Catalytic Electrophilic Halogenation of Arenes with Electron- Substituents

The electrophilic halogenation of arenes is perhaps the simplest method to prepare aryl halides, which are important structural motifs in agrochemicals, materials, and pharmaceuticals. However, the nucleophilicity of arenes is weakened by the electron-withdrawing substituents, whose electrophilic halogenation reac-tions usually require harsh conditions and lead to limited substrate scopes and applications. Therefore, the halogenation of arenes containing electron-withdrawing groups (EWGs) and complex bioactive compounds under mild conditions has been a long-standing challenge. Herein, we describe Bronsted acid-catalyzed halogenation of arenes with electron-withdrawing substituents under mild conditions, providing an efficient protocol for aryl halides. The hydrogen bonding of Bronsted acid with the protic solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) enables this transformation and thus solves this long-standing problem.

Automated summary

The electrophilic halogenation of arenes is a common method to prepare aryl halides, but reactions of arenes with electron-withdrawing substituents usually require harsh conditions and have limited substrate scopes. This study describes a mild protocol for the halogenation of arenes with electron-withdrawing substituents catalyzed by Bronsted acid, providing an efficient method for the synthesis of aryl halides.