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

Author:

Zhang Yuliang1,Zhang Yang1,Ge Xizhen2,Wang Zhen3,Yu Xinhong1ORCID,Qiu Hong1,Wang Liqin1

Affiliation:

1. East China University of Science and Technology Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education Shanghai Key Laboratory of New Drug Design

2. College of Biochemical Engineering, Beijing Union University

3. College of Pharmacy, Linyi University

Abstract

AbstractA one-pot, three-component reaction involving SNAr-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.

Funder

National Natural Science Foundation of China

Science and Technology Commission of Shanghai Municipality

Key Research and Development Project of Shandong Province

Publisher

Georg Thieme Verlag KG

Subject

Organic Chemistry,Catalysis

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