title: Nitrogen dynamics and reactivity of chiral aziridines: generation of configurationally stable aziridinyllithium compounds.
abstract: Diastereomeric oxazolinylaziridines (R,R)-9 and (R,S)-9 have been regioselectively lithiated at the α-position with respect to the oxazolinyl ring. The resulting aziridinyllithium compounds proved to be chemically and configurationally stable under the experimental conditions used, thus furnishing, upon trapping with electrophiles, chiral 2,2-disubstituted aziridines, in contrast to the corresponding α-lithiated oxazolinyloxiranes that have been reported to be chemically stable but configurationally unstable. This peculiar behavior of the nitrogen-bearing heterocycle has been rationalized on the basis of DFT calculations and the observed dynamics of the aziridine nitrogen atom. The DFT analysis allowed the disclosure of a solvent-dependent differing stability of diastereomeric lithiated aziridines (R,R)-9-Li and (R,S)-9-Li, suggesting η(3)-coordinated oxazolinylaziridinyllithium compounds as likely intermediates. Such intermediates could be the result of a dynamically controlled lithiation that relies on the preliminary formation of a complex between the lithiating agent and the oxazolinyl ring. According to this model, the competing complexation of the lithiating agent by the lone pair of electrons on the aziridine nitrogen would cause addition to the oxazoline C=N bond, thus ending up with the formation of oxazolidines, which are precursors of useful chiral ketoaziridines. The proposed model has been also supported by estimating the nitrogen inversion barrier by dynamic NMR spectroscopic experiments.
authors.affiliation: Dipartimento Farmaco-Chimico, University of Bari, Aldo Moro, Via E. Orabona 4, 70125-Bari, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Degennaro
authors.forename: Rosmara
authors.initials: R
authors.lastname: Mansueto
authors.forename: Elisa
authors.initials: E
authors.lastname: Carenza
authors.forename: Rosanna
authors.initials: R
authors.lastname: Rizzi
authors.forename: Saverio
authors.initials: S
authors.lastname: Florio
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pratt
authors.forename: Renzo
authors.initials: R
authors.lastname: Luisi
mesh_terms: D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001388:Aziridines; D009942:Organometallic Compounds; D010080:Oxazoles; C064210:oxazolidine; D008094:Lithium; D009584:Nitrogen