Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Abstract

AbstractThe RhII‐catalyzed cycloaddition cascade of an indolyl‐substituted α‐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.