via O-Acylation was achieved using a chiral organotin as the catalyst. Alkyl- and aryl-substituted 1,3-amino alcohols were resolved with excellent efficiencies to afford the recovered 1,3-amino alcohols and acylative products with high enantioselectivities, with s factors up to >600. Notably, the chiral organotin catalyst was more selective for anti-1,3-amino alcohols than for syn-isomers. A Gram-scale reaction with loading using 2 mol% catalysts demonstrated the utility of this protocol.

Kinetic Resolution of Tertiary Alcohols by Chiral Organotin-Catalyzed O-Acylation.

A novel highly enantioselective method for the kinetic resolution of racemic tertiary alcohols has been achieved through chiral organotin-catalyzed intermolecular acylation of the hydroxyl group. This process has demonstrated a broad substrate scope (both alkyl- and aryl-substituted tertiary alcohols) with high enantioselectivity under mild reaction conditions, affording the corresponding products and the recovered tertiary alcohols with high enantioselectivities, with s factors up to >200.

Inverted Circularly Polarized Luminescence Behavior Induced by Helical Nanofibers through Chiral Co-Assembly from Achiral Liquid Crystal Polymers and Chiral Inducers.

Chiral supramolecular assembly can provide a powerful strategy for developing circularly polarized luminescence (CPL)-active materials by forming helices or superhelices into single or multiple components. Herein, we chose three achiral liquid crystal polymers (LC-P1/P2/P3) and chiral binaphthyl-based inducers (R/S-M) with anchored dihedral angles to construct chiral co-assemblies and explore the induced CPL behavior from pyrenyl (Py) emitters in achiral LC polymers through the regulation of helical nanofibers during the supramolecular co-assembly process. Most interestingly, chiral co-assembly (R/S-M)0.1-(P3)0.9 emitted an inverted blue-colored CPL signal during thermal annealing treatment at the glass transition temperature due to the flexible main chain of the LC polymer (LC-P3). The strongest blue-colored CPL emission for the (R/S-M)0.1-(P3)0.9 spin-coated film (λem = 455 nm, |gem| = 6.47 × 10-2, ΦF = 48.5%) could be detected by using thermal annealing treatment at 105 °C.

Enantioselective Construction of Tertiary α-Alkyl Fluoride via BTM-Catalyzed Fluorination of α-Alkynyl-Substituted Acetic Acids.

The isothiourea-catalyzed enantioselective construction of tertiary α-fluoro stereogenic centers has been demonstrated by using branched alkynyl-substituted acetic acids as starting materials, providing a broad range of optically active tertiary α-alkyl fluorides in high enantioselectivity (up to 97% ee). Furthermore, this methodology was proven to be scaled up to a Gram scale without loss of enantioselectivity.

Synthesis and Chiroptical Properties of Planar Chiral Azahelicenes Based on [2.2]Paracyclophane.

Three pairs of planar chiral heteroarenes were synthesized using palladium-catalyzed Buchwald-Hartwig coupling and hypervalent iodine-mediated oxidative cyclization from optically pure 4-amino[2.2]paracyclophane. Among them, an enantiomer of planar chiral azahelicene was found to have circularly polarized luminescence activity that was remarkably stronger than that of planar chiral heteroarenes.

Planar Chiral B-N Heteroarenes Based on [2.2]Paracyclophane as Circularly Polarized Luminescence Emitters.

Planar chiral boron-nitrogen heteroarenes based on [2.2]paracyclophane were successfully synthesized in a few steps as a new family of circularly polarized luminescence emitters. It represents the first case of boron-nitrogen heteroarenes with planar chirality. Those compounds have been demonstrated to exhibit strong circularly polarized luminescence signals and high quantum yields, in both solution and doped film (with glum up to 5.0 × 10-3 and Φsolution up to 73%).

Planar Chiral [2.2]Paracyclophane-Based Thermally Activated Delayed Fluorescent Materials for Circularly Polarized Electroluminescence.

This work describes the construction of a novel planar chiral [2.2]paracyclophane-based thermally activated delayed fluorescence (TADF)-active molecule with circularly polarized luminescence (CPL). The combination of the bulky planar chiral phenoxazinephane (PXZp) donor based [2.2]paracyclophane and triazine acceptor enables the highly efficient luminescence performances and excellent CPL properties. The enantiomers exhibit excellent TADF activities, the energy difference (ΔEST) between singlet and triplet of the molecule is only 0.03 eV. Notably, through solution-process, a yellow CP-OLEDs based on the molecule as the emitting layers displays high maximum brightness (Lmax) up to 34 293 cd m-2, maximum external quantum efficiency (EQEmax) up to 7.8% and remarkable CP-EL signal with gEL factor up to 4.6 × 10-3.

