Total Synthesis of Metaphanine and Oxoepistephamiersine

Abstract Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium‐catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer–Villiger oxidation followed by a MeNH 2 triggered skeletal reorganization cascade to construct the benzannulated aza [4.4.3]propellane, and a strategically late‐stage regio‐/diastereoselective oxidative annulation of sp 3 C−H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular.