Synthesis and stereochemistry assignment of (3R,5R)- and (3S,5R)-4-benzyl-3-(3,4-dimethoxyphenyl)-5-phenyl-1,4-oxazin-2-ones

• Published in: Journal of molecular structure Vol. 1194; pp. 204 - 210
• Main Authors: Grajewska, Agnieszka, Rozwadowska, Maria D., Gzella, Andrzej
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.10.2019
• Subjects: 1,4-Oxazin-2-one; Configuration determination; Diastereoselective synthesis; NMR; Petasis reaction; X-ray; Configuration determination; Petasis reaction; Diastereoselective synthesis; NMR; X-ray; 1,4-Oxazin-2-one
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.05.091

The diastereoselective synthesis of 3,5-disubstituted 1,4-oxazin-2-ones, the valuable intermediates on the route to tetrahydroisoquinoline derivatives, was based on the Petasis reaction in which (R)-(−)-N-benzyl-2-phenylglycinol was used as the amine component. It was demonstrated that the configuration of the newly generated C3 stereogenic centers in synthesized compounds, as well as in other 3,5-disubstituted 1,4-oxazin-2-ones, could be established simply by 1H NMR spectral data analysis. The absolute configuration of the major isomer was additionally confirmed by single crystal X-ray analysis. [Display omitted] •Diastereoselective synthesis of 3,5-disubstituted-1,4-oxazin-2-ones.•The configuration of the newly generated C3 stereogenic center established by 1H NMR.•No derivatization or special measurements required for configuration assignment.•The absolute configuration of the (3R,5R)-isomer confirmed by X-ray analysis.