Total Synthesis and Structural Revision of a Harziane Diterpenoid

The first total synthesis of nominal harziane diterpenoid 1 is disclosed, whose spectral characteristics did not match those of the reported natural product. Stereochemical analysis and subsequent synthesis of the epimeric tertiary alcohol led to reassignment of configuration of the natural product as shown for 2. At the heart of the synthesis is an enyne cycloisomerization that sets a key quaternary stereocenter within a cyclobutane with high diastereocontrol. The route features strategies for the synthesis of the highly congested 6-5-7-4 carbon skeleton characteristic of the caged harziane diterpenoids.