Hoch effiziente, präparative chromatographische Enantiomerentrennung von 2-Phenyl-1,3-dioxin-4-onen an Cellulose-triacetat und Cuprat-Additionen zu β-Hydroxycarbonsäure-Derivaten

Abstract

The 2-Phenyl-dioxinones 1 and 2 are resolved on cellulose-triacetate columns (medium pressure, eluent MeOH, separation factors α = 2.0–2.3, injection of g amounts). The enantiomerically pure formyl- and acetylacetate derivatives, thus available undergo diastereoselective (97–99% ds) 1,4-additions with CuCl-doped Grignard reagents or with cuprates to give the dioxanones 5,9, and 10. Eventually, 3-hydroxy-carboxylic acids, esters, and O-benzyl-protected acids (6, 8, 11–13) can be prepared with >96% enantiomeric excess; otherwise not readily available derivatives with a tertiary 3-hydroxy group are accessible by this route (see 11, 12). Two peculiar stereoselective reactions are reported: i) the inversion of configuration upon bromination of the dioxinone 2 ((–)-(R)-2 → (+)-(S)-4) and ii) the highly diastereoselective (91% ds) cleavage of the 2-phenyl-dioxanone 10 with D₂/Pd-C(→13). Configurational assignments are based on nuclear Overhauser effects (NOE) and on chemical correlations.