Radical cations nucleophilic trapping

Oxidative Alkoxylation of Nitrones to a-Alkoxy Nitrones and a-Alkoxy Substituted Nitroxyl Radicals The first direct experimental evidence of the possibility to carry out radical cation nucleophilic addition to nitrones with the formation of nitroxyl radicals has been cited in Section 2.4. Further, such a reaction route was referred to as inverted spin trapping this route is an alternative to a conventional spin trapping (508-512). Realization of either mechanism depends on the reaction conditions namely, on the strength of both nucleophile and oxidant. The use of strong oxidants in weak nucleophilic media tends to favour the radical cation mechanism... 

The progress of intramolecular PET-reactions involving alkenyl phthalimides in essentially influenced by the solvent [29]. Upon irradiation in MeCN, [n2 + a2]-addition to the C(0)-N bond takes place and benzazepinediones are obtained. In alcohol, the intermediary formed radical cation is trapped in an aw/z -Markovnikov fashion depending on the polarity as well as the nucleophilicity of the solvent [30]. Recently, Xue et al. described an interesting modification of the latter process using tetrachloro-phthalimides with remote hydroxy alkyl substituents (13) [31]. During... 

Several classes of such fragmentation reactions have been studied in detail in order to understand the effect of substituents, the stereoelectronic requirements, and the effects of the medium and of nucleophiles. The mesolytic fragmentation of bibenzyls with the reduction of the radical and nucleophilic trapping of the cation is the main process for stabilized fragments, typical examples being cumyl or benzhydryl (see Equation 4.12). The relative stability of radical and cation makes the cleavage selective for Ar Ar. " ... 

Fragmentation of alkoxy radicals finds use in construction of medium-size rings.364 One useful reagent combination is phenyliodonium diacetate and iodine.365 The radical formed by fragmentation is normally oxidized to the corresponding carbo-cation and trapped by iodide or another nucleophile. 

The efficiency of this injection system depends upon the reaction conditions. 02) which traps the first formed radical 6, reduces the yield of enol ether 8. Therefore, we are using our assay under anaerobic conditions. Also, the pH of the solution influences the product ratio because it changes the nucleophilicity of the water. Figure 1 shows how the efficiency of the electron transfer is reduced as the pH value increases from 5.0 to 7.0 [5]. This is in accord with an increase of the nucleophilicity of water, which traps the radical cation (7—>9+10) in competition to the electron transfer step (7—>8). 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

Scheme 1. Mechanism of trapping of BP radical cation by a nucleophile (Nu).

This scheme can be extended by using mixtures of dienes with electron-deficient alkenes such as acrylonitrile. Due to its nucleophilic nature, addition of radical 68 to acrylonitrile is faster than addition to butadiene. The resulting ambiphilic adduct radical then adds to butadiene to form a relatively unreactive allyl radical. Oxidation and trapping of the allyl cation by methanol lead, as before, to products such as 72 and 73, which are composed of four components the radical precursor 67, acrylonitrile, butadiene and methanol (equation 30)17,94. 

In a rare example of the use of phenylselenides as radical precursors in the generation of alkene radical cations by the fragmentation approach, Giese and coworkers generated a thymidine C3/,C4/ radical cation by expulsion of diethyl phosphate. Trapping experiments were conducted with methanol and with allyl alcohol (Scheme 16), when nucleophilic attack was followed by radical cyclization [66]. 

Crich and Gastaldi investigated the nucleophilic trapping of a dihydronaphthalene radical cation by octyl alcohol and noted that the stereoselectivity of the reaction, while not high, was a function of the substrate stereochemistry (Scheme 19) [134]. In terms of the general mechanism for fragmentation... 

Scheme 19 Nucleophilic trapping of a dihydronaphthalene radical cation by octyl alcohol...

The advantage of the nitro group as radical precursor is best seen in the context of intramolecular nucleophilic trapping of alkene radical cations by nitrogen nucleophiles, when no cyclization was observed prior to treatment... 

Extended studies later showed that the radical cation mechanism of equations (6) and (7) is prevalent in strongly oxidizing systems (Eberson, 1992 Eberson and Nilsson, 1993), especially under photolytic conditions where excited states are formed (Eberson, 1994). The latter normally can act as strong oxidants or reductants, as in equation (11), and thus can create radical ions under seemingly mild conditions. Since this type of mechanism was judged to be much more common than thought, the name inverted spin trapping was coined for it in view of the inverted situation of electron demand which appears when an electron is formally transferred between the spin trap and the nucleophile or electrophile see equations (13)-(16). 

Another mechanistically useful nucleophile is acetate ion and related carboxylates. Acetate ion is difficult to oxidize (Eberson, 1963) and reacts with radical cations in a bond-forming reaction (Eberson and Nyberg, 1976). The oxidation product, the acetoxyl radical, has properties which make trapping it very unlikely in that its decarboxylation rate constant is 1.3 X 109 s 1 (Hillborn... 

For the same reasons the forms RED with relatively positive potentials seem to be stable to air in a pure state or a pure solution. In the presence of some acid, however, the colour of the radical cation SEM develops rapidly. The acid traps the highly nucleophilic Of formed in the course of autoxidation. Thus SEM and especially OX are no loiter removed from the redox-equilibrium since anions of low nucleo-philicity are provided by the added acid. 

Radical cations of 2-alkylidene-l,3-dithianes can be generated electrochemically by anodic oxidation using a reticulated vitreous carbon (RVC) anode <2002TL7159>. These intermediates readily react with nucleophiles at C-1. Upon removal of the second electron, the sulfur-stabilized cations were trapped by nucleophilic solvents, such as MeOH, to furnish the final cycloaddition products. Hydroxy groups <20010L1729> and secondary amides <2005OL3553> were employed as O-nucleophiles and enol ethers as C-nucleophiles (Scheme 50) <2002JA10101>. 

In addition to nucleophilic capture by alcohols, nonprotic nucleophiles also react with these intermediates. For example, the distonic dimer radical cation 96 + can be trapped by acetonitrile a hydride shift, followed by electron return, gave rise to the pyridine derivative 131. Similar acetonitrile adducts are formed in the electron-transfer photochemistry of terpenes such as ot- and (3-pinene ° or sabinene. ... 

Rate constants for quenching of 1-7 by methanol and acetic acid in hexane solution from fluorescence quenching and quantum yield data are 10 M l-s-l-. Limiting quantum yields for adduct formation are 0.1. The observation of reactions of protic solvent with 1-7 but not 1-t may reflect the longer lifetime and/or enhanced reactivity of the cyclic molecule. While photo-induced nucleophilic addition is a common reaction of aryl olefins, it is normally observed to occur only under conditions of electron-transfer sensitization (139). Under these conditions, it is the aryl olefin cation radical which undergoes nucleophilic attack. The reaction of 1-7 with protic solvents appears to be the only reported example of nucleophilic trapping of an aryl olefin it,it singlet state (140). 

Dimer formation can be quenched by conducting the experiment in a nucleophilic solvent, and the product obtained is characteristic of radical cation trapping. The anti-Markovnikov addition of acetone across the C-C single bond of the methylated analogue, eq. 41 (116,117),... 

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