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 diastereos electivity from chiral 3'-benzyloxyamino imides 2, 3, and 8 by treatme nt with triethylamine in the presence of either TiCl4 or AlMe2Cl. 2 an d 3 are easily obtained by a diastereoselective conjugate addition of O-benzylhydroxylamine promoted by Lewis acids to alpha,beta-unsaturate d imides 1. The synthesis of 3'-(benzyloxyamino)propanoyl 8 is perform ed by addition to the acryloyl compound 6 of N-BOC O-benzylhydroxylami ne followed by deprotection. The cyclization of 2 and 3 affords comple te trans selectivity and yields up to 97% of the corresponding 3'-alky l 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 s tudy has been made to rationalize the trans selectivity observed in th e cyclization of 2 and 3. AM1 computations allow us to deduce that the reaction proceeds through cyclic titanium or aluminum enolate formati on, and they reveal that enolates leading to trans aziridines are more stable than those leading to cis.