Asymmetric Kinetic Resolution of 2‐Aryl Oxetanes by Dinuclear Titanium Radical Catalysis

ABSTRACT 2‐Aryl oxetanes are valuable strained‐ring synthons, yet a broadly useful chemical kinetic resolution of this substrate class has remained largely unavailable. Here we report a dinuclear (salen)titanium‐catalyzed radical ring‐opening strategy for the kinetic resolution of 2‐aryl oxetanes under mild conditions. The reaction accommodates diverse aryl‐, heteroaryl‐, and drug‐conjugated substrates, delivering enantioenriched oxetanes with high regio‐ and enantioselectivity. The resulting oxetanes serve as versatile chiral platforms and enable concise, modular, and enantio‐retentive access to pharmaceutically relevant targets, including ( S )‐Atomoxetine, ( S )‐Nisoxetine, and ( S )‐Fluoxetine. Mechanistic studies support a Curtin–Hammett‐type stereochemical model in which diastereomeric Ti–oxetane intermediates, differentiated by an unusual ligand–substrate C–H···π interaction, display distinct stability/reactivity relationships during C─O bond homolysis. Beyond establishing a broadly useful kinetic resolution of 2‐aryl oxetanes, this work reveals an unusual mode of attractive ligand–substrate recognition in salen–titanium radical catalysis.