Synthesis of new functionalized aziridine-2- and azetidine-3-carboxylic acid derivatives of potential interest for biological and foldameric applications.

A short synthesis of alkyl 2-(bromomethyl)aziridine-2-carboxylates and alkyl 3-bromoazetidine-3-carboxylates was developed involving amination, bromination, and base-induced cyclization of alkyl 2-(bromomethyl)acrylates. The aziridines are the kinetically favored cyclization products and could be transformed into 3-bromoazetidine-3-carboxylic acid derivatives via thermal isomerization. The new small-membered azaheterocyclic α- and β-amino acid derivatives contain a bromo-substituted carbon center as a useful moiety for functionalization. Transformation of these functionalized azaheterocycles via nucleophilic substitution with carbon, sulfur, oxygen, and nitrogen nucleophiles and via elaboration of the amino and carboxyl group provided a broad range of new conformationally constrained aziridine-2- and azetidine-3-carboxylic acid derivatives, which are of interest from a biological point-of-view as well as for applications in the field of foldamers.