Synthesis and Absolute Configuration of 2-Substituted Cyclopentanamines
In an asymmetric synthesis 2-substituted cyclopentanamines are obtained from racemic cyclopentanones by means of reductive amination in a three-step procedure. Condensation of the ketones 3(n) with optically active l-phenylethylamines yields imine mixtures 4(n), which are hydrogenated with Raney nickel to give the optically active, diastereomerically pure secondary amines 5(n). Hydrogenolysis with Palladium-on-charcoal leads to high grade enantiomerically pure primary amines 6(n) with good yields. The relative configuration of the amines 5(n) and 6(n) is elucidated by 'H and "C NMR techniques. The absolute configuration is determined by X-ray analysis of the 4-bromobenzamide 8 of the primary amine (+)-6(n)e and with the help of CD of the salicylidenes 9(n). The kinetically controlled asymmetric hydrogenation with a first order transformation as proved reaction mechanism in the cyclohexanamine line is confirmed for this investigation. The hydrogenation runs like- induced to the cis-configurated amines 5(n) and 6(n), respectively.
Optisch aktive Cyclopentanamine besitzen als Bausteine fur enantiomerenreine Arzneistoffe eine gewisse Bedeutung. Unser besonderes Interesse galt dem (+)-bzw. (-)-cis-2-Phenylcyclopentanamin (l), das als Racemat zu dem potenten hypoglykamischen Lactamimid 2 umgesetzt wurde2).
Wir haben uns daher in Fortsetzung unserer friiheren A r b e i t e ~~~-~) mit der asymmetrischen Synthese von 2-substituierten Cyclopentanaminen 6(n) durch hydrierende Aminierung') befah.
Das in Lit.3.4) beschriebene Verfahren (s. Schema 1) 1aBt sich jedoch nicht ohne weiteres auf 2-substituierte Cyclopentanone 3(n) iibertragen. Man erhalt hier in geringerer Ausbeute