Synthesis of Indoles through Domino Reactions of 2‐Fluorotoluenes and Nitriles

Indoles are essential heterocycles in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. Among indoles, 2‐aryl indoles have been described as privileged scaffolds. Advanced herein is a straightforward, practical, and transition‐metal‐free assemb...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-08, Vol.58 (32), p.11033-11038
Main Authors: Mao, Jianyou, Wang, Zhiting, Xu, Xinyu, Liu, Guoqing, Jiang, Runsheng, Guan, Haixing, Zheng, Zhipeng, Walsh, Patrick J.
Format: Article
Language:English
Subjects:
2-fluorotoluenes
Aromatic compounds
Cascade chemical reactions
Cesium fluorides
Cyanide
domino reactions
Indoles
Nitriles
nitrogen heterocycles
Organic chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Indoles are essential heterocycles in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. Among indoles, 2‐aryl indoles have been described as privileged scaffolds. Advanced herein is a straightforward, practical, and transition‐metal‐free assembly of 2‐aryl indoles. Simply combining readily available 2‐fluorotoluenes, nitriles, LiN(SiMe3)2, and CsF enables the generation of a diverse array of indoles (38 examples, 48–92 % yield). A range of substituents can be introduced into each position of the indole backbone (C4 to C7, and aryl groups at C2), providing handles for further elaboration. Indoles galore: A remarkably easy synthesis of indoles is introduced. Simply combining 2‐fluorotoluenes, benzonitriles, base, and CsF followed by heating results in the formation of 2‐aryl indoles with diverse substitution patterns.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201904658