Stereoselective 1,3-dipolar cycloadditions of nitrones derived from amino acids. Asymmetric synthesis of N-(alkoxycarbonylmethyl)-3-hydroxypyrrolidin-2-ones

Abstract

Diastereoselective asymmetric 1,3-dipolar cycloadditions of N-(alkoxycarbonylmethyl) nitrones derived from glycine, alanine and phenylalanine have been studied both experimentally and theoretically. Asymmetric induction is evaluated by either introducing a chiral group at the nitrone nitrogen atom or by using Oppolzer's sultam acrylamide. In both cases the sense of the asymmetric induction is the same, the (3R,5R)-isomer being preferentially obtained. The best results were observed with the chiral dipolarophile, which afforded an only isomer in all cases. The obtained isoxazolidines are easily transformed into the corresponding 5-substituted-3-hydroxypyrrolidin-2-ones. DFT studies are in a qualitative agreement with the observed experimental results. © 2013 Elsevier Ltd. All rights reserved.