An efficient synthesis of substituted prolines by the selective reduction and reductive cyanation of 2-pyrrolidones

Substituted pyrrolidones undergo selective reduction using Cp2ZrHCl (Schwartzʹs reagent) to form Δ1-pyrrolines, which can be isolated or directly cyanated and hydrolyzed to the corresponding proline. Short syntheses of glutamic semialdehyde (ethyl ester), the marine metabolite (2S,5S)-pyrrolidine-2,5-dicarboxylic acid, and the conformationally constrained amino acid 5,5-dimethylproline, are reported.