SYNTHESIS, STRUCTURE END REACTIONS OF CHIRAL OXAZINONES DERIVED FROM L-EPHEDRINE

Optically pure 4,5-dimethyl-3,6-diphenylperhydro-1,4-oxazin-2-one 4 and 4,5-dimethyl-6-phenyl-3-(2-phenylvinyl)perhydro-1,4-oxazin-2-one 5 have been prepared by condensation of ephedrine, potassium cyanide and benzaldehyde or cinnamaldehyde. The lithium enolates of compounds 4 and 5 reacted with halogenoalkanes in a stereospecific manner (six-attack) to give the 3-substituted derivatives 10-15. The structures of 10 and 12 were established by X-ray diffraction, while the stereochemistry of the other compounds was determined by correlation of their H-1 NMR and CD spectra. The allylic enolate of 5 was selectively hydroxylated with oxygen or m-CPBA at the alpha-site to give 16. Palladium-catalysed substitution of 16 acetate with malonate or phenoxide ions occurred also at the alpha-site. Acid-catalysed rearrangement of 16 in ethanol gave an 2-ethoxyperhydro-1,4-oxazin-3-one 20 which reacted with trimethylsilyl cyanide to give a 2-cyano derivative 22.