Acid-mediated coupling of γ-hydroxybutenolides and aldehydes: synthesis of a new class of spirocyclic ketal-lactones

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), γ-methyl-γ-hydroxybutenolide reacts with aromatic aldehydes to generate a new class of stereochemically rich spirocyclic ketal-lactones in good yields and with excellent stereoselectivities. We believe that this process takes place through the in situ generation of protoanemonin followed by a Prins reaction. Herein, we describe this discovery, along with substrate scope and preliminary mechanistic studies.