Synthesis Of N-arylquinone Atropisomers By Organocatalytic N-arylation/oxidation Tande

Axial chirality is a type of chirality in which a molecule contains two pairs of chemical groups in a non-planar arrangement around the chiral axis.Axial chiral compounds exist widely in natural products and drug molecules and are used in asymmetric catalysis as catalysts and chiral ligands.As an axial-chiral compound with unique structure,diarylamines and related scaffolds are among the most common structural motifs in a myriad of biologically active natural products and pharmaceuticals such as the FDA-approved drugs bosutinib and binimetinib,and other non-nucleoside reverse transcriptase(NNRT)and vascular endothelial growth factor receptor(VEGFR)inhibitors.Because of their low rotation barrier,diarylamine atropisomers are configurationally unstable and readily interchangeable.Compared to the synthesis of other stable atropisomers,the introduction of axial chirality into diarylamines and related scaffolds remains challenging.Using 2,4,6-triisopropyl chiral phosphate(CPA)derived from BINOL skeleton as catalyst,we achieved the enantioselective coupling reaction between quinones and aniline,and constructed a series of C-N axis chiral n-aryl quinone resistance isomers containing intramolecular N-H-O hydrogen bond stability.The reaction has good yield(up to 84%)and excellent enantioselectivity(up to 99%).Gram scale experiments further demonstrate the practicality of the reaction.In addition,this method provides a good reference for the synthesis of secondary amine resistance isomers with various structures.