2-Isoxazolidineethanols: An NMR study of the effect of intramolecular H-bonding on the population of nitrogen invertomers and inversion process

Abstract

A series of ( βR, 5R)- and ( βR, 5S)-2,5-disubstituted isoxazolidines: 5-(substituent)-β-phenyl-2-isoxazolidineethanols, have been prepared by asymmetric nitrone cycloaddition reactions and their NMR spectra recorded over a wide range of temperatures. The spectra at low temperatures indicate the presence of the ( βR, 5S) diasteromer almost exclusively as a single invertomer having trans disposition of the substituents at N(2) and C(5), while the ( βR, 5R) diasteromer remained as a mixture of two interconverting invertomers in deuterated chloroform. The effect of H-bonding – intramolecular in CDCl 3 and intermolecular in CD 3OD – on the population ratio of the invertomers and nitrogen inversion process has been investigated. The nitrogen inversion barriers are determined using complete line-shape analysis, and their dependence on solvent is discussed. Due to steric factor the trans-invertomers are found to be more stable than their cis counterparts.