Preparative Resolution of Heterocyclic Acetals Derived from Glycine, Mercapto-acetic Acid, β-Alanine, and Formyl- or Acetylacetic Acid by Recycling Chromatography on Chiraspher and Temperature Dependence of Separation Factors

Chiraspher, a polymer of ethyl N-acryloylphenylalanine on spherical silica gel, is used for the preparative separation by recycling chromatography of the enantiomers of oxazolidinones rac-5, thioxolanone rac-6, per-hydropyrimidinone rac-7, and dioxinones rac-9 and 10 derived from the acids listed in the title (Figs. 1–5). The oxazolidinones rac-1a, -2, and -4 show a peculiar peak of the separation efficiences upon lowering the Chiraspher-column temperature to 15° (Fig. 6). In some cases, multigram amounts of enantiomerically pure heterocycles could thus be prepared. The absolute configurations of most enantiomers are assigned. First applications of the tert-butyl 5-oxo-2-phenyloxazolidine-3-carboxylate (5) as a nucleophilic chiral glycine building block are described (products 13–16, Scheme 2). A list of enantiomerically pure 1,3-dioxinones is presented (Table 1), showing a correlation between their absolute configuration, sense of optical rotation, and elution behavior on Chiraspher.