Asymmetric syntheses of trans-3,4-disubstituted 2-piperidinones and piperidines

Abstract A convenient and practical method for the preparation of chiral 4-aryl-2-piperidinone from 3-arylglutaric anhydride and ( S )-methylbenzylamine is described. Acylation or alkylation at the α-carbon of the chiral 4-aryl-2-piperidinone product afforded chiral trans -3,4-disubstituted 2-piperidinone derivatives and reduction of the chiral 2-piperidinones with lithium aluminum hydride provided the corresponding enantiomerically pure trans -3,4-disubstituted piperidines. This methodology has been successfully applied to the synthesis of the anti-depressant paroxetine.