Asymmetric Reductive Amination of Cycloalkanones, IX: Asymmetric Synthesis of GABA-related Cycloaliphatic Amino Acids

Article abstract of DOI:10.1002/ardp.19893220803

We report the asymmetric synthesis of optically active cis-1- aminocyclopentane/hexane-2-acetic- and -2-propionic acid-hydrochlorides 5.First in a four-step-procedure racemic 1-cycloalkanone-2-acetic- and -2-propionic acid derivatives 1 are converted with the chiral auxilary R-(+)- and S-(-)-1-phenylethylamines into mixtures of the isomeric imines 2, which yield the cis-configurated secondary amines 3 by hydrogenation with Raney-nickel.Hydrogenolysis of the hydrochlorides 3 over Pd/C gives the primary cis-1-aminocyclopentane-2-acetic- and -2-propionic acid derivative hydrochlorides 4, which are saponified under acidic conditions to the respective optically active primary amino acid hydrochlorides 5.The relative configuration was deduced from (1)H-NMR-spectra.The absolute configuration of the enantiomerically highly pure compounds was determined by means of CD-correlation spectroscopy of 4.