Olefin epoxidation mechanism

As stated above, czs-stilbene is a frequently used substrate for the study of olefin epoxidation mechanisms [100] because of mechanistic information associated with the ratio of the cis- and frazzs-isomers in the stilbene oxide product. Catalytic f-BuOOH epoxidation of czs-stilbene was performed, with our Mn (Me2EBC)Cl2 catalyst, under and product analysis shows that czs-stilbene oxide contains 25 0.3% incorporation of from atmospheric 02 versus 1.7 0.3% in a control experiment using ordinary air, whereas frzzzzs-stilbene oxide contains 55.1 1% incorporation of O from O2 versus 2.6 1% incorporation in a control experiment. Similar incorporation ratios are expected for the cis- and frzzzzs-stilbene oxides if all epoxidation products result from only one reaction pathway and a single reactive intermediate. However, the incorporation of in czs-stilbene oxide (25 0.3%) is definitely different from that in frzzzzs-stilbene oxide (55.1 1%). This result leads to the conclusion that, at least two distinct reactive intermediates occur in these epoxidation reactions. This is also consistent with the results described above for norbomylene epoxidation. 

From the energetics point of view, the epoxidation act should occur more easily (with a lower activation energy) in the coordination sphere of the metal when the cleavage of one bond is simultaneously compensated by the formation of another bond. For example, Gould proposed the following (schematic) mechanism for olefin epoxidation on molybdenum complexes [240] ... 

Mechanism of Olefin Epoxidation by Transition Metal Peroxo Compounds... 

During the last three decades, peroxo compounds of early transition metals (TMs) in their highest oxidation state, like TiIV, Vv, MoVI, WV1, and Revn, attracted much interest due to their activity in oxygen transfer processes which are important for many chemical and biological applications. Olefin epoxidation is of particular significance since epoxides are key starting compounds for a large variety of chemicals and polymers [1]. Yet, details of the mechanism of olefin epoxidation by TM peroxides are still under discussion. 

An important finding is that all peroxo compounds with d° configuration of the TM center exhibit essentially the same epoxidation mechanism [51, 61, 67-72] which is also valid for organic peroxo compounds such as dioxiranes and peracids [73-79], The calculations revealed that direct nucleophilic attack of the olefin at an electrophilic peroxo oxygen center (via a TS of spiro structure) is preferred because of significantly lower activation barriers compared to the multi-step insertion mechanism [51, 61-67]. A recent computational study of epoxidation by Mo peroxo complexes showed that the metallacycle intermediate of the insertion mechanism leads to an aldehyde instead of an epoxide product [62],... 

An important improvement in the catalysis of olefin epoxidation arose with the discovery of methyltrioxorhenium (MTO) and its derivatives as efficient catalysts for olefin epoxidation by Herrmann and coworkers [16-18]. Since then a broad variety of substituted olefins has been successfully used as substrates [103] and the reaction mechanism was studied theoretically [67, 68, 80]. 

For the model olefin ethene, we again investigated various epoxidation mechanisms (Figure 7) [67]. As before for the group VI metals, insertion was found to exhibit significantly higher activation barriers. 

The first quantum-chemical investigation of the mechanism of olefin epoxidation in flnoroalcohols was carried out by Shaik et al. [54], In the absence of kinetic data, a monomolecular mode of activation by the fluorinated alcohols for aU reaction pathways was assnmed [54],... 

We point out that the mechanism sketched in path A of Scheme 11 is in agreement with the kinetic and spectroscopic data collected from several research groups. On the other hand, a series of contradictions was encountered in fitting the experimental data into the mechanism proposed in path B. Furthermore, several other papers have appeared in the last decade, based on both experimental results and theoretical calculations, supporting an epoxidation mechanism involving a direct oxygen atom transfer to olefins. For selected examples, see References 34, 145-155. 

Mechanism. The following types of evidence ere pertinent in selecting on acceptable mechanism for olefin epoxidation by means of peroxy acids (1) the nature of the peroxy acid and the electronic effect of eubBtituents on its reactivity (2) the electronic effect of substituents on the reactivity of the olefin component (3) stereochemical factors affecting the reactivity of the olefin (4) the possibility of acid dialysis (5) solvent effects and (6) neighboring group effects. 

The most common method for the epoxidation of imines is the peracid203-205 and oxone206-210 oxidation. Two mechanisms have been put forward the concerted mechanism (analogous to an olefin epoxidation) and the two-step mechanism proceeding through an intermediate. On the basis of recent investigations the latter mechanism seems to be more likely (equation 40)204,208,211. 

In fact, the mechanism of olefin epoxidation by alkylperoxy radicals accepted in the literature is generally presented by the following scheme [143] ... 

