Asymmetric Synthesis of Hispidanin A and Related Diterpenoids

We report on our accomplishment of the asymmetric synthesis of hispidanin A 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 hispidanin A, 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 hispidanin A.