Nistanaki_2019_Angew.Chem.Int.Ed.Engl_58_1724

Disclosed is a five-step synthesis of (+/-)-vibralactone, a biologically active terpenoid natural product. A key photochemical valence isomerization of 3-prenyl-pyran-2-one produces both the all-carbon quaternary stereocenter and the beta-lactone at an early stage. Cyclopropanation of the resulting bicyclic beta-lactone produces a strained housane structure that is converted to the natural product through a sequential ring expansion and reduction strategy. This concise and modular route to the natural product provides the shortest total synthesis of (+/-)-vibralactone reported to date.