Synthesis of 4,6-unsubstituted 2-aminodihydropyrimidine-5-carboxylates through sequential staudinger/aza-wittig/cyclization reactions

Yoshio Nishimura, Hidetsura Cho

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

A novel method for constructing the dihydropyrimidine skeleton is developed. The method involves three sequential reactions: (1) the Staudinger reaction of (E)-ethyl 3-azido-2-{[(tert-butoxycarbonyl)amino]methyl}acrylate with triphenylphosphine; (2) aza-Wittig reaction of the resulting iminophosphorane with isocyanate; (3) intramolecular cyclization of the carbodiimide intermediate to give 4,6-unsubstituted 2-aminodihydropyrimidine-5-carboxylates in high overall yield. The method can be applied to various aromatic isocyanates, with substrates having electron-withdrawing groups showing high reactivities. In the case of aliphatic benzyl isocyanate, the reaction provides bicyclic dihydropyrimidine as the major product. The N-protecting group (Boc) can easily be removed to obtain N-unsubstituted dihydropyrimidines. All dihydropyrimidines in this study were previously unavailable and are difficult to synthesize by conventional methods.

Original languageEnglish
Article numberst-2014-u0779-l
Pages (from-to)233-237
Number of pages5
JournalSynlett
Volume26
Issue number2
DOIs
Publication statusPublished - 2015 Jan

Keywords

  • Staudinger reaction
  • aza-Wittig reaction
  • cyclization
  • dihydropyrimidine
  • heterocycles

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis of 4,6-unsubstituted 2-aminodihydropyrimidine-5-carboxylates through sequential staudinger/aza-wittig/cyclization reactions'. Together they form a unique fingerprint.

Cite this