Resolution via diastereomeric amides of enantiopure 1,4-benzoxathian-2- and 3-carboxylic acids and determination of their configuration

Abstract

1,4-Benzoxathiane, 2- or 3-substituted, is an important scaffold, and despite its presence in several therapeutic agents, it is chemically unexploited. Furthermore, only a few examples in literature report this moiety in its enantiopure form. Here, taking advantage to the formation of diastereomeric amides by using (S)-phenylethylamine, which show significant differences in terms of ¹ H-nuclear magnetic resonance (NMR) spectra and other physical chemical properties, we defined for the first time the absolute configuration of each amide, both 2- or 3-substituted. Moreover, the diastereomeric amides were further hydrolyzed in acid conditions, letting to the achievement of the corresponding 1,4-benzoxathian carboxylic acids.

Keywords: (S)-phenylethylamine; 1,4-benzoxathiane-2-carboxamide; 1,4-benzoxathiane-3-carboxamide; 1H NMR comparison; absolute configuration determination; chiral HPLC; diastereomeric amides.