Origin of Scission Selectivity for Phosphoranyl Radicals in Photoredox Catalysis

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.