Peroxo intermediates

AH of the commercial inorganic peroxo compounds except hydrogen peroxide are described herein, as are those commercial organic oxidation reactions that are beheved to proceed via inorganic peroxo intermediates. Ozonides and superoxides are also included, but not the dioxygen complexes of the transition metals. 

Transition-metal-catalyzed oxidations may or may not proceed via peroxocomplexes. Twelve important industrial organic oxidation processes catalyzed by transition metals, many of which probably involve peroxo intermediates, have been tabulated (88). Even when peroxo intermediates can be isolated from such systems, it does not necessarily foUow that these are tme intermediates in the main reaction. 

Likewise, within mechanism B, the /r-peroxo intermediate may be susceptible to reversible one-electron reduction to anionic [(dipor)Co202], which may become important only at potentials <0.5 V. There is some indication that the formally peroxo adducts, [(dipor)Co2 02 )], formed by addition of O2 to fully reduced (dipor)Co2, may undergo reversible reduction. Protonation of the anionic species may be followed by its hydrolysis, releasing H2O2. 

The latter binding mode has been observed for oxyhemocyanin (77) and in a dicopper(II) peroxide complex (78). Figure 2 illustrates structures for the peroxo intermediate which are most compatible with its spectroscopic parameters, as well as another, less likely, possibility (51). 

Fig. 2. Possible structures for a diiron(III) peroxide unit in the peroxo intermediate consistent with available Raman and Mossbauer spectroscopic data. The symbols N and 0 designate nitrogen and oxygen donor atoms of histidine and glutamate residues, respectively. Some of the latter must be bidentate to fill the coordination spheres.

Fig. 3. Proposed routes for conversion of the peroxo intermediate to intermediate Q, one involving loss of water (left-hand side) and one not (right-hand side). In the former case the resulting diiron(IV) oxo species could bind an oxygen atom with one iron, or the oxygen could be bound symmetrically by both iron atoms. Although written as an iron(IV) oxo species, Q can also be formulated as an iron(III) oxyl radical complex (35,51).

Fig. 4. Substrate first binds to the complete system containing all three protein components. Addition of NADH next effects two-electron reduction of the hydroxylase from the oxidized Fe(III)Fe(III) to the fully reduced Fe(II)Fe(II) form, bypassing the inactive Fe(II)Fe(III) state. The fully reduced hydroxylase then reacts with dioxygen in a two-electron step to form the first known intermediate, a diiron(III) peroxo complex. The possibility that this species itself is sufficiently activated to carry out the hydroxylation reaction for some substrates cannot be ruled out. The peroxo intermediate is then converted to Q as shown in Fig. 3. Substrate reacts with Q, and product is released with concomitant formation of the diiron(III) form of the hydroxylase, which enters another cycle in the catalysis.

As a part of their ongoing investigations into the reaction of dioxygen with copper(I) complexes to identify copper-superoxo/peroxo intermediate species, Schindler and co-workers51-53 have also provided examples of a number of mononuclear copper(II) complexes (Table 1) (as well as copper(I) Section 6.6.4.2.1). 

Protein-[Fe24+02]4+ - —x Protein-[Fe26+022 ]4+ (peroxo intermediate) (3)... 

Phosphines offer the advantage of forming the strongest bonds to oxygen. In that sense their reactions should be most preferred. The steri-cally-encumbered reagent P(o-Tol)3 was oxidized slowly by this method. With 25 mM of the phosphine in air and 5% 25, only 10% (o-Tol)3PO was formed after 16 h. When 1.0 mM P(p-Tol)3 was also added at the start, then the yield of (o-Tol)3PO was 6.3 mM (25%) at the same time 1.0 mM (p-Tol3)PO (100%) was obtained. It is likely that the para isomer initiates formation of the peroxo intermediate more efficiently. 

In one family of experiments, a pair of phosphine reagents was used to evaluate the relative reactivities of PyO towards the peroxo intermediate. The reactivity ratio proved to be independent of the PyO used, consistent with the absence of the Py group in the intermediate. The most reactive phosphines were those with electron-donating substituents (57). 

Fig. 29. Geometry-optimized structure of the three stable Ti-peroxo intermediates (a) rj1-monodentate complex, (b) i72-bidentate complex, and (c) i71-02H2 complex [from Cora et al. (59)].

