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Enantioselective Aziridination of Cyclic Enals Facilitated by the Fluorine‐Iminium Ion Gauche Effect
Author(s) -
Molnár István Gábor,
Tanzer EvaMaria,
Daniliuc Constantin,
Gilmour Ryan
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303586
Subject(s) - iminium , enantioselective synthesis , chemistry , nitrene , pyrrolidine , fluorine , ion , substituent , diethylamine , carbamic acid , stereochemistry , medicinal chemistry , catalysis , organic chemistry
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.