A visible-light-induced cascade radical cyclization of alkenyl fluoroalkyl ketones is developed, producing various α-R_f cycloalkanols in promising yields with up to >20 : 1 dr selectivity. DFT calculations suggest that the fluorine effect plays an important role in this reaction.

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.