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Taming nitrogen stereogenicity: enantioselectivity control at a reluctant center
Darshini Ramachandran1, Akkattu T Biju1
1Department of Organic Chemistry, Indian Institute of Science Bangalore 560012 India atbiju@iisc.ac.in.
Abstract:
Nitrogen-centered chirality represents a compelling yet challenging frontier in stereochemistry, with broad implications in biologically active molecules and asymmetric synthesis. Unlike carbon stereocenters, isolation of stable nitrogen stereocenters is challenging due to their low pyramidal inversion barriers enabling rapid interconversion between the enantiomeric forms, thus obscuring nitrogen-centered chirality. Recent advances have highlighted the critical role of substituent effects in modulating the (de)stabilization of the pyramidal ground state and the planar transition state. The ability to manipulate the substituent effects has enabled the construction of both quaternary and trivalent nitrogen stereocenters. This Perspective aims to provide a comprehensive overview of the mechanistic principles, substrate design strategies, and synthetic methodologies, highlighting the recent progress and future opportunities in the field of nitrogen-centered chirality.
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