Streamlined Synthesis of Eudesmane Sesquiterpenoids through Site-switchable Olefin Functionalization Strategy

Herein, we demonstrate a concise synthesis of oxidized eudesmanes using a late-stage site-selective olefin functionalization strategy. To implement this strategy, we synthesized a common intermediate comprising two identical olefins within a hydroxy-carrying eudesmane core via an asymmetric tandem Michael addition and Aldol reaction, along with an Au(I)-catalyzed Alder-ene reaction. Subsequent late-stage site-selective olefin hydrogenation and epoxidation techniques were employed to synthesize nine eudesmane congeners without using protecting groups. This study highlights the applicability and effectiveness site-selective functionalization of identical olefins in facilitating the access to intricate terpenes and their derivatives.