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

Article abstract of DOI:10.1016/S0040-4020(99)00091-5

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.