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

Abstract

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.