Enantioselective aziridination of cyclic enals facilitated by the fluorine-iminium ion gauche effect

Chemistry : a European Journal
István Gábor MolnárRyan Gilmour

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.

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Citations

Feb 18, 2016·Chemical Reviews·Liang HongRui Wang
Jul 12, 2016·The Journal of Organic Chemistry·Eddy I JiménezMarcos Hernández-Rodríguez
Oct 28, 2016·Chemistry : a European Journal·Felix ScheidtRyan Gilmour
Mar 11, 2017·Organic & Biomolecular Chemistry·Shelli A MillerNicholas E Leadbeater
Dec 2, 2014·Chemical Communications : Chem Comm·M C HollandR Gilmour
Jul 30, 2014·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Eva-Maria Tanzer
Sep 20, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Carles Rodríguez-Escrich, Miquel A Pericàs
Feb 24, 2015·Angewandte Chemie·Mareike C Holland, Ryan Gilmour
Jan 30, 2021·Chemistry : a European Journal·Rajarshi MondalZackaria Nairoukh
Jun 13, 2018·Accounts of Chemical Research·Marialuisa Aufiero, Ryan Gilmour
Sep 2, 2017·Organic Letters·Sebastian FrankowskiŁukasz Albrecht
Jun 8, 2019·The Journal of Organic Chemistry·Shea L Johnson, Michael K Hilinski

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