Generation of perthiyl radicals for the synthesis of unsymmetric disulfides.

Zhou, Fei; He, Xiaochun; Zhou, Mi; Li, Na; Wang, Qingqing; Zhang, Xuemei; Lian, Zhong · Nat Commun · 2025

basic_science · Level V

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Abstract

Unsymmetric disulfides are prevalent in natural products and are essential in medicinal chemistry and materials science, but their robust synthesis poses significant challenges. In this paper, we report an expeditous transition-metal-free methodology for synthesizing unsymmetric disulfides through the addition of perthiyl radicals to alkenes. This study marks the use of generating perthiyl radicals by reacting SO<sub>2</sub> with unactivated alkyl (pseudo)halides (Cl/Br/I/OTs). Various primary, secondary and tertiary alkyl (pseudo)halides substituted with different functional groups successfully function as suitable reactants. The formation of perthiyl radicals and their involvement in the reaction process are verified through mechanistic studies and DFT calculations. Overall, this method leverages readily available alkyl electrophiles and alkenes alongside SO<sub>2</sub> in a single reaction setup to efficiently form both carbon-sulfur and sulfur-sulfur bonds simultaneously.