Scalable Iron-Catalyzed Radical Bromochlorination of Alkenes with HCl under Thermal Conditions

Abstract

Herein, an efficient and sustainable iron-catalyzed radical bromochlorination of alkenes is disclosed, proceeding under conventional thermal conditions with excellent chemo- and regioselectivity. The reaction employs exceptionally affordable and ubiquitous hydrochloric acid both to activate N-bromosuccinimide for bromine radical generation and to serve as the chlorine source, while Fe(III)-Cl acts as the chlorine-atom transfer mediator via a radical ligand transfer process. This method features operational simplicity, a remarkably short reaction time (just 1 min), and multigram scalability. Moreover, the protocol demonstrates robust synthetic potential and versatility in the late-stage, site-selective bromochlorination of pharmaceutical scaffolds and bioactive molecules. Mechanistic investigations combining control experiments with DFT calculations support a plausible iron-mediated radical pathway.