Highly diastereo- and enantioselective aziridination of α,β-unsaturated amides with diaziridine and mechanistic consideration on its stereochemistry

Hiroyuki Ishihara, Kiyoto Hori, Hiroyasu Sugihara, Yoshio Ito, Tsutomu Katsuki

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27 Citations (Scopus)

Abstract

During studies of aziridination of α,β-unsaturated amides with diaziridine, we found that we could prepare both the cis- and trans-aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3-monosubstituted diaziridine 2 was suitable for the trans-selective aziridination, employment of 3,3-dialkyldiaziridine 1 resulted in the formation of cis-aziridine carboxamides, irrespective of the geometry of the substrate (Scheme 1 and Tables 1 and 2). To elucidate the unique nonstereospecificity and to expand these aziridinations to asymmetric ones, several optically active diaziridines were newly prepared. Aziridination with an optically active 3-monosubstituted diaziridine, 3-cyclohexyl-1-[(1R)-1-phenylethyl]diaziridine 16, proceeded smoothly with high trans-selectivity as well as excellent enantioselectivity (up to 98% ee; see Table 3). On the other hand, highly enantioselective cis-aziridination was achieved (> 99% ee) with optically active 3.3-dimethyl-1-[(1R)-1-phenylethyl]diaziridine 15, though the yield was low (4%). This aziridination was considered to proceed stepwise by way of the enolate intermediate (Scheme 2). Careful inspection of the stereochemistry and its solvent-dependence suggested that the diastereoselection of the reaction was kinetically controlled: the 1,4-addition of N-lithiated diaziridine was a crucial step for determination of the stereochemical course of the aziridination (Figs. 2-4).

Original languageEnglish
Pages (from-to)4272-4286
Number of pages15
JournalHelvetica Chimica Acta
Volume85
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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