Collective Total Synthesis of Casbane Diterpenes: One Strategy, Multiple Targets

Of the more than 100 casbane diterpenes known to date, only eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not single but variety of derivatives into reach, especially highly oxygenated and arguably relevant members this family. The key design elements are catalyst-controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension resulting stereoisomeric cyclopropane building blocks chemoselective hydroboration/cross-coupling, efficient closure strained macrobicyclic framework ring-closing alkyne metathesis. A hydroxy-directed catalytic trans-hydrostannation allows for late-stage diversity. These virtues manifested in concise total syntheses depressin, yuexiandajisu A, ent-pekinenin C. last compound turned out be identical euphorhylonal structure which had clearly misassigned.