Overriding Stereochemical Outcomes in Cyclase Phase Total Synthesis: Enantioselective Synthesis of Habiterpenol and Dasyscyphin A

Herein, we report the enantioselective total syntheses of habiterpenol and dasyscyphin A. By exploiting a quaternary carbon stereocenter epimerization protocol, we could override the intrinsic stereochemical bias of polyolefin cyclization reactions. Accordingly, we achieved the efficient and selective construction of the polycyclic scaffolds of both meroterpenoid natural products that bear an unconventional cis-hydrindane motif. This work demonstrates the utility of stereocenter remodeling in reprogramming the outcomes of biomimetic cyclizations, thus enabling the rapid synthesis of terpenoid frameworks that deviate from the prototypical all-trans-ring fusions.