Bromine radical-enhanced HAT activity leading to stoichiometric couplings of methylarenes with acid chlorides

Abstract

The stoichiometric coupling of readily available methylarenes and diverse acid chlorides into α-aryl ketones, a valued structural motif present in pharmacologically relevant molecules, has been developed. The utility of this protocol is demonstrated by the late-stage acylation of biologically active molecules in a stoichiometric manner. Mechanistic investigation reveals that the photocatalytically generated bromine radical acts as a hydrogen atom abstraction reagent and delivers a nucleophilic benzyl radical, which is intercepted by nickel-catalyzed cross coupling to accomplish benzylic acylation.