Synthesis of enantiomerically pure aziridine-2-imides by cyclization of chiral 3′-benzyloxyamino imide enolates

Aziridine-2-imides are prepared both in high yield and high diastereoselectivity from chiral 3'-benzyloxyamino imides 2, 3, and 8 by treatment with triethylamine in the presence of either TiCl4 or AlMe2Cl. 2 and 3 are easily obtained by a diastereoselective conjugate addition of O-benzylhydroxylamine promoted by Lewis acids to alpha,beta-unsaturated imides 1. The synthesis of 3'-(benzyloxyamino)propanoyl 8 is performed by addition to the acryloyl compound 6 of N-BOC O-benzylhydroxylamine followed by deprotection. The cyclization of 2 and 3 affords complete trans selectivity and yields up to 97% of the corresponding 3'-alkyl aziridines 4 and 5, while the cyclization of 8 affords a mixture of diasteroisomers 11, 12 in 86/14 ratio and a 95% yield. A mechanistic study has been made to rationalize the trans selectivity observed in the cyclization of 2 and 3. AM1 computations allow us to deduce that the reaction proceeds through cyclic titanium or aluminum enolate formation, and they reveal that enolates leading to trans aziridines are more stable than those leading to cis.