Asymmetric ion-pairing catalysis of the reversible cyclization of 2'-hydroxychalcone to flavanone: Asymmetric catalysis of an equilibrating reaction

Lukas Hintermann, Claudia Dittmer

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Abstract

The asymmetric catalytic cyclization of the simple 2'-hydroxychalcone (1) to flavanone (2), a model for the chalcone isomerase reaction, has been realized as a catalytic asymmetric ion-pairing process with chiral quaternary ammonium salts (e.g., 9-anthracenylmethlycinchoninium chloride; 9-Am-CN-Cl) and NaH as small-molecule co-catalyst. In toluene/CHCl 3 solution, the process reaches an intrinsic enantioselectivity of up to S = 14.4 (er = 93.5:6.5). The reversible reaction proceeds in two steps: A fast initial reaction approaches a quasi-equilibrium with K R/S = 4.5, followed by a second, slow racemization phase approaching K rac = 9. A simple mechanistic model featuring a living ion-pairing catalysis with full reversibility is proposed. Deuterium transfer from co-solvent CDCl 3 to product 2 and isolation of a Michael conjugate formed from 2 and 1 demonstrate the intermediacy of flavanone enolate ion pairs. A kinetic model shows good agreement with the experimentally observed, peculiar, time-dependent evolution of the species concentrations and the enantiomeric excess of 2. The reaction is a chemical model of the chalcone isomerase enzymatic reaction. Furthermore, it is an ideal model for studying the characteristic behavior of reversible asymmetric catalyses close to their equilibria.

Original languageEnglish
Pages (from-to)5573-5584
Number of pages12
JournalEuropean Journal of Organic Chemistry
Issue number28
DOIs
StatePublished - Oct 2012

Keywords

  • Asymmetric catalysis
  • Enzyme models
  • Natural products
  • Oxygen heterocycles
  • Reaction mechanisms

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