Asymmetric synthesis of novel highly sterically constrained (2S,3S)-3- methyl-3-trifluoromethyl- and (2S,3S,4R)-3-trifluoromethyl-4- methylpyroglutamic acids

Vadim A. Soloshonok, Chaozhong Cai, Victor J. Hruby, Luc Van Meervelt

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Asymmetric synthesis of the novel highly sterically constrained (2S,3S)- 3-methyl-3-trifluoromethyl-and (2S,3S,4R)-3-trifluoromethyl-4- methylpyroglutamic acids has been developed via diastereoselective Michael addition reactions between a Ni(II) complex of the chiral non-racemic Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone (BPB) and the corresponding trifluoromethyl-containing crotonates. Of particular synthetic interest is the reaction of the glycine Ni-complex with ethyl 3- trifluoromethyl crotonate featuring excellent diastereoselectivity (>98% de) as a result of complete stereochemical discrimination between the methyl and trifluoromethyl groups. A mechanistic rationale for the observed kinetically controlled stereochemical outcome is discussed.

Original languageEnglish (US)
Pages (from-to)12045-12058
Number of pages14
JournalTetrahedron
Volume55
Issue number41
DOIs
StatePublished - Oct 8 1999

Keywords

  • Addition reactions
  • Amino acids and derivatives
  • Asymmetric synthesis
  • Mechamism

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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