Total Syntheses of Kopsaporine, Kopsinol and Kopsiloscine A

Kopsia alkaloids represent a complex class of natural products bearing a polycyclic ring system with two or three consecutive quaternary carbon centers. In this article, we report the first total synthesis of Kopsaporine related alkaloids. Features of our structure‐unit‐based strategy are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza‐Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an olefin migration vinylogous alkylation to establish the C20 all‐carbon quaternary center, an iridium complex mediated radical addition to fuse the aspidofractine framework, an unprecedented IBX oxidation to introduce the α‐hydroxyketone moiety, and a bioinspired retro‐Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A. A unified strategy for the synthesis of Kopsia monoterpenoid indole alkaloids is described. Key transformations developed are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza‐Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an iridium complex mediated radical addition to fuse the aspidofractine framework, and an IBX oxidation to introduce the α‐hydroxyketone moiety.