Ex‐Situ Generation of Bis(trifluoromethyl)disulfide and Applications to Trifluoromethylthiolation Reactions

Abstract

AbstractHerein, a convenient and operationally simple protocol for the ex‐situ generation of bis(trifluoromethyl)disulfide from the readily available and commercial Langlois reagent is reported. The one‐step synthesis of the toxic and volatile CF3SSCF3 is performed in a two‐chamber reactor with simple PPh3 and N‐bromosuccinimide as the activator, allowing for the safe handling and tandem utilization in direct trifluoromethylthiolation reactions. The versatility of the ex‐situ generated CF3SSCF3 is demonstrated in known electrophilic, nucleophilic, and a radical trifluoromethylthiolation reactions. Furthermore, the application of the CF3SSCF3 in a copper‐catalyzed cross‐coupling with boronic acids is disclosed, showing good to excellent yields of trifluoromethyl‐substituted aryl products, including pharmaceutically relevant molecules.