Short, Divergent, and Enantioselective Total Synthesis of Bioactive ent-Pimaranes

We present the first total synthesis of eight ent-pimaranes via a short and enantioselective route (11-16 steps). Key features of the divergent synthesis are a Sharpless asymmetric dihydroxylation, a Bronsted acid catalyzed cationic bicyclization, and a mild Rh-catalyzed arene hydrogenation for rapid access to a late synthetic branching point. From there on, selective functional group manipulations enable the synthesis of ent-pimaranes bearing different modifications in the A- and C-rings.

Automated summary

We have achieved the total synthesis of eight ent-pimaranes for the first time via a short and enantioselective route (11-16 steps). Key features of this divergent synthesis include Sharpless asymmetric dihydroxylation, Bronsted acid catalyzed cationic bicyclization, and mild Rh-catalyzed arene hydrogenation, enabling rapid access to a late synthetic branching point. Selective functional group manipulations further allow for the synthesis of ent-pimaranes with different modifications in the A- and C-rings.