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 -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 (sigma(C-H)sigma(C-F)*; F-...N+). Consequently, one of the shielding groups on the fluorine-bearing carbon atom is positioned above the -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 -fluoroamino acids. Crystallographic analyses of both the aziridines and their derivatives are disclosed.