2-Isoxazolinium salts and 3-isoxazolines: Exploratory chemistry and uses for the synthesis of branched amino polyols and amino acids

Abstract

2-Isoxazolines represent a well known class of heterocycles, readily accessible in particular by 1,3-dipolar cycloaddition of nitrile oxides to alkenes. 2-Isoxazolines are easily transformed into 2-isoxazolinium salts by N-methylation, and further into 3-isoxazolines by deprotonation. In contrast to the parent system, less is known concerning the chemistry of the derived classes, and potential applications in synthesis. - 2-Isoxazolinium salts, due to their iminium part, are prone to the attack of nucleophiles, and examples for this, addition of hydride (reduction) and C-nucleophiles like methylmagnesium bromide, cyanide, methane nitronate, and malonate are given. With these adducts, syntheses of β-and α-amino acids with OH-containing side chains have been effected. The cyanide products also are useful as precursors of branched, unsymmetrical 1,2-diamino polyols. - On the other hand, 3-isoxazolines due to their oxy-enamine part, represent species with nucleophilic sites and therefore react with electrophilic reagents. Examples given are [3+2] cycloadditions with nitrile oxides, [2+2] cycloadditions with dimethyl acetylenedicarboxylate, and [2+1] cycloaddition in the form of epoxidation which, however, led to a dihydro-1,3-oxazine nitrone by initial attack at the nitrogen atom, in an unprecedented oxidation/N-dealkylation/rearrangement sequence.