Microwave-assisted ring expansion of N-acetyl 3 0 -unsubstituted aziridine in the presence of Lewis acids Giuliana Cardillo, p Luca Gentilucci, Massimo Gianotti and Alessandra Tolomelli Dipartimento di Chimica ªG. Ciamicianº, Universita Á degli Studi di Bologna and C.S.F.M., via Selmi 2, 40126 Bologna, Italy Received 2 November 2000; revised 2 January 2001; accepted 18 January 2001 Abstract ÐThe microwave-assisted ring expansion of N-acetyl 3 0 -unsubstituted aziridine-2-imides and N-acetyl 3 0 -unsubstituted aziridine- 2-esters to oxazolines is reported. The regioselectivities of the rearrangements depend upon the reaction conditions, such as the Lewis acid selected and the solvent. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction In recent years there has been an increasing interest in the use of aziridine-2-carboxylates 1 as intermediates for the synthesis of biologically active compounds, such as a- and b-amino acids or b-lactam antibiotics. In this ®eld we have developed a new strategy towards the synthesis of stereode®ned aziridines. Indeed, we obtained aziridine-2-carboxylate derivatives following several synthetic pathways, such as the well known Gabriel± Cromwell reaction performed on unsaturated chiral imides 2 or the 1,4-addition of O-benzylhydroxylamine to a,b- unsaturated imides, followed by cyclization to the corre- sponding trans aziridine. 3 The stereochemical results of both these reactions were controlled using 1,5-dimethyl-4- phenylimidazolidin-2-one as a chiral auxiliary. This hetero- cycle is available in both enantiomerically pure forms, starting from (1)- or (2)-ephedrine. 4 N-Acyl activated aziridines easily afford ring opening in the presence of a nucleophile through an S N 2 mechanism 1 or can be transformed into the corresponding oxazolines through a ring expansion reaction in the presence of Lewis acids. 5 The ring expansion of activated aziridines promoted by azaphilic Lewis acids has recently been the object of attention and both chemical evidence and ab initio calculations show that this reaction occurs with retention of the pre-existing stereogenic centers. 5,6 These results have been con®rmed by us through 1 H NMR experiments 7a and chemical transformations, 7b performed on the optically active trans N-acyl-3-substituted aziridine-2-imides. These compounds spontaneously rearrange in CHCl 3 , in the absence of Lewis acid, affording exclusively trans oxazo- line-4-imides, under complete regiocontrol and with retention of the con®gurations. These results show that the presence of an alkyl substituent at C3 0 of the imide deriva- tive strongly favors the formation of oxazoline-4-imides. The same protocol, carried out on 3 0 -unsubstituted aziri- dines, afforded a mixture of regioisomers, whose ratio strongly depended on the Lewis acid selected for the acti- vation and on the reaction conditions. These observations prompted us to further investigate the ring expansion of 3 0 - unsubstituted-aziridines. 2. Results and discussion The aziridine 1 was synthesized following the procedure reported elsewhere. 2,3 The ring expansion of 1 to afford 2 or 3 was performed in the presence of several Lewis acids in equimolar amounts with respect to 1, in different solvents, under normal conditions at room temperature (Scheme 1). The results obtained are reported in Table 1. The selected data, reported in Table 1, show that MgBr 2 ´Et 2 O favors the formation of oxazoline 2, while BF 3 ´Et 2 O gives oxazoline 3 as the major product. This result shows that the reaction could occur via attack of the carbonyl at both C3 0 and C2 0 ring carbon atoms, depending Tetrahedron 57 (2001) 2807±2812 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(01)00123-5 Keywords: aziridine; oxazoline; microwaves; Lewis acids; rearrangement. p Corresponding author. Tel.: 151-2599570; fax: 151-2099456; e-mail: cardillo@ciam.unibo.it Scheme 1.