Short Scalable Route to Apiaceae Sesquiterpene Scaffolds: Total Synthesis of 4-epi-Epiguaidiol A

The oxy-Cope/ene reaction cascade to form a locked elemane conformer allows the short scalable synthesis of versatile Apiaceae scaffolds. The divergent fate of the obtained macrocyclic germacrane is surveyed under cationic and dioxygeninduced Prins-type reaction conditions to allow the diastereoselective synthesis of oxidized Apiaceae guaiane congeners and the total synthesis of 4-epi-epiguaidiol A. Additionally, the unprecedented reduction of a hydrogen-bond-biased guaiane substrate permits the chemoselective synthesis of desoxo-jungiaguaiane.

Automated summary

In this study, the oxy-Cope/ene reaction cascade was used to form a locked elemane conformer, enabling the short and scalable synthesis of versatile Apiaceae scaffolds. The divergent fate of the obtained macrocyclic germacrane was explored under different reaction conditions, leading to the diastereoselective synthesis of oxidized Apiaceae guaiane congeners and the total synthesis of 4-epi-epiguaidiol A. Additionally, the reduction of a hydrogen-bond-biased guaiane substrate allowed for the chemoselective synthesis of desoxo-jungiaguaiane.