Asymmetric Total Synthesis of Eremophilanolide Sesquiterpene Xylareremophil and Its Congeners

The first asymmetric, protecting group free total synthesis of eremophilanolide sesquiterpenes, xylareremophil (1), 2α,3α-epoxymairetolide A (2), and 2,3-seco-2,3-olide-1-deoxygenmairetolide F (3), is concisely achieved with a longest linear route of five to eight steps, starting from the known (5S)-5,6-dimethyl-2-cyclohexenone as the chiral starting material. This synthetic approach mainly features an oxa-Pauson–Khand reaction of the highly functionalized chiral aldehyde precursor, forging a γ-butenolide-fused tricyclic core framework of eremophilanolides in a one-step manner. This study provides a novel strategic perspective for the divergent synthesis of the eremophilanolide sesquiterpenes.