Aziridines are found in natural products such as mitomycin, porfiromycin, and mitiromycin,
which are potent antitumor and antibiotic agents [1]. More than being just an important
functionality in itself, the aziridines offer potential synthetic pathways to products which may
otherwise be less accessible [2]. Some examples include pathways to novel amino acids and β-
lactams, the latter being important synthons in the syntheses of potent antibiotic drugs [3].
Moreover, optically active aziridines are also used as ligands in asymmetric catalysis [4].
Several aziridination procedures, which make use of hydroxylamine derivatives, have been
described so far in the literature. The earliest example involves addition of methoxyamine to
conjugated enones and treatment of the Michael adduct with sodium alkoxide, allowing isolation
of a wide range of α-ketoaziridines, including optically active compounds [5]. We have recently
experienced that acyloxyamino derivatives possessing an activating β-carbonyl group gave α-
ketoaziridines on treatement with sodium alkoxides [6]. As a continuation of this work, we
developed a simple procedure for preparation of α-ketoaziridines from α, β-unsaturated ketones
using hydroxylamine hydrochloride as aziridination agent (Scheme 1). The synthetical protocol
consists in three steps: (i) addition of hydroxylamine to α,β-unsaturated ketones; (ii)
regioselective O-acetylation of β-hydroxiamino-ketones and (iii) aziridine ring-closure of β-
acetoxyamino-ketones (where R1/R2/R3 – alkyl, aryl and cycloalkyl) .

The overall yields in aziridines 4 were fairly good. Depending on the R2,R3 substituents, the
target compounds were obtained either as E/Z pair or as single E – isomer.
References:
1. H. M. I. Osborn, J. Sweeney, J. Tetrahedron Asym., 1997, 8, 1693; Y. Na, S. Wang, H. Kohn, J.
Am. Chem. Soc., 2002, 124, 4666.
2. W. McCoull, F. A. Davis, Synthesis, 2000, 8, 1347.
3. D. Tanner, P. Somfai, Tetrahedron, 1988, 44, 619; C. Xiong, W. Wang, C. Cai, V. Hruby, J. Org.
Chem., 2002, 67, 1399.
4. D.Tanner, A. Harden, F. Johansson, P. Wyatt, P.G. Andersson, Acta Chem.Scand., 1996, 361.
5. D. L. Nagel, P. B. Woller, N. H. Cromwell, J. Org. Chem. 1971, 36, 3911; P. Muller, C. Fruit,
Chem. Rev., 2003, 103, 2905; H. Sugihara, K. Daikai, X.L. Jin, H. Furuno, J. Inanaza, Tetrahedron
Lett., 2002, 43, 2735.
6 C. Uncuta, E. Bartha, C. I. Tanase, A. Tanase, O. Costan, M. Ciuca, N. Vanthuyne, C. Roussel,
Arkivoc, 2006, X, 42.