Origin of Scission Selectivity for Phosphoranyl Radicals in Photoredox Catalysis

Abstract Phosphoranyl radicals are versatile synthetic intermediates that can form downstream radicals through α- and β-scission. However, the unclear origin of scission selectivity hinders the rational design of new transformations using these elementary steps. Here we report a comprehensive study of phosphoranyl radical scission mechanisms for sulfonamide nucleophiles. Using a combination of experimental, computational, and machine-learning-driven strategies, the primary factors influencing selectivity in these transformations were uncovered. Computational and experimental studies revealed an unexpected Curtin–Hammett scenario and demonstrated the impact of reaction stoichiometry on selectivity outcomes. Statistical modeling enabled selectivity prediction via an interpretable linear regression model, which revealed that small, electron-poor phosphines favor β-scission. Taken together, these studies expose the interplay of reaction conditions, phosphine properties, and alkene properties, which can be used to control selectivity in phosphoranyl-radical-mediated reactions of sulfonamides. These insights were harnessed to develop a photoredox-catalyzed phosphine-mediated hydrosulfonylation reaction of alkenes, the development of which makes primary sulfonamides the first example of a nucleophile with switchable scission selectivity controlled only by phosphine and reaction conditions for phosphoranyl-radical-mediated reactions.