Radical pathways

A radical pathway has been proposed to account for the isolation of (381)-(383) from the irradiation of the 3//-indazole (380) (73T1833). Results of sensitization and quenching experiments suggest that the reaction proceeds from the excited singlet state. 

Treatment of 2-methylthiirane with t-butyl hydroperoxide at 150 °C in a sealed vessel gave very low yields of allyl disulfide, 2-propenethiol and thioacetone. The allyl derivatives may be derived from abstraction of a hydrogen atom from the methyl group followed by ring opening to the allylthio radical. Percarbonate derivatives of 2-hydroxymethylthiirane decompose via a free radical pathway to tar. Acrylate esters of 2-hydroxymethylthiirane undergo free radical polymerization through the double bond. 

A chemical synthesis of prostaglandins by a free radical pathway through an endoperoxide intermediate showed a strong stereochemical preference for the formation of the endoperoxides having cis alpha and omega appendages. 

Following the radical pathway" the next step is a homolytical cleavage of the N-R bond. The rearrangement to yield the tertiary amine 3 then proceeds via an intermediate radical-pair 4a. The order of migration is propargyl > allyl > benzyl > alkyl ... 

Most fatty acids have an even number of carbon atoms, so none are left over after /3-oxidation. Those fatty acids with an odd number of carbon atoms yield the three-carbon propionyl CoA in the final j3-oxidation. Propionyl CoA is then converted to succinate by a multistep radical pathway, and succinate enters the citric acid cycle (Section 29.7). Note that the three-carbon propionyl group should properly be called propnnoyl, but biochemists generally use the non-systematic name. 

Homolytic and free radical pathways in reactions of organochromium complexes. J. H. Espenson, Prog. Inorg. Chem., 1983, 30,189-212 (85). 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Failure to observe polarization in a particular reaction is significant only to the extent that any negative evidence is significant. If other evidence points to a radical pathway for the reaction, it may well be worth checking that the nuclear relaxation times for nuclei in the product are not unexpectedly short and also that polarization is not observable in a different spectral region from that expected for the final product owing to the formation of a metastable intermediate. 

When the migrating group is allyl, an additional concerted ([2,3] sigmatropic) pathway for rearrangement becomes available. In this an allylic shift must also occur. Nevertheless, the radical pathway is not always excluded. For example, rearrangement of ylids such as 36 (R = CHs.CO) leads to product 37 (R = CH3.CO) in which the allylic protons adjacent to the amido-nitrogen atom appear in emission (D. G. Morris, 1969). No polarization is observed in the much readier... 

The reaction conditions, normally applied, are those described in chap. 2 for the radical pathway. These are a platinum anode, high current densities, no additives and a slightly acidic medium. However, the dimerizations shown in Table 2, No. 2, also gave in some cases good yields at a carbon anode in acetonitrile-water [52] or at a baked carbon anode in methanol [48]. With propionic and butyric acid an unusually high portion of alkene is formed at the cost of the dimer. 

By the radical pathway l, -diesters, -diketones, -dienes or -dihalides, chiral intermediates for synthesis, pheromones and unusual hydrocarbons or fatty acids are accessible in one to few steps. The addition of the intermediate radicals to double bonds affords additive dimers, whereby four units can be coupled in one step. By way of intramolecular addition unsaturated carboxyhc acids can be converted into five raembered hetero- or carbocyclic compounds. These radical reactions are attractive for synthesis because they can tolerate polar functional groups without protection. 

N2, and bromine trifluoride at 25-35°C " are also highly regioselective for tertiary positions. These reactions probably have electrophilic, not free-radical mechanisms. In fact, the success of the F2 reactions depends on the suppression of free-radical pathways, by dilution with an inert gas, by working at low temperatures, and/or by the use of radical scavengers. 

The third reason for favoring a non-radical pathway is based on studies of a mutant version of the CFeSP. This mutant was generated by changing a cysteine residue to an alanine, which converts the 4Fe-4S cluster of the CFeSP into a 3Fe-4S cluster (14). This mutation causes the redox potential of the 3Fe-4S cluster to increase by about 500 mV. The mutant is incapable of coupling the reduction of the cobalt center to the oxidation of CO by CODH. Correspondingly, it is unable to participate in acetate synthesis from CH3-H4 folate, CO, and CoA unless chemical reductants are present. If mechanism 3 (discussed earlier) is correct, then the methyl transfer from the methylated corrinoid protein to CODH should be crippled. However, this reaction occurred at equal rates with the wild-type protein and the CFeSP variant. We feel that this result rules out the possibility of a radical methyl transfer mechanics and offers strong support for mechanism 1. 

For example, photolysis of a suspension of an arylthallium ditrifluoro-acetate in benzene results in the formation of unsymmetrical biphenyls in high yield (80-90%) and in a high state of purity 152). The results are in full agreement with a free radical pathway which, as suggested above, is initiated by a photochemically induced homolysis of the aryl carbon-thallium bond. Capture of the resulting aryl radical by benzene would lead to the observed unsymmetrical biphenyl, while spontaneous disproportionation of the initially formed Tl(II) species to thallium(I) trifluoroacetate and trifluoroacetoxy radicals, followed by reaction of the latter with aryl radicals, accounts for the very small amounts of aryl trifluoroacetates formed as by-products. This route to unsymmetrical biphenyls thus complements the well-known Wolf and Kharasch procedure involving photolysis of aromatic iodides 171). Since the most versatile route to the latter compounds involves again the intermediacy of arylthallium ditrifluoroacetates (treatment with aqueous potassium iodide) 91), these latter compounds now occupy a central role in controlled biphenyl synthesis. 

We have now seen two pathways for adding HBr across a donble bond the ionic pathway (which gives Markovnikov addition) and the radical pathway (which gives anti-Markovnikov addition). Both pathways are actnally in competition with each other. However, the radical reaction is a mnch faster reaction. Therefore, we can control the regiochemistry of addition by carefully choosing the conditions. If we use a radical initiator, like ROOR, then the radical pathway will predominate, and we will see an anti-Markovnikov addition. If we do not use a radical initiator, then the ionic pathway will predominate, and we will see a Markovnikov addition ... 

Cp2Ti(PMe3)2 catalyzes the reductive cyclization of the enones 44 to the cyclopentanols 46 via the metallacyclic intermediates 45 (Scheme 27) [64-66]. The cleavage of the titanium-oxygen bond in the metallacycles 45 by a hydrosilane provides a route to the generation of the active catalyst. The net transformation resembles the above-mentioned complementary radical pathway, which affords the opposite isomer. 

The addition of chlorine or bromine to benzene—one of the few overall addition reactions of a simple benzene nucleus—has also been shown to proceed via a radical pathway, i.e. it is catalysed by light and by the addition of peroxides, and is slowed or prevented by the usual inhibitors. With chlorine this presumably proceeds ... 

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