A Three-Component Approach to (Hetero)arenes with Two N-Containing Heterocycle Motifs

Abstract

A one-pot, three-component reaction involving S_NAr-decarboxylative redox isomerization starting from an electron-withdrawing group bearing fluorobenzaldehyde or fluorothiophenecarbaldehyde (electron-pair diacceptor), secondary amine, and trans-4-hydroxy-l-proline or indoline-2-carboxylic acid (electron-pair donor) has been developed to give N-[(pyrrolylmethyl)-substituted (het)aryl]- and N-[(indolyl­methyl)-substituted (het)aryl]pyrrolidines, -piperidines, -morpholines, and -azocanes. The highlights of this protocol are its great convenience in the simultaneous construction of a C(sp²)–N bond and a C(sp³)–N bond with simple operation; the reaction can be performed on a gram scale. This efficient one-pot multicomponent reaction has potential as a novel method for drug synthesis, especially involving polycyclic compounds.

Key words

three-component reaction - one-pot reaction - S_NAr-decarboxylative redox isomerization - polycyclic compounds - N-alkyl pyrroles - N-alkyl indoles

Publication History

Received: 08 June 2022

Accepted after revision: 08 August 2022

Accepted Manuscript online:
08 August 2022

Article published online:
09 September 2022

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