Stereospecific Asymmetric N-Heterocyclic Carbene (NHC)-Catalyzed Redox Synthesis of Trifluoromethyl Dihydropyranones and Mechanistic Insights

Alyn T. Davies, James E. Taylor, James Douglas, Christopher J. Collett, Louis C. Morrill, Charlene Fallan, Alexandra M. Z. Slawin, Gwydion Churchill, Andrew D. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

N-Heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder reactions of alpha-aroyloxyaldehydes with beta-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (E)- or (Z)-beta-trifluoromethyl enones forming syn- or anti-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor 1 and an achiral NHC precursor.

Original languageEnglish
Pages (from-to)9243-9257
Number of pages15
JournalThe Journal of Organic Chemistry
Volume78
Issue number18
DOIs
Publication statusPublished - 20 Sept 2013

Keywords

  • Diels-alder reactions
  • Organocatalytic michael addition
  • Enantioselective synthesis
  • Enolate equivalents
  • Medicinal chemistry
  • Catalyzed reactions
  • Carbonyl-compounds
  • 4+2 Cycloaddition
  • Aldehydes
  • Enals

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