Radical anions esters

The proposed mechanism for the conversion of the furanone 118 to the spiro-cyclic lactones 119 and 120 involves electron transfer to the a -unsaturated methyl ester electrophore to generate an anion radical 118 which cyclizes on the /3-carbon of the furanone. The resulting radical anion 121 acquires a proton, giving rise to the neutral radical 122, which undergoes successive electron transfer and protonation to afford the lactones 119 and 120 (Scheme 38) (91T383). 

For the mechanistic course of the reaction the diketone 5 is assumed to be an intermediate, since small amounts of 5 can sometimes be isolated as a minor product. It is likely that the sodium initially reacts with the ester 1 to give the radical anion species 3, which can dimerize to the dianion 4. By release of two alkoxides R 0 the diketone 5 is formed. Further reaction with sodium leads to the dianion 6, which yields the a-hydroxy ketone 2 upon aqueous workup ... 

We have seen similar radical anions generated from ketones in pinacol reduction with sodium or magnesium (p. 218), and also from esters with sodium in the acyloin condensation (p.218). 

Biradicals have also been encountered as intermediates in the Mg reduction of ketones to pinacols (p. 218) and, as radical anions, in the acyloin condensation of esters (p. 218). The thermolysis of cyclopropane (131) to propene (132) at 500° is also believed to involve... 

Scheme 11.16 Diastereocontrol via chelate effect stereoselective 5-exo-trig cyclization on to a cumulated Jt-bond of a chelated ester-substituted ketyl radical anion 50 [74]. a 94 6 mixture of diastereomers.

The product ratio for 152/153 is similar to those observed in compounds 141 and 144. The isolation of 150 and 151 implicates the formation of dioxocarbocation intermediates (154, 155) that can be trapped by water to give hemiorthoesters and ultimately the ester products (equation 75). The photogenerated p-nitrobenzyl anion also can be detected by the EPR spectrum of the corresponding radical anion through electron transfer88. 

As a final example in this section, we may consider the i/ .vo-di spl acernen l of the nitro group itself. Liu and Zhao68 have investigated the substitution of the nitro group in a series of 4-nitrobenzoate esters by the phenylthiolate anion. Here the process again involves radical species, but now it is the radical anions of the nitro compounds which are observed as well as the thiophenoxyl radical which could be trapped. 

This has been applied to the cyclization of dihalides [45, 46], nonconjugated, unsaturated ketones [47] and esters [48], oxoalkylpyridinium salts [49], aldehydes and unsaturated nitriles [50], halides, and unsaturated esters [51], The umpoled acceptors, mostly radical anions or carban-ions (see Scheme 1), can also be used in intermolecular reactions such as acylation, alkylation, or carboxylation (Eq. 5). 

Formally related reactions are observed when anthracene [210] or arylole-fines [211-213] are reduced in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the yield of acylated products largely depends on the counterion of the reduced hydrocarbon species. It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the carboxylic acid by ion-pair formation. In contrast to alkylation, acylation is assumed to prefer an Sn2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species. The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [211-213]. 

Esters of ethenetetracarboxylic acid, (37), and disubstituted (fluoren-9-ylidene)me-thane derivatives, (38), are reduced sequentially to radical anions and dianions [2, 68, 84, 85]. Only the dianions are sufficiently basic to be useful as EGBs [53,86]. For (37), the two reduction potentials are separated by 0.2 V [68], and even with a working potential allowing formation only of the radical anion, the dianion can be formed by disproportionation. The protonated form of the dianionic EGBs, (37H) and (38H) , will normally be stable in solution since the pK values of the dihydro products are expected to be in the range 12 to 16. 

