Synthesis of Enantiomerically Pure Aziridine-2-imides by Cyclization of Chiral 3‘-Benzyloxyamino Imide Enolates

Abstract

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 α,β-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 tr...