Synthesis, structure and reactions of chiral oxazinones derived from L-ephedrine

Abstract

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 (si-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 ¹H NMR and CD spectra. The allylic enolate of 5 was selectively hydroxylated with oxygen or m-CPBA at the α-site to give 16. Palladium-catalysed substitution of 16 acetate with malonate or phenoxide ions occurred also at the α-site. Acid-catalysed rearrangement of 16 in ethanol gave an 2-ethoxyperhydro-1, 4-oxazin-3one 20, which reacted with trimethylsilyl cyanide to give a 2-cyano derivative 22.