Allenamide-Initiated Cascade [2+2+2] Annulation Enabling the Divergent Total Synthesis of (-)-Deoxoapodine, (-)-Kopsifoline D and (±)-Melotenine A.

Abstract

A facile method for the construction of the aspidosperma core from indoles functionalized with a nonterminal N-allenamide and dimethyl methylenemalonate is described. Various polysubstituted tetracyclic spiroindolines (27 examples) were afforded in good yields (61-90 %) with >99/1 dr and >99/1 Z/E selectivity under mild conditions. The annulation reaction provides straightforward access to the tetracyclic spiroindoline skeleton with substituents at the C5 position occurring in many natural products. As an application of this reaction, the total synthesis of three important natural products, (-)-deoxoapodine, (-)-kopsifoline D and (±)-melotenine A, was possible in short routes from tryptamine.