Computational Investigations of Transition Metal Based Catalyzed Organic Transformations

Abstract

Chapter one provides a comprehensive overview of transition metal complexes, with a focus on the catalytic roles of iron complexes in reaction mechanisms, particularly oxidation reactions mediated by Fe(IV)O species, including non-heme variants. It reviews relevant literature on biologically inspired enzymes and biomimetic complexes, discussing key concepts like Two-State Reactivity and electron/proton transfer mechanisms. The chapter also examines the impact of ligand and metal substitutions on Fe-oxo reactivity, highlighting the role of carboxylate-rich macrocycles and mediators. It identifies key gaps in the current literature, with particular attention to recent advancements in the field. These insights are critical for guiding the rational design of next-generation catalysts that aim to improve performance and selectivity. The chapter concludes by outlining the objectives of the current research, which seeks to address these identified gaps. Chapter two introduces the core principles and methods of computational chemistry, starting with quantum mechanics and the Schrödinger equation. It covers approximations like the Born-Oppenheimer and Hartree-Fock methods, addressing their limitations in electron-electron correlations. The chapter also explores post-Hartree-Fock methods and Density Functional Theory (DFT), highlighting its balance between efficiency and accuracy. Key computational tools, such as Gaussian 16 for geometry optimization and Chemcraft for molecular visualization, are discussed. The chapter lays the foundation for understanding computational chemistry techniques used in the research, setting the stage for further exploration. Chapter three presents a DFT study on C–H activation reactivity and quantum mechanical tunneling in catalysis by a non-heme iron(IV)-oxo complex, [FeIV(O)(dpaq-X)]+. The study incorporates solvent and counter-ion corrections to eliminate self-interaction errors. The dpaq ligand was modified at the 5-position of its quinoline moiety, resulting in dpaq-X, and its reactivity was compared with the original dpaq-H. Various electron-donating (e.g., –N(CH3)2, –OMe) and electron-withdrawing (e.g., –NO2, –SO2CF3) substituents were studied. The reactions favored two-state reactivity (TSR), with the S = 2 state crossing the S = 1 path during the reaction. This was confirmed by the tunneling-corrected kinetic isotope effect (KIE), which matched experimental data for the S = 2 state. Over 90% of C–H activation reactions proceeded via quantum mechanical tunneling at room temperature. More electron-donating groups increased tunneling contributions and KIE, supporting the anti-electrophilic tunneling control reactivity hypothesis. These results suggest the potential for designing metal-based catalysts by tuning ligands and substituents to optimize catalytic efficiency through tunneling effects. Chapter four presents a DFT study comparing the C–H activation reactivity of high-valent iron-oxo and ruthenium-oxo complexes, focusing on four compounds: [Ru(IV)O(tpy-dcbpy)] (1), [Fe(IV)O(tpy-dcbpy)] (1'), [Ru(IV)O(TMCS)] (2), and [Fe(IV)O(TMCS)] (2'). The tpy-dcbpy macrocycle framework includes 2,2':6’,2’’-terpyridine, and 5,5’-dicarboxy-2,2’-bipyridine, while TMCS is TMC with an axially tethered –SCH2CH2 group. Compounds 1 and 2' are experimentally synthesized, and 1' and 2 maintain the macrocycle integrity with different metal centers. Three substrates—dihydroanthracene, benzyl alcohol, and ethyl benzene—were used for C–H activation. Fe(IV)O complexes showed greater reactivity than Ru(IV)O complexes, and the tpy-dcbpy macrocycle exhibited higher reactivity than TMCS, regardless of the metal. The study examined factors influencing reactivity, including spin state, steric effects, distortion energy, electron acceptor orbital energy, and quantum mechanical tunneling. Fe(IV)O complexes displayed enhanced two-state reactivity with a quintet state, while Ru(IV)O complexes had only a triplet state. Fe(IV)O also had lower acceptor orbital and distortion energies, supporting its increased reactivity. Hydrogen tunneling contributed significantly to C–H activation, especially for Ru, though it did not change the reactivity trend. The study concluded that enzymes prefer Fe over Ru as a cofactor for C-H activation due to these reactivity differences. Chapter five presents a DFT analysis of the impact of a carboxylate-rich macrocycle on the reactivity of a non-heme Fe(IV)O complex in C–H activation. The study uses the non-heme iron oxo complex [FeIV(O)(N4Py)]2+ (1) as the base compound, which is modified to form [FeIV(O)(nBu-P2DA)] (2) by replacing two pyridine donors with carboxylate groups. Two other complexes (3 and 4) are modeled with progressively more carboxylate groups. The study finds that the reactivity increases with more carboxylate groups (1 < 2 < 3 < 4), aligning with experimental results for complexes 1 and 2. Factors affecting reactivity include spin inversion, available space for the abstractor, deformation energies, and the electrophilicity of the metal center. Hydrogen tunneling plays a role but doesn’t significantly alter the reactivity trend. The findings suggest that incorporating more carboxylate groups could inspire the development of more efficient oxidants with carboxylate-enriched ligated macrocyclic compounds. Chapter six presents a computational study on Fe(IV)O-catalyzed C–H activation, enhanced by N-hydroxy mediators. The analysis focuses on the Fe(IV)O complex [Fe(IV)-ON4Py]2+ (1) with mediators N-hydroxyphthalimide (NHPI) and N-hydroxyquinolinimide (NHQI), examining three substrates: ethylbenzene, cyclohexane, and cyclohexadiene. The results show that the mediators significantly improve reactivity, with complex 1 predominantly following the S = 1 pathway, as indicated by the primary H/D kinetic isotope effect. The cleavage of the NO−H bond is more favorable than C–H activation, explained by the slower self-exchange reaction rate for C–H bonds compared to O–H bonds. Aminoxyl radicals, more reactive than Fe(IV)O species, are quickly generated, reducing activation energy. The study aligns with the Bell-Evans-Polanyi principle, showing that the mediator route is preferred. NHQI is more efficient than NHPI, and the kinetic isotope effect supports the role of quantum mechanical tunneling. This study highlights the potential for developing more effective mediators, encouraging further exploration to improve metal-oxo complex reactivity.