Total Synthesis of (−)-Mitrephorone A Enabled by Stereoselective Nitrile Oxide Cycloaddition and Tetrasubstituted Olefin Synthesis

A highly enantio­selective and diastereo­selective total synthesis of the diterpenoid (−)-mitre­phorone A is presented. Key to the synthesis are stereo­controlled 1,4-semihydrogenation of a 1,3-diene to a tetrasubstituted double bond, enzyme-catalyzed malonate desymmetrization, and highly diastereo­selective nitrile oxide cycloaddition. The streamlined strategy is a considerable improvement to those reported earlier in terms of diastereo- and enantio­selectivity. For the first time, the combination of modern Pd-cross-coupling with Cr-catalyzed reduction allows for rapid access to tetrasubstituted olefins with full stereo­control.