Hydrogen atom abstraction, radical-mediated

Iron complexes or microsomal nonheme iron are undoubtedly obligatory components in the microsomal oxidation of many organic compounds mediated by hydroxyl radicals. In 1980, Cohen and Cederbaum [27] suggested that rat liver microsomes oxidized ethanol, methional, 2-keto-4-thiomethylbutyric acid, and dimethylsulfoxide via hydrogen atom abstraction by hydroxyl radicals. Then, Ingelman-Sundberg and Ekstrom [28] assumed that the hydroxylation of aniline by reconstituted microsomal cytochrome P-450 system is mediated by hydroxyl radicals formed in the superoxide-driven Fenton reaction. Similar conclusion has been made for the explanation of inhibitory effects of pyrazole and 4-methylpyrazole on the microsomal oxidation of ethanol and DMSO [29],... 

An inner-sphere hydrogen atom abstraction from the alcohol by a peroxo metal complex, thus forming a coordinated ketyl radical [(CH3)2—C —O—V(0)(00H)]" , has been proposed for the aerobic oxidation of alcohols catalyzed by peroxidic molybdenum and vanadium derivatives (Scheme 16). While in the case of Mo-catalyzed reaction the H2O2 produced is quantitatively converted to products (ketone and H2O), in the vanadium mediated process, hydrogen peroxide accumulates . In this latter case, the direct involvement of a vanadium monoperoxo species has been substantiated by ESI-MS data. 

The photo-oxidation of n-butane has been modelled by ab initio and DFT computational methods, in which the key role of 1- and 2-butoxyl radicals was confirmed.52 These radicals, formed from the reaction of the corresponding butyl radicals with molecular oxygen, account for the formation of the major oxidation products including hydrocarbons, peroxides, aldehydes, and peroxyaldehydes. The differing behaviour of n-pentane and cyclopentane towards autoignition at 873 K has been found to depend on the relative concentrations of resonance-stabilized radicals in the reaction medium.53 The manganese-mediated oxidation of dihydroanthracene to anthracene has been reported via hydrogen atom abstraction.54 The oxidation reactions of hydrocarbon radicals and their OH adducts are reported.55... 

Very few reports describe the use of radical methods in the construction of large ring heterocycles (>7). A peroxydicarbonate-mediated hydrogen atom abstraction from an aldimine followed by cyclization onto an aromatic ring has been applied to the synthesis of dibenzoxazepines 237 [95T12143]. The yield of the heterocyclic product is low. 

The reactivity of these heterocycles towards hydrogen atom abstraction at C-2 has been shown to increase in the expected order, from 1,3-dioxane, through 1,3-oxathiane, to 1,3-dithiane. Hydrogen atom abstraction from C-2 in 4-methyl-1,3-dioxane, 2,4-dimethyl-1,3-dioxane, and 2-ethyl-4-methyl-1,3-dioxane has also been investigated <77MI 608-01 >. The radical-mediated alkylation of 2-stannyl-l,3-dithianes (67) with alkenes and enol ethers has been observed (Equation (30)) <92CL1229>. 

First, the flexibility of the iron-sulfur center gives it the potential to exist under different [2Fe-2S], [3Fe-4S], [4Fe-4S] forms. Whether this has functional importance remains to be determined. Very recently the Fnr protein, the pyruvate formate lyase and the biotin synthase were shown to share this property [48-50]. Second, its reducing power allows it to inject electrons into protein-bound AdoMet, as a prerequisite for the formation of an essential glycyl radical. Third, this radical is used for ribose activation, by hydrogen atom abstraction. It is likely that this reaction is mediated by a cysteinyl radical [53]. Fourth, formate is used as the hydrogen donor for ribose reduction [38]. 

These questions may be pertinent to every chapter in this book. For this chapter specifically, some additional questions arise What does radical-mediated mean Can a radical hydrogen-atom abstraction meet the requirements of C—H activation Does it depend on the particular mechanism of the reaction, the C—H BDE, or the timing of the radical abstraction step How can a researcher be sure that absolutely no transition metals are present and active during the reaction What if a transition metal is an additive, but only serves as an electron shuttle and does not specifically cleave to or react with the C—H bond ... 

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