Abstract Asymmetric entry to the bicyclic core structure of (+)-hyperforin is presented. The developed synthetic strategy features a carefully orchestrated stereochemical relay from the single chiral center residing within (–)-Wieland–Miescher ketone and an intramolecular aldol reaction to cast the [3.3. 1] bicyclic scaffold found in a diverse array of polycyclic polyprenylated acylphloroglucinols.