Sulfur is found in roughly 25% of active pharmaceutical ingredients (APIs) (Scheme 1A). This privilege arises from sulfur's ability to exist in a diverse array of structurally unique functional groups with distinct chemical properties. Sulfur-containing drugs generally fall into 10 distinct categories defined by these functional groups and, in turn, their biological activities. A few notable categories include thioethers, sulfoxides, and sulfones with examples of approved APIs in each category depicted in Scheme 1A. Remarkably, these can act as related functional group classes due to metabolic interconnectivity (thioether to sulfoxide to sulfone redox interconversion). 1f For this reason, thioethers are often used as 'prodrugs' to increase permeability, reduce toxicity and mediate site-specific targeting. Analogously, in the preparation of sulfoxide and sulfone drugs and drug candidates, thioethers are frequently used as key retrosynthetic targets upstream of final oxidation manipulations. Given the ubiquity of thioethers, sulfoxides, and sulfones in biologically active compounds, numerous thioetherification (C-S coupling) strategies have been reported. Traditionally, arylthioethers are synthesized from thiols and electron deficient aryl halides using strong bases, polar solvents, and high temperatures via nucleophilic aromatic substitution (SNAr) (Scheme 1B). State-of-the-art thioetherification involves transition metal (TM) catalysts that generally display broader scope but usually at higher cost (Scheme 1B). 2d,e Additionally, while nitrogen containing heterocycles are present in nearly 82% of small molecule drugs, TM catalysts are often challenged with these motifs due to catalyst poisoning. Recent photochemical innovations provide ambient temperature alternatives to SNAr and TM catalyzed approaches to thioethers (Scheme 1B). 2d,e Although most reports utilize photoredox or metallaphotoredox catalysis, one noteworthy exception requires no photocatalyst (PC) (White LED, Cs2CO3, DMSO) (Scheme 1C). 2e,f Developed by Miyake and co-workers, this reaction proceeds through a unique mechanism involving intermolecular charge transfer (CT) via a thiolate-aryl halide electron donor-acceptor (EDC) complex prior to C-S bond formation. Perhaps more impressive is the reaction's general utility, low cost and simple setup. In our continued effort to implement photochemical transformations in pharmaceutical synthesis, we became motived to implement these conditions. Through this endeavor, we have discovered a thioetherification method that does not require light, transition metals or an exogenous base. This simple methodology enables the synthesis of a diverse array of products that could be conveniently synthesized and isolated. 2j Mechanistic investigation revealed a distinct proposed mechanism termed proton transfer dual ionization (PTDI) SNAr. Furthermore, a datascience-driven workflow that combined high-throughput experimentation (HTE) and machine learning (ML) algorithms was implemented to gain a refined understanding of when a reaction will be successful. The resultant classification model accurately predicted reaction outcomes enabling the synthesis of ten complex targets.