Ring-opening reactions of 3 -aryl-1-benzylaziridine-2-carboxylates and application to the asymmetric synthesis of an amphetamine-type compound

Nucleophilic ring-opening reactions of 3-aryl-1-benzylaziridine-2-carboxylates were examined by using O-nucleophiles and aromatic C-nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O-nucleophiles as a major reaction path in the ring-opening reactions of aziridines carrying an electron-poor aromatic moiety, whereas mixtures containing preferentially the syn-diastereoisomer were generally obtained when electron-rich aziridines were used (Tables 1–3). In the reactions of electron-rich aziridines with C-nucleophiles, SN2 reactions yielding anti-type products were observed (Table 4). Reductive ring-opening reaction by catalytic hydrogenation of (+)-trans-(2S,3R)-3-(1,3-benzodioxol-5-yl)aziridine-2-carboxylate (+)-trans-3c afforded the corresponding α-amino acid derivative, which was smoothly transformed into (+)-tert-butyl [(1R)-2-(1,3-benzodioxol-5-yl)-1-methylethyl]carbamate((+)-14) with high retention of optical purity (Scheme 6).