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

All four diastereomers of 3 - (trans-2-nitrocyclopropyl) alanine (3) were prepared by asymmetrically induced a-C alkylation of the glycine moiety in the [(S)- or (R)-Schiff base]Ni-II 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-2nitrocyclopropyl)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. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.