Synthesis and Spin Trapping Stereochemistryof the Chiral Spin Trap, 5,5-Dimethyl-3-phenylpyrroline-1-oxide

Abstract

A chiral spin trap, 5,5-dimethyl-3-phenylpyrroline-1-oxide (5), and several hydroxylamines were synthesized. The structures and conformations of these compounds were investigated mainly by 1H NMR spectroscopy. This spin trap was used to trap carbon- and oxygen-centered radicals. The corresponding hydrogen spin adduct was prepared by oxidizing the hydroxylamine to the nitroxide radical. By the combination of 1H NMR and EPR results, it was shown that the conformation with the phenyl group of C-3 at the equatorial position is exclusively populated and its lifetime is long compared with the EPR time-scale. Addition of carbon-centered radicals to 5 leads to trans adducts whereas oxygen-centered radicals formed cis isomers. These could be confirmed by the investigation of the monovalent oxidation products of the hydroxylamines. The preference for these conformers is explained by the competition between steric and stereoelectronic effects. Despite the racemic nature of 5 and the formation of a new chiral center(s) in the spin adducts, the presence of different diastereomers would not be observed by EPR whereas 1H NMR studies of some of the nitrones showed clear evidence of diastereomeric mixtures. However, the spin adduct of sec-hydroxybutyl radical showed some linewidth effects which could be attributed to the presence of two groups of diastereomers that were resolved by ENDOR spectroscopy. In general, the spin adducts of 5 are closely related to those of the well known DMPO, but the presence of a phenyl substituent at the 3-position results in a variation of the β-H coupling constants. In contrast to DMPO, 5 can scavenge short-lived radicals in aqueous and non-aqueous solutions.