N,2,3,4-Tetrasubstituted Pyrrolidines through Tandem Lithium Amide Conjugate Addition/Radical Cyclization/Oxygenation Reactions.

Enantioselective syntheses of densely functionalized pyrrolidines deriving their chirality from ( R)-1-(phenyl)ethylamine are reported. Allylic amines and β-substituted-α,β-unsaturated esters are used as the building blocks in this one-pot reaction. Single electron transfer (SET) oxidation served to merge the reactivities of anionic enolate and radical intermediates. Ferrocenium hexafluorophosphate, which is easy to prepare, store and handle, was applied as SET oxidant and persistent free radical TEMPO served as the oxygenating agent introducing a protected hydroxy function, which proved to be beneficial for further derivatization. Exclusive 2,3- trans and up to 6:1 3,4- cis/trans diastereoselectivities were achieved in the targeted tetrasubstituted pyrrolidines. [ABSTRACT FROM AUTHOR]