A Failed Late-Stage Epimerization Thwarts an Approach to Ineleganolide

Significant efforts were made to complete a synthesis of the complex norcembranoid ineleganolide via a seemingly attractive strategy involving late-stage creation of the central seven-membered ring. While the two key enantioenriched building blocks were made via high-yielding sequences and their convergent union was efficient, the critical C4–C5 bond of this sterically congested natural product could never be forged. Several interesting examples of unexpected acid–base behavior and unanticipated proximity-induced reactivity accounted for most of the problems in the execution of the synthesis plan.