Enhancing Memory of Chirality in Phosphorus‐Centered Radicals by Inductive Deceleration of Pyramidal Inversion

The realization of stereospecific radical reactions-particularly those involving heteroatom-centered radicals-remains a formidable challenge due to the rapid configurational inversion (racemization) of transient radical intermediates. This study presents a general strategy to enhance the memory of chirality (MOC) in radicals by exploiting the inductive effect of substituents. Through DFT calculations, we demonstrate that the pyramidal inversion barrier of phosphorus-centered radicals can be dramatically increased by substitution with highly electronegative atoms. This deceleration of inversion enables stereoretentive transformations of enantiopure H-phosphinates under mild, radical conditions. A series of stereospecific phosphoryl radical reactions, including alkene hydrophosphonylation, intramolecular arylphosphonylation, phosphorylation-cyclization of isocyanates, and aryl migration reactions, were successfully developed, providing access to diverse P(V)-stereogenic compounds with high efficiency (up to 99% yield) and excellent stereospecificity (up to >99% es). The utility of this approach is highlighted by the late-stage functionalization of densely functionalized pharmaceuticals, bioactive molecules, and a liquid crystal. This work establishes a foundational principle for achieving stereochemical control in radical reactions via rational tuning of the radical intermediate's configurational stability.