2,6‐Piperidinediones, I. Synthesis of the Racemates and the Enantiomers of 3,3‐Disubstituted 2,6‐Piperidinediones

Abstract

The synthesis of the racemates and the enantiomers of the 3,3-disubstituted 2,6-piperidinediones 3a-3g is performed in three ways, depending on the C-3 substituents. The 3-cyclohexylpiperidinedione 3h is obtained as racemic and optically active compound by hydrogenation of the cyclohexenyl compound 3e with PdlC. The N-methylpiperidinediones 7a and 7b are obtained by methylation of 3a and 3b with CH2Nz. 2,6-Piperidmdione, 1. Mitt.: Synthese der Racemate und der Enantiomere von 3,3-disubstituierten 2,CPiperidmdionenDie Synthese der Racemate und der Enantiomere der 3,3-disubstituierten 2,6-Piperidindione 3a-3g gelingt in Abhangigkeit von den C-3-Substituenten auf drei unterschiedlichen Wegen. Das 3-cyclohexylsubstituierte Piperidindion 3h wird in racem. und optisch aktiver Form durch Hydrierung der Cyclohexenylverbindung 3e mit Pd/C erhalten. Die N-methylierten Piperidindione 7a und 7b werden durch Methylierung von 3a und 3b mit Diazomethan hergestellt.Some years ago we found') the absolute configuration of the hypnotically more active enantiomer of glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) to be R(+). In this paper we describe the syntheses of the racemates and the enantiomers of the 3,3-disubstituted 2,6-piperidinediones 3a-3g. The syntheses were performed depending on the C-3-substituents via three different pathways A-C shown in scheme 1. Scheme 1: Pathway A: Michael addition e y z + CHz=CH-C\ 40 NaOMe_ 0 7 "