Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones

Sreejith P. Shankar, Monica Sani, Giancarlo Terraneo, Matteo Zanda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Herein we report the highly asymmetric aza-Michael reactions of alpha,beta-enones (2-enoylthiazoles) with metalated chiral oxazolidinones under different reaction conditions and for different substituents at the beta-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.

Original languageEnglish
Pages (from-to)1341-1345
Number of pages5
JournalSynlett
Issue number8
DOIs
Publication statusPublished - 15 May 2009

Keywords

  • asymmetric
  • aza-Michael Reaction
  • diastereoselectivity
  • noncatalytic
  • oxazolidinone
  • beta-amino acids
  • conjugate addition
  • enantioselective synthesis
  • alpha,beta-unsaturated compounds
  • stereoselective-synthesis
  • cyclohexyl sulfonates
  • derivatives
  • enones
  • water

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