Nitrones and nucleobase-containing spiro-isoxazolidines derived from isatin and indanone: solvent-free microwave-assisted stereoselective synthesis and theoretical calculations

Abstract

The spiro-oxindoles have found wide application because of their antiviral properties. However, in the literature few examples of synthesis of their precursors, oxindole-nitrones, are reported. In this paper, we initially present a rapid and efficient synthetic approach to ketonitrones by solvent-free microwave-assisted reaction between isatin or indanone derivatives and various hydroxylamines. The synthetic protocol is facile, clean, fast, high-yielding and stereoselective. Then, we explored the possibility to synthesize nucleobase-containing spiro-isoxazolidines with isatin and indanone nuclei by solvent-free MW-assisted 1,3-dipolar cycloaddition, obtaining good results in yields (74–85%), and regio- and diastereoselectivity. Theoretical calculations were done to analyze the difference of reactivity of isatin and indanone derivatives with hydroxylamines.