Design and Synthesis of Iron and Ruthenium Catalysts with Metal-Centered Chirality for Asymmetric Catalysis

Chiral transition metal catalysts featuring metal-centered chirality, where chirality arises from a stereogenic metal center, have garnered significant attention in recent years, with numerous examples demonstrating exceptional catalytic performance. While this concept has predominantly been applied to noble metals due to their inherent configurational stability, this thesis focuses on the development and study of C2-symmetric chiral-at-metal iron(II) and ruthenium(II) catalysts as well as stereogenic-at-metal iron(II) catalysts. 3.1 Chiral-at-Iron Complexes and Ligand Tuning: This work explores how the electronic properties of N-heterocyclic carbene (NHC) ligands influence the configurational stability of chiral-at-iron complexes. Replacing imidazol-2-ylidene (nNHC) with benzimidazol-2-ylidene, which increases π-acceptor properties, yielded a highly robust chiral-at-iron catalyst. π-Acceptor properties were quantified using GANTER’s 77Se NMR method. This catalyst achieved asymmetric hetero-DIELS–ALDER reactions with excellent stereoselectivity (up to 98:2 dr and 94% ee) even under open-flask conditions. 3.2 Impact of MIC Ligands on Stability and Activity: Substituting nNHC with 1,2,3-triazol-5-ylidene (MIC) ligands, which exhibit enhanced σ-donor and reduced π-acceptor properties as determined via 77Se NMR, and 1J(C−H) coupling constant analysis, resulted in a labile stereogenic iron center. Unexpectedly, this more electron-rich complex exhibited superior catalytic activity in nitrene-mediated ring-closing C(sp3)−H amidation of benzoyloxyureas. These findings highlight the influence of ligand electronic properties on the activity of iron catalysts in nitrene transfer reactions. 3.3 Generation of Non-Racemic Iron MIC Complexes: To synthesize non-racemic iron MIC complexes, the pyridyl substituent was functionalized with a chiral pinene moiety, enabling the selective formation of a single stereoisomer upon ligand coordination. This pinene-modified iron MIC complex catalyzed the ring-closing C(sp3)−H amidation of benzoyloxyureas to 2-imidazolidinones, achieving an enantiomeric ratio of up to 92:8. 3.4 Stereogenic-at-Iron Complexes via Axially Chiral Ligands: Another strategy to achieve stereogenic-at-metal iron catalysts involved the introduction of axially chiral ligands into the coordination sphere. These ligands not only fixed the configuration of the iron center but also allowed for systematic tuning of electronic and steric properties, paving the way for enhanced catalytic design. 3.5 Chiral-at-Ruthenium Mesoionic Carbene Complexes A new class of C2-symmetric chiral-at-ruthenium(II) mesoionic carbene (MIC) complexes was developed, featuring strongly σ donating MIC ligands. These complexes exhibited enhanced catalytic activity for enantioselective intramolecular ring-closing C(sp3)−H amination of aliphatic azides, eliminating the need for a phosphine co-catalyst. This improvement is attributed to increased electron density at the ruthenium center, as confirmed by 99Ru NMR analysis. This electron-rich environment facilitated the cleavage of coordinated azides into N2 and ruthenium nitrene intermediates, which underwent highly stereoselective C(sp3)−H amination (up to 94% ee). Notably, the comparable enantioselectivity of ruthenium MIC and NHC catalysts is attributed to their similar geometries and steric environments at the active sites.