An oxidopyrylium cyclization/ring-opening route to polysubstituted α-hydroxytropolones.

α-Hydroxytropolones are a class of molecules with therapeutic potential against several human diseases. However, structure-activity relationship studies on these molecules have been limited due to a scarcity of efficient synthetic methods to access them. It is demonstrated herein that α-hydroxytropolones can be generated through a BCl(3)-mediated ring-opening/aromatization/demethylation process on 8-oxabicyclo[3.2.1]octenes. Used in conjunction with an improved method based on established oxidopyrylium dipolar cycloadditions, several polysubstituted α-hydroxytropolones can be accessed in three steps from readily available α-hydroxy-γ-pyrones.