Litcius/Paper detail

Tandem C/N-Difunctionalization of Nitroarenes: Reductive Amination and Annulation by a Ring Expansion/Contraction Sequence

Gen Li, Marissa N. Lavagnino, Siraj Z. Ali, Shicheng Hu, Alexander T. Radosevich

2022Journal of the American Chemical Society77 citationsDOIOpen Access PDF

Abstract

A synthetic method for the reductive transformation of nitroarenes into ortho-aminated and -annulated products is reported. The method operates via the exhaustive deoxygenation of nitroarenes by an organophosphorus catalyst and a mild terminal reductant to access aryl nitrenes, which after ring expansion, are trapped by amine nucleophiles to give dearomatized 2-amino-3H-azepines. Treatment of these ring-expanded intermediates with acyl electrophiles triggers 6π electrocyclization to extrude the nitrogen atom and restore aromaticity of the phenyl ring, which delivers via C–H functionalization 2-aminoanilide and benzimidazole products.

Topics & Concepts

ChemistryNucleophileNitreneElectrophileAnnulationRing (chemistry)Combinatorial chemistryAminationBenzimidazoleAmine gas treatingTandemReductive aminationMedicinal chemistryCatalysisStereochemistryOrganic chemistryComposite materialMaterials scienceCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsCatalytic Cross-Coupling Reactions