Synthesis of (+)-Lineariifolianone and Related Cyclopropenone-Containing Sesquiterpenoids

Abstract

A synthesis of the proposed structure of lineariifolianone has been achieved in eight steps and 9% overall yield starting from (+)-valencene, leading to a reassignment of the absolute configuration of this unusual cyclopropenone-containing natural product. Key steps in the synthetic route include kinetic protonation of an enolate to epimerize the C7 stereocenter and a stereoconvergent epoxide opening to establish the trans-diaxial diol functionality. The syntheses of the enantiomers of two other closely related natural products are also reported, confirming that all three compounds belong to the eremophilane class of sesquiterpenoids.