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

Abstract

Of the more than 100 casbane diterpenes knownt o date,o nly the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis.Outlined herein is ac onceptually new approach that brings not as ingle but avariety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family.T he key design elements are ac atalyst-controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross-coupling,a nd the efficient closure of the strained macrobicyclic framework by ring-closing alkyne metathesis.A hydroxy-directed catalytic trans-hydrostannation allows for late-stage diversity.These virtues are manifested in the concise total syntheses of depressin, yuexiandajisu A, and ent-pekinenin C. The last compound turned out to be identical to euphorhylonal A, the structure of which had clearly been misassigned. Figure 1. Selection of naturally occurring casbaned iterpenes.