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A Cycloaddition–Cyclization Combined Approach to Enantiopure 3‐Glycinyl‐4‐hydroxypyrrolidines and 3‐Substituted 4‐Hydroxyprolines
Author(s) -
Aouadi Kaïss,
AbdoulZabar Juliane,
Msaddek Moncef,
Praly JeanPierre
Publication year - 2014
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.201402215
Subject(s) - nitrone , enantiopure drug , chemistry , cycloaddition , alkene , enantiomer , stereochemistry , cyclopropanation , glycine , medicinal chemistry , organic chemistry , amino acid , enantioselective synthesis , catalysis , biochemistry
The cycloaddition between ( E )‐ or ( Z )‐1,4‐dichloro‐2‐butene and a menthone‐derived nitrone as a glycine equivalent afforded dichlorinated isoxazolidine‐based cycloadducts. The stereochemistry of these adducts was controlled by the configuration of the starting alkene and nitrone. An amino group was generated either by reductive cleavage of the isoxazolidine N–O bond or by azidation and a subsequent reduction, which triggered in both routes a cyclization reaction that proceeded through a chloride displacement. This approach afforded unprecedented 3‐substituted 4‐hydroxyproline derivatives and (α S ,3 R ,4 S )‐3‐glycinyl‐4‐hydroxypyrrolidine. Both enantiomers of the reported products can be prepared by using one or the other nitrone enantiomer.