Site-Selective Olefin Functionalization Simplifies the Synthesis of Eudesmane Sesquiterpenes

Late-stage site-specific functionalization of olefins is an underutilized tool in the total synthesis of natural products. Herein, we disclose a short synthesis of oxidized eudesmanes through a site-selective olefin functionalization strategy. To implement this strategy, we synthesized a common intermediate embodying two olefins and hydroxy-carrying eudesmane core via an asymmetric tandem Michael addition and Aldol reaction, and Au(I)-catalyzed Alder-ene reaction. The late-stage site-selective olefin hydrogenation and epoxidation techniques were employed for synthesizing nine eudesmane congeners without using protecting groups. This work demonstrates the efficacy of site-selective olefin functionalization strategy in enhancing the accessibility of complex terpenes and their analogs.