Acid-promoted sequential cationic cyclizations for the synthesis of (±)-taiwaniaquinol B

A formal total synthesis of (±)-taiwaniaquinol B starting from (E/Z)-citral has been accomplished by sequential cationic cyclizations promoted by acids. The cyclization to an α-cyclogeranyl ketone derivative is promoted by Lewis acid, whereas the use of Brønsted acid promotes an olefin isomerization leading to undesired cyclizations. The final ring formation to give the hydrofluorenone skeleton is promoted by Brønsted acid. Thus, the choice of the acid in each step critically determined the cationic reaction pathways and cyclization outcome.

Sequential treatment of dienone 3 with Lewis then Brønsted acid promoted cyclizations resulting in a synthesis of taiwaniaquinol B.