In practice, reduction of 35 (—2.43 V vs SCE) in the presence of 3,5-dimethylphenol as a proton donor, tetra- -butylammonium hexafluorophos-phate as the supporting electrolyte, and DMF as the solvent, led to the y-hydroxy ester 40 and lactone 41 [22]. No sign of any material resulting from cyclization onto the alkene was detected. It was concluded that radical cyclization does not occur in this instance, and that the homogeneous electron transfer rate exceeds that of a 5-exo-trig radical cyclization, thereby implying the operation of either a radical anion or carbanion cyclization pathway. 

Probably the most familiar radical reactions leading to 1,2-D systems are the so called acyloin condensation and the different variants of the "pinacol condensation". Both types of condensation involve an electron-transfer from a metal atom to a carbonyl compound (whether an ester or an aldehyde or a ketone) to give a radical anion which either dimerises directly, if the concentration of the species is very high, or more generally it reacts with the starting neutral carbonyl compound and then a second electron is transferred from the metal to the radical dimer species (for an alternative mechanism of the acyloin condensation, see Bloomfield, 1975 [29]). 

Reactions reminiscent of pinacol reduction take place if esters are treated with sodium in aprotic solvents. The initially formed radical anion dimerizes and ultimately forms an a-hydroxy ketone, an acyloin. Such acyloin conden-... 

Cyclo-coupling between arylalkenes and an aliphatic ester function is achieved by electrolysis in tetrahydrofuran using cathode and anode both of magnesium in an undivided cell. The first electron addition is to the arylalkene. The bond forming steps involves nucleophilic attack by radical-anions or dianions derived from the alkene. Magnesium ions generated at the anode are essential to the process. The... 

Dimerization is the characteristic reaction of radical-anions from activated alkenes. The rate constants for dimerization are high and the conjugate acids from such alkene radical-anions in many cases have low pKa values and. The data in Table 3.4 were obtained by following the changes in uv-absorbance after pule-radiolysis of the substrate in an aqueous buffer. Attachment of a solvated electron leads to the radical-anion. Changes in the initial absorbance with pH lead to determination of the pKg value, while the dimerization rate can be determined from changes in absorbance over a longer time scale. Radical-anions from esters and amides are pro-... 

Esters of aromatic acids in aprotic solvents form radical-anions detected by cyclic voltammetry on a short time scale [144]. Ethyl benzoate has E° = -2,19 V V5. see [145], Follow-up reactions of radical-anions from methyl and ethyl benzoate result from protonation by extraneous water. rm-Butyl benzoate radical-anion undergoes very rapid cleavage of the alkyl-oxygen bond to give benzoate ion and rerf-butyl radical. 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

The characterization of the semiquinone radical anion species of PQQ in aprotic solvents was undertaken to provide information about the electrochemistry of coenzyme PQQ and to give valuable insight into the redox function of this coenzyme in living systems <1998JA7271>. The trimethyl ester of PQQ and its 1-methylated derivative were examined in aprotic organic solvents by cyclic voltammetry, electron spin resonance (ESR), and thin-layer UV-Vis techniques. The polar solvent CH3CN was found to effectively solvate the radical anion species at the quinone moiety, where the spin is more localized, whereas the spin is delocalized into the whole molecule in the nonpolar solvent CH2CI2. 

The acyloin condensation is closely related to the radical anion coupling forming pinacolate anions two ester radical anions couple to form a dianion, which readily loses two alkoxide ions. The resulting diketone then is reduced by sodium, first to a semidione radical anion, then to the dianion. Finally, aqueous work-up produces the acyloin. Acyloins are convenient precursors for the generation of semidione radical anions. ... 

The procedure reported here is based on a reaction discovered by Bunnett and Creary, and was first employed for preparative purposes by Bunnett and Traber.3 It is attractive because of the high yield obtained, the ease of work-up, and the cleanliness of the reaction. The reaction is believed to occur by the SRN1 mechanism, which involves radical and radical anion intermediates.2,4 The SRN1 arylation of other nucleophiles, especially ketone enolate ions,5 ester enolate ions,6 picolyl anions,7 and arenethiolate ions,8 has potential application in synthesis. 

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