Asymmetric Synthesis of HispidaninA and Related Diterpenoids

作者：Cao, Wei; Deng, Heping; Sun, Ying; Liu, Bo^*; Qin, Song^*

来源：Chemistry - A European Journal, 2018, 24(36): 9120-9129.

DOI：10.1002/chem.201801156

• Diels-Alder reaction
• hispidaninA
• cyclization
• radical reactions
• total synthesis

We report on our accomplishment of the asymmetric synthesis of hispidaninA and its natural precursor, a labdane diterpenoid. In the first generation of synthesis, a semi-synthesis strategy was employed to construct a labdane-type diterpenoid, a natural precursor of hispidaninA, in which Barton's photolytic remote functionalization was employed as a key transformation. In addition, the totarane-type dienophile counterpart was derived from commercially available (-)-scalareol. In the second generation of synthesis, key elements included an iron-catalyzed radical cascade to access the labdane-type diene on the basis of hydrogen atom transfer, and an enantioselective cationic polyene cyclization furnished the totarane-type dienophile. Reaction optimization and mechanistic analysis of the radical cascade reaction was conducted. Furthermore, the [4+2] cycloaddition reaction was achieved in excellent yield and selectivity under thermal conditions, which has been rationalized by using DFT transition-state analysis and paved the way for final accomplishment of the total synthesis of hispidaninA.

• 出版日期2018-6-26
• 单位四川大学