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

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.