Asymmetric synthesis and stereochemistry of chiral cis- and trans-3-alkyl-4-aminopiperidines

• DOI: 10.1007/s10593-012-1052-9
• Publication Date: 2012-09-01T15:25:15Z
• Authors: G. V. Grishina; E. R. Luk’yanenko; A. A. Borisenko; M. Yu. Antipin
• Keywords: 01 natural sciences; 0104 chemical sciences

Chiral nonracemic 3-substituted cis- and trans-4-aminopiperidines, which are precursors of anilidopiperidine analgesics, were obtained by diastereoselective synthesis from 1-methyl- and 1-benzyl-4-[(S)-1-phenylethyl]iminopiperidines, using the following reaction sequence: metalation with lithium diethylamide, alkylation with alkyl halides, and hydride reduction or hydrogenation over Raney nickel. The steric direction of the reaction, three-dimensional structure, preferred conformation, and absolute configuration of the resultant aminopiperidines were determined.