A Cycloaddition-Cyclization Combined Approach to Enantiopure 3-Glycinyl-4-hydroxypyrrolidines and 3-Substituted 4-Hydroxyprolines

作者：Aouadi Kaiss^*; Abdoul Zabar Juliane; Msaddek Moncef; Praly Jean Pierre

来源：European Journal of Organic Chemistry, 2014, 2014(19): 4107-4114.

DOI：10.1002/ejoc.201402215

• Nitrogen heterocycles
• Cycloaddition
• Cyclization
• Enantioselectivity
• Chiral auxiliaries

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 (alpha S,3R,4S)-3-glycinyl-4-hydroxypyrrolidine. Both enantiomers of the reported products can be prepared by using one or the other nitrone enantiomer.

• 出版日期2014-7