Oxygen Insertion Mechanisms

FIGURE 18. Nonsynchronous concerted mechanism for hydrocarbon oxidation. (From Newcomb et cd., 1995). 

The theoretical treatments of the MMO meehanism are based on high level quantum mechanical methods that form models of the diiron site in which the ligand geometry is built from X-ray erystallographie studies and other biophysieal techniques. The caleulations of Siegbahn and eoworkers based on density functional theory that were described briefly above led to 

FIGURE 19. Mechanism of hydrocarbon oxidation and racemization by formation of a 5-coordinate carbon intermediate. (Adapted from Shilov and Shteinman, 1999). 

Andersson, K. K., Elgren, T. E., Que, L., Jr., and Lipscomb, J. D., 1992, Accessibility in the active site of methane monooxygenase the first demonstration of exogenous ligand binding to the diiron center, J. Am. Chem. Soc. 114 871 ln8713. 

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A. Bravo, H. R. Bjprsvik, F. Fontana, F. Minisci, A. Serri, Radical versus "oxenoid" oxygen insertion mechanism in the oxidation of alkanes and alcohols by aromatic peracids. New synthetic developments, J. Org. Chem. 61 (1996) 9409. 

A theoretical study on the oxidation of methane, propane and isobutane with dioxirane, dimethyldioxirane, difluorodioxirane and methyl(trifluoromethyl)di-oxirane has provided a rational for the formation of radical intermediales when dioxygen is rigorously excluded and supported the generally accepted, highly exothermic, concerted oxygen insertion mechanism for the oxidation under typical preparative conditions. The activation barriers for the oxidation of methane (44.2), propane (30.3) and isohutane (22.4 kcal mol" ) with dimethyldioxirane have been evaluated [48e]. Perfluorodialkyloxaziridines are also mild and selective reagents for the hydroxylation of alkanes [49] ... 

The mechanism of aliphatic hydroxylation by cytochrome monoxygenases would appear to Involve a direct oxygen-insertion with retention of configuration. For exan le, when S-(+)-l- H-ethylbenzene was incubated with liver microsomes, the 1-phenylethanol produced in the reaction consisted of 92% of the R isomer and only 87. of the S isomer.83 pheno-barbital pretreatment diminished the stereoselectivity of this reaction. 63, 64 ihe reaction of the a a-dideutero-derivative exhibited an isotope effect of 1.8 when compared to the undeuterated substrate, consistent with an oxygen-insertion mechanism. In certain examples of aliphatic hydroxylation, however, it appears from the absence of an isotope effect with labeled substrates that the insertion reaction is not the rate-limiting step.85-67... 

During the insertion mechanism, the metal is inserted into the carbon-oxygen bond. The insertion is promoted by a strong metal—oxygen interaction. It is thought that unreduced metal ions may play an important role in the insertion mechanism (electrophilic catalysis). The type of the catalyst, the method of preparation, and the additives can influence the concentration and stability of these ions. 

This view is supported by the formation of alcohols and aldehydes, which is not possible via mechanism 1. For the formation of these oxygenates, insertion of CO is necessary. Therefore, several authors and first of all M. E. Dry26 proposed a combined mechanism where hydrocarbons are mainly formed via CH2 insertion and oxygenates via CO insertion. We extend this proposal by the assumption that hydrocarbons are also formed via CO insertion in the same way as oxygenates. 

Suggestive evidence for the protonation of diphenylcarbene was uncovered in 1963.10 Photolysis of diphenyldiazomethane in a methanolic solution of lithium azide produced benzhydryl methyl ether and benzhydryl azide in virtually the same ratio as that obtained by solvolysis of benzhydryl chloride. These results pointed to the diphenylcarbenium ion as an intermediate in the reaction of diphenylcarbene with methanol (Scheme 3). However, many researchers preferred to explain the O-H insertion reactions of diarylcarbenes in terms of electrophilic attack at oxygen (ylide mechanism),11 until the intervention of car-bocations was demonstrated by time-resolved spectroscopy (see Section III).12... 

Reinhold and Bruni studied the metabolism of 7,9-dideuterioellipticine (17) in rats and found that deuterium originally at position 9 was completely lost during the mammalian hydroxylation process (147). Proton and carbon-13 NMR and mass spectral analyses confirmed the complete elimination of deuterium at position 9, thus ruling out the occurrence of an NIH shift mechanism in the hydroxylation of ellipticine. An oxygen-insertion process was rationalized to account for the mechanism of aromatic hydroxylation in rats since this would not be expected to display the NIH shift but should demonstrate an isotope effect. It was... 

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],... 

The direct attack of the front-oxygen peroxo center yields the lowest activation barrier for all species considered. Due to repulsion of ethene from the complexes we failed [61] to localize intermediates with the olefin precoordinated to the metal center, proposed as a necessary first step of the epoxidation reaction via the insertion mechanism. Recently, Deubel et al. were able to find a local minimum corresponding to ethene coordinated to the complex MoO(02)2 OPH3 however, the formation of such an intermediate from isolated reagents was calculated to be endothermic [63, 64], The activation barriers for ethene insertion into an M-0 bond leading to the five-membered metallacycle intermediate are at least 5 kcal/mol higher than those of a direct front-side attack [61]. Moreover, the metallacycle intermediate leads to an aldehyde instead of an epoxide [63]. Based on these calculated data, the insertion mechanism of ethene epoxidation by d° TM peroxides can be ruled out. 

Density functional calculations reveal that epoxidation of olefins by peroxo complexes with TM d° electronic configuration preferentially proceeds as direct attack of the nucleophilic olefin on an electrophilic peroxo oxygen center via a TS of spiro structure (Sharpless mechanism). For the insertion mechanism much higher activation barriers have been calculated. Moreover, decomposition of the five-membered metallacycle intermediate occurring in the insertion mechanism leads rather to an aldehyde than to an epoxide [63]. 

Application of metal salts and well-defined metal complexes in ROP has enabled the exploitation of a three-step coordination-insertion mechanism, first formulated in 1971 by Dittrich and Schulz [17]. This proceeds through coordination of lactide by the carbonyl oxygen to the Lewis acidic metal center, leading to the initiation and subsequent propagation by a metal alkoxide species. This species can be either isolated or generated in situ by addition of an alcohol to a suitable metal precursor to result in the formation of a new chain-extended metal alkoxide, as shown in Scheme 3 [16]. 

Recent DFT calculations by Sarzi-Amade and his collaboratorsmay well have resolved this mechanistic difference between a biradicaloid TS (Scheme 7, path b) and a mechanism involving discrete long-lived free radicals (Scheme 8). Oxygen insertion into the C—H bond of isobutane by DMDO was studied computationally at the unrestricted B3LYP level. Transition structures that were diradicaloid in nature were found to lead to... 

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