An efficient synthesis of aziridines from ephedrines

The reaction of chlorodeoxyephedrine hydrochlorides with one, two, and three molar equivalents of base was studied. Isochlorodeoxypseudoepherines were identified and assigned by 1H and 13C NMR data as intermediate compounds in the formation of cis-aziridines. Erythro and threo ephedrinethylethers were isolated as new compounds and analyzed by spectroscopic data. In addition, the erythro isomer was studied by X-ray diffraction.

Pseudoephedrines 2 are transformed to chlorodeoxypseudoephedrines 3, which react with bases to produce cis-aziridines 9. Threo chlorodeoxy-derivatives 3a are thermally converted to a mixture of threo/erythro isomers. Isochlorodeoxypseudoephedrines 8a and 8b are identified as intermediates and ephedrinethylether 10ae was isolated as the only product from the reaction of chlorodeoxyephedrine 4a with base in ethanol.Figure optionsDownload as PowerPoint slide

(1R,2S)-(−)-Ephedrinylethylether hydrochlorideC12H20NOCl[α]D20=-68.5 (c 3.08, ethanol)Source of chirality: (1S,2S)-(+)-pseudophedrineAbsolute configuration: (1R,2S)

cis-(2R,3S)-2-Methyl-3-phenylaziridineC9H11N[α]D20=+69.1 (c 4.43, CHCl3)Source of chirality: (1R,2R)-(+)-norpseudoephedrineAbsolute configuration: (2R,3S)

cis-(2S,3R)-1,2-dimethyl-3-phenylaziridineC10H13N[α]D20=-131.0 (c 0.8, ethanol)Source of chirality: (1S,2S)-(+)-pseudoephedrineAbsolute configuration: (2S,3R)