Substitution, radical nucleophilic, unimolecular reactions

A large number of radical reactions proceed by redox mechanisms. These all require electron transfer (ET), often termed single electron transfer (SET), between two species and electrochemical methods are very useful to determine details of the reactions (see Chapter 6). We shall consider two examples here - reduction with samarium di-iodide (Sml2) and SRN1 (substitution, radical-nucleophilic, unimolecular) reactions. The SET steps can proceed by inner-sphere or outer-sphere mechanisms as defined in Marcus theory [19,20]. 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

This chain reaction is analogous to radical chain mechanisms for nucleophilic aliphatic nucleophilic substitution that had been suggested independently by Russell and by Komblum and their co-workers. The descriptive title SrnI (substitution radical-nucleophilic unimolecular) was suggested for this reaction by analogy to the SnI mechanism for aliphatic substitution. The lUPAC notation for the SrkjI reaction is (T -t- Dm -t- An), in which the symbol T refers to an electron transfer. When the reaction was carried out in Ihe presence of solvated electrons formed by adding potassium metal to the ammonia solution, virtually no aryne (rearranged) products were observed. Instead, reaction of 95c produced only 98 (40%) and 94 (40%) but no 99, and reaction of 96c produced 99 (54%) and 94 (30%) with only a trace of 98. ... 

I. Additions. Radicals can react with anionic species to give radical anion adducts as shown for radical 11. Such addition reactions are steps in chain reaction processes described as SrnI (unimolecular radical nucleophilic substitution) reac-... 

Since the pioneering studies of Bunnett [3], the scope of the unimolecular radical nucleophilic substitution (SrnI) reaction has increased considerably, and today this approach is well established for the formation of aryl-carbon and aryl-heteroatom bonds. The SrnI reaction is a chain process which includes radicals and radical anions as intermediates the reaction mechanism is depicted in Scheme 13.1 [1]. 

Radical substitution reactions and their mechanisms and applications have been reviewed several times [189,190]. Thiophene participates well in radical reactions. There are reviews describing both unimolecular radical nucleophilic substitutions (SrnI) [191] and homolytic aromatic substitutions (HAS) of thiophenes [192]. The formation of thiophene radicals from peroxides, thienylamines and iodothiophenes has been discussed [192]. 

For unactivated aromatic and heteroaromatic substrates, where a polar substitution is not favorable, nucleophilic substitution is feasible through processes that involve electron transfer (ET) steps. In these reactions, an aromatic compound bearing an adequate leaving group is substituted at the ipso position by a nucleophile in a unimolecular radical nucleophilic substitution mechanism (or S,y.jl), which is a chain process that involves radicals and radical anions as intermediates. 

C-C bond cleavage reactions are in most cases unimolecular processes, however, the possibility that C-C bond fragmentation occurs through a nucleophilically assisted pathway has been clearly shown in the three-electron Sn2 reactions between arylcyclopropane radical cations and nucleophiles which proceed stereospecilically with inversion of configuration at the carbon atom undergoing nucleophilic substitution (Scheme 45, 1-CN = 1-cyanonaphthalene) [188, 189]. 

The reaction, a versatile synthetic tool, is initiated by generation of a radical anion. The designation Sr I indicates that the reaction is a nucleophilic substitution proceeding through a radical intermediate and that the rate-limiting step is unimolecular decay of the radical anion intermediate formed from the substrate (see a review by Bunnett, J. F. Acc. Chem. Res. 1978, 11, 413-420). Sr I reactions occur with both aliphatic and aromatic compounds. 

The mechanistic description refers to a nucleophilic substitution via a radical intermediate that proceeds by unimolecular decomposition of a radical anion derived from the reactant. There are two families of such reactions that have been developed... 

The acronym Sr I connotates a free radical chain Substitution reaction in which the new bond is formed by attack of a Radical (R ) upon a Nucleophile (N ) and in which the bond to the nucleofuge (X) is broken in a unimolecular process. When ally lie rearrangement is involved, the process is termed Sr T... 

Nevertheless, several kinetic studies have shown that certain nucleophilic substitution reactions of aryl diazonium ions are first order and independent of the concentration of the nucleophilic species. Solvent effects, isotope effects, and substituent effects are also in agreement with a rate-determining unimolecular decomposition of the aryl diazonium ion. In other reactions, an adduct of the nucleophile and diazonium ion is a distinct intermediate. Substitution results when nitrogen is eliminated from the adduct. Finally, substitution can occur via radical... 

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