An Initiator-Free Electrochemical Approach to Radical Thiol–Ene Coupling in a Microfluidic Reactor

The anti-Markovnikov addition of thiyl radicals, generated via one-electron oxidation of thiols, to C=C double bonds is a useful method for synthesizing unsymmetrical sulfides and has been widely applied in the preparation of pharmaceuticals and functional materials. However, conventional radical thiol-ene reactions require metal-based photoinitiators or organic photosensitizers, raising concerns about product isolation and environmental impact. Herein, we demonstrate an initiator-free thiol-ene coupling via electrochemical oxidation of thiols. Using a microfluidic electrochemical reactor, the electrochemically generated thiyl radicals undergo rapid and selective addition to alkenes, affording thioethers in reasonable yields. Substrate scope studies involving 13 alkenes and 13 thiols indicate that thiol acidity (p<i>K</i>_a), alkene electronic properties, and steric effects play key roles in determining reaction efficiency. Although further optimization is required to improve yields and broaden substrate scope, this electrochemical approach highlights the potential of thiol-ene coupling as a sustainable tool in green synthetic chemistry.