Interrupted Barton–Zard Reaction/Friedel–Crafts Alkylation Telescoped Reaction for the Synthesis of Pyrrolo[3,4‐b]indole Cores

An interrupted Barton–Zard reaction/Friedel–Crafts alkylation telescoped reaction provides aryl-substituted pyrrolo[3,4-b] cores in moderate-to-good yields as mostly single diastereomers. The reaction is tolerant of a wide range of electron-deficient indoles and (hetero)aromatic nucleophiles, offering a modular approach for the synthesis of multi-substituted polycyclic skeletons.

Abstract

A dearomatization reaction between electron-deficient indoles and α,α-diaryl-substituted methyleneisocyanides, followed by in situ Friedel–Crafts alkylation, is described. In a telescoped reaction mediated by a Brønsted base in the first step and a Brønsted acid in the second step, aryl-substituted pyrrolo[3,4-b]indole cores are generally obtained in moderate-to-good yields and with high diastereoselectivity. The reaction tolerates a wide range of 3-nitroindoles and aryl nucleophiles; however, the substrate scope of isocyanide derivatives is limited. The developed methodology offers a modular approach for the synthesis of multi-substituted polycyclic cores.

Zum Volltext