Aryl radicals, sources

As shown in other sections of this chapter, overall attention has shifted from diazonium salts as aryl radical sources to bromo- or iodobenzenes. One of the few recent attempts to improve the classical Pschorr cyclization using diazonium ions as starting materials led to the discovery of new catalysts [119]. Results from a first samarium-mediated Pschorr type show the variety of products that can be expected from intramolecular biaryl syntheses under reductive conditions (Scheme 22). Depending on the substitution pattern of the target aromatic core and the reaction conditions, either the spirocycle 60, the biphenyl 61, or the dearomatized biphenyl 62 were formed as major product from 63 [120]. 

Gomberg-Bachmann Reactions 5.1 Biphenyls New Aryl Radical Sources... 

Heterocyclic compound Aryl radical Source Total aryla- tion (%) Positions of substitution (and yields where quoted) Ref. 

In the intermediate complexe of free radical arylation, it is necessary to oxidize the reaction intermediate to avoid dimerization and disporportio-nation (190-193, 346) In this case isomer yield and reactivity will be highest with radical sources producing very oxidative radicals or in solvents playing the role of oxidants in the reaction. The results are summarized in Tables III-29 and III-30. 

IV-Nitrosqanilides are an alternative source of aryl radicals. There is a close mechanistie relationship to the decomposition of azo compounds. The JV-nitrosoanilides rearrange to intermediates that have a nitrogen-nitrogen double bond. The intermediate then decomposes to generate aryl radieals. ... 

Modifications of this method, such as the use of the more stable diazonium trifluoroacetates and the decomposition of benzenedia-zonium zincichloride with zinc dust, have been used as sources of aryl radicals, although not in the arylation of heterocyclic compounds. Pyridine, quinoline, and thiophene can be phenylated by treatment with benzenediazonium chloride and aluminum trichloride. ... 

Packer and Richardson (1975) and Packer et al. (1980) made use of the fact that electrons can be generated in water by y-radiation from a 60Co source (Scheme 8-29) to induce a free radical chain reaction between diazonium ions and alcohols, aldehydes, or formate ion. It has to be emphasized that the radiolytically formed solvated electron in Scheme 8-29 is only a part of the initiation steps (Scheme 8-30) by which an aryl radical is formed. The aryl radical initiates the propagation steps shown in Scheme 8-31. Here the alcohol, aldehyde, or formate ion (RH2) is the reducing agent (i.e., the electron donor) for the main reaction. The process is a hydro-de-diazoniation. 

Packer et al. (1981) found that y-irradiation reduces arenediazonium tetrafluoro-borates to aryl radicals. Packer and Taylor (1985) investigated the y-irradiation of 4-chlorobenzenediazonium tetrafluoroborate by a 60Co source in the presence of 1 alone or I- +13 . The major product in the presence of iodide was 4,4 -dichloroazo-benzene. With I- + 1 ", however, it was 4-chloroiodobenzene. Two other investigations of the reactivity of aryl radicals with iodine-containing species are important for the understanding of the chain process of iodo-de-diazoniation that starts after formation of the aryl radical. Kryger et al. (1977) showed that, in the thermal decomposition of phenylazotriphenylmethane, the rate of iodine abstraction from I2 is extremely fast (see also Ando, 1978, p. 341). Furthermore, evidence for the formation of the radical anion V2 was reported by Beckwith and Meijs (1987) and by Abey-wickrema and Beckwith (1987) (see Sec. 10.11). 

In the classical procedure, base is added to a two-phase mixture of the aqueous diazonium salt and an excess of the aromatic that is to be substituted. Improved yields can be obtained by using polyethers or phase transfer catalysts with solid aryl diazonium tetrafluoroborate salts in an excess of the aromatic reactant.177 Another source of aryl radicals is A-nitrosoacetanilides, which rearrange to diazonium acetates and give rise to aryl radicals via diazo oxides.178... 

