Catalyst‐Controlled Stereoselective Olefin Metathesis as a Principal Strategy in Multistep Synthesis Design: A Concise Route to (+)‐Neopeltolide

Abstract Molybdenum‐, tungsten‐, and ruthenium‐based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo‐ and enantioselective route that furnishes the anti‐proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring‐opening/cross‐metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring‐closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z ‐selective cross‐metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.