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

Abstract

Comprehensive Summaryα‐Fluoroalkyl (Rf) 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‐Rf cycloalkanols in promising yields with up to >20 : 1 dr selectivity. A radical chain mechanism involving an intramolecular radical addition to the α‐Rf 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 CORf and energy barrier of the HAT between alkoxy radicals and THF, which may be valuable for controllable transformations of fluorinated molecules.