Concise Synthesis of (±)-Stephadiamine via Vinylogous Wenker Cyclization.

A short and diastereoselective synthesis of stephadiamine is presented. The carbocyclic framework of the alkaloid was built in the opening step through a homoconjugate addition-Wittig olefination cascade with a modified Schweizer-Fuchs cyclopropyl phosphonium salt. The challenging aza[4.3.3]propellane was subsequently installed through a vinylogous substitution of an allylic hydroxy group with a primary amine that was developed for the purposes of the synthesis. After a series of oxidations, a second α-tertiary amine was introduced through a diastereoselective Strecker reaction, thus establishing the syn-diamine motif. Finally, an undesired retro-Strecker pathway was circumvented by using an azide functionality to mask the primary amine during a late-stage lactonization, thus enabling the completion of the synthesis in 12 steps.