(Het)aryl Difluoromethyl-Substituted beta-Alkoxyenones: Synthesis and Heterocyclizations

Maksym Ya Bugera, Karen Tarasenko, Ivan S. Kondratov*, Igor I. Gerus, Bohdan V. Vashchenko, Viktor E. Ivasyshyn, Oleksandr O. Grygorenko*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

An efficient approach to the preparation of β-alkoxyenones bearing (het)aryl difluoromethyl substituents is described. The method included acylation of acyclic or cyclic vinyl ethers with (het)aryl difluoroacetyl chlorides. The method worked well for most substrates, except aryl-substituted derivatives bearing electron-donating groups in o- or p-positions, and heteroaromatic compounds bearing sufficiently basic nitrogen atom. Synthetic utility of (het)aryl difluoromethyl-substituted β-alkoxyenones as CCC bis-electrophiles was demonstrated by heterocyclizations with common 1,2- and 1,3-bis-nucleophiles leading to compounds with (het)aryl–CF2–(het)aryl motif, in particular (het)aryl difluoromethyl-substituted pyrazoles, isoxazoles, and pyrimidines – promising chemotypes for drug discovery.

Original languageEnglish
Pages (from-to)1069-1077
Number of pages9
JournalEuropean Journal of Organic Chemistry
Volume2020
Issue number9
DOIs
Publication statusPublished - 8-Mar-2020
Externally publishedYes

Keywords

  • Organofluorine compounds
  • Heterocycles
  • Diarylmethanes
  • Condensation
  • ETHYL BROMODIFLUOROACETATE
  • REGIOSELECTIVE SYNTHESIS
  • IONIC LIQUID
  • FLUORINE
  • DERIVATIVES
  • ACID
  • ACTIVATION
  • INHIBITORS
  • DISCOVERY
  • PYRIDINES

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