An Approach for the Generation of γ-Propenylidene-γ-butenolides and Application to the Total Synthesis of Rubrolides.

Design and synthesis of a new class of γ-butenolides, viz. β-aryl-γ-propenylidene-γ-butenolides, have been reported from β-aryl-Z-enoate propargylic alcohols in the presence of acid. Isolation of β-aryl-γ-propenylidene-γ-butenolides and their O18-isomer confirmed the intermediacy of the allenyl-lactonium ion as well as the cyclic-hemiacetal during the proposed mechanism. By utilizing the β-aryl-γ-methylenecyclohexenylidene-γ-butenolides as starting materials, a highly stereoselective and efficient approach has been developed for the syntheses of frameworks of rubrolide natural products. This strategy was further extended for the total synthesis of rubrolide E.