Issue 23, 2023

Straightforward synthesis of N-arylindoles via one-pot Fischer indolisation–indole N-arylation

Abstract

A microwave-promoted, one-pot, three-component synthesis of N-arylindoles has been developed, utilising sequential Fischer indolisation then copper(I)-catalysed indole N-arylation. Novel arylation conditions were identified that use a simple and cheap catalyst/base system (Cu2O/K3PO4) in an environmentally benign solvent (ethanol), with no requirement for ligands, additives or exclusion of air or water, and microwave irradiation enabled significant acceleration of this commonly sluggish process. These conditions were designed to dovetail with Fischer indolisation, and the resulting one-pot, two-step sequence is rapid (total reaction time = 40 minutes), operationally straightforward, generally high yielding and it draws upon readily available hydrazine, ketone/aldehyde and aryl iodide building blocks. This process shows broad substrate tolerance and we have demonstrated its utility in the synthesis of 18 N-arylindoles bearing varied and useful functionality.

Graphical abstract: Straightforward synthesis of N-arylindoles via one-pot Fischer indolisation–indole N-arylation

Supplementary files

Article information

Article type
Paper
Submitted
21 Apr 2023
Accepted
19 May 2023
First published
26 May 2023
This article is Open Access
Creative Commons BY license

RSC Adv., 2023,13, 15993-15997

Straightforward synthesis of N-arylindoles via one-pot Fischer indolisation–indole N-arylation

M. Lintott and A. Perry, RSC Adv., 2023, 13, 15993 DOI: 10.1039/D3RA02658B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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