Total Synthesis of Eudesmanolides Alantolactone, Isoalantodiene, Alloalantolactone, and 5α,6α-Epoxyalantolactone

We report a 13-step total synthesis of the sesquiterpenoid lactone alantolactone and the first total syntheses of isoalantodiene, alloalantolactone, and 5α,6α-epoxyalantolactone. Key steps feature the intramolecular Diels–Alder cycloaddition of furan with an unactivated 1,1-disubstituted alkene to establish a quaternary carbon center, a palladium-catalyzed α-alkenylation of ketene silyl acetals, and a strain-promoted isomerization of a complex oxabicycle. We also describe the first enantioselective approach to this class of natural products.