Iron-based biomimetic oxidations

Fig ure 13.3 Biomimetic oxidation of organic compounds mediated by high-valent metal-oxo complexes. 

Regarding the iron coordination geometry, the most active catalysts exhibit two available cis-coordination sites that facilitate the activation of the oxidant. Conversely, relatively inactive complexes usually show only one available coordination site or have two available sites in a trans position. As stated before, iron-based enzymatic systems in nature involve the formation of high-valent metal intermediates within the catalytic cycle. Similarly, oxo-iron complexes have been proposed as the main intermediate for artificial oxidation processes. Depending on the iron complex, the type of oxidant and substrate and the mechanism involved in the oxidation process, this intermediate could be a Fe =0 or H0-Fe =0 species. Wieghard et al. 

Fe =0] using Mossbauer spectroscopy, and three years later Miinck, Nam and Que Jr. reported the first ciystal structure of a synthetic 

The catalytic activity of these oxo-Fe complexes has also been investigated in detail. For example, the first one isolated, [TMC-Fe =0] , displayed catalytic activity in the transfer of orygen towards triphenylphosphine (PhaP), yielding the corresponding phosphine oxide Ph3P=0. Other interesting iron-based catalytic processes are the oxidative M-deallylation of 

N-diall lamines and the oxidation of thioanisoles (SR2) to generate sulfoxides (R2SO)7  

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The development of more sustainable methodologies is of particular interest to afford carbonyl compounds with industrial and biological interest. In this context, iron-based alcohol oxidations may be of great use. Since cytochrome P450 was presented as an active catalyst in the synthesis of carbonyl compounds,biomimetic synthetic complexes have also been used in this context, e.g. TPA-Fe =0. In the proposed mechanism, the oxidation of the alcohol takes place via a-CH hydrogen-atom abstraction, followed by an electron transfer to yield the corresponding carbonyl compound and an iron(ii) complex that could be reoxidised toward the active catalytic species, L-0=Fe(iv) (Scheme 13.27). 

Clearly, while porphyrin complexes are obvious candidates for modelling these kinds of biomimetic oxidations, a range of non-heme iron complexes based on macrocyclic and podand ligand have also proved to be successful structural and functional mimics.19 To take one example, Figure 12.13 shows the X-ray structure of the iron (IV) tetramethylcyclam (tmc) oxo complex [Felv(tmc)(0)(MeCN)]2+... 

Iron porphyrins have been studied extensively over the past 30 + years as model systems of cytochrome P450.13 Biomimetic model studies included variants in axial ligands (thiolate and other bases), the oxidation of alkanes, olefins, sulfides, and amines, and utilization of several oxidants such as hypochlorite (bleach), iodoso-benzene (ArlO), hydrogen peroxide, and organic peroxides (ROOH). The first-generation models employed the mevo-tetraary I porphyrins (Figure 3.5). These were... 

A mild aerobic palladium-catalyzed 1,4-diacetoxylation of conjugated dienes has been developed and is based on a multistep electron transfer46. The hydroquinone produced in each cycle of the palladium-catalyzed oxidation is reoxidized by air or molecular oxygen. The latter reoxidation requires a metal macrocycle as catalyst. In the aerobic process there are no side products formed except water, and the stoichiometry of the reaction is given in equation 19. Thus 1,3-cyclohexadiene is oxidized by molecular oxygen to diacetate 39 with the aid of the triple catalytic system Pd(II)—BQ—MLm where MLm is a metal macrocyclic complex such as cobalt tetraphenylporphyrin (Co(TPP)), cobalt salophen (Co(Salophen) or iron phthalocyanine (Fe(Pc)). The principle of this biomimetic aerobic oxidation is outlined in Scheme 8. 

At least two systems can be cited as catalysts of peroxide oxidation the first are the iron (III) porphyrins (44) and the second are the Gif reagents (45,46), based on iron salt catalysis in a pyridine/acetic acid solvent with peroxide reagents and other oxidants. The author s opinion is that more than systems for stress testing these are tools useful for the synthesis of impurities, especially epoxides. From another point of view, they are often considered as potential biomimetic systems, predicting drug metabolism. Metabolites are sometimes also degradation impurities, but this is not a general rule, because enzymes and free radicals have different reactivity an example is the metabolic synthesis of arene oxides that never can be obtained by radical oxidation. 

A problem with the formation of the ternary ES—02 adduct is that it entails an attack of triplet 02 on the singlet substrate, which is a forbidden reaction. However, the presence of iron(III) may provide a mechanism for relaxing this barrier, as suggested by biomimetic studies showing that oxidative cleavage of catechols can be catalyzed by iron(III) centers [145,146], Building on this important early work, Que and coworkers synthesized a series of [Fe(L)(dbc)] complexes where L is a tetradentate tripodal ligand based on trimethylamine with... 

Other biomimetic reactions are based on the catalytic properties of metal ions. Many enzymes require metal ions that function, in one way or another, in oxidation-reduction processes. The wide range of such metal-ion reactions precludes mentioning more than a few in addition to the iron-porphyrin class, and in addition to chlorophyll, a number of enzymes require cobalamin as cofactor ferridoxin and high-potential iron proteins require iron-sulfur clusters, and nitrog-... 

Biomimetic Cu(II) and Fe(II) complexes with bis- and tris-pyridyl amino and imino thioether ligands and vacant (or potentially so) coordination positions (Fig. y are active as catalyst precursors for the solvent- and halogen-free MW-assisted oxidation of 1-phenylethanol by TBHP, in the presence of pyridazine or other N-based additives. Maximum TOF of 5220 h (corresponding to 87% yield) was achieved just after 5 min of reaction time under the low power MW irradiation. The same authors reported" the catalytic activity of related copper, iron, and vanadium systems with mixed-N,S pyridine thioether hgands. The Cu and Fe complexes proved to be useful catalysts in various MW-assisted alcohol oxidations with TBHP, at 80 °C. Thus, 5-containing ligands can also be used to create effective catalyst precursors. 

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