Synthesis of Indoles via Domino Reactions of 2-Methoxytoluene and Nitriles

J Org Chem. 2023 Apr 21;88(8):5147-5152. doi: 10.1021/acs.joc.2c02128. Epub 2022 Dec 15.

Abstract

2-Arylindoles are privileged structures widely present in biologically active molecules. New sustainable synthetic routes toward their synthesis are, therefore, in high demand. Herein, a mixed base-promoted benzylic C-H deprotonation of commercially available ortho-anisoles, addition of the resulting anion to benzonitriles, and SNAr to displace the methoxy group provide indoles. A diverse array of 2-arylindoles is prepared with good yields (>30 examples, yields up to 99%) without added transition metal catalysts.