Keto-Enol-Tautomerism and Configurational Isomerism of 2,6-Disubstituted 4-Piperidone-3,5-dicarboxylates [1]

The dialkyl 2,6-dialkylsubstituted 4-piperidone-3,5-dicarboxylates were synthesized by a Mannich procedure. Depending on the substitution at the nitrogen keto-enol-tautomerism and a configurational isomerism at C 2 is observed. The structure o f the N-substituted piperidone 24 E (C 18H29N 0 5) has been determined by X-ray analysis: it is characterized by an enol structure o f the /?-ketoester and an axial position o f the alkyl group at C2 and an equatorial one o f the alkyl group at C6. The O -H O hydrogen bond shows characteristic values o f a strong hydrogen bond. The N-unsubstituted piperidones adopt a ketone structure with the allequatorial position o f all substituents. This stereochemistry is confirmed for other enolic and ketone analogues by NM R spectroscopic methods. To work out the reason for the different thermodynamic stabilities o f the different stereochemical structures o f N-substituted and N-unsubstituted piperidones, various semiempirical calculations were done for series o f simple pairs o f carbonyl/enol tautomers, substituted acetoacetates, oxoglutarate as well as o f syste­ matically varied substituted cyclohexanone, 4-oxacyclohexanone and 4-piperidone deriva­ tives.