Productive Asymmetric Synthesis of All Four Diastereomers of 3‐(trans‐2‐Nitrocyclopropyl)alanine from Glycine with (S)‐ or (R)‐2‐[(N‐Benzylprolyl)amino]benzophenone as a Reusable Chiral Auxiliary

Abstract

AbstractAll four diastereomers of 3‐(trans‐2‐nitrocyclopropyl)alanine (3) were prepared by asymmetrically induced α‐C alkylation of the glycine moiety in the [(S)‐ or (R)‐Schiff base]NiII complex 7, employing racemic trans‐1‐(iodomethyl)‐2‐nitrocyclopropane (8) as the alkylating agent. A notable difference in solubility between the two diastereomeric products 9a/9b [when (S)‐7 was used as starting material] or 9d/9e [when (R)‐7 was employed] allowed for their separation from the same reaction mixture. All the diastereomers of 3‐(trans‐2‐nitrocyclopropyl)alanine (3) were produced upon brief exposure of the alkylation products 9 to dilute hydrochloric acid, with subsequent purification by ion‐exchange chromatography and crystallization. The absolute configurations of the nickel complexes 9a−e were established by X‐ray crystallographic analyses. In addition, the X‐ray crystal structure of (2S,1′S,2′R)‐3 was determined to confirm the convergence of the configurations of the parent nickel complexes 9 with those of the amino acids 3 derived from them. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)