Thermodynamic vs. kinetic control in the stereoselective intramolecular conjugate addition of amide enolates leading to chiral trans-3,4- disubstituted pyrrolidin-2-ones

Roberta Galeazzi, Giovanna Mobbili, Mario Orena

Research output: Contribution to journalArticlepeer-review

Abstract

Intramolecular conjugate addition of amide enolates to α,β- unsaturated esters was found to give either of the diastereomeric trans-3,4- disubstituted pyrrolidin-2-ones 6, 10 or 7, 11 as the major products, by choosing the appropriate reaction conditions. The cyclisation performed with NaH in THF afforded mainly 6 and 10, whereas by using sodium ethoxide in ethanol the major products of the cyclisation were isomers 7 and 11, with the opposite configuration at both C-3 and C-4. This behaviour was explained by thermodynamic vs. kinetic control and supported by molecular mechanics and quantomechanical calculations.

Original languageEnglish
Pages (from-to)4029-4042
Number of pages14
JournalTetrahedron
Volume55
Issue number13
DOIs
Publication statusPublished - Mar 26 1999

Keywords

  • Cyclisation
  • Michael reaction
  • Pyrrolidinones
  • Stereoselection

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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