Reactivity of 2-halo-2H-azirines. Part 3: q Dehalogenation of 2-halo-2H-azirine-2-carboxylates Teresa M. V. D. Pinho e Melo, * Ana L. Cardoso and Anto ´nio M. d’A. Rocha Gonsalves Departamento de Quı ´mica, Faculdade de Cie ˆncias e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal Received 2 September 2002; revised 24 December 2002; accepted 5 February 2003 Abstract—The dehalogenation of 2-halo-3-phenyl-2H-azirine-2-carboxylates is described. Using sodium borohydride and tributyltin hydride 3-phenyl-2H-azirine-2-carboxylates were obtained in moderate yields. The synthesis of a new 2-bromo-2H-azirines with a chiral auxiliary, 10-phenylsulfonylisobornyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate, is reported. Its dehalogenation led to 10-phenyl- sulfonylisobornyl 2H-azirine-2-carboxylate as single stereoisomer together with the formation of 10-phenylsulfonylisobornyl acetate. q 2003 Elsevier Science Ltd. All rights reserved. 1. Introduction 2H-Azirines are very important class of compounds not only due to their theoretical interest but also because they are versatile building blocks for organic synthesis. 2 Chiral derivatives bearing a carboxylic acid group or an ester group at C-2 are of particular interest since some of these substituted 2H-azirines are naturally occurring antibiotics. In fact azirinomycin (1), isolated from Streptomyces auras cultures, and its methyl ester exhibit antibiotic activity. Moreover, both enantiomers of (R)-(þ)- and (S)-(2)- dysidazirine 2 and (S)-(þ)-antazirine 3 were isolated from the marine sponge Dysidea fragilis. Therefore, the develop- ment of new asymmetric synthesis of 2H-azirine-2- carboxylates has recently attracted great attention. 3 Chiral 2H-azirines have been prepared by elimination reaction of N-substituted aziridines namely dehydro- chlorination of N-chloroaziridines, 3a Swern oxidation of aziridines 3b and elimination from N-sulphynilaziridines. 3d The latest procedure has been used in the asymmetric synthesis of (R)-(þ)- and (S)-(2)-disydazirine. These interesting methods involve nevertheless the use of high enantiopure aziridine esters as starting materials. A different approach has also been described consisting in an alkaloid- mediated Neber reaction (Scheme 1). 3c We have developed a very general route to 2-halo-2H- azirines starting from a-oxophosphorus ylides which allows the synthesis of a range of 2-iodo-, 2-bromo and 2-chloro- 2H-azirines. The 2H-azirines, including 2-halo-2H-azirine- 2-carboxylate derivatives, are obtained by our synthetic procedure as racemic mixtures. 4 Our aim was to achieve the synthesis of chiral 2H-azirine-2- carboxylates by dehalogenation of these 2-halo-2H-azirine- 2-carboxylates. The synthetic strategy should be a process involving an intermediate (carbocation or radical) with a chiral auxiliary to control the configuration of the new chiral center. Two reducing agents, which allow the formation of the referred intermediates are sodium borohydride and tributyltin hydride. The approach could be the synthesis of the chiral esters of 2-halo-2H-azirine-2-carboxylic acids followed by the dehalogenation reaction. 0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4020(03)00248-5 Tetrahedron 59 (2003) 2345–2351 q See Ref. 1. Keywords: dehalogenation; 2-halo-2H-azirine-2-carboxylates; chiral 2H- azirine-2-carboxylates. * Corresponding author. Fax: þ351-239-826-068; e-mail: tmelo@ci.uc.pt