A concise total synthesis of pyrovellerolactone using a rhodium-catalyzed [(3 + 2) + 2] carbocyclization reaction

Abstract

A concise and highly convergent three-step total synthesis of the lactarane natural product, pyrovellerolactone, is described. The key step involves a regio- and diastereoselective rhodium-catalyzed [(3 + 2) + 2] carbocyclization of an alkenylidenecyclopropane with a 4-hydroxybut-2-ynoate followed by an in situ intramolecular lactonization to generate the tricyclic core in a single operation. This represents the first example of a higher-order [3 + 2 + 2] carbocyclization reaction in total synthesis, which is likely to provide an important strategy for the construction of related targets within this sesquiterpene family.