Ni-cyclam, Ni(CR), or Ni(tet a) can be used efficiently as catalyst in DMF, and in the presence of NH4CIO4 as proton source [71-74]. Ni species generated electrochemically react rapidly with organic halides to generate alkyl, alkenyl, or aryl radicals which add intramolecularly to a double or triple bond, then leading to cyclopentanoids (Table 7, entries 3-7a). 

The usual sources used for the homolytic aromatic arylation have been utilized also in the heterocyclic series. They are essentially azo- and diazocompounds, aroyl peroxides, and sometimes pyrolysis and photolysis of a variety of aryl derivatives. Most of these radical sources have been described in the previous review concerning this subject, and in other reviews concerning the general aspects of homolytic aromatic arylation. A new source of aryl radicals is the silver-catalyzed decarboxylation of carboxylic acids by peroxydisulfate, which allows to work in aqueous solution of protonated heteroaromatic bases, as for the alkyl radicals. 

There are some inherent limits to the usefulness of such reactions. Radical substitutions are only moderately sensitive to substituent directing effects, so that substituted reactants usually give a mixture of products. This means that the practical utility is limited to symmetrical reactants, such as benzene, where the position of attack is immaterial. The best sources of aryl radicals for the reaction are aryl diazonium ions and A -nitroso-acetanilides. In the presence of base, diazonium ions form diazoxides, which decompose to aryl radicals.151... 

Free radical substitution of pyridines usually occurs principally at position 2 (Table 25), which is in agreement with theoretical calculations (69CCC1110). 2-Substitution is more favored in methylation than in phenylation of pyridine. This suggests that the methyl has more nucleophilic character than the phenyl radical. Furthermore, methylation of pyridine in acidic solution gives 13-fold excess of 2- over 4-substitution, although the overall yield is low. Alkyl and aryl radicals have been generated from diverse sources (Table 25). 

Allyloxy)iodoarenes react with Sml2 to yield radical anions, which undergo thermal fragmentation. The resulting aryl radicals can cyclize to dihydrobenzofurans (Entries 8-10, Table 15.9). The radical obtained after cyclization can be reduced and treated with a proton source such as water or an alcohol to yield alkanes, or with carbonyl compounds to yield alcohols (Entry 10, Table 15.9). 

Termination steps in SrnI reactions compete with the propagation steps and, although these processes have aroused considerable mechanistic and theoretical speculation (see Chapter 9 in ref. 18), their effects, with several important exceptions, are not significant. For example the self-coupling of aryl radicals (equation 11) does not appear to occur under the conditions used for the SrnI reaction. One potentially disruptive termination step is reduction of the intermediate aryl radical (equation 6). The source of the reducing electron can be a dissolving metal (or solvated electron), one of the radical anion intermediates in the reaction (ArNu- or ArX- ), an electrode, or the nucleophile itself. These termination... 

The ability of diazonium salts to act as radical scavengers for nucleophilic alkyl radicals was first discovered in mechanistic studies on the Meerwein arylation [96]. Shortly after, this concept was applied for the functionalization of a limited group of activated alkenes [97-99]. The much greater synthetic potential of this functionalization type, which arises from the successful use of non-activated alkenes as substrates, has recently been investigated. In a typical reaction, as illustrated in Scheme 19, the diazonium salt 48 acts as source for aryl radicals 49 and as radical scavenger [100]. 

Benzotriazoles, when irradiated at a wavelength of 300 nm, have turned out to be convenient sources for the previously unknown 2-amino-substituted aryl radical (Scheme 34) [150]. From a solution of benzotriazole 88 in benzene, 2-aminobiphenyl 89 was isolated in quantitative yield. This elegant approach... 

Radical arylations of phenols differ in some respects from those of phenolates (Scheme 37). First, the decreased nucleophilicity of the phenol, such as 100, allows the use of unmasked aryl diazonium chlorides 101 as radical sources. Given that an efficient reductant is present in the reaction mixture and that the diazonium salt is added slowly, biphenyl alcohols 102 can be prepared in moderate to good yields [153,154]. In this way, the concentration of the salt 101 is kept low at any time and homocoupling reactions (addition of the aryl radical to diazonium ions) as well as azo coupling to the phenol 100 can be successfully overcome. 

---