Through the Looking Glass: NMR Spectroscopy and Computational Analysis Synergize in Unraveling Dynamic Chiral Recognition Phenomena

This dissertation explores how small energetic differences drive chiral recognition, using advanced nuclear magnetic resonance spectroscopy (NMR) techniques, mass spectrometry, kinetic isotope effects and computational chemistry. It addresses three main areas: the origins of enantioselectivity in a peptide-catalyzed reaction, unusual stereochemical pathways in a transition-metal-catalyzed allylic alkylation, and new benzene-1,3,5-tricarboxamides (BTA)-based alignment media for improved enantiodiscrimination. Project A reveals the mechanistic basis of a highly selective peptide-catalyzed kinetic resolution, showing that both binding strength and catalyst dynamics contribute to enantioselection and that solvent effects arise from a balance of binding and reaction rates. Project B explains unusual stereoselectivity in palladium-catalyzed allylic alkylation of cyclobutenes, demonstrating that ligand choice controls product configuration through a novel stereoconvergent mechanism and distinct nucleophilic attack pathways. Project C investigates modular BTA-based liquid-crystal alignment media that enhance enantiodiscrimination in residual dipolar coupling (RDC)-based structure analysis. Together, these studies deepen the understanding of chiral recognition and provide new tools for stereochemical analysis and insight into asymmetric synthesis.