Generation of aryl radicals from in situ activated homolytic scission: driving radical reactions by ball milling

Abstract

The need for an operationally straightforward application of radical chemistry has led researchers to explore practical strategies to obtain and trap radicals. Herein, we report a mechanoradical generation method by direct C–N bond breaking of aryldiazonium salts using NaCl as an activator. This method opens a new pathway to radical reactions ranging from (hetero)arylation, cascade addition, and hydrogen atom transfer (HAT)-addition to cross-coupling. The mechanism of the radical generation process involves the ionic exchange between NaCl and aryldiazonium tetrafluoroborates and the mechanical “homolytic scission” (as induced by the counterion) of the in situ formed reactive chloride compounds. The scaling-up experiments, the late-stage modification of pharmaceutical agents, and the synthesis of bioactive compounds and pharmaceuticals further demonstrate the utility and practicality of this method.