Synthesis of enantio- and diastereoiso-merically pure substituted prolines via condensation of glycine with olefins activated by a carbonyl group

Abstract
The glycine fragment in the nickel(II) complex (1) formed from the Schiff′s base of glycine and (S)-o-[(N-benzylprolyl)amino]benzophenone (2) undergoes base-catalysed Michael addition to acrylaldehyde, α-methylacrylaldehyde, (E)-crotonaldehyde, (E)-cinnamaldehyde, and methyl vinyl ketone. No products of 1,2-addition were found in the Et3N-catalysed reactions. Addition followed by epimerization of the isomeric complexes proceeds with high diastereoselectivity at Cα(90%) and Cβ of the corresponding amino acid side chains. After chromatographic separation, the diastereoisomerically pure complexes were decomposed and the resulting dihydropyrrole-2-carboxylic acids reduced with NaBH3CN to give (S)-proline, trans-3-methyl-(S)-proline, trans-5-phenyl-(S)-proline, and a mixture of cis- and trans-5-methyl-(S)-prolines. The chiral auxiliary (2) was recovered in 80–90% yield.