Formal Synthesis of Aspidosperma Alkaloids via the Intramolecular [3 + 2] Cycloaddition of 2-Azapentdienyllithiums

Abstract

[reaction: see text] A formal synthesis of the Aspidosperma alkaloids aspidospermidine, aspidospermine, and quebrachamine is reported through an efficient preparation of Stork's penultimate intermediate. The key step of the sequence involved an intramolecular [3 + 2] cycloaddition of the 2-azapentadienyllithium 21 formed in situ from the corresponding imine 1, which after N-alkylation of the resulting cycloadduct provided 2 in excellent yield. The synthesis represents a new disconnection of the classical tricyclic ketone used for appendage of the requisite indole.