Gabriel-Cromwell reaction

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

Scheme 2.16 Synthesis of vinylaziridines by the Gabriel-Cromwell reaction.

The Gabriel-Cromwell reaction is a convenient strategy for the synthesis of vinylaziridines. Treatment of 4,5-dibromopent-2-enoate 50 with primary amines 51 in the presence of DBU afforded the corresponding conjugated aziridines 52 in 63-80% yields (Scheme 2.16) [28]. The use of DBU has proven to be essential for the successful conversion. 

Oligopeptides and amino aci containing an aziridine 2-carboxylate group have been prepared using a solid phase version of the Gabriel-Cromwell reaction (i.e., 127 129) <99TL6503>... 

The Gabriel-Cromwell reaction of amines with chiral c/., 3-unsaturated a-bromo carbonyl compounds was exploited for the synthesis of aziridine-2-carboxylic acid derivatives. 79 This procedure was optimized for a solid support synthesis in which the peptide resin was acylated with 2,3-dibromopropanoic acid active ester in the presence of 3 equivalents of NMM to produce directly on resin the a-bromoacrylamide for the addition of amines to produce the aziridine ring. 80 ... 

The principles of the Gabriel-Cromwell reaction were applied to a solid-phase synthesis by Fihgheddu s group (Scheme 9.1). Compound 1 was prepared from Wang resin and... 

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

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