As observed from reaction (6.19) and experimental data [41,120,121], ROOH satisfactorily replaces molecular oxygen and the reducer. When oxidized with hydroperoxides in the presence of iron porphyrin catalysts (cytochrome P-450 analogs), olefins mostly convert to allyl oxidation products, namely unsaturated alcohols and ketones, whereas the quantity of epoxides does not exceed 1% [122], According to current suggestions [121] such behavior of iron porphyrin catalysts is explained by olefin epoxidation with the cata-lyst-ROOH complex by the heterolytical mechanism according to the following equation ... 

Aromatic hydrocarbons are subject to cytochrome P-450-catalyzed hydroxylation in a process that is similar to olefin epoxidation. As discussed in Section IV. G, halogen migration observed during the hydroxylation of 4-ClPhe and similar substrates, led to the discovery of a general mechanism of oxidation that invokes arene oxide intermediates and the NIH shift. Arene oxides and their oxepin tautomers have not been isolated as products of metabolism of benzenoid compounds, but their presence has been inferred by the isolation of phenols, dihydrodiols and dihydrophenolic GSH conjugates derived therefrom262. 

The compehtion of one-electron pathways is sometimes detectable in the epoxidations catalyzed by transition metal catalysts [67]. However, in the epoxidahon of unhindered olefins on TS-1, the typical radical products are below the detection limits. Their presence could no longer be neglected when the rate of epoxidation is so slow as to become comparable to that of homolytic side reactions, for example with bulky olefins (see also Section 18.11). It is possible that, within these limits only, the epoxide is produced in part through the addition of a radical peroxy intermediate to the double bond [68, 69]. Even so, a homolytic pathway has again been proposed as a generally vahd epoxidation mechanism [7]. 

The number of metal zeolites and their application to the epoxidation of olefins rose in parallel from the late 1980s. TS-2, Ti,Al-P, Ti-P, Ti-MWW and, rarely, Ti-MOR are catalysts that have been studied in some detail [7-9, 35, 77-84]. TS-2 behaves, according to the few studies published, similarly to TS-1. The greater spaciousness of pores in Ti-Beta zeolites and of external cups in Ti-MWW allows the epoxidation, under mild conditions, of olefins unable to diffuse in TS-1 and TS-2, such as methylcyclohexenes, cyclododecene, norbornene, camphene and methyl oleate [80-83]. Steric constraints still prevail over electronic factors, however, as in medium pore Ti-zeolites, even in the epoxidation of linear olefins (Table 18.9). It is generally believed that active sites and epoxidation mechanisms are not significantly different from those of TS-1. 

Figure 9. Epoxidation mechanism proposed by Bartlett (53). The cis-olefin gives rise to a cis-epoxide.

Yudanov, I. V., Gisdakis, P., Di Valentin, C., Rosch, N. Activity of peroxo and hydroperoxo complexes of Ti(IV) in olefin epoxidation. A density functional model study of energetics and mechanism. Eur. J. Inorg. Chem. 1999, 2135-2145. 

Mechanism of olefin epoxidation catalyzed by cytochrome P450 enzymes 04CRV3947. 

Although, as stated above, olefin epoxidation is commonly referred to as an electrophilic oxidation, recent theoretical calculations suggest that the electronic character of the oxygen transfer step needs to be considered to fully understand the mechanism [451]. The electronic character, that is, whether the oxidant acts as an electrophile or a nucleophile is studied by charge decomposition analysis (CDA) [452,453]. This analysis is a quantitative interpretation of the Dewar-Chatt-Dimcanson model and evaluates the relative importance of the orbital interactions between the olefin (donor) and the oxidant (acceptor) and vice versa [451]. For example, dimethyldioxirane (DMD) is described as a chameleon oxidant because in the oxidations of acrolein and acrylonitrile, it acts as a nucleophile [454]. In most cases though, epoxidation with peroxides occurs predominantly by electron donation from the 7t orbital of the olefin into the a orbital of the 0-0 bond in the transition state [455,456] (Fig. 1.10), so the oxidation is justifiably called an electrophilic process. 

D. V. Deubel, G. Frenking, P. Gisdakis, W. A. Herrmann, N. Rosch, J. Sundermeyer, Olefin epoxidation with inorganic peroxides, solutions to four long-standing controversies on the mechanism of oxygen transfer, Acc. Chem. Res. Zl (2004) 645. 

P. Gisdakis, 1. V. Yudanov, N. Rdsch, Olefin epoxidation by molybdenum and rhenium peroxo and hydroperoxo compounds A density functional study of energetics and mechanisms, Inorg. Chem. 40 (2001) 3755. 

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