A Radical-Based Construction of the Khayanolide Tetracyclic Framework Enabled by a Cyclization Cascade and Alcohol-Mediated Hydrogen Atom Transfer

A radical-based approach to the construction of the khayanolide tetracyclic framework is described. A cage-forming radical cyclization cascade enabled rapid assembly of the highly congested 5-6-5-6 carbon skeleton. In the course of these studies, an unprecedented stereoselective radical reduction at C5 was uncovered, proceeding via intramolecular hydrogen atom transfer from an alcohol O-H bond under low-valent titanium-mediated conditions. Mechanistic experiments support this unusual hydrogen atom transfer process.