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.