Development of charged octahedral metal complexes for chiral NMR analysis

Abstract

The growing importance of chiral compounds in synthetic, medicinal, and biological chemistry continues to advance the search for efficient and practical methods for chiral analysis. This thesis describes various chiral NMR analysis using charged octahedral metal complexes as chiral solvating agents. In chapter 1, a gallium-based anionic complex is developed for 1H NMR chiral analysis of alcohol compounds. This analytical method is further used to rapidly determine enantiomeric excess and conversion in a kinetic resolution and an asymmetric synthesis. Chapter 2 introduces a cationic cobalt complex as an efficient 1H NMR chiral solvating agent working for carbonyl compounds including esters, amides, ketones, and aldehydes. In chapter 3, a combined experimental and computational study is reported to understand the chiral recognition process of cationic cobalt complexes with carbonyl compounds. The tetradentate N2O2 ligand controls the metal-center chirality, and the bidentate diamine ligand plays an important role in the chiral discrimination of carbonyl compounds. Chapter 4 demonstrates chiral analysis of fluorine-containing compounds using 19F NMR spectroscopy. The highly sensitive 19F NMR with a broad range of chemical shift allows simultaneous chiral analysis of multianalyte solution. Lastly, in chapter 5, an in situ fluorine-labeling protocol is developed for an efficient chiral 19F NMR analysis of amines and alcohols without fluorine group. Moreover, structure-dependent 19F NMR signals enables determination of absolute configuration.