Oxenoid mechanisms

Hamilton674 proposed the oxenoid mechanism shown in Scheme 5 for both the model and enzymatic systems. (The iron-dioxygen complex is assumed to react as an oxenoid species and transfer an oxygen atom to the substrates S.)... 

The oxenoid mechanism implicates the insertion of an oxygen atom (oxenoid) across the C-H bond of the hydrocarbon (Hamilton et al., 1973). This mechanism is evidently energetically preferable, since it is accompanied by the formation of three bonds, two of which, O-H and C-O, are extremely strong and compensate the rupture of the relatively weak C-H and 0-0 bonds. The transition state, however, involves the formation of a three-membered ring with oxygen, whose formation is accompanied by a strain with an energy of about 30 kcal/mole. More over, the insertion of O to C-H or H-H bonds is a symmetrically forbidden process. 

Dioxiranes, generated by the oxidation of ketones with KHSOs, insert an oxygen atom into alkane C—H bonds with retention of configuration by an oxenoid mechanism related to that found for peracids. Tertiary C—H bonds are hydroxylated and react faster than secondary CH2 groups, which are completely oxidized to the ketone. Conversions of up to 50% have been observed." CF3(Me)C02 is a more recently developed reagent of the same type. These easily prepared reagents have considerable promise for organic synthesis. 

Hamilton suggested that the model systems (at least some of them) interact with the substrates via a so-called oxenoid mechanism similar to that of monooxygenase functioning. Since the reaction, in many aspects, parallels the processes with carbenes (addition to the multiple bond, insertion into the C-H bond), in the oxenoid mechanism an oxygen atom (oxene) inserts into the C-H bond without an intermediate formation of free radicals ... 

Two alternative mechanisms have been proposed for the crucial step of the oxidation process the oxenoid mechanism of direct oxygen atom insertion and the radical mechanism of C-H bond cleavage with subsequent recombination in the cage ( oxygen rebound radical mechanism) (Scheme XI.8). 

Later, by studying carefully the product patterns in the Udenfriend system and in a system in which hydrogen peroxide was reduced by the Fe /EDTA complex in the presence of ascorbate, it was postulated by Staudinger and Ullrich that besides hydroxyl radicals a second hydroxylation mechanisms must be present, which was characterized by a random distribution of phenolic products in contrast to the electrophilic pattern observed with OH radicals. This mechanism, called the oxenoid mechanism, was found in all systems consisting of autoxidizing metal ions, but hydroxyl radicals were usually the predominant hydroxylating species. 

The mechanism of aromatic hydroxylation is of special interest in view of its relevance to monooxygenase action. The "oxenoid" mechanism proposed by Hamilton involves the transfer of an oxygen atom from the active intermediate (an oxometal species) formed from the catalyst. This type of mechanism is supported by the NIH-shift, i.e, migration of an H-atom from the hydroxylation site to the adjacent position via an arene oxide intermediate. The NIH-shift has been observed in non-enzymatic hydroxylations, pointing to the involvement of oxometal species in various oxygenations (dehyrogenations). 

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