New methodology for the preparation of N-tosyl aziridine-2-carboxylates Liliana Marzorati, * Giovana C. Barazzone, Marco A. Bueno Filho, Blanka Wladislaw and Claudio Di Vitta * Instituto de Quı ´mica da Universidade de Sa ˜o Paulo, Av. Prof. Lineu Prestes 748, 05508-000 Sa ˜o Paulo, Brazil Received 15 June 2007; revised 6 July 2007; accepted 9 July 2007 Available online 13 July 2007 Abstract—N-Tosyl aziridine-2-carboxylate methyl esters were prepared from methyl N-tosyl-L-serinate or N-tosyl-L-threoninate, tosyl chloride, and K 2 CO 3 , under phase-transfer catalysis (PTC) conditions. The same methodology, as applied to the tert-butyl N-tosyl-L-serine amide, afforded the corresponding newly prepared aziridine-2-carboxamide, as an enantiomerically pure compound. Ó 2007 Elsevier Ltd. All rights reserved. Aziridines, three-membered nitrogen heterocycles, are constituents of several molecules presenting biological activity, for example, azinomycins and mytomycins. 1 In analogy to epoxides, aziridines react with nucleo- philes, via ring opening reactions, allowing the introduc- tion of an ethylamino group in a wide range of substrates. 1,2a–g,k The preparation of substituted aziri- dines has been extensively reviewed. 1,2a–d,i–l In particu- lar, N-tosyl aziridines, used for chemical fixation of CO 2 , 3 as ligands, 4 and as precursors of aminoacids 5 and of other synthetic targets, 2f,g have been prepared from (i) alkenes via nitrene insertion 6 or aminohalogen- ation, 7 (ii) sulfinimines via aza-Darzens type additions, 8 (iii) b-hydroxy-a-aminoesters by intramolecular Mitsun- obu cyclization, 9 and by ring closure of the correspond- ing N,O-ditosylated derivatives 10 or of the N-trityl-O- tosyl derivative. 2e,5 However, for the preparation of enantiomerically pure 1 and 2, only two methods 2e,5,10 are described in the literature (Scheme 1). By the first method, 2e,5 1 and 2 were obtained in ca. 50% yield, after a rather long sequence. The applicability of method 2 10b is limited by the instability of the N,O- ditosylated intermediate 3, prone to b-elimination. 5,10a However, we were able to circumvent such drawbacks performing a one step phase-transfer catalyzed aziridin- ation of N-tosyl-L-serine or N-tosyl-L-threonine methyl esters. In our hands, the attempted preparation of N,O-ditosyl- L-serine ethyl ester 10a (3, R=H, R 0 = Et; Scheme 1; method 2), to be used as precursor of the corresponding aziridine, failed due to the easy formation of N-tosyl dehydroalanine ethyl ester. It should be mentioned that a similar result was described by Baldwin et al. 5 for the direct bis-tosylation of methyl L-serinate hydrochloride in homogeneous medium. However, when we submitted methyl N-tosyl-L-serinate or methyl N-tosyl-L-threoni- nate (Scheme 2; 4a,b) to reaction with tosyl chloride and K 2 CO 3 , in a PTC solid–liquid system, the ring clo- sure reaction of a putative N,O-di-tosylated intermedi- ate was prevalent over any competitive reaction, including racemization of the stereogenic centers (Scheme 2). Under these conditions, compounds 1 and 2 could be prepared either from the amino esters hydrochlorides or from the N-tosylated aminoesters in moderate to good yield (Table 1). Considering the aziridination reactions of 4a and 4b, performed in the presence of the quaternary ammonium catalyst Aliquat 336 (Table 1, entries 3 and 4), a straightforward reaction mechanism may be envisaged, as consisting of: (i) deprotonation of the tosylated nitro- gen of 4 at the water liquid film that coats the solid potassium carbonate, the so called ‘omega phase’, 11 0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2007.07.054 * Corresponding authors. Tel.: +55 11 30912178; fax: +55 11 38155579 (L.M.); e-mail: lmarzora@iq.usp.br Tetrahedron Letters 48 (2007) 6509–6513