C–H & O–H Bond Activation by High-valent Fe-bTAML Complexes

Kuiry, Himangshu (2025) C–H & O–H Bond Activation by High-valent Fe-bTAML Complexes. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Himangshu Kuiry (18RS108)) 18RS108.pdf - Submitted Version Restricted to Repository staff only Download (12MB)

Abstract

The functionalization of alkanes via C–H bond activation holds considerable industrial and environmental relevance. Despite this importance, C(sp³)–H bonds are inherently challenging to activate due to their high bond dissociation enthalpies (~100 kcal mol⁻¹), they lack coordinating atoms within the hydrocarbon framework, and exhibit only minor differences in bond dissociation energies among various C–H bonds in the molecule. Nature has evolved to perform such transformations by employing various heme and non-heme-based metalloenzymes under ambient conditions. Replicating such efficiency in synthetic systems, however, has long remained a formidable task. Inspired by these natural enzymes, researchers have devoted extensive efforts to designing artificial catalysts capable of performing similar transformations. Over the years, substantial progress has been made, particularly with heme and non-heme iron and manganese-based complexes incorporating ligand frameworks such as porphyrin, TPP, TMC, and TAML. Nonetheless, only a limited number of catalytic platforms can effectively target and activate strong C–H bonds. For many of these systems, the proposed mechanism involves hydrocarbon oxidation through an initial hydrogen atom abstraction (HAA) step. As a result of extensive exploration by Mayer and others, we have a well-developed understanding of the factors that drive HAA reaction at high-valent oxidants according to the thermodynamic square scheme. In the case of prototype Mn(O) complexes, the feasibility of C–H activation is dictated by the thermodynamic strength of the O–H bond formed in the corresponding Mn⁻¹-OH species generated after HAA. Literature indicates that the BDE of O–H bonds in Mn⁻¹-OH complexes can reach up to ~90-95 kcal mol⁻¹, suggesting that most current metal-oxo intermediates remain too sluggish oxidants for cleaving stronger C–H bonds. In literature, instead of metal-oxo, a handful of other metal complexes bearing diverse functional groups (Mn–X, X= F, Cl, NO3, etc) have been found to promote both C–H and O–H bond activation. Similar to metal-oxo systems, the outcome of the hydrogen atom abstraction (HAA) process in these complexes is largely determined by the bond dissociation energy (BDE) of the X–H bond generated in the product. This limitation prompted us to explore alternative complexes (Mn–X) that can activate such strong C–H bonds under optimized reaction conditions and to investigate their hydrogen atom abstraction (HAA) mechanisms. In contrast, such synthetic metal-oxo complexes are generally restricted to oxygenation reactions of organic substrates, whereas in nature, related metal complexes participate in a variety of functionalization processes, including chlorination, azidation, bromination, and other transformations. These insights highlight the need for further investigation into hydrogen atom abstraction processes of the existing metal-oxo intermediate, and exploring their potential in different types of C–H functionalization. Chapter I includes a comprehensive literature survey highlighting the significance of C–H bond functionalization, the inherent challenges in C–H bond activation, and the remarkable efficiency and selectivity with which nature achieves this transformation. The discussion further explores the underlying processes and the key factors that can be tuned to influence the outcomes of C–H bond functionalization reactions mediated by both metal–oxo and non–oxo complexes. Chapter II discusses the hydrogen atom abstraction reaction of O–H and C–H bonds by an alternative non-oxo high valent iron-fluoride complex [FeIV(F)-(PhMe)bTAML]-. The high-valent Fe(IV)–F complex was generated from [FeIII(F)–(PhMe)bTAML]²⁻ by oxidation with Magic Blue–PF₆ in DCM at room temperature. Both complexes were thoroughly characterized using UV–vis, EPR spectroscopy, mass spectrometry, EXAFS, and Mössbauer spectroscopy. Kinetic studies and product analyses revealed a potential-driven hydrogen atom transfer (HAT) mechanism in the oxidation of phenols and hydrocarbons. It was also observed that the analogous [FeIV(Cl)-(PhMe)bTAML]⁻ complex was completely unreactive toward hydrogen atom transfer (HAT) of O–H and C–H bonds. In contrast, the [FeIV(F)-(PhMe)bTAML]⁻ complex exhibited a significantly higher reactivity, driven by its high pKa value (pKa > 16) and the favourable formation of HF (BDE ≈ 135 kcal mol⁻¹) as the product. Chapter III discusses the synthesis of two high-valent FeIV–cyanide complexes: a five-coordinated [FeIV(CN)(bTAML)]⁻ and a six-coordinated [FeIV(CN)2(bTAML)]²⁻ complex. Both were comprehensively characterized using UV-Vis, EPR, IR spectroscopies, and mass spectrometry, along with single-crystal X-ray diffraction (SC-XRD). These complexes exhibited the ability to oxidize O–H bonds in a range of phenols and C–H bonds in various hydrocarbons at room temperature. Notably, the six-coordinated complex showed significantly enhanced (~250 times higher) hydrogen atom abstraction (HAA) reactivity compared to its five-coordinated counterpart. Kinetic isotope effect (KIE) measurements revealed a substantial KIE of ~13, confirming that HAA is the rate-limiting step. Hammett analysis of both complexes yielded positive ρ values, indicating that the basicity of the complex plays a key role in facilitating HAT. Interestingly, no correlation was found between ln(k2) and either the bond dissociation energy (BDE) or redox potential (E) of the substrates. However, an inverse relationship was observed between ln(k2) and the pKa of the substrates, suggesting that the HAA mechanism in these high-valent Fe-CN complexes is primarily pKa-driven HAT. Chapter IV discusses the manipulation of the HAA and rebound step of the hydroxylation reaction by [FeV(O)-(NO₂)bTAML]⁻ complex to tune the halogenation reaction of a wide variety of substrates. This study investigates the reaction intermediates, kinetics, and mechanism of the halogenation reaction mediated by [FeV(O)-(NO₂)bTAML]-. The observation of rearranged chlorinated products in norcarane and the lack of stereoretention in cis-dimethylcyclohexane indicate the involvement of a long-lived, cage-escaped carbon radical intermediate. UV–Vis and EPR spectroscopic analyses confirm [FeV(O)–(NO2)bTAML]⁻ as the reactive species. Furthermore, the observed 3°:2° selectivity in hydrocarbons, the kinetic isotope effect (KIE), and the product distribution collectively point to hydrogen atom abstraction (HAA) by [FeV(O)–(NO2)bTAML]⁻ as the rate-determining step. Chapter V includes the use of PCET (HAA) reaction for the formation of FeV(O) for the selective oxidation of alcohols to their corresponding aldehydes/ketones using a biomimetic iron complex, [FeIII(OH₂)-bTAML]⁻, as the redox mediator using water as an oxygen source. Mechanistic studies show the involvement of a high-valent FeV(O) species, [FeV(O)-bTAML]⁻ formed via PCET (overall 2H⁺/2e⁻) from [FeIII(OH⁻)-bTAML]⁻ at 0.77 V (vs Fc⁺/Fc). Moreover, electrokinetic studies for the oxidation of C–H bonds indicate a second-order reaction with the C–H abstraction by FeV(O) being the rate-determining step. The overall mechanism, studied using linear free energy relationships and radical clocks, indicates a “net hydride” transfer leading to the oxidation of the alcohol to the corresponding aldehyde.

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