Homolytic reactions hydrogen atoms

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

FIGURE 24.21 A mechanism for the methylmalonyl-CoA mntase reaction. In the first step, Co is rednced to Co dne to homolytic cleavage of the Co —C bond in cobalamin. Hydrogen atom transfer from methylmalonyl-CoA yields a methylmalonyl-CoA radical that can undergo rearrangement to form a snccinyl-CoA radical. Transfer of an H atom regenerates the coenzyme and yields snccinyl-CoA. 

The competitive method employed for determining relative rates of substitution in homolytic phenylation cannot be applied for methylation because of the high reactivity of the primary reaction products toward free methyl radicals. Szwarc and his co-workers, however, developed a technique for measuring the relative rates of addition of methyl radicals to aromatic and heteroaromatic systems. - In the decomposition of acetyl peroxide in isooctane the most important reaction is the formation of methane by the abstraction of hydrogen atoms from the solvent by methyl radicals. When an aromatic compound is added to this system it competes with the solvent for methyl radicals, Eqs, (28) and (29). Reaction (28) results in a decrease in the amount... 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

Where does the hydrogen atom in the product of hydro-de-diazoniation, 2-chloro-nitrobenzene (8.66), come from in CH3OD It was found (Bunnett and Takayama, 1968 b Broxton and Bunnett, 1979) that in the reaction of Scheme 8-47 the deuterium content of 2-chloronitrobenzene was 79%, a figure which is not close to either zero or 100%. For other substituted benzenediazonium ions a very wide range of D incorporation was observed. This range is consistent with hydro-de-diazoniation by both homolytic and a competitive anionic mechanism. The anionic pathway is favored by an increase in methoxide ion concentration. 

In triethylamine instead of benzene the reaction products are completely different, and are indicative of a homolytic process involving an initial electron transfer from triethylamine followed by a hydrogen atom transfer. Scheme 10-68 gives the major products, namely 1,3,5-tri-tert-butylbenzene (10.36, 20%), the oxime 10.39 (18%), formed from the nitroso compound 10.38, and the acetanilide 10.37 (40%). ESR and CIDNP data are consistent with Scheme 10-68. In their paper the authors discuss further products which were found in smaller yields. 

The reaction endothermicity establishes a minimum for the activation energy whereas abstraction of a hydrogen atom from carbon is a feasible step in a chain process, abstraction of a hydrogen atom from a hydroxyl group is unlikely. Homolytic cleavage of an O-H bond is likely only if the resulting oxygen radical is stabilized, such as in phenoxy radicals formed from phenols. 

The mechanism of action, and organization of the catalytic sites, in hydrogenases are different from a solid catalyst such as platinum. For a start, the reaction of H2 with hydrogenase involves heterolytic cleavage into a hydron and a hydride. This contrasts with the reaction of H2 at the surface of a metal such as platinum, which is usually considered to involve the homolytic cleavage into two hydrogen atoms. Moreover in the enzyme, the catalyst is a cluster of metal ions (with oxidation states +2 or -h3) rather than the metal (oxidation state 0). 

It was proposed that an initially generated silyl radical 3, by reaction of i-BuO radical and polysilane 2, attacks another silicon atom in the same backbone to give a cyclic polysilane that contains an acyclic chain and another silyl radical (Scheme 8.1) [12]. The last silyl radical can either cyclize or abstract a hydrogen atom from another macromolecule, thus propagating the chain degradation. The reaction in Scheme 8.1 is an example of intramolecular homolytic substitution (ShO, a class of reactions discussed in Chapter 6. 

Termination reactions convert radicals to closed-shell compounds. Radical-radical coupling reactions are the reverse of homolytic cleavage reactions and are common, but radicals with (3-hydrogen atoms also react in disproportionation reactions as shown for 13. The selectivity of radical-radical terminations is low because the... 

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