Mechanistic Insights on the ortho-Hydroxylation of Aromatic Compounds by Non-heme Iron Complex: A Computational Case Study on the Comparative Oxidative Ability of Ferric-Hydroperoxo and High-Valent Fe^IV═O and Fe^V═O Intermediates

Abstract

ortho-Hydroxylation of aromatic compounds by non-heme Fe complexes has been extensively studied in recent years by several research groups. The nature of the proposed oxidant varies from Fe(III)-OOH to high-valent Fe(IV)═O and Fe(V)═O species, and no definitive consensus has emerged. In this comprehensive study, we have investigated the ortho-hydroxylation of aromatic compounds by an iron complex using hybrid density functional theory incorporating dispersion effects. Three different oxidants, Fe(III)-OOH, Fe(IV)═O, and Fe(V)═O, and two different pathways, H-abstraction and electrophilic attack, have been considered to test the oxidative ability of different oxidants and to underpin the exact mechanism of this regiospecific reaction. By mapping the potential energy surface of each oxidant, our calculations categorize Fe(III)-OOH as a sluggish oxidant, as both proximal and distal oxygen atoms of this species have prohibitively high barriers to carry out the aromatic hydroxylation. This is in agreement to the experimental observation where Fe(III)-OOH is found not to directly attack the aromatic ring. A novel mechanism for the explicit generation of non-heme Fe(IV)═O and Fe(V)═O from isomeric forms of Fe(III)-OOH has been proposed where the O···O bond is found to cleave via homolytic (Fe(IV)═O) or heterolytic (Fe(V)═O) fashion exclusively. Apart from having favorable formation energies, the Fe(V)═O species also has a lower barrier height compared to the corresponding Fe(IV)═O species for the aromatic ortho-hydroxylation reaction. The transient Fe(V)═O prefers electrophilic attack on the benzene ring rather than the usual aromatic C-H activation step. A large thermodynamic drive for the formation of a radical intermediate is encountered in the mechanistic scene, and this intermediate substantially diminishes the energy barrier required for C-H activation by the Fe(V)═O species. Further spin density distribution and the frontier orbitals of the computed species suggest that the Fe(IV)═O species has a substantial barrier height for this reaction, as the substrate is coordinated to the metal atoms. This coordination restricts the C-H activation step by Fe(IV)═O species to proceed via the π-type pathway, and thus the usual energy lowering due to the low-lying quintet state is not observed here.

Applications of density functional theory to iron-containing molecules of bioinorganic interest

“…Theoretical studies of such biomimetic models may not only identify the key elements that determine their chemical reactivities, but may also provide insight into intermediates and reactivities of parent enzymes (Shaik et al, 2007a; de Visser et al, 2013). To date, DFT calculations have been applied extensively to various types of non-heme iron species (Scheme 1) (Bassan et al, 2002, 2005a,b; Roelfes et al, 2003; Decker and Solomon, 2005; Kumar et al, 2005; Quinonero et al, 2005; Berry et al, 2006; Bernasconi et al, 2007, 2011; de Visser, 2006, 2010; Hirao et al, 2006a, 2008a,b, 2011; Rohde et al, 2006; Decker et al, 2007; de Visser et al, 2007, 2011; Johansson et al, 2007; Noack and Siegbahn, 2007; Sastri et al, 2007; Sicking et al, 2007; Bernasconi and Baerends, 2008, 2013; Comba et al, 2008; Dhuri et al, 2008; Fiedler and Que, 2009; Klinker et al, 2009; Wang et al, 2009a, 2013b; Cho et al, 2010, 2012a, 2013; Geng et al, 2010; Chen et al, 2011; Chung et al, 2011b; Seo et al, 2011; Shaik et al, 2011; Vardhaman et al, 2011; Wong et al, 2011; Ye and Neese, 2011; Gonzalez-Ovalle et al, 2012; Gopakumar et al, 2012; Latifi et al, 2012; Mas-Ballesté et al, 2012; McDonald et al, 2012; Van Heuvelen et al, 2012; Ansari et al, 2013; Kim et al, 2013; Lee et al, 2013; Sahu et al, 2013; Tang et al, 2013; Ye et al, 2013; Hong et al, 2014; Sun et al, 2014). The intriguing reactivity patterns of these complexes are the result of active involvement of electrons in d-type MOs, which gives rise to multi-state scenarios (Shaik et al, 1998; Schröder et al, 2000; Schwarz, 2011).…”

Aromatic C–F Hydroxylation by Nonheme Iron(IV)–Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations

“…Both Fe IV (O) and Fe V (O) species were proposed as active oxidants in the absence of direct spectroscopic evidence. 6–20 …”

“…Calculations suggested that part of the reason for the low reactivity of triplet Fe IV (O) was because of steric clash between the incoming aromatic substrate and the equatorial ligands, which blocked access to the key π * acceptor orbitals on the Fe IV (O) unit. 6,7,25,32 …”

Iron-catalysed oxidation and halogenation of organic matter in nature

“…Specifically, an Fe II complex may be oxidised to Fe III and then coordinate H 2 O 2 . The resulting Fe III hydroperoxido complexes themselves are known to be strong oxidants [98] but may also produce ferryl species and OH radicals (homolytic cleavage of the O-O bond). [99,100] Moreover, coordination of H 2 O 2 to the Fe II precursor and subsequent homolytic cleavage of the O-O bond may lead to an Fe IV (OH) 2 complex, a tautomer of the reactive ferryl complex.…”