Anion-Radical Ring Closure

Electroreductive one-electron initiation of cyclization was described for the series of E,E-, 1-dibenzoyl-l,6-heptadiene and its derivatives (Roh et al. 2002, Felton and Bauld 2004). In this case, the catalytic effect was also observed (the actual consumption of electricity was substantially less than theoretical). The same bis(enones) can also be cyclized on the action of the sodium salt of chrysene anion-radical in THF, but with no catalytic effect. Optimum yields were obtained only when 70-120 mol% of the initiator was used, relative to a substrate (Yang et al. 2004). The authors suggest that tight ion pairing of the sodium cation with the product anion-radical in THF (which is a somewhat nonpolar solvent) slows down the intermolecular electron transfer to the bis(enone) molecules. Such an electron transfer would be required for chain propagation. 

The first (reversible) electron transfer generates the ketyl anion-radical. The ketyl moiety then attacks the aryl group in the ortho position. The resulting cyclohexadienyl radical is reduced to a cyclohexadienyl anion by a second electron transfer, and the anion is finally protonated. HMPA as 

Ion-radical reactions also open convenient routes to fused benzoheterocycles as a result of intramolecular cyclization. The fused heterocycles are useful as compounds of potential physiological activity. Many of them are used as medications. Certainly, only those syntheses that do not change the functional groups needed to provide or enforce the curative effect, are of interest. At the same time, it is desirable to exclude acidic agents that lead to the splitting of the final heterocycles, which 

With conventional methods, the formation of indole derivatives from anilines proceeds at the expense of both unsubstituted ortho positions in the phenyl ring. This leads to undesirable by-products. Particularly, the formation of by-products takes place during Fischer s synthesis of benzohet-erocycles. In the previously described ion-radical variant of the synthesis, only one indole isomer is formed—the isomer that corresponds strictly to the structure of the starting haloaniline. 

The anion-radical mechanism for these syntheses is based on the following facts. The reactions require photo- or electrochemical initiation. Oxygen inhibits the reactions totally, even with photoirradiation. Indoles are formed from o-iodoaniline only the meta isomer does not give rise to indole. Hence, the alternative aryne mechanism (cine-substitution) is not valid. What remains as a question is the validity of the ion-radical mechanism exclusively to the substitution of the acetonyl group for the halogen atom in o-haloareneamine or also for intramolecular condensation. 

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Alkylimidazolinm tetraflnoroborates are, for example, ionic liquids at room-temperature that can provide an anion to stabilize an intermediate cation-radical with no possibility of nucleophilic attack on it. Ionic liquids have a huge memory effect, and their total friction is greater than that of conventional polar solvents. Thus, the total friction of l-ethyl-3-methylimidazolium hexafluoro-phosphate is about 50 times greater than that of AN (Shim et al. 2007). The solvent effects of ionic liquids on ion-radical ring closures deserve a special investigation. The ring closure reactions can be, in principal, controlled by solvent effects. 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

Ring Closure Involving Radicals. Reduction of an aromatic halide goes through a radical-anion, which loses a halide ion. If the rate of this cleavage (k2) is very high, the radical will be formed close to the electrode and will accept an electron to form a carbanion. 

Photoinduced electron transfer from the amine to C6o to yield a radical ion pair is suggested to be the initial step for the formation of 54a-b. This is followed by deprotonation of the amine cation by the fullerene anion to give an a-aminoalkyl and HC6o radical pain [134], Subsequent combination of the radical pair leads to the final product. Formation of 55 is likely to be initiated by PET from 54b to C6o. This is then followed by successive intermolecular proton transfer, hydrogen abstraction, and ring closure to give l,2-H2C6o and 55 (Scheme 21). 

Substituted 2,3-dihydro-l-H-indoles 26 are accessible by the versatile application of a 5-exo ring closure process during the propagation cycle in the SRN1 reaction [67]. Following the initial ET and fragmentation of the radical anion of the substrate, the... 

In the photostimulated reaction of SCH2C02Et ions with 2-bromo-3-cyano or 3-bromo-4-cyano pyridines, the substitution product formed is deprotonated, and the anion formed reacts with the cyano group to give ultimately the ring closure substitution products 304 (90%) and 305 (98%), respectively. The yields are high, because in these cases fragmentation of the radical-anion intermediates does not take place288. 

These results suggest that anion 328 is unable to initiate the process, a reaction that is performed by the enolate ion of acetone. However, the rate of the coupling reaction between the anion of acetone and the radical intermediate formed is slower than the rate of intramolecular ring closure reaction of the radical. 

However, the ring closure of substituted hexatriene radical cations has been reported (a) Barkow, A. and Griitzmacher, H.-F. (1994). Inti, J. Mass Spectrom Ion Proc. 142,195 It should also be noted that the ring closure of a hexatriene radical anion has also been reported (b) Fox, M.A. and Hurst, J.R. (1984). J. Am. Chem. Soc. 106, 7626... 

The radical anion appears to be a key intermediate in the overall mechanism. Stork and succeeding workers have applied this to useful intramolecular ring closures in which Li/NHs or Na+, Ar have initiated the reaction probably at carbonyl (equation 87) - . Typically, 5- rather than 6-membered rings are formed. 

In THF after 60 min 10% 151 and 90 % 152 were found. In diethylether the rearrangement is somewhat slower (60% 152). Addition of TMEDA to the ether solution accelerates the ring closure after 30 min 94 % of 152 was detected. These results lead to the conclusion that radical tests by cyclization of what is thought to be the phenyl radical 135 must be carried out at low (—78 °C) temperature at which the anion 150 cyclizes very slowly after 120 min in THF at —78 °C only the non-cyclized 151 is detected. 

Carbon attack of the carbonyl group of cyclopropyl ketones has also been achieved in dimerization reactions under McMurry and photochemical conditions. Conceivably, the reactions take place via radical anion intermediates. Photodimerization does not occur if structural features of the substrate facilitate intramolecular reactions such as ring opening, ring expansion, and ring closure. Radical... 

Equation 16 illustrates a celebrated example where ring closure competes with vicinal hydride shift (a common form of atom transfer in cations, which does not take place in free radicals or anions). The gas phase reaction was explored by preparing the dimethylfluoronium ion, (CH3)2F" , by y-radiolysis of fluoromethane. Exothermic methylation of a sample of C-yd-phenethyl chloride (where the asterisk in equation 16 symbolizes the labeled position) in the gas mixture gives a vibrationally excited ion that loses chloromethane to form two isomeric ions, a-phenethyl cation and spirooctadienyl cation (sometimes called ethylenebenzenium). Nucleophilic attack by methanol in the reaction mixture yields PhCH(CH3)OCH3, whose isotopic label remains almost entirely at the methyl group. The recovered PhCH2CH20CH3 contains equally distributed between the two methylene positions. The spirooctadienyl ion does not isomerize to a-phenethyl cation, even though DFT calculations predict the latter to be 55 kJ/mol more stable. 

Pathways (la) and (Id) are the most frequent routes employed for the electrochemical generation of radicals. The radicals can be used in homocoupling, heterocoupling and addition reactions. In some cases these reactions have to compete with further oxidation or reduction of the radicals (see Sections 2.6.3.5 and 2.6.4.3). Electrogenerated radical ions (lb), (le), (If), cations (Ic) and anions (Ig) have been very efficiently used in electroorganic synthesis, e.g. for cathodic hydrodimerization, anodic dehydrodimerization, anodic substitution, cathodic cleavage or ring closure reactions [2, 5, 6]. These conversions are not treated in this review. 

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