Unrevealing the nitrogen elusive chirality of 3-sulfanyl and 3-sulfinyl N-tosyl isoindolinones by ECD spectra: an experimental and theoretical investigation

Chemistry. 2024 Mar 18:e202400232. doi: 10.1002/chem.202400232. Online ahead of print.ABSTRACTThe nitrogen-hybridization/pyramidalization of two solvated N-tosylisoindolinone derivatives having chiral residues in adjacent (I) or adjacent and distal (II) position has been investigated by a theoretical-computational procedure based on Molecular Dynamics simulations and Quantum-Chemical calculations. After validation of our strategy in providing a reliable repertory of conformations through the modeling of the electronic circular dichroism (EDC) spectra, the electronic features associated with N-pyramidalization were further characterized by Natural Bond Order (NBO) analysis. Using the N-geometry found in crystal structures as a reference, our findings reveal that the presence of neighbouring chiral centers generates sharper N-pyramidalization in solution than in the solid state, both in I and II. Furthermore, although NBO analysis confirms that the N-lactam mostly retains the sp2 character, its slight configurational distortion (ξI = 13°; ξII = 21°) emerges significantly in the chiroptical activities exhibited by I and II in ECD spectra, thereby substantiating these N-lactams as configurationally stable chiral centers.PMID:38494944 | DOI:10.1002/chem.202400232

Source: Chemistry - March 18, 2024 Category: Chemistry Authors: Laura Palombi Marta Monti Erica Scarel Valerio Morlacci Mauro Stener Massimiliano Aschi Source Type: research