Radical-nucleophilic aromatic substitution electron transfer

Since its discovery from Bunnett in 1970 [1], the radical-nucleophilic aromatic substitution, iinimo-lecular (the reaction), has been widely used to achieve new C—C or C-heteroatom bonds. In these reactions, a compound bearing an adequate leaving group is substituted at the ipso position by a nucleophile (Nu"), and this process involves electron transfer (ET) steps. The global reaction is depicted in Equation 10.1 ... 

Almost quantitative radical nucleophilic aromatic substitution reactions were reported by Corsico and Rossi from the reaction of nucleophile trimethylstannyl ions with mono-, di- and trichloro-substituted aromatic substrates in Hquid ammonia.The chain process shown in Scheme 9 requires an initiation step, and it can be either Hght induced or be a spontaneous electron transfer from the nucleophile to the aromatic substrate. 

Equation 2.1). Three propagation steps then follow, including dissociation of the radical anion to an aryl radical and X- (Equation 2.2). In contrast, the corresponding alternative SN1 reaction would lead to the much less stable aryl cation (the empty p-orbital is part of the a-framework, and so cannot be stabilised by the n -electrons). The aryl radical then reacts rapidly with another nucleophile (Y in general or NH2- in this case) to give another radical anion (Equation 2.3) then electron transfer from one radical anion to another reactant molecule (Equation 2.4) initiates another chain. The overall consequence of the three propagation steps is nucleophilic aromatic substitution (Equation 2.5). 

Kita and Tohma found that exposure of p-substituted phenol ethers to [bis(tri-fluoroacetoxy)iodo]benzene 12 in the presence of some nucleophiles in polar, less nucleophilic solvents results in direct nucleophilic aromatic substitution [Eq. (84)] [156]. Involvement of a single-electron transfer (SET) from phenol ethers to A3-iodane 12 generating arene cation radicals was suggested by the detailed UV-vis and ESR studies. SET was involved in the oxidative biaryl coupling of phenol ethers by 12 in the presence of BF3-Et20 [157]. 

One way of carrying out nucleophilic aromatic substitution reactions under mild conditions is the Ar RNl process, which is initiated by (usually, but not necessarily, photoinduced) electron transfer to an aryl halide, e.g., from an enolate Cleavage of the resulting aryl radical anion with loss of a halide anion gives an aryl radical that combines with the enolate, thus forming the desired aryl-carbon bond. 

Processes involving a single-electron transfer (SET) step and cation-radical intermediates can occur in the reactions of X - or X -iodanes with electron-rich organic substrates in polar, non-nucleophilic solvents. Kita and coworkers first found that the reactions of p-substituted phenol ethers 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of some nucleophiles in fluoroalcohol solvents afford products of nucleophilic aromatic substitution 31 via a SET mechanism (Scheme 1.5) [212,213]. On the basis of detailed UV and ESR spectroscopic measurements, it was confirmed that this process involves the generation of cation-radicals 30 produced by SET oxidation through the charge-transfer complex of phenyl ethers with the hypervalent iodine reagent [213,214],... 

Primer and Rosenthal (25) have demonstrated that the reaction of O2 with nitro substituted aromatic halides occurs via an electron transfer from O2 to the substituted benzene to yield the anion radical which is subsequently scavenged by molecular oxygen (equation 26). They were able to distinguish this reaction pathway from direct addition of O2 to the aromatic ring as in normal nucleophilic aromatic substitution by utilizing... 

Many synthetically important aromatic substitutions are effected by nucleophilic reagents. Unlike nucleophilic substitution at saturated carbon, aromatic substitution rarely, if ever, occurs as a single step. Rather, intermediates are involved. Three broad mechanistic classes can be recognized addition-elimination, elimination-addition, and radical or electron-transfer processes. Undoubtedly the most broadly useful substrates for nucleophilic aromatic substitution are the aryl-diazonium salts and these compounds will be the first topic. 

The photo-NOCAS reaction was first described by McMahon and Arnold and is a photonucleophilic Sfj2Ar aromatic substitution between dicyanobenzene and an olefin in the presence of electron donor photosensitizers (phenanthrene or biphenyl) in acetonitrile-methanol solutions. This reaction system has been researched extensively in recent times. As shown in Scheme 6, the single electron transfer from olefin to photo-excited electron-deficient dicyanobenzene forms the cation radical of the olefin, which initiates a quenching reaction with nucleophile solvent methanol molecules and forms the methoxyalkyl radical. Addition of an electron transfer photosensitizer (phenanthrene or biphenyl) to the reaction mixture increases the efficiency of the reaction simply by absorbing more Hght. The excited state of the photosensitizer donates an electron to dicyanobenzene to give the photosensitizer radical cation and dicyanobenzene radical anion. The photosensitizer radical cation then oxidizes the olefin. 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

Nucleophilic substitution is the widely accepted reaction route for the photosubstitution of aromatic nitro compounds. There are three possible mechanisms11,12, namely (i) direct displacement (S/v2Ar ) (equation 9), (ii) electron transfer from the nucleophile to the excited aromatic substrate (SR wlAr ) (equation 10) and (iii) electron transfer from the excited aromatic compound to an appropriate electron acceptor, followed by attack of the nucleophile on the resultant aromatic radical cation (SRi w 1 Ar ) (equation 11). Substituent effects are important criteria for probing the reaction mechanisms. While the SR wlAr mechanism, which requires no substituent activation, is insensitive to substituent effects, both the S/v2Ar and the Sr+n lAr mechanisms show strong and opposite substituent effects. 

The addition of the nucleophile to the aryl radical is the reverse of the cleavage of substituted aromatic anion radicals that we have discussed in Section 2 in terms of an intramolecular concerted electron-transfer-bondbreaking process and illustrated with the example of aryl halides. The present reaction may thus be viewed conversely as an intramolecular concerted electron-transfer-bond-forming process. The driving force of the reaction can be divided into three terms as in (131). The first of these, the... 

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