Brønsted Acid Catalysis Permits Electrophilic Halogenation of Electron-Deficient Arenes

Key words

electrophilic halogenation - electron-deficient arenes - Brønsted acid catalysis - hexafluoroisopropanol

Significance

Song, Jiao, and co-workers report a Brønsted acid-catalyzed electrophilic halogenation of electron-deficient arenes by using readily available halogenation reagents and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a hydrogen-bond activator. Numerous sensitive electron-withdrawing substituents are tolerated under the reaction conditions, yielding various aryl halides in moderate to excellent yields.

Comment

Experimental investigations provide support for an electrophilic mechanism in which both 2-methyl-5-nitrobenzenesulfonic acid (m-NBSA) and HFIP synergistically activate the halogenating reagent. The authors have developed an effective halogenation system for a broad scope of challenging electron-deficient arenes with excellent functional-group tolerance. The potential of the method is demonstrated by late-stage halogenation of bio­active molecules and by a successful application in drug synthesis.

Publikationsverlauf

Artikel online veröffentlicht:
20. September 2022