Synthesis and N-functionalization of isoxazolidines: a new approach to nucleoside analogues

A straightforward synthetic approach for the preparation of non N-functionalized isoxazolidines from BF3-catalyzed 1,3-cycloaddition reactions between methyl glyoxylate oxime and alkenes is described. Subsequently, isoxazolidines were N-functionalized with three chemically active groups (2-chloroethyl, cyanomethyl and 2-acetoxyethyl), thus allowing the preparation of a wide array of N-functionalized isoxazolidines. The compounds were characterized by means of 1H and 13C NMR spectroscopy and mass spectrometry. X-ray analysis was used for stereochemical elucidation.