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

ABSTRACT 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.