Catalytic Asymmetric Total Synthesis of (+)‐Chamaecydin and (+)‐Isochamaecydin and their Stereoisomers

terpene quinone methides and their non-natural stereoisomers, which feature the presence of an unprecedented spiro[4.4]nonane-containing 6-6-6-5-5-3 hexacyclic skeleton. Resting on a chiral phosphinamide-catalyzed enantioselective reduction of 2,2-disubstituted cyclohexane-1,3-dione, a concise route for the synthesis of enantioenriched 6-6 bicyclic fragment was developed. The 6-6 ring fragment and the five-membered ring fragment were unified via a metal-halogen exchange/intermolecular addition reaction. Subsequently, the central 6-5 bicyclic ring system was constructed through a Michael/aldol cascade. The successful establishment of these strategic transformations allowed for an efficient and rapid construction of spiroannulated 6-6-6-5-5 pentacarbocyclic core via a convergent manner. Finally, the total syntheses of naturally occurring (+)-chamaecydin and (+)-isochamaecydin and their corresponding 1',5'-stereoisomers have been achieved divergently by appropriately orchestrating the reaction sequence including isopropyl incorporation, oxidation state adjustment, and carbonyl group-directed regio- and stereoselective cyclopropanation at a late stage.