Electrophilic C-radicals

Intramolecular Aromatic Substitutions with Electrophilic C-Radicals... 

Scheme 10. Intramolecular aromatic alkylation with electrophilic C-radicals...

Scheme 13.16 Hemolytic aromatic substitution using electrophilic C-radicals.

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

The synthesis of a-substituted phosphonates 89, via the electrophilic addition of phosphorylated C-radicals 88 (generated by reaction of BujSnH to the readily accessible a-phosphoryl sulfides (or selenides)) and electrophilic addition to electron rich alkenes, has been described [57] (Scheme 26). A large excess of alkene is necessary to minimize the competitive formation of the undesired compound 90 resulting from direct reduction of the initial radical 88. The ratio 89/90 has been measured for each example. The synthesis of the a-mono- or a,a-di-substituted (R or phosphonates 89 shows that the free radical approach... 

Halogenation, and particularly chlorination, unlike most radical reactions, is markedly influenced by the presence in the substrate of polar substituents this is because Cl, owing to the electronegativity of chlorine, is markedly electrophilic (c/. p. 314), and will therefore attack preferentially at sites of higher electron density. Chlorination will thus tend to be inhibited by the presence of electron-withdrawing groups, as is seen in the relative amounts of substitution at the four different carbon atoms in 1-chlorobutane (78) on photoehemically initiated chlorination at 35° ... 

Methyl tricyclo[4.1.0.0 ]heptane-l-carboxylate gives a cation-radical in which the spin density is almost completely localized on C-1 while the positive charge is on C-7. The revealed structural feature of the intermediate cation-radical fairly explains the regioselectivity of N,N-dichlorobenzenesulfonamide addition to the molecular precursor of this cation-radical. In the reaction mentioned, the nucleophilic nitrogen atom of the reactant adds to electrophilic C-7, and the chlorine radical attacks C-1 whose spin population is maximal (Zverev and Vasin 1998, 2000). 

Hydrogen abstraction from a position a to the oxygen of alcohols and ethers provides a simple route to a-oxyalkyl radicals. Resonance stabilization and polar factors have been used to explain the ease of radical attack on these substrates. Recent studies appear to exclude the possibility that the oxygen atom in position a to the free C-radical may cause stabilization by resonance. The ease of hydrogen abstraction Avould be determined only by polar factors, arising with electrophilic radicals (X ) in contributions from the polar forms 13-15 to the transition state. 

As for ethers and alcohols, the ease of hydrogen abstraction is determined by polar factors when operating with electrophilic radicals (X ). The polar character is influenced by the same factors as for ethers and alcohols, i.e., a back-donation of charge from nitrogen to the a-C radical accentuates the nucleophilic character. The influence of the abstracting species in the case of dimethylformamide is shown by the results given in Table V, where the attack of carbamoyl and a-amidomethyl radicals... 

In accordance with these early findings, a recent detailed study of the perfluorination of neopentane by Adcock [36] found the order of hydrogen reactivity to be CH3 > CH2F > CHF2 by a comparison of statistical and actual yields of the hydrofluorocarbon products obtained upon polyfluorination. Thus, the hydrogen abstraction step 2 a (Table 1) becomes less favourable as the C-H bond becomes increasingly electron poor and, consequently, less reactive towards highly electrophilic fluorine radicals. 

Polar effects can also be important in atom transfer reactions. 4 In an oft-cited example (Scheme 13), the methyl radical attacks the weaker of the C—H bonds of propionic acid, probably more for reasons of bond strength than polar effects. However, the highly electrophilic chlorine radical attacks the stronger of the C—H bonds to avoid unfavorable polar interactions. As expected, the hydroxy hydrogen remains intact in both reactions. 

An intermediacy of electrophilic alkoxyl radicals (e.g., tert-butoxyl radical) possibly generated in the reaction mixture, which exhibit polarity matching with ethereal a-C-H bonds, may also be considered. Studies on the mechanism are in progress. 

The addition of the peroxyl radical to the double bond is governed by the electron density in the alkene bond and by electrophility of the radical. The rate constants of addition reactions increase with an increase of electron density on the double bond and with the increase of the electrophilic character of a radical (Table 6). The considerably larger electrophility of acyl peroxy radical (CH3CO3, C6H5CC>3) may explain by 5 orders faster addition of acyl peroxyl radicals [69] to a-methyl styrene at 20 °C. Electrophility of radicals leads to the marked reduction of activation energy of addition to alkenes methyl peroxyl radical has 47 kJ/mol, while acetyl peroxyl radical has 19 kJ/mol [70]. 

Temperature can alter not only the rate of vapor phase halogena-tions but also the nature of the products [rule (4), Section II, C, 2]. Previously the uncertainty was expressed as to whether kinetic or thermodynamic factors underlie this behavior. Others have assumed, without sound evidence, that kinetic factors are decisive and that the change in orientation signifies a switch in mechanism from electrophilic to radical character. However, further speculation on this point must await equally imaginative experimentation. 

In co-polymerization of 838g with STY at 80 °C, the cross-propagation is favored, consistent with electrophilic sulfanyl radicals adding rapidly to electron-rich STY, and nucleophilic styryl radicals adding rapidly to electron-deficient acrylate double bond (Scheme 169) <2006MI2475>. 

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