Enantioselective Total Synthesis of (+)‐Dracocephalone A, (+)‐Dracocequinone A, and (−)‐Dracocequinone B by Oxabridge Construction With Oxygen

Oxa‐bridged 20‐norabietane diterpenoids, which are characterized by unique 6‐oxabicyclo[3.2.1]octane and 2‐oxabicyclo[2.2.2]octane frameworks in compact tetracyclic cores, exhibit high structural complexity and interesting biological activity. We report the enantioselective synthesis of (+)‐dracocephalone A, (+)‐dracocequinone A, and (−)‐dracocequinone B, featuring two strategic oxygen‐engaged transformations. The 2‐oxabicyclo[2.2.2]octane frameworks are constructed via a late‐stage oxygen‐mediated oxabridge reorganization of 6‐oxabicyclo[3.2.1]octane precursors. In this cascade reaction, a redox‐neutral disproportionation reaction generates reduced phenolic and oxidized cyclohexadienone intermediates simultaneously, followed by an oxabridge reorganization through selective C10–O bond cleavage and regiospecific 1,6‐conjugate addition. The 6‐oxabicyclo[3.2.1]octane framework is formed efficiently through an oxygen‐engaged oxabridge cyclization. The oxabridge construction strategy demonstrated in this work will allow streamlined syntheses of oxa‐bridged bioactive natural products and their structural analogs.