[2.2]Paracyclophane-Based Isothiourea-Catalyzed Highly Enantioselective α-Fluorination of Carboxylic Acids.

Planar chiral [2.2]paracyclophane-based isothiourea catalysts have been prepared over a few simple steps in high yields. In the presence of these catalysts, highly efficient catalytic enantioselective fluorination of carboxylic acids has been accomplished, providing a broad range of optically active α-fluoroesters in high yield and excellent enantioselectivity.

Computational Design of Enhanced Enantioselectivity in Chiral Phosphoric Acid-Catalyzed Oxidative Desymmetrization of 1,3-Diol Acetals.

A general method for the highly enantioselective desymmetrization of 2-alkyl-substituted 1,3-diols is presented. A combination of computational and experimental studies has been utilized to understand the origin of the stereocontrol of oxidative desymmetrization of 1,3-diol benzylideneacetals. DFT calculations demonstrate that the acetal protecting group is highly influential for high enantioselectivity, and a simple but effective new protecting group has been designed. The desymmetrization reactions proceed with high enantioselectivity for a variety of substrates. Moreover, the reaction conditions are also shown to be effective for desymmetrization of 2,2-dialkyl-substituted 1,3-diols, which provides chiral products bearing acyclic all-carbon quaternary stereocenters. The method has been applied to the formal synthesis of indoline alkaloids.

Chiral-Organotin-Catalyzed Kinetic Resolution of Vicinal Amino Alcohols.

A highly efficient kinetic resolution of racemic amino alcohols has been achieved for the first time with a chiral tin catalyst. A chiral organotin compound with 3,4,5-trifluorophenyl groups at the 3,3'-positions of the binaphthyl framework enabled this transformation with excellent yield and high enantioselectivity. The process tolerates aryl- and alkyl-substituted amino alcohols and a variety of other substrates, affording the corresponding products in high enantioselectivity and with s factors up to >500.

Advances in asymmetric visible-light photocatalysis, 2015-2019.

Asymmetric visible-light photocatalysis has recently drawn considerable attention of the scientific community owing to its unique activation modes and significance for the enantioselective green synthesis. In this review, the recent advances in the visible-light-triggered enantioselective synthesis, classified by different catalytic strategies, are summarized. The progress achieved in this area inspires us to develop new strategies, including the combination of photocatalysis with other catalytic modes and the design and synthesis of multifunctional chiral photocatalysts, in an attempt to incorporate chirality into the photo-mediated chemical transformations.

Parallel Kinetic Resolution of Unsymmetrical Acyclic Aliphatic syn-1,3-Diols.

Disclosed is a mild, reliable, and enantioselective catalytic parallel kinetic resolution of unsymmetrical acyclic aliphatic syn-1,3-diol derived acetals mediated by chiral phosphoric acid. This method provides stereoselective access to a variety of syn-1,3-diols as valuable building blocks with high enantioselectivity. Moreover, this mild system allows for site-selective protection of optically pure syn-1,3-diols in excellent regioselectivity.

Development of Planar Chiral Iodoarenes Based on [2.2]Paracyclophane and Their Application in Catalytic Enantioselective Fluorination of ß-Ketoesters.

The design and synthesis of novel planar chiral iodoarenes based on [2.2]paracyclophane is reported. A process of highly enantioselective oxidative fluorination of a ß-ketoester with 3HF-Et3N as a nucleophilic fluoride source mediated by these new hypervalent iodine catalysts has been developed. This represents the first highly enantioselective reaction catalyzed by planar chiral hypervalent iodine.

Catalytically Enantioselective Synthesis of Acyclic α-Tertiary Amines through Desymmetrization of 2-Substituted 2-Nitro-1,3-diols.

Highly enantioselective synthesis of acyclic α-tertiary amines through asymmetric desymmetrization is reported. This approach is based on chiral phosphoric acid mediated, enantioselective, oxidative desymmetrization of 2-substituted 2-nitro-1,3-diolbenzylidine acetals in the presence of DMDO as an oxidant. The method allows for the formation of a wide variety of chiral 2-nitro-1,3-diols in high enantioselectivity, which could be transformed into optically pure, unnatural α-alkyl series. The synthetic utility of this method has been further demonstrated by the expedient construction of the core structure of natural products manzacidins enantioselectively.

A catalytic enantioselective approach to tetrol bearing vicinal all-carbon quaternary stereogenic centers.

The first highly enantioselective catalytic protocol for selective manipulation of tetrol benzylidene acetals through chiral phosphoric acid mediated oxidative desymmetrization is reported. This efficient approach provides a general access to vicinal all-carbon quaternary stereogenic center structural motifs, as well as structures containing vicinal tertiary and quaternary stereocenters enantioselectively. The synthetic utility has been furthermore demonstrated by transformations and gram-scale processes.