Concise Synthesis of (±)‐Fortuneicyclidins and (±)‐Cephalotine B Enabled by Pd‐Catalyzed Dearomative Spirocyclization**

Abstract

Total syntheses of C11‐oxygenated Cephalotaxus alkaloids, fortuneicyclidins A and B, and cephalotine B, were achieved. The key for the synthesis is a Pd‐catalyzed dearomative spirocyclization of bromofurans with N‐tosylhydrazones, followed by acid‐mediated tandem transformation to construct the tetracyclic skeleton with the C11‐oxygen functional group. Chemo‐selective and catalytic functional group conversions of the tetracyclic intermediate completed the synthesis of fortuneicyclidins and cephalotine B in 8 and 9 steps, respectively.

Catalytic Asymmetric Polycyclization of Tertiary Enamides with Silyl Enol Ethers: Total Synthesis of (−)-Cephalocyclidin A

“…For a notable example, (−)-cephalocyclidin A, a cytotoxic pentacyclic cephalotaxus alkaloid biosynthetically derived from its venerable parent natural molecule (−)-cephalotaxine, possesses the fused N -containing [5,5,5] tricycles with a bridge linkage to the piperonyl substituted arene. An elegant asymmetric total synthesis of (−)-cephalocyclidin A has been accomplished by Kim’s group via a chiral pool-based strategy . In pursue of a catalytic enantioselective total synthesis, we envisaged a synthetic route with application of this tandem polycyclization as well as a late stage 6- exo radical cyclization to assemble the bridge cycle which is rarely employed in such complex settings (Scheme ).…”