Fragmentations of bicyclic ketoesters and synthetic efforts toward eleutherobin

Abstract

An unprecedented anionic condensation, fragmentation, and elimination sequence from the coupling of bicyclo[2.2.1]heptenones with aldehydes is described. This reaction leads to the stereoselective formation of disubstituted five-membered rings which are present in a wide array of bioactive molecules. Oxabicyclo[2.2.1]heptenone 106 also undergoes two-carbon ring expansions when subjected to anionic conditions and Michael acceptors. As an outgrowth of this interesting chemistry, we have been able to access the carbon skeleton of oxygenated cembranoids by subjecting bis-activated ene-yne to the enolate from oxabicyclo[2.2.1]heptenone 106. In order to demonstrate the synthetic utility of the anionic condensation, fragmentation, and elimination reaction, we have applied it to the synthesis of nortetillapyrone.