Ion Hydration Enables Generality in Asymmetric Catalysis: Desymmetrization to P‐Stereogenic Triarylphosphine Derivatives

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.