Ion Hydration Enables Generality in Asymmetric Catalysis: Desymmetrization to <i>P</i>‐Stereogenic Triarylphosphine Derivatives

Abstract Asymmetric synthesis relies on seamless transmission of stereochemical information from a chiral reagent/catalyst to a prochiral substrate. The disruption by substrates’ structural changes presents a hurdle in innovating generality‐oriented asymmetric catalysis. Here, we report a strategy for substrate adaptability by exploiting a fundamental physicochemical phenomenon—ion hydration, in developing remote desymmetrization to access P ‐stereogenic triarylphosphine oxides and sulfides. Compared to existing methods, this approach does not require pre‐installed ortho substituents and avoids the use of Grignard/organolithium reagents. Simply tuning the water/ion ratio in the reaction media tailors the water‐mediated ionic substrate–catalyst preorganization to counterbalance the structural changes in the substrates, thus further increasing the diversity of enantioenriched P ‐stereogenic compounds. This study shows that it is viable and practical to precisely manipulate ionic interactions through tuning the dynamic ion hydration in situ, thereby adding a distinctive dimension to catalyst engineering in the pursuit of substrate generality in asymmetric catalysis.