Cross-Electrophile Coupling of Benzyl Halides and Disulfides Catalyzed by Iron

Abstract

Cross-electrophile couplings are influential reactions that typically require a terminal reductant or photoredox conditions. We discovered an iron-catalyzed reaction that couples benzyl halides with disulfides to yield thioether products in the absence of a terminal reductant and under photoredox conditions. The disclosed platform proceeds without sulfur-induced catalyst poisoning or the use of an exogenous base, supporting a broad scope and circumventing undesired elimination pathways. We applied the developed chemistry in a new mode of disulfide bioconjugation, drug synthesis, gram-scale synthesis, and product derivatization. Lastly, we performed mechanistic experiments to better understand the stereoablative reaction between two electrophiles. Disulfides and benzylic thioethers are imperative for biological and pharmaceutical applications but remain severely understudied in comparison to their ethereal and amino counterparts. Hence, we expect this platform of iron catalysis and the downstream applications to be of interest to the greater scientific community.