We have developed an asymmetric aza-Wacker-type cyclization of N-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the C═C double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a syn-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is cis to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps.

<div>Due to the good clinical efficacy in treating Novel Coronavirus Pneumonia (NCP) resulted from </div><div> </div><div>SARS-CoV-2, as the traditional Chinese medicine(TCM) prescription, Lianhua Qingwen Formula </div><div>(LQF) was composed into the Diagnosis and Treatment Programs of 2019 New Coronavirus<br></div><div> </div><div>Pneumonia (from fourth to seventh editions) formulated by the National Health Commission of China. </div><div> </div><div>Aiming to prevent and treat viral influenza, LQF was patented from 2003 in China, and passed the </div><div> </div><div>Phase II clinical trial by FDA in the United States in 2015. However, the molecular mechanism of LQF </div><div> </div><div>anti SARS-CoV-2 pneumonia is still not clear. It is shown that the docking scores of three components </div><div> </div><div>in LQF including Rutin, Forsythoside E, and Hyperoside to main protease of SARS-CoV-2 are very </div><div>large as -9.1, -9.0 and -8.7 kcal/mol, respectively, which are even better than those of Lopinavir at -7.3<br></div><div> </div><div>kcal/mol. Importantly, the binding modes between active compounds and protein were verified via </div><div> </div><div>molecular dynamics (MD) simulation and calculation all the binding free energies at MM-PBSA level. </div><div> </div><div>Note that these donor-acceptor systems were stabilized by non-polar interactions including hydrogen </div><div> </div><div>bonds and hydrophobic interactions. At last, from the constructed component-target-pathway network, </div><div> </div><div>it is shown that the components in LQF are related important pathways to improve the human immunity </div><div> </div><div>such as T cell, B cell receptor signaling, natural killer cell mediated cytotoxicity, as well as anti</div><div> </div><div>inflammatory pathways including Fc epsilon RI, ErbB, MAPK signaling and so on. The present </div><div> </div><div>investigation represents the first report on the molecular mechanism of LQF as NCP inhibitor</div>

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A Pd -catalyzed oxidative tandem cyclization was developed for the construction of fused 5,6-bicyclic N, O-heterocycles. This reaction was enabled by the combined use of a 3-methylpyridine ligand and pentafluorobenzoic acid additive. A range of heterocyclic products with different substituents could be prepared in moderate to good yields via this methodology. Several transformations, including a scaled-up preparation of product 2 a, were also carried out showing the good applicability of our methodology.

Enantioselective ring-contraction reactions have not been widely reported. We have developed an enantioselective ring contraction of 5,6-dihydro-2H-benzo­[b]­[1,4]­oxazocines, affording enantiomerically enriched 3,4-dihydro-2H-1,4-benzoxazine derivatives as single regioisomers. An acidic additive is necessary in order to obtain the products with good yields and enantiomeric ratios (up to 93% yield, 98:2 er). The reaction was successfully performed on a gram scale, and the products can be derivatized easily.