Reactions of Heterocycles with Nucleophilic Radicals

The reaction of nucleophilic radicals, under acidic conditions, with heterocycies containing an imine unit is by far the most important and synthetically useful radical substitution of heterocyclic compounds. Pyri-dines, quinolines, diazines, imidazoles, benzothiazoles and purines are amongst the systems that have been shown to react with a wide range of nucleophilic radicals, selectively at positions a and y to the nitrogen, with replacement of hydrogen. Acidic conditions are essential because A-protonation of the heterocycle 

Several methods have been employed to generate the required carbon-centred radical, many depending on the initial formation of oxy or methyl radicals, which then abstract hydrogen or iodine from suitable substrates, as illustrated below. The re-aromatisation of the intermediate radical-cation is usually brought about by its reaction with excess of the oxidant used to form the initial radical. 

In contrast to the oxidative generation of radicals described above, redactions of alkyl iodides nsing tris(trimethylsilyl)silane also produces alkyl radicals under conditions suitable for Minisci-type substitution. Carboxylic acids (a-keto acids) are also useful precursors for alkyC° and/or acyC radicals via silver-catalysed peroxide oxidation, or from their l-hydroxypyridine-2-thione derivatives, the latter in non-aqueous conditions. 

An instructive and useful process is the two-component coupling of an alkene with an electrophilic radical the latter will of course not react with the protonated heterocycle, but after addition to the alkene, a nucleophilic radical is generated, which will react.  

When more than one reactive position is available in a heterocyclic substrate, as is often the case for pyridines for example, there are potential problems with regioselectivity or/and disubstitution (since the product of the first substitution is often as reactive as the starting material). Regioselectivity is dependent to a certain extent on the nature of the attacking radical and the solvent, but may be difficult to control satisfactorily.  

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Reactions of heterocycles with nucleophilic radicals The Minisci reaction" ... 

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