Nucleophilic capture radical cation substitution

Nucleophiles, when they are used in the presence of cupric perchlorate, capture the cation-radicals initially formed. Instead of benzidines, the para-substituted dialkylanilines were obtained. In this a manner, A,A-dialkylanilines with halo or thiocyanato moieties in para positions were prepared in good yields under the same (simple) conditions. Scheme 7.13 illustrates the sequence of the transformations observed. The products are useful intermediates in the synthesis of dyes, drugs, and color cinema formulations. 

RBSctions of Radical Anions With Radicals. The coupling of arene or alkene radical anions with radicals is an important reaction, and one that has significant synthetic potential. For example, radicals formed by nucleophilic capture of radical cations couple with the acceptor radical anion, resulting in (net) aromatic substitution. Thus, the l-methoxy-3-phenylpropyl radical (113 R = H) couples with dicyanobenzene radical anion loss of cyanide ion then generates the substitution product 132.2 + ... 

In some cases the nucleophilic capture of a radical cation is followed by coupling with the radical anion (or possibly with the neutral acceptor), resulting ultimately in an aromatic substitution reaction. Thus, irradiation of 1,4-dicyanobenzene in acetonitrile-methanol (3 1) solution containing 2,3-dimethylbutene or several other olefins leads to capture of the olefin radical cation by methanol, followed by coupling of the resulting radical with the sensitizer radical anion. Loss of cyanide ion completes the net substitution reaction [144]. This photochemical nucleophile olefin combination, aromatic substitution (photo-NOCAS) reaction has shown synthetic utility (in spite of its awkward acronym). 

Many radical cations derived from cyclopropane (or cyclobutane) systems undergo bond formation with nucleophiles, typically neutralizing the positive charge and generating addition products via free-radical intermediates [140, 147). In one sense, these reactions are akin to the well known nucleophilic capture of carbocations, which is the second step of nucleophilic substitution via an Sn 1 mechanism. The capture of cyclopropane radical cations has the special feature that an sp -hybridized carbon center serves as an (intramolecular) leaving group, which changes the reaction, in essence, to a second-order substitution. Whereas the SnI reaction involves two electrons and an empty p-orbital and the Sn2 reaction occurs with redistribution of four electrons, the related radical cation reaction involves three electrons. 

Steric factors have been mentioned they are not expected to play a major role. In fact, several radical cations have been captured by attack on highly congested centers [154, 156]. The ring-opening substitution of tricyclane radical cation, 81 +, occurred exclusively at the tertiary carbon [215] whereas that of 82 occurred at the tertiary carbon further removed from the dimethyl-substituted bridge, i.e., at the less hindered of two tertiary carbons, not at the quaternary carbon [216]. These results clearly show that the nucleophilic substitution at the cyclopropane one-electron bond is subject to conventional steric hindrance and is not subject to inverse steric effects [154]. 

However, the evidence increasingly points to the substitution reactions as simply being an adjunct of the general scheme for radical rearrangement and as taking place via nucleophilic capture of one or other of the radical cation/anion pairs or of the free-radical cation. 

Exactly how the stabilized aromatic cation radical is converted into the nuclear chlorinated product, is not at present fully understood. As represented in eqn (135), nucleophilic substitution could arise from initial capture of the aromatic cation radical by chloride ion involving appropriate substituted cyclohexadienyl-type radicals ( ArHCl), in which case the substitution pattern (at least the ortho/para ratio of products) might be expected to resemble more those from typical homolytic aromatic substitution processes rather than those from electrophilic substitutions, as observed experimentally. At present, there is a scarcity of significant mechanistic information relating to nucleophilic capture of aromatic cation radicals, although in every reported case [vide infra) the position of substitution corresponds with that arising from comparable electrophilic processes. 

An intermediate that cannot be observed spectroscopically might be trapped by added reagents. In Chapter 5 we discussed the use of spin trap reagents to capture transient radicals for analysis by EPR spectrometry. Another example can be seen in the studies that led to the bromonium ion mechanism for the addition of bromine to frans-2-butene (14) to produce meso-2,3-dibromobutane (15, equation 6.7). Adding a nucleophile such as methanol to the reaction mixture led to a product incorporating the nucleophile (16) as shown in equation 6.8, which suggested that a cation may be an intermediate in the reaction. Additional evidence is necessary to determine the structure of the intermediate (i.e., bromonium ion or bromine-substituted carbocation), but that is a matter of detail once the existence of an intermediate of some kind is established. 

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