Total Synthesis and Configurational Validation of (+)-Violapyrone C

Abstract

Gold(I)-catalyzed intramolecular 6-endo-dig cyclization of tert-butyl ynoates afforded alpha-pyrone cores of violapyrones. Moreover, this reaction was successfully applied to the stereospecific syntheses of (+)- and (-)-violapyrone C, which allowed the absolute configuration of natural (+)-violapyrone C to be assigned by comparison of the optical rotations. This first total synthesis, which proceeded in 22% yield over 10 steps from (S)-(-)-2-methylbutanol, features silver(I) oxide promoted monobenzylation of 1,4-butanediol, Wittig ole-fination, Claisen condensation, Corey-Fuchs reaction, and gold(I)-catalyzed alpha-pyrone synthesis.