Dirk Trauner on Mythryl: “Stephadiamine, take two. A second synthesis is justifiable if you…”

@dirktrauner.bsky.social

Stephadiamine, take two. A second synthesis is justifiable if you (a) radically change the strategy and (b) develop new methodology along the way. Congratulations, Ana Vi, on bringing this one home! pubs.acs.org/doi/10.1021/...

pubs.acs.orgConcise Synthesis of (±)-Stephadiamine via Vinylogous Wenker CyclizationA 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.

25/6/26, 2:45 pm1 repost8 likes

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