Chemistry of 2,4,6-tri-tert-butylanilides possessing isolable rotational isomer

Nobutaka Ototake, Osamu Kitagawa

Research output: Contribution to journalReview article

Abstract

Amide C-N bond in 2,6-di-tert-butylanilides has a high rotational barrier and the individual amide rotational isomers can be isolated at ambient temperature. These anilides have been reported by Chupp et al. in 1967, but no systematic study with anilide substrates other than a - haloacetoanilides, or the stereoselective synthesis of anilide rotamers have been reported. In addition, the structural properties of these anilides have not been investigated in detail. We succeeded in the highly selective stereodivergent synthesis of Z- and E-rotamers of various N-allyl-2,4,6-tri-tert-butylanilides through Pd(0) and Pd (II) catalyzed N-allylation of O-allyl-N-(2,4,6-tri-tert-butylphenyl) imidates. Moreover, the relative thermodynamic stabilities of the obtained anilide rotamers were clarified. Specific reactivity of 2,4,6-tri-tert-butylanilide derivatives was also found. For examples, in intramolecular Diels-Alder reaction of N-ally 2-furoyl amides, 2,4,6-tri-tert-butylphenyl group on the nitrogen atom remarkably accelerated the reaction. Although the reaction of ordinal anilide anion with alkyl halide gives N-alkylation product, the alkylation with 2,4,6-tri-tert-butylanilide anion preferentially proceeded on the oxygen atom to give O-alkyl imidate. O-Benzyl imidate, which was obtained by the reaction with benzyl bromide, was used as bezylation reagent of alcohols and carboxylic acids. In contrast to rotational rigidity of 2,4,6-tri-tert-butylanilide, in the anilide enolates, interconversion between the rotamers readily occurs at ambient temperature, and their reaction with electrophiles gave rotamer mixtures of the products in a ratio that depends on the reactivity of the electrophiles. Furthermore, as an application of this isomerization reaction, switching between the anilide rotamers was achieved.

Original languageEnglish
Pages (from-to)575-583
Number of pages9
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume76
Issue number6
DOIs
Publication statusPublished - 2018 Jan 1

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Keywords

  • Allylation
  • Anilides
  • Benzylation
  • Enolates
  • Imidates
  • Isolable rotamers
  • Isomerization
  • Palladium
  • Switching

ASJC Scopus subject areas

  • Organic Chemistry

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