Total Syntheses of Polycyclic Diterpenes Phomopsene, Methyl Phomopsenonate, and iso -Phomopsene via Reorganization of C-C Single Bonds.

The first total syntheses of polycyclic diterpenes phomopsene ( 1 ), methyl phomopsenonate ( 2 ), and iso -phomopsene ( 3 ) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1 - 3 . This work enables us to determine that the correct structure of iso -phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.