Crystallization-induced diastereomer transformation assists the diastereoselective synthesis of 4-nitroisoxazolidine scaffolds

Abstract

This communication describes a solution to the vexing problem of synthesis of 4-nitroisoxazolidine rings from cyclic nitrones and β-nitrostyrenes. The trans-endo adduct 2 is quantitatively synthesised from E-β-nitrostyrene under mild conditions avoiding purification, while the trans-exo adduct 4 is obtained at higher temperatures. Furthermore, a Crystallization-Induced Diastereomer Transformation (CIDT) process was used to epimerise the NO₂ bond from 2 to the cis-exo adduct 3 with total conversion assisted by the para-halogen substitution of the aromatic ring without any additives. By combining these approaches, we can establish a simple synthetic methodology that allows the diastereoselective synthesis of three diastereoisomers, overcoming the previous problems described in the literature.