An enantioselective route to paeonilactone A via palladium- and copper-catalyzed reactions

We herein report on a formal total synthesis of paeonilactone A involving p alladium-, copper-, and enzyme-catalyzed reactions starting from 1,3-cycloh exadiene. The key step in the synthesis, a palladium(II)-catalyzed 1,4-oxyl actonization of a conjugated diene, simultaneously introduces two of the ox ygen substituents required for the target molecule. The synthesis also incl udes our recently developed copper(I)-catalyzed cross-coupling reaction bet ween dienyltriflates with Grignard reagents, introducing one of the methyl groups present in the target molecule. This new approach toward paeonilacto ne A allows complete control of all four stereogenic centers and is the fir st enantioselective route toward paeonilactone A starting from an achiral s ubstrate.