A One-Pot Oxidation/Enantioselective Oxa-Michael Cascade

Jorgen S. Willemsen, Rik P. Megens, Gerard Roelfes, Jan C. M. van Hest, Floris P. J. T. Rutjes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

A laccase/(2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO) mediated oxidation was combined with an aqueous, enantioselective copper-catalyzed Michael addition reaction of water in one pot. The copper catalyst was also immobilized onto DNA to induce enantioselectivity in the reaction. Low conversions were observed when the reactions were performed simultaneously, caused by an undesired reaction of an oxidised TEMPO intermediate. We increased the conversions by using a stepwise approach. Thus, after completion of the oxidation, the first reaction was stopped by inhibiting the enzyme with HCO2K and reducing the reactive TEMPO intermediate. Next, the Michael addition reaction was started by adding the Cu catalyst. By applying this strategy, an efficient two-step one-pot sequence, proceeding with 20% ee, was realized. The yield and ee of the second reaction were not affected by the oxidation reaction.

Original languageEnglish
Pages (from-to)2892-2898
Number of pages7
JournalEuropean Journal of Organic Chemistry
Volume2014
Issue number14
DOIs
Publication statusPublished - May-2014

Keywords

  • One-pot reactions
  • Homogeneous catalysis
  • Enzyme catalysis
  • Michael addition
  • Synthetic methods
  • Oxidation
  • AQUEOUS-MEDIA
  • ASYMMETRIC-SYNTHESIS
  • GREEN CHEMISTRY
  • LACCASE
  • WATER
  • COMBINATION
  • REDUCTION
  • CATALYST
  • ENZYMES
  • NANOREACTOR

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