Practical and Site-Selective Photoinitiated C(sp3)–H Bond Chlorination of Ketones, (E)-1,3-Enones, and Alkylbenzenes by Chloramine-T and N-Chlorosuccinimide

Abstract

A practical photoinitiated synthetic method for the site-selective γ - and α-chlorination of C(sp³)–H bonds of ketones, (E)-1,3-enones, and alkylbenzenes by chloramine-T (CAT) and N-chlorosuccinimide (NCS) under blue LED (λ<inf>max</inf> = 456 nm) light irradiation is reported. Mechanistic studies suggest the reaction to proceed via a radical pathway where the chlorination reagent dichloramine-T (DCT) is generated in situ from the reaction of CAT with NCS. Its premised controlled formation along with that of the carbon-centered radical species derived from the substrate is thought to contribute to product site-selectivity. The developed protocol operates under mild reaction conditions at room temperature and demonstrates excellent functional group tolerance as exemplified by the site-selective γ-C(sp³)–H bond chlorination of carboxylic esters and amides, and late-stage functionalization of several bioactive natural products and drug molecules. The study also highlights the potential of CAT for the first time as a versatile and controllable chlorine radical atom source for site-selective halogenation reactions, expanding its synthetic utility beyond traditional applications.