Two Remarkable Epimerizations Imperative for the Success of an Asymmetric Total Synthesis of (+)-Aigialospirol.

Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of (+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis. Through modeling, we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis, thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product synthesis. Most importantly, calculations allowed us to fully understand the nature and the mechanistic course of these two epimerizations that were imperative to the total synthesis efforts.