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

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 reveal distinct stability/reactivity relationships between 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.