Ethylene‐Mediated Template‐Free, Enyne Metathesis Gives Macrolactone 1,3‐Dienes: Synthesis of Polvolide and Muscolide From Renewable Feedstocks

A template‐free, stereodefined strategy for the synthesis of macrocyclic 1,3‐diene lactones from renewable feedstocks derived from castor and oleic oils is reported. An endo ‐selective ring‐closing ethylene‐mediated enyne metathesis (RCEYM) proceeds with complete E ‐selectivity across a 10–17‐membered ring‐size range, overcoming the intrinsic stereochemical limitations of conventional macrocyclic ethylene‐mediated enyne metathesis. Subsequent hydrogenation affords methyl‐substituted macrolactones with musky odor profiles. The utility of this approach is demonstrated through the efficient synthesis of Polvolide and Muscolide, providing sustainable access to valuable perfumery macrocycles.