ENANTIOSELECTIVE SYNTHESIS OF 3,3-DISUBSTITUTED 4-PIPERIDINONES ON NEUTRAL ALUMINA

The asymmetric synthesis of 3,3-disubstituted 4-piperidinones has been performed on neutral alumina without a solvent by Michael-type alkylation of chiral imine derivatives of 3-substituted 4-piperidinones with electron-deficient alkenes. The highest enantioselectivity has been achieved using (S)- or (R)-1-phenylethylamine as a chiral auxiliary. The enantioselectivity of the alkylation depends on the structure of the 4-piperidinones and the chiral amines. The enantiomeric excess of the new (+)- and (-)-enantiomers of 3,3-disubstituted 4-piperidinones was established by H-1 NMR spectroscopy using chiral shift reagents and their absolute configuration was determined by circular dichroism curve correlation.