Design and Application of Chiral Aniline-Embedded Ligand Systems for Enantioselective Earth-Abundant Metal Catalysis

The development of sustainable catalytic methods based on earth-abundant metals has become increasingly important as an alternative to precious-metal catalysis in organic synthesis. In contrast to platinum-group metals, earth-abundant metals such as nickel, cobalt and iron are inexpensive, abundant, and attractive from both environmental and geopolitical perspectives. However, their broader application in asymmetric catalysis remains challenging because of their preference for single-electron pathways and their sensitivity to air, moisture, and oxidation state changes. In this thesis, ligand design was used as a central strategy to address these challenges and to develop enantioselective transformations catalyzed by nickel and cobalt complexes. The first part of this work describes the development of a nickel-catalyzed enantioselective [2+2+2] cycloaddition of diynes with heterocumulenes, including carbon dioxide and isocyanates, enabled by chiral N-heterocyclic carbene (NHC) ligands. This transformation provides direct access to chiral spirocyclic 2-pyrones and 2-pyridones, motifs of considerable relevance in medicinal and synthetic chemistry with high yield and enantioselectivity up to 99% yield and 96.5:3.5 er. Broad substrate scope was demonstrated for both heterocumulene and diyne partners, and the reaction was shown to be scalable without significant loss of efficiency or stereoselectivity. These studies establish a new enantioselective route to spirocyclic heterocycles. The second part of this thesis focuses on the development of cobalt-catalyzed enantioselective cyclopropanation of unactivated alkenes using dibromomethane as a safe methylene source. C2-symmetric chiral PDI ligands were designed from chiral aniline building blocks. The corresponding cobalt complexes were prepared and evaluated in the cyclopropanation reaction. We could optimize the reaction condition provided cyclopropane products up to 61% yield and 46% ee with possible inversion of stereoselectivity by ligand modification. Although the level of asymmetric induction remains moderate, this work shows the potential of chiral PDI ligands in enantioselective earth-abundant metal catalysis The third part of this thesis investigates an iron-catalyzed double [2+2+2] cycloaddition with the goal of developing an atroposelective and diastereoselective double [2+2+2] cycloaddition using chiral redox-active ligand frameworks. Inspired by Goswamiâ s Feâ dipimp system, chiral aniline-derived ligands were incorporated into iminopyridine to provide a chiral environment. Nevertheless, the chiral ligand was revealed to have no significant enantioinduction in this reaction system, and only moderate diastereoselectivity was observed, which was not improved using chiral ligands. Overall, this thesis highlights how rational ligand design can unlock new asymmetric reactivity in earth-abundant metal catalysis. By developing chiral NHC-supported nickel catalysis for heterocumulene [2+2+2] cyclo