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

Cross-electrophile couplings are influential reactions that typically require a terminal reductant or photoredox conditions. We discovered an iron-catalyzed reaction that couples benzyl halide starting materials with disulfide building blocks to yield thioether products in the absence of a terminal reductant and photoredox conditions. The disclosed platform proceeds without sulfur-induced catalyst poisoning or the use of 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 motifs in biological and pharmaceutical applications, among other areas, that are severely understudied in comparison to their ethereal and amino counterparts. Hence, we expect this platform of iron catalysis and the downstream applications, including drug synthesis and a new form of bioconjugation, are of interest to the greater scientific community.