Synthesis of perfluoroaryl sulfides at electron-poor arenes via an SNAr step with an unexpected mechanism

Perfluoroaryl groups are a recurring motif in materials and pharmaceutical chemistry. Here, we report a method to couple perfluoroarenes and thiols to yield perfluoroaryl sulfides via a nucleophilic aromatic substitution (SNAr) step. The discussed synthesis strategy can be applied at ambient conditions or conducted as industrial processes with either ball mill or flow techniques. In addition, it tolerates a large variety of functional groups, thus allowing it to be used for late-stage functionalization. The nature of the proposed reaction is a nucleophilic attack of a thiol group at an electron-poor aromatic ring, which is expected to feature a stepwise mechanism involving a “Meisenheimer complex” as an intermediate. However, computational simulations predict a concerted mechanism for the process. The preference for a concerted or stepwise SNAr pathway is rationalized through a Marcus-type argument considering the relative stability of the reactant, intermediate, and product species.