Development of Indolo-Bicyclo[3.1.1]Heptane as a Carbazole Isostere Through Radical Indolization of Bicyclo[1.1.0]Butanes.

Abstract

Semisaturated ring systems with a balanced fraction of C(sp3) have garnered increasing attention in drug development. In this study, we propose indolo-bicyclo[3.1.1]heptane as a potential carbazole isostere and present a novel strategy for synthesizing this new semisaturated polycyclic scaffold. The synthesis involves using bicyclo[1.1.0]butanes (BCBs) as radical precursors/terminators in the Fukuyama radical indolization reaction with 2-alkenylarylisocyanides, providing a highly efficient approach to construct a tricyclic system in a single step. These reactions represent a rare example of two functional groups (isonitrile and alkene) being sequentially involved in the cyclization process within BCB chemistry.