From Center-to-Multilayer Chirality: Asymmetric Synthesis of Multilayer Targets with Electron-Rich Bridges.

Asymmetric synthesis of new atropisomerically multilayered chiral targets has been achieved by taking advantage of the strategy of center-to-multilayer chirality and double Suzuki-Miyaura couplings. Diastereomers were readily separated via flash column chromatography and well characterized. Absolute configuration assignment was determined by X-ray structural analysis. Five enantiomerically pure isomers possessing multilayer chirality were assembled utilizing anchors involving electron-rich aromatic connections. An overall yield of 0.69% of the final target with hydroxyl attachment was achieved over 11 steps from commercially available starting materials.

Asymmetric Catalytic Approach to Multilayer 3D Chirality.

Invited for the cover of this issue is Guigen Li and co-workers at Texas Tech University and Nanjing University. The cover artwork shows that chirality phenomena exists in the universe and in nature, including at micro and molecular levels. Read the full text of the article at 10.1002/chem.202100700.

Asymmetric Catalytic Approach to Multilayer 3D Chirality.

The first asymmetric catalytic approach to multilayer 3D chirality has been achieved by using Suzuki-Miyaura cross-couplings. New chiral catalysts were designed and screened under various catalytic systems that proved chiral amide-phosphines to be more efficient ligands than other candidates. The multilayer 3D framework was unambiguously determined by X-ray structural analysis showing a parallel pattern of three layers consisting of top, middle and bottom aromatic rings. The X-ray structure of a catalyst complex, dichloride complex of Pd-phosphine amide, was obtained revealing an interesting asymmetric environment nearby the Pd metal center. Three rings of multilayer 3D products can be readily changed by varying aromatic ring-anchored starting materials. The resulting multilayer products displayed strong luminescence under UV irradiation and strong aggregation-induced emission (AIE). In the future, this work would benefit not only the field of asymmetric synthesis but also materials science, in particular polarized organic electronics, optoelectronics and photovoltaics.

Synthesis of Functionalized Chromene and Chroman Derivatives via Cesium Carbonate Promoted Formal [4 + 2] Annulation of 2'-Hydroxychalcones with Allenoates.

A new strategy has been established for the synthesis of functionalized chromene and chroman derivatives via a Cs2CO3-catalyzed domino addition of 2'-hydroxychalcone derivatives with allenoates, which can serve as a general avenue for the construction of multireplaced chromene derivatives. Chemoselectivity of this synthesis was found to depend on substituents on substrates. Good to excellent yields were achieved under simple and mild conditions at room temperature.

I2/KI-Mediated Oxidative N-N Bond Formation for the Synthesis of 1,5-Fused 1,2,4-Triazoles from N-Aryl Amidines.

An I2/KI-mediated oxidative N-N bond formation reaction is described. This new and environmentally benign approach allows for the convenient synthesis of a variety of 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.

Triple-Columned and Multiple-Layered 3D Polymers: Design, Synthesis, Aggregation-Induced Emission (AIE), and Computational Study.

Conjugated polymers and oligomers have great potentials in various fields, especially in materials and biological sciences because of their intriguing electronic and optoelectronic properties. In recent years, the through-space conjugation system has emerged as a new assembled pattern of multidimensional polymers. Here, a novel series of structurally condensed multicolumn/multilayer 3D polymers and oligomers have been designed and synthesized through one-pot Suzuki polycondensation (SPC). The intramolecularly stacked arrangement of polymers can be supported by either X-ray structural analysis or computational analysis. In all cases, polymers were obtained with modest to good yields, as determined by GPC and 1H-NMR. MALDI-TOF analysis has proven the speculation of the step-growth process of this polymerization. The computational study of ab initio and DFT calculations based on trimer and pentamer models gives details of the structures and the electronic transition. Experimental results of optical and AIE research confirmed by calculation indicates that the present work would facilitate the research and applications in materials.

Synthesis of Diastereoenriched α-Aminomethyl Enaminones via a Brønsted Acid-Catalyzed Asymmetric aza-Baylis-Hillman Reaction of Chiral N-Phosphonyl Imines.

An effective chiral GAP methodology for preparing α-aminomethyl enaminones through a (R)-CSA-catalyzed asymmetric aza-Baylis-Hillman reaction is reported. Excellent yields and high diastereoselectivity could be obtained under mild conditions and convenient GAP techniques. The confirmations of the absolute configuration of N-phosphonyl imine and chiral enaminone by X-ray diffraction provides an explicit explanation of the chirality mechanism for GAP chemistry.

Enantioselective assembly of multi-layer 3D chirality.

The first enantioselective assembly of sandwich-shaped organo molecules has been achieved by conducting dual asymmetric Suzuki-Miyaura couplings and nine other reactions. This work also presents the first fully C-C anchored multi-layer 3D chirality with optically pure enantiomers. As confirmed by X-ray diffraction analysis that this chiral framework is featured by a unique C2 -symmetry in which a nearly parallel fashion consisting of three layers: top, middle and bottom aromatic rings. Unlike the documented planar or axial chirality, the present chirality shows its top and bottom layers restrict each other from free rotation, i.e., this multi-layer 3D chirality would not exist if either top or bottom layer is removed. Nearly all multi-layered compounds showed strong luminescence of different colors under UV irradiation, and several randomly selected samples displayed aggregation-induced emission (AIE) properties. This work is believed to have broad impacts on chemical, medicinal and material sciences including optoelectronic materials in future.

Multilayer 3D Chirality and Its Synthetic Assembly.

3D chirality of sandwich type of organic molecules has been discovered. The key element of this chirality is characterized by three layers of structures that are arranged nearly in parallel fashion with one on top and one down from the center plane. Individual enantiomers of these molecules have been fully characterized by spectroscopies with their enantiomeric purity measured by chiral HPLC. The absolute configuration was unambiguously assigned by X-ray diffraction analysis. This is the first multilayer 3D chirality reported and is anticipated to lead to a new research area of asymmetric synthesis and catalysis and to have a broad impact on chemical, medicinal, and material sciences in future.

Design, synthesis, and biological evaluation of new N(4)-Substituted 2'-deoxy-2'-fluoro-4'-azido cytidine derivatives as potent anti-HBV agents.

A series of new 2'-deoxy-2'-ß-fluoro-4'-azido-ß-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N(4)-substituents were designed and synthesized. Antiviral screening in HepG2.2.15 cells identified three analogs (1a, 1d &1g) with good anti-HBV activity and low cytotoxicty. Of them, compound 1g exhibited significant inhibitory activity on both HBV antigens secretion (EC50, HBsAg = 9 nM, EC50, HBeAg = 0.25 µM) and viral DNA replication (intracellular, EC50 = 0.099 µM; extracellular, EC50 < 0.01 µM).