In a recent paper a detailed mechanistic study of this reaction was presented (108). The first step is the reversible binding of oxygen by forming a u-peroxo species. This intermediate reacts further via an irreversible step to the hydroxylated product. The kinetic measurements at high pressure were performed at -20°C, since at room temperature no peroxo intermediate can be observed. The forward reaction of the Cu(I) complex with oxygen is characterized by a strongly... 

The peroxo intermediate would then undergo iron (III) hydrolysis (Equations (19.4) and (19.5)) to give first the p-oxobridged Fe(III) dimer and then upon addition of another two molecules of H20, a protein-[Fe20(0H)2] species at the ferroxidase centre ... 

It is instructive to compare the properties of metal peroxo and alkyl (or hydro) peroxo groups for the case of Ti because experimental structures of both types are known [117, 119-121] and Ti compounds are catalysts for such important processes as Sharpless epoxidation [22] and epoxidation over Ti-silicalites [122], where alkyl and hydro peroxo intermediates, respectively, are assumed to act as oxygen donors. Actually, the known Ti(t 2-02) complexes are not active in epoxidation. [121-124] However, there is evidence [123] that (TPP)Ti(02) (TPP = tetraphenylporphyrin) becomes active in epoxidation of cyclohexene when transformed to the cis-hydroxo(alkyl peroxo) complex (TPP)Ti(OH)(OOR) although the latter has never been isolated. 

Fig. 5. Catalytic cycle of cytochrome P450. The substrate HR binds to the resting enzyme A to form intermediate B, which is reduced by one electron to form C and then reacts with dioxygen. The resulting ferric-peroxo intermediate D is reduced by one equivalent to form the transient oxyferrous intermediate E, which proceeds quickly to intermediate F with release of a molecule of water. F is designated Fe(V)=0 to indicate that it is oxidized by two equivalents greater than A and not to imply anything about the true oxidation state of the iron. Intermediate F then transfers an oxygen atom to the substrate to regenerate the resting enzyme. The peroxide shunt refers to the reaction of B with hydrogen peroxide to produce the intermediate F, which can then proceed to product formation.

Some of these ideas incorporating a pterin radical are outlined in Fig. 9. Here the pterin serves as an electron donor to the oxy intermediate to give the peroxy di-anion. The substrate, L-Arg, itself serves as the proton donor to the peroxo intermediate as proposed by Crane et al. (80), which is required for heterolytic cleavage of the peroxide 0—0 bond. The proton delivery machinery outlined in Fig. 9 could also help to explain why peroxide itself cannot support the conversion of L-Arg to N°-hydroxy-L-Arg (126). The reaction may require a potent base like... 

Fig. 20. A hypothetical model of one possible binding mode for a diatomic ligand to HO-1. Both Aspl40 and Argl36 should interact with a ligand via an ordered water molecule. Whether or not these residues are critical in an arid-base catalytic process or are simply used to sterically orient an iron-linked peroxo intermediate remains unknown.

Scheme 2 Formation of a niobium peroxo intermediate and subsequent reactions...

The obvious candidates for the two competing reactions are those shown in Eqs. (24) and (25). The mechanisms of the two reactions are probably similar, although it was not possible to show whether reaction 25 produced isobutene. The expected chemistry is shown in more detail in Eq. (32). In a less appealing possibility, the tentative peroxo intermediate would cleave homolytically to yield alkyl and alkoxyl radicals, a route that is thermodynamically much less favorable than reaction 32. 

McLain, J. L. Lee, J. Groves, J. T. Biomimetic oxygenations related to cytochrome P450 metal- and metal-peroxo intermediates, Biomimetic Oxidations Catalyzed by Transition Metal Complexes , Ed. Meunier, B. Imperial College Press London, 2000, pp. 91-169. 

In contrast, the sex pheromone of the female housefly is (Z)-9-tricosene, a hydrocarbon apparently formed by an oxidative decarboxylative process from a precursor aldehyde by an enzyme that requires NAD-PH and 02 and is apparently a cytochrome P450.140 Oxidative deformylation by a cytochrome P450 converts aldehydes to alkenes, presumably via a peroxo intermediate.117 Formation of an alkene by decarboxylation has also been proposed,141 but a mechanism is not obvious. 

Once again, the overall reaction is believed to involve two-electron oxidations to a ruthenium(IV) oxo species but in this case oxidation to a monomeric dioxoruthenium(IV) intermediate apparently takes place. Loss of 02 occurs via a peroxo intermediate (equations 95-98, equation 96 occurs stepwise).283 The need for the cis isomer is then obvious. Unfortunately, catalyst instability (only about 30 electrons can be transferred per molecule) means that this interesting system is not... 

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