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

Abstract

Development of robust d 3 -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-d 3 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 SCD 3 and ArSO 2 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 d 3 -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.