Electrophilic substrates, reduction

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

In addition to investigating the effect of changing the voltage sweep rate and of addition of nucleophiles/bases (oxidation) or electrophiles/acids (reductions), the preliminary work often also includes investigation of how the voltammograms are affected by changes in the substrate concentration. 

Recently, the arylation of several specific primary amines have been studied because of the potential biological relevance of the products or products further downstream in a synthetic sequence. For example, cyclopropylamine was shown to be a viable substrate for the coupling under standard conditions [203]. Reactions of 7-azabicyclo[2.2.1]heptane have also been conducted [204] under relatively standard conditions, but with bis(imidazol-2-ylidene) as ligand. Complexes of this ligand and DPPF showed similar catalytic activities, which proved to be superior to those of most bis(phosphine)s. ortfio-Halo anilines were also studied, in this case to provide access to carbolines after use of the halogen as a means of effecting cycliza-tions by an electrophilic or reductive C-C bond formation with the other N-aryl group [205]. 

Polyhalogenated aromatic hydrocarbons (e.g. hex-achlorobenzene (HCB, CeCle) and polychorobiphenyls (PCBs)) are rapidly degraded by superoxide ion in DMF to bicarbonate and halide ions. Because halogen-bearing intermediates are not detected, the initial nucleophilic attack is the rate-determining step. The rates of reaction exhibit a direct correlation with the electrophilicity of the substrate (reduction potential) (e.g. CeCle, E° = -1.48 V vs. SCE ki/[S] = 1 X lO M- s and 1,2,4-C6H3C13, E° = -2.16 V ki/[S] = 2x 10-2 M- s ). 

Table 8-1 Redox Potentials for the Single-Electron (a) Oxidation of HO and Other Oxy Anion Bases and (b) Reduction of Electrophilic Substrates in Water and in Acetonitrile... 

We remarked that the first step of the radical-anion chain mechanism (Fig. 4) can be considered as a reduction of the halide by the nucleophile. Consequently, we tried to use well known reductants such as zinc. However, no reaction occurred when the halide is placed in the presence of zinc in various solvents. By analogy with the thiophenoxide condensation, we attempted the transformation in DMF under slight pressure. Consumption of the reagents was only observed when electrophilic substrates, such as carbonyl compounds, are present since the beginning of the reaction. These Barbier like condensations started more easily in pyridine than in DMF (ref. 19). Moderate yields were obtained with aldehydes as substrates (Fig. 6). 

Table 15 Redox potentials for the single-electron (a) oxidation of HO and other oxyanion bases and (b) reduction of electrophilic substrates in water and in acetonitrile...

In Part 2 of this book, we shall be directly concerned with organic reactions and their mechanisms. The reactions have been classified into 10 chapters, based primarily on reaction type substitutions, additions to multiple bonds, eliminations, rearrangements, and oxidation-reduction reactions. Five chapters are devoted to substitutions these are classified on the basis of mechanism as well as substrate. Chapters 10 and 13 include nucleophilic substitutions at aliphatic and aromatic substrates, respectively, Chapters 12 and 11 deal with electrophilic substitutions at aliphatic and aromatic substrates, respectively. All free-radical substitutions are discussed in Chapter 14. Additions to multiple bonds are classified not according to mechanism, but according to the type of multiple bond. Additions to carbon-carbon multiple bonds are dealt with in Chapter 15 additions to other multiple bonds in Chapter 16. One chapter is devoted to each of the three remaining reaction types Chapter 17, eliminations Chapter 18, rearrangements Chapter 19, oxidation-reduction reactions. This last chapter covers only those oxidation-reduction reactions that could not be conveniently treated in any of the other categories (except for oxidative eliminations). 

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