Chemoselective Construction of Polycyclic Heterocycles Containing a [6‐6‐5] or [7‐6‐5] Tricyclic Core Skeleton from a 2‐Isocyanophenyl Propargylic Ester

Abstract

Functionalized isocyanide chemistry represents an important research area in organic synthesis. A structurally unique 2-isocyanophenyl propargylic ester has been designed to incorporate the reactivity of isocyanide and propargylic ester functionalities. Thus, the reaction of 2-isocyanophenyl propargylic ester and 2-aminoaromatic aldimine facilitates the synthesis of a wide range of polycyclic benzo[b] indolo [3,2-h][1,6] naphthyridine derivatives. Furthermore, reaction with 2-hydroxyaromatic aldimine enables the divergent synthesis of both the aforementioned scaffolds and structurally distinct diazabenzo [f] naphtho[2,3,4-ij] azulenes featuring a [7-6-5] core skeleton. Experimental results and DFT calculations suggest that these transformations likely proceed by the in situ generation of a strained cyclopropenimine species followed by [3+2] cycloaddition. Next, switchable nucleophilic attack/ring expansion/aromatization and nucleophilic addition/ring expansion/elimination account for the observed selectivity.