Synthesis of a Quaternary N,N′‐Aminal‐Containing A–E Ring System of Palau′amine via an Enamide‐Type Overman Rearrangement Reaction

Abstract

We present a synthesis of the pentacyclic A–E ring system of palau′amine, a member of the dimeric pyrrole‐imidazole alkaloid (PIA) family. The synthesis features tandem elimination–Michael addition reaction to obtain cis‐fused bicyclo[3,3,0]octane, followed by stereoselective ketone reduction, and further elaboration to obtain the tetracyclic precursor for the Overman rearrangement reaction. The enamide‐type Overman rearrangement reaction generated the N,N′‐aminal quaternary asymmetric center at C10, and ring closure provided the desired pentacycle.