Diastereoselective Construction of α‐Fluoroalkyl Cycloalkanols via Radical Alkylation of α‐Fluoroalkyl Ketones†

Comprehensive Summary α‐Fluoroalkyl (R f ) alcohols are privileged motifs in drugs and pharmaceutically active compounds. As such, it is highly desirable to develop efficient methods for assembling these scaffolds. Herein, a visible‐light‐induced cascade radical cyclization of alkenyl fluoroalkyl ketones is developed, producing a variety of decorate α‐R f cycloalkanols in promising yields with up to >20 : 1 dr selectivity. A radical chain mechanism involving an intramolecular radical addition to the α‐R f carbonyl group and a subsequent intermolecular hydrogen atom transfer (HAT) has been proposed. Density functional theory (DFT) calculations indicate that a fluorine effect contributes to the radical addition to carbonyls by lowering the π* (C=O) orbital energy of COR f and energy barrier of the HAT between alkoxy radicals and THF, which may be valuable for controllable transformations of fluorinated molecules.