Enantioselective and collective total synthesis of pentacyclic 19--clerodanes.

We report herein the collective asymmetric total synthesis of seven pentacyclic 19--clerodane diterpenoids, namely (+)-teucvin (+)-cracroson A, (+)-cracroson E, (+)-montanin A, (+)-teucvisin C, (+)-teucrin A, and (+)-2-hydroxyteuscorolide. An ytterbium-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of 4-methyl-2-pyrone with a chiral C5-substituted cyclohexa-1,3-dienol silyl ether is the key feature of the synthesis, which provides the common -decalin intermediate with five continuous stereocenters in excellent yield and stereoselectivity. From this diversifiable intermediate, the total synthesis of (+)-teucvin and (+)-2-hydroxyteuscorolide was realized in thirteen and eighteen steps, respectively. From (+)-teucvin, five other pentacyclic 19--clerodanes were divergently and concisely generated through late-stage oxidation state adjustments.