Electrophiles transition metal peroxides

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

Transition metals can be divided into two groups according to the characteristics of theii peroxides. The first group comprises those metals that, in their highest oxidation states, have no d electrons, e.g., Ti4+ and W6+, These metals form peroxides from hydrogen peroxide. The peroxo species act as electrophiles. 

Thiols are susceptible to oxidation by peroxides, molecular oxygen, and other oxidizing processes (e.g., radical-catalyzed oxidation) (Fig. 67). Because thiols easily complex with transition metals, it is believed that most thiol autoxidation reactions are metal-catalyzed (108). Autoxidation of thiols is enhanced by deprotonation of the thiol to the thiolate anion. Thiol oxidation commonly leads to disulfides, although further autoxidation to the sulfinic and, ultimately, sulfonic acid can be accomplished under basic conditions. Disulfides can be reduced back to the thiol (e.g., upon addition of a reducing agent such as dithiothreitol). Thiols are nucleophilic and will readily react with available electrophilic sites. For a more thorough discussion, see Hovorka and Schoneich (108) and Luo et al. (200). 

An appreciable number of monographs and reviews deal with the meth-Q rsi,275,329-333 jjjg j j.gg gj jpunt of experimental work that has been performed provides a possibility for establishing favorable conditions of epoxidation with regard to the roles of the catalyst, the organic hydroperoxide, the structure of the olefin, and the medium. Simitar to the hydrogen peroxide-transition-metal complex reaction, this is an electrophilic reaction (Eq. 30). ... 

After Mo, vanadium is the second most abundant transition metal in the ocean and is certainly beneficial and probably essential for man. It is used in the form of a V prosthetic group in V-dependent haloperoxidases, which utilise hydrogen peroxide to oxidise a halide ion into a reactive electrophilic intermediate. There has been extensive debate as to whether a final transition metal ion is an essential trace element, as was originally proposed over 50 years ago — it has been widely accepted as an essential element for over 30 years. We discuss Mo and W together with V and Cr in Chapter 17. 

High valent early transition metal derivatives are known to catalyze the epoxidation of alkenes by peroxides (e.g., t-butylhydroperoxide) through the formation of active metal-peroxy species, which deliver the metal linked oxygen, acting as an electrophile, to the alkene. More substituted alkenes are then more reactive tlian monosubstituted ones. Hydrogen peroxide may also give the epoxidation by this same mechanism. The formed epoxides are... 

Alkanes can be oxidized in the presence of some transition metal complexes in aqueous and acidic media For example, in concentrated sulfuric acid the oxidative properties of the complexes are enhanced. Solutions of derivatives of palladium(II), platinum(III), manganese(III) and mercury(II) as well as some other compounds (hydrogen peroxide, ammonium persulfate, nitric acid and even concentrated sulfuric acid itself) can be used as oxidants. In the cases of metal-free oxidants the active species are apparently electrophiles such as NO2 or SO3I-C (for nitration of aromatics, see, for example, recent publication [40] and references therein). 

Oxidation of polyunsaturated fatty acids (PUFA) in lipoproteins may be mediated by reactive species such as radicals, transition metals, other electrophiles, and by enzymes. Once initiated, oxidation of lipids may proceed by a chain reaction, illustrated in Fig. 4 (R5). In step I, an oxidant captures an electron from a PUFA to produce a lipid radical. In step 2, after rearrangement, the conjugated diene radical reacts rapidly with singlet oxygen to produce a lipid peroxide radical, which is the kinetically preferred reaction (step 3) (B5). The chain can be terminated if the lipid radical reacts with an antioxidant to produce a stable peroxide (step 4). Otherwise, the peroxyl radical can react with another polyunsaturated fatty acid as shown in step 5 to perpetuate a chain reaction. The chain reaction requires production of lipid peroxides, giving it the name peroxidation. Fatty acids oxidized in the core are largely triglycerides and cholesterol esters, while toward the outer layer fatty acids in phospholipids are oxidized. 

Whereas the Cyt P-450 mechanism resembles the chemical oxidation by hyper-valent transition metal oxidants through an electrophilic attack (nature s permanganate), the FAD-dependent mechanism parallels the oxidation of organic compounds by peroxides or peracids, which act as nucleophiles (nature s m-chloro-... 

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