Asymmetric Synthesis of 2H-Azirine 2-Carboxylate Esters

Abstract

2H-Azirine 2-carboxylate esters (5), the smallest unsaturated nitrogen heterocycle, are readily prepared in enantiomerically pure form via the base-induced elimination of sulfenic acid (RSOH) from nonracemic N-sulfinylaziridine 2-carboxylate esters (4). Optimum yields were obtained when the aziridine was treated with TMSCl at -95 degrees C followed by LDA, which was attributed to the improved leaving group ability of an silicon-oxonium species. By using this new methodology the first asymmetric syntheses of the marine cytotoxic antibiotics (R)-(-)- and (S)-(+)-dysidazirine (2) were accomplished.

Product Class 7: Imines

“…When the Swern oxidation is performed on an aziridine-2-carboxylate without a C3 proton, the corresponding 2H-azirine-3-carboxylate is obtained in good yield. [442] This methodology has been adapted to accomplish the asymmetric synthesis of azirinephosphonates substituted with an aryl group. In this case, a mixture of both regioisomers, the 2H-azirine-2-phosphonate and the 2H-azirine-3-phosphonate, is obtained.…”

“…The leaving group capacity of the sulfinyl moiety can be improved by treatment with chlorotrimethylsilane at -95 8C prior to elimination with lithium diisopropylamide. [442] Scheme 49 Synthesis of 2H-Azirines by Elimination from 1-Tosylaziridines [442,448] LDA ( Methyl (2R)-2-Methyl-3-phenyl-2H-azirine-2-carboxylate (125, R 1 = R 2 = Me); Typical Procedure: [442] In a 25-mL oven-dried flask was placed (+)-methyl (2R,3S)-2-methyl-3-phenyl-1-(4-tosyl)aziridine-2-carboxylate (0.09 g, 0.27 mmol) in THF (9 mL) under argon. The soln was cooled to -78 8C and 1 M LDA in THF (0.37 mmol) was added slowly.…”

Asymmetric Syntheses with Aziridinecarboxylate and Aziridinephosphonate Building Blocks

“…Upon treatment with base, such aziridines may undergo ring-opening reactions to give a-amino-a,b-unsaturated carboxylates [74,94,95]. As an example, treatment of 111 (Scheme 3.39) with TMSI/Et 3 N gave 116 in 64 % yield [74].…”

“…[3+2] Cycloaddition reactions of aziridine-2-carboxylic esters have also been used The marine cytotoxic antibiotic (R)-(-)-dysidazirine (286; Scheme 3.102) was prepared for the first time by Davis and co-workers from N-sulfinylaziridine 244 [95]. Treatment of N-sulfinylaziridine 244 with LDA at -95°C in the presence of TMSCl afforded 286 in 62 % yield [95].…”

Three‐Membered Heterocycles. Structure and Reactivity

“…A convenient workaround to this problem was found by using Swern conditions, which effects the same transformation in 86% overall yield [278]. Davis and coworkers have reported an interesting eliminative pathway by treating Nsulfinyl or N-sulfonylaziridines (e.g., 225) with lithium diisopropylamide (LDA) at low temperature [279,280]. Methyleneaziridines can easily be isomerized to azirines, since the latter lie about 9 kcal mol À1 lower in energy [281].…”