Highly Diastereo- and Enantioselective Aziridination of α,β-Unsaturated Amides with Diaziridine and Mechanistic Consideration on Its Stereochemistry

✍ Scribed by Hiroyuki Ishihara; Kiyoto Hori; Hiroyasu Sugihara; Yoshio N. Ito; Tsutomu Katsuki

• Book ID: 102253494
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: German
• Weight: 192 KB
• Volume: 85
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200290012

✦ Synopsis

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‐[(1__R__)‐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‐[(1__R__)‐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).