SYNTHESIS OF ENANTIOPURE 3-SUBSTITUTED PYRROLINE N-OXIDES BY HIGHLY REGIOSELECTIVE OXIDATION OF THE PARENT HYDROXYLAMINES - A MECHANISTIC RATIONALE

The syntheses of four new, differently O-substituted 3-hydroxypyrrolin e N-oxides and the first 3-amino analogue have been performed by the u se of a strategy involving double nucleophilic displacement of the cor responding dimesylates by hydroxylamine and oxidation of the resulting 1-hydroxypyrrolidines. The regioselectivity data of the oxidation rea ctions nicely confirm the mechanistic hypothesis, which explains the d ependence on the electronic nature of the substituent. The trend of th e regioselectivity ratio has useful predictive value. Practical comple te regioselection has been obtained by substitution with a benzoyloxy functionality. The O-allyl-substituted nitrone is not stable in the re action conditions, undergoing immediately an intramolecular cycloaddit ion reaction with complete stereocontrol and inversion of regio- and s tereoselectivity with respect to the intermolecular case.