Transformative reactions in nitroarene chemistry: C–N bond cleavage, skeletal editing, and N–O bond utilization

Abstract

Nitroarenes are highly versatile building blocks in organic synthesis, playing a pivotal role in various reactions. Common transformations involving nitroarenes include nucleophilic aromatic substitution (S_NAr) reactions, where the nitro group functions both as a potent electron-withdrawing group that activates the aromatic ring and as a leaving group facilitating the substitution. Additionally, the direct transformation of nitro groups, such as reduction-driven syntheses of amines and carboxylic acids, as well as ipso-substitution S_NAr reactions, have been extensively explored. Interactions between ortho-nitro groups and neighboring substituents also provide unique opportunities for selective transformations. However, beyond these well-established processes, direct transformations of nitro groups have been relatively limited. In recent years, significant advancements have been made in alternative methodologies for nitro group transformations. This review focuses on the latest progress in novel transformations of nitroarenes, with emphasis on three major categories: (i) functional group transformations involving C–N bond cleavage in nitroarenes, (ii) skeletal editing via nitrene intermediates generated by N–O bond cleavage, and (iii) the utilization of nitroarenes as an oxygen source through N–O bond cleavage. These developments under-score the expanding utility of nitroarenes in modern organic synthesis.