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

Abstract

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.