title: Stereocontrolled lithiation/trapping of chiral 2-alkylideneaziridines: investigation into the role of the aziridine nitrogen stereodynamics.
abstract: The origin of the stereoselectivity in the lithiation/trapping of 2-alkylideneaziridines bearing a chiral group as the nitrogen substituent was investigated. Optimal reaction conditions were discovered by in situ FT-IR monitoring. In addition, it has been found that the solvent and the alkene substitution pattern are important factors able to impart a switch in stereoselectivity. While lithiation of the alkylideneaziridine ring flanked by either a fully substituted or a Z-configured alkene pendant occurs stereoselectively in THF, in contrast unsubstituted 2-methyleneaziridine undergoes lithiation in toluene with the opposite sense of stereoinduction. Lithiation experiments, on deuterium labelled 2-alkylideneaziridines, confirmed the configurational stability of the lithiated intermediates. A model based on complexation and proximity effects was proposed to rationalize the reactivity. This model assumes that slowly equilibrating N-invertomers undergo deprotonation (lithiation) at different rates and that the stereochemical outcome is established during the deprotonation step.
authors.affiliation: Department of Pharmacy - Drug Sciences University of Bari "A. Moro", Via E. Orabona 4, 70125, Bari, Italy. renzo.luisi@uniba.it.
authors.forename: Rosmara
authors.initials: R
authors.lastname: Mansueto
authors.forename: Leonardo
authors.initials: L
authors.lastname: Degennaro
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Brière
authors.forename: Karen
authors.initials: K
authors.lastname: Griffin
authors.forename: Michael
authors.initials: M
authors.lastname: Shipman
authors.forename: Saverio
authors.initials: S
authors.lastname: Florio
authors.forename: Renzo
authors.initials: R
authors.lastname: Luisi
mesh_terms: D001388:Aziridines / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
chemical_list: D001388:Aziridines; C033132:aziridine; D008094:Lithium; D009584:Nitrogen