2,5-Disubstituted pyrrolidines: synthesis by enamine reduction and subsequent regioselective and diastereoselective alkylations

Methodology for the diastereoselective synthesis of 2,5-disubstituted pyrrolidines by reduction of enamines derived from pyroglutamic acid is reported; the nature of nitrogen protection was found to be critical for the stereochemical control of the reaction outcome. Regioselective manipulation of the C-2 and C-5 substituents is possible, providing access to differently substituted pyrrolidines for a limited number of cases.