Rosmara Mansueto

Nitrogen Dynamics and Reactivity of Chiral Aziridines: Generation of Configurationally Stable Aziridinyllithium Compounds

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.

Nitrogen Stereodynamics and Complexation Phenomena as Key Factors in the Deprotonative Dynamic Resolution of Alkylideneaziridines: A Spectroscopic and Computational Study

The present work is aimed at shedding light on the origin of the stereoselectivity observed in the reactions of chiral heterosubstituted organolithiums, generated by lithiation of alkylideneaziridines. Factors such as the nitrogen inversion barrier, the stereochemistry at the nitrogen atom, the substitution pattern of the alkylideneaziridines, and the reaction conditions are taken into consideration. The interplay between nitrogen stereodynamics and complexation phenomena seems to be crucial in determining the stereochemical outcome of the lithiation/trapping sequence. The findings were rationalized by a synergistic use of NMR experiments, run on the lithiated intermediates, alongside computational data. It has been demonstrated that, in such systems, the stereochemistry-determining step is the deprotonation reaction, and a model based on a deprotonative dynamic resolution has been proposed. Such findings could find application in dynamic systems other than aziridines.

Lithiated oxazolinyloxiranes and oxazolinylaziridines: key players in organic synthesis

Abstract This paper focuses on α-lithiated oxazolinyloxiranes and oxazolinylaziridines, their generation, reactions, and synthetic applications. The ability of the oxazoline ring in providing stabilization to such α-heterosubstituted carbanions either through electronic effects and coordinative action has been stressed as well as the contribution to the configurational stability or instability of such species. IR spectroscopic data, multinuclear NMR investigations, and ab initio calculations planned to get insights on chemical properties and structural features have been carried out. A number of new reactions including alkylations, addition reactions, hydroxyalkylations, cyclopropanations, lactonizations, and rearrangements have been discovered, giving access to a variety of substances including: aziridinolactones, epoxylactones, aryl alkanones, polysubstituted cyclopropanes, cyclopropanefused lactones, dihydro-oxazoloisoquinolines, diversely functionalized oxazolines, and products that can be derived from them by synthetic elaboration.