Silver-Catalyzed 1,2-Thiosulfonylation of Alkenes: Development of a Nucleophilic d3-Methylthiolating Reagent

Development of robust d₃-methylthiolating reagents represents an attractive synthetic method to access deuterated molecules in the field of drug discovery. Here, we report a straightforward strategy to prepare electrophilic S-methyl-d₃ arylsulfonothioates in one-step without column purification. These reagents exhibit good radical reactivity toward silver-catalyzed vicinal thiosulfonylation of alkenes or 1,6-enynes on water. As a result, simultaneous incorporation of both SCD₃ and ArSO₂ units into unsaturated carbon–carbon bonds with 100% atom economy has been established. Moreover, the ATRA adducts with >99% D incorporation can serve as nucleophilic d₃-methylthiolating synthons via retro-Michael addition under mild basic conditions, providing a good alternative in trideuteromethylthiolating alkyl iodides to access corresponding trideuteromethyl sulfides with high efficiency.