Enantioselective Aziridination of Cyclic Enals Facilitated by the Fluorine‐Iminium Ion Gauche Effect

The enantioselective, organocatalytic aziridination of small, medium and macro‐cyclic enals is reported using (S)‐2‐(fluorodiphenyl methyl)‐pyrrolidine. Central to the reaction design is the reversible formation of a β‐fluoroiminium ion intermediate, which is pre‐organised on account of the fluorine‐iminium ion gauche effect. This conformational effect positions the fluorine substituent synclinal‐endo to the electropositive nitrogen centre thus benefiting from favourable stereoelectronic and electrostatic interactions (σ_C?H→σ_C?F*; F^δ?…?N⁺). Consequently, one of the shielding groups on the fluorine‐bearing carbon atom is positioned above the π‐system, forming the basis of an enantioinduction strategy. Treatment of this intermediate with a “nitrene” source furnished a series of novel, optically active aziridines (e.r. up to 99.5:0.5). Further derivatisation of the product aziridines gives facile access to various amino acid derivatives, including β‐fluoroamino acids. Crystallographic analyses of both the aziridines and their derivatives are disclosed.