Direct nucleophilic addition to N-alkoxyamides

Yuta Yanagita, Hugh Nakamura, Kenji Shirokane, Yusuke Kurosaki, Takaaki Sato, Noritaka Chida

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long-standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N-alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N-alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N-alkoxy group formed a five-membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL-H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter- and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α-trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five- and six-membered lactams, and macrolactams.

Original languageEnglish
Pages (from-to)678-684
Number of pages7
JournalChemistry - A European Journal
Volume19
Issue number2
DOIs
Publication statusPublished - 2013 Jan 7

Keywords

  • allylation
  • amides
  • cyanation
  • nucleophilic addition
  • synthetic methods

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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