Total synthesis of the alkaloid (±)-aspidophytine based on carbonyl ylide cycloaddition chemistry

The Rh-II-catalyzed cycloaddition cascade of an indolyl-substituted alpha-diazo imide was used for the total synthesis of the complex pentacyclic alkaloid (+/-)-aspidophytine. Treatment of the resulting dipolar cycloadduct with BF3.OEt2 induces a domino fragmentation cascade. The reaction proceeds by an initial cleavage of the oxabicyclic ring and formation of a transient N-acyl iminium ion which reacts further with the adjacent tert-butyl ester and sets the required lactone ring present in aspidophytine. A three-step sequence was then used to remove both the ester and OH groups. Subsequent functional group manipulations allowed for the high-yielding conversion to (+/-)-aspidophytine.