Formal Synthesis of the Akuammiline Alkaloid (±)-Strictamine via a (4 + 2) Annulation Reaction With a Donor–Acceptor Cyclobutane

Abstract

The akuammiline alkaloids are complex monoterpene indole natural products with a rigid cage-like architecture and diverse biological activities. Among them, strictamine has posed a longstanding synthetic challenge due to its congested quaternary carbon center and complex polycyclic framework. Herein, we report a concise formal synthesis of (±)-strictamine enabled by a silylium-catalyzed intramolecular (4 + 2) annulation with a donor–acceptor cyclobutane, delivering the target in 13 steps from tryptamine.