Two-step synthesis of multi-substituted amines by using an N-methoxy group as a reactivity control element

Makoto Yoritate, Tatsuhiko Meguro, Naoya Matsuo, Kenji Shirokane, Takaaki Satou, Noritaka Chida

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The development of a two-step synthesis of multi-substituted N-methoxyamines from N-methoxyamides is reported. Utilization of the N-methoxy group as a reactivity control element was the key to success in this two-step synthesis. The first reaction involves a N-methoxyamide/aldehyde coupling reaction. Whereas ordinary amides cannot condense with aldehydes intermolecularly due to the poor nucleophilicity of the amide nitrogen, the N-methoxy group enhances the nucleophilicity of the nitrogen, enabling the direct coupling reaction. The second reaction in the two-step process was nucleophilic addition to the N-methoxyamides. Incorporation of the N-methoxy group into the amides increased the electrophilicity of the amide carbonyls and promoted the chelation effect. This nucleophilic addition enabled quick diversification of the products derived from the first step. The developed strategy was applicable to a variety of substrates, resulting in the elaboration of multi-substituted piperidines and acyclic amines, as well as a substructure of a complex natural alkaloid.

Original languageEnglish
Pages (from-to)8210-8216
Number of pages7
JournalChemistry (Weinheim an der Bergstrasse, Germany)
Volume20
Issue number26
DOIs
Publication statusPublished - 2014 Jun 23

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Amides
Amines
Aldehydes
Nitrogen
Piperidines
Alkaloids
Chelation
Substrates

Keywords

  • amides
  • nitrogen
  • nucleophilic addition
  • piperidine
  • reactivity control

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Two-step synthesis of multi-substituted amines by using an N-methoxy group as a reactivity control element. / Yoritate, Makoto; Meguro, Tatsuhiko; Matsuo, Naoya; Shirokane, Kenji; Satou, Takaaki; Chida, Noritaka.

In: Chemistry (Weinheim an der Bergstrasse, Germany), Vol. 20, No. 26, 23.06.2014, p. 8210-8216.

Research output: Contribution to journalArticle

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