title: Enantioselective aziridination of cyclic enals facilitated by the fluorine-iminium ion gauche effect.
abstract: 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 (σC-H →σC-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.
authors: Organisch-Chemisches Institut and Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany), Homepage: www.uni-muenster.de/Chemie.oc/gilmour.
authors: István Gábor
authors: IG
authors: Molnár
authors: Eva-Maria
authors: EM
authors: Tanzer
authors: Constantin
authors: C
authors: Daniliuc
authors: Ryan
authors: R
authors: Gilmour
mesh_terms: D001388:Aziridines / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D005461:Fluorine / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000737:chemistry; D055672:Static Electricity; D013237:Stereoisomerism
chemical_list: D001388:Aziridines; D007477:Ions; D011759:Pyrrolidines; D005461:Fluorine; C032519:pyrrolidine
keywords: aziridination; catalysis; enantioselectivity; fluorine; gauche effect; pre-organisation