Highly regioselective synthesis of functionalized aminonitriles starting from 2-(ω-cyanoalkyl)aziridines

1-arylmethyl-2-(bromomethyl)aziridines were transformed into the corresponding 2(cyanomethyl)aziridines and 2-(2-cyanoethyl)aziridines upon treatment with potassium cyanide in DMSO and α-lithiated trimethylsilylacetonitrile in THF, respectively. Further elaboration of 1-arylmethyl-2-(cyanomethyl)aziridines afforded 4-amino-2-butenenitriles, 3,4diaminobutanenitriles and 2-aminocyclopropanecarbonitriles. Additionally, 1-arylmethyl-2-(2cyanoethyl)aziridines were efficiently converted into biologically relevant 2-(aminomethyl)cyclopropanecarbonitriles. Introduction 2-(Bromomethyl)aziridines 1 comprise a peculiar and scarcely evaluated class of constrained β-halo amines with high synthetic potential due to the presence of three different electrophilic carbon atoms and the nucleophilicity of the nitrogen atom. Furthermore, these synthons can be prepared in high yield and high purity using simple and straightforward methodologies, and their relative stability allows a long shelf life. Based on these features, 2-(bromomethyl)aziridines 1 can be considered as functional substrates in organic synthesis suitable for a plethora of organic transformations towards different classes of target compounds. However, little or no information could be found in the literature regarding their reactivity profile and their utility as building blocks, especially concerning non-activated 1-alkyl-2-(halomethyl)aziridines. These observations formed the onset of an in-depth investigation of the reactivity and applicability of 2(bromomethyl)aziridines, which has revealed the enormous synthetic potential of these substrates in organic chemistry. N 1 Br R electrophilic carbon atoms nucleophilic nitrogen atom