Two-Step Synthesis ofN-Sulfonyl Aziridines from Epoxides

Abstract

A convenient and high-yielding two-step synthesis of Nsulfonyl aziridines starting from epoxides is described. The method, which involves epoxide ring opening with sulfonamides and subsequent mesylation-cyclisation, is particularly suitable for variation of the N-sulfonyl substituent; 18 examples are presented.Aziridines have an ever-improving reputation as useful intermediates in synthetic organic chemistry. 1 As such, several different approaches and methodologies have been developed for the synthesis of aziridines. 1-3 With reference to the preparation of N-sulfonyl aziridines, close inspection of the different approaches reveals that they mostly generate N-toluenesulfonyl (N-tosyl) aziridines. Methodology for the synthesis of 'non-tosyl' aziridines is far less developed and/or typically low yielding. We are interested in developing new organolithium-mediated reactions of aziridines and our previous work has focused on the use of N-tosyl aziridines. 4,5 With a view to investigating other N-sulfonyl aziridines in the organolithium chemistry, we needed a reliable, high yielding and simple route to a range of N-sulfonyl aziridines 1 and 2 ( Figure 1). Figure 1The most straightforward route to N-sulfonyl aziridines 1 and 2 would be sulfonylation of the NH aziridine, which can be produced by Staudinger reduction of the azido alcohol (generated by ring opening of the corresponding epoxide). 6 In our hands, this three-step route is often lowyielding. 7,8 Alternatively, different iodinanes PhI=NSO 2 R in combination with Cu(I) or Cu(II) salts can be used in the direct aziridination of alkenes, 9 and we have exploited this in previous studies. 8,10,11 Some different iodinanes were prepared by Andersson and co-workers 12 and Protasiewicz and co-workers; 13 the iodinanes can also be generated in situ, as reported by Dauban and Dodd. 14 In addition, N-SES-protected (SES: trimethylsilylethylsulfonyl) aziridines have been prepared using this approach. 15 Overall, however, the iodinane methodology mostly employs PhI=NTs, is generally moderate to low yielding, and often works best with an excess of the alkene. N-Sulfonyl aziridines can also be prepared from alkenes using electrophilic Br + and N-chloramine sulfonamide salts (RSO 2 NCl -Na + ), as pioneered by Sharpless 16 and Komatsu. 17 These reactions almost always use commercially available chloramine-T 4,5,7,16-18 (introduction of an N-tosyl group), but Sharpless and co-workers have also used tBuSO 2 NCl -Na + . 19 Finally, three-step routes from epoxides to N-sulfonyl aziridines via epoxide ring opening using sulfonamides, activation, and cyclisation have been reported by Albanese 20 and Jacobsen. 21 Although both routes had not varied the sulfonamide significantly, the Albanese route appeared ideal for our purposes of generating a range of N-sulfonyl aziridines 1 and 2 from the corresponding epoxides. 22,23 The general approach we have optimised is summarised in Scheme 1. In particular, we have streamlined this approach into a two-step synthesis by cyclising the crude a...

Diversity-oriented synthesis of chemically recyclable poly(sulfonamide ester)s through organocatalytic aziridine-based multicomponent polymerization

“…Bis(hydroxy sulfonamide) 6 was isolated in 91% yield by precipitation. Through the mesylation/cyclization reaction, 47 bis(hydroxy sulfonamide) 6 transformed to the monomer bis(aziridine) 1a in 81% yield. 1,5-pentanediol was water soluble and isolated in the aqueous phase.…”

“…Polymer Chemistry tion, 47 bis(hydroxy sulfonamide) 6 transformed to the monomer bis(aziridine) 1a in 81% yield. 1,5-pentanediol was water soluble and isolated in the aqueous phase.…”

Aziridines and azetidines: building blocks for polyamines by anionic and cationic ring-opening polymerization

“…This route might be extended to other N-sulfonyl groups. 134 Another route, starting from epoxides, was used by Bergman and Toste 124 to synthesize 2-n-decyl-N-methanesulfonyl aziridine (MsDAz). Thomi and Wurm 133 followed this procedure to synthesize 2-(oct-7-en-1-yl)-N-mesylaziridine.…”