TEMPO-Regulated Regio- and Stereoselective Cross-Dihalogenation with Dual Electrophilic X+ Reagents

Main observation and conclusion A TEMPO catalyzed cross-dihalogenation reaction was established via redox-regulation of the otherwise complex system of dual electrophilic X+ reagents. Formally, the ICl, BrCl, I-2 and Br-2 were generated in-situ, which enabled high regio- or stereoselective access to a myriad of iodochlorination, bromochlorination and homo-dihalogenation products with a wide spectrum of functionalities. With its mild conditions and operational simplicity, this method could enable wide applications in organic synthesis, which was exemplified by divergent synthesis of two pharmaceuticals. Detailed mechanistic investigations via radical clock reaction, pinacol ring expansion and Hammett experiments were conducted, which confirmed the intermediacy of halonium ion. In addition, a dynamic catalytic model based on the versatile catalytic role of TEMPO was proposed to explain the selective outcomes.

Automated summary

A TEMPO-catalyzed cross-dihalogenation reaction was established through redox-regulation of dual electrophilic X+ reagents, enabling high regioselective access to various halogenated products. It has wide applications in organic synthesis and the intermediacy of halonium ion was confirmed through mechanistic investigations.