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N ,2,3,4‐Tetrasubstituted Pyrrolidines through Tandem Lithium Amide Conjugate Addition/Radical Cyclization/Oxygenation Reactions
Author(s) -
Kafka František,
Pohl Radek,
Císařová Ivana,
Mackman Richard,
Bahador Gina,
Jahn Ullrich
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600621
Subject(s) - chemistry , enantioselective synthesis , allylic rearrangement , amide , lithium amide , combinatorial chemistry , conjugate , hexafluorophosphate , derivatization , organic chemistry , medicinal chemistry , catalysis , ionic liquid , mathematical analysis , mathematics , high performance liquid chromatography
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.