Abstract:
Balancing act: The correct balance of electronic factors in the naphthazarin and isocoumarin fragments facilitates the acid-mediated spiroketalization step to afford the key densely functionalized spiroketal (see picture; EOM=ethoxymethyl) in the formal synthesis of (±)-γ-rubromycin. A novel regioselective allyloxylation/Claisen rearrangement of 2-azido-1,4-naphthoquinone provides access to the highly oxygenated naphthazarin fragment.