Xiaoze Bao

An Organocatalytic Asymmetric Friedel–Crafts Addition/Fluorination Sequence: Construction of Oxindole–Pyrazolone Conjugates Bearing Vicinal Tetrasubstituted Stereocenters

A highly efficient and practical one-pot sequential process, consisting of an organocatalytic enantioselective Friedel-Crafts-type addition of 4-nonsubstituted pyrazolones to isatin-derived N-Boc ketimines and a subsequent diastereoselective fluorination of the pyrazolone moiety, is developed. This reaction sequence delivers novel oxindole-pyrazolone adducts featuring vicinal tetrasubstituted stereocenters with a 0.5 mol % catalyst loading in high yield with excellent enantio- and diastereocontrol. Notably, chloro, bromo, and thioether functionalities can be readily incorporated, rendering a broad diversity of the product.

Asymmetric chlorination of 4-substituted pyrazolones catalyzed by natural cinchona alkaloid

A natural quinidine-catalyzed asymmetric chlorination of 4-substituted pyrazolones is developed, affording products with a quaternary chiral chlorine-attached carbon centre in high yield with excellent enantioselectivity. The low catalyst loading (1 mol%), broad substrate scope, and facile and valuable transformation of the product highlight the practical utility of this process.

Novel Tartrate-Based Guanidines for Enantioselective Fluorination of 1,3-Dicarbonyl and α-Cyano Carbonyl Compounds

A novel library of chiral guanidines featuring the tartaric acid skeleton is easily accessed with tunable steric and electronic properties. A guanidine molecule of this library with an incorporated 2,6-diisoaniline fragment was identified as a suitable promoter for the enantioselective fluorination of 1,3-dicarbonyl and α-cyano carbonyl compounds to furnish the fluorinated product with up to 84 % ee and 99 % yield using N-fluorobenzenesulfonimide (NFSI) as the fluorinating agent.

Asymmetric Construction of a Multi-Pharmacophore-Containing Dispirotriheterocyclic Scaffold and Identification of a Human Carboxylesterase 1 Inhibitor

A catalytic asymmetric [3 + 2] cyclization of novel 4-isothiocyanato pyrazolones and isatin-derived ketimines was developed, delivering a wide range of intriguing dispirotriheterocyclic products in high yield with excellent diastereoselectivity and enantioselectivity. A chiral sulfoxide derivative of this dispirocyclic product was identified to be a promising hit of the human carboxylesterase 1 inhibitor, and the significant difference of the activity between two enantiomers emphasized the importance of this asymmetric process.