S. A. Abdulganeeva

Steric control of the asymmetric synthesis of N-substitued 2-methyl-4-piperidones

Transmission of the iodomethylate of 1,2-dimethyl-4-piperidone by (S)-sec-butylamine gives 1-(S-sec-butyl)-2S-methyl-4-piperidone in 33% optical yield while transamination by (S)-l-methyl-2-phenylethylamine gives a 1:1 diastereomeric mixture of 1-(l-methyl-2-phenylethyl)-2 -methyl-4-piperidone.The decrease in the optical yield is related to the facile opening of the piperidone ring at the C-N bond with subsequent recyclization. The13C MIR data indicate that all the diastereomers of the 4-piperidones obtained are in the chair conformation with predominantly equatorial orientation of the methyl group at C(2). The chiral optical properties were studied and the absolution configurations of the 4-piperidones obtained were established.

Asymmetric synthesis and absolute configuration of 1-α-phenylethyl-2,5-dimethyl-4-piperidone isomers

Reaction of the methyl iodide of trans-1,2,5-trimethyl-4-piperidone with S-α-phenylethylamine proceeds asymmetrically and leads in 66% optical yield to the formation of the cis- and trans-diastereomeric pair of 1-(α-phenylethyl)-2,5-dimethyl-4-piperidone, in which the new asymmetric centers possess the 2S,5S- and 2S,5R-configurations, respectively. According to x-ray structural analysis, the minor trans-1-(α-phenylethyl)-2,5-dimethyl-4-piperidone component possesses the 2R,5S-configuration. The occurrence of asymmetric synthesis accompanying transamination was confirmed via the preparation of enantiomers of trans-2,5- and trans-1,2,5-trimethyl-4-piperidones.

New method of synthesis of 3-alkyl-4-piperidones

A new method is presented for the synthesis of 3-substituted 4-piperidones by alkylation of lithium derivatives of 4-(α-phenylethylimino) piperidines using alkyl halides.

First asymmetric synthesis of 4-piperidones. Preparation of optically active diastereomers of 1-α-phenylethyl-2-methyl-4-piperidone

The fundamental possibility of carrying out the asymmetric synthesis of 4-piperidones on the basis of the transamination of 1-substituted 2-methyl-4-piperidone methiodides by optically active α-phenylethylamine was demonstrated; the optical yield of the asymmetric transamination is 50%. The occurrence of asymmetric synthesis was confirmed by the isolation of enantiomers of 2-methyl-4-piperidol by reduction of the individual diastereomers of 1-α-phenyl-ethyl-2-methyl-4-piperidone to the corresponding 4-piperidols with subsequent removal of the chiral substituent attached to the nitrogen atom.

Synthesis, molecular structure, and absolute configuration of 1-α-pheitylethyl-3-(2-cyanoethyl)-4-piperidone

The Michael addition of acrylonitrile to the pyrrolidine enamine of 1-(S-α-phenyl-ethyl)-4-piperidone proceeds with the formation of. a 1:1 mixture of l-(S-α-phenyl ethyl)-3-(2-cyanoethyl)-4-piperidone diastereomers. A diastereomer isolated in pure form was shown by x-ray diffraction structural analysis to have S-configuration of the new chiral center at C(3) of the piperidone ring.

Synthesis of 3-substituted 4-piperidones

It has been shown that the addition of methyl acrylate and acrylonitrile to the pyrrolidine enamines of 1-methyl-, (1S)-α-phenylethyl-, (1S)-sec-butyl-, 1,2-dimethyl-, and 1,3-dimethyl-4-piperidone results in the formation of 3- or 5-substituted 4-piperidones, depending on the reaction conditions and the structure of the enamine. The formation of a pair of diastereomers of the 3-substituted 4-piperidones in a 1∶1 ratio takes place when there is a chiral substituent on the nitrogen atom In the piperidone ring.