Arylation with Nucleophilic C-Centered Radicals

Stable longlived cyclohexadienyl radical 66 can either dimerize to give 69 or disproportionate to form cyclohexadiene 70 and arene 68. Moreover, H-abstraction from cyclohexadienyl radical 66 directly leads to arene 68. 

Side reactions are often observed in these intermolecular radical arylations, one major limitation being the slow reaction of the alkyl radical with the arene. The tert-butyl radical addition onto benzene occurs at 79 °C with a rate constant of 3.8 X 10 M s [103], which is far below the rate constant of an efficient radical reaction. Consequently, side reactions-including rearrangement, dimerization and 

The radical alkylation of protonated heteroaromatic compounds-the so-called Minisci reaction-has been intensively investigated [2e, g, 111]. Protonated hetero-arenes are electron-deficient substrates, which react with nucleophilic radicals with high regioselectivity to yield the corresponding homolytic aromahc substitution products. For para-substituted pyridine derivatives the reaction occurs with complete regioselectivity at the 2-position, whereas for nonprotonated pyridines, arylations occur with low regioselectivity and in low yields. 

These reactivity trends show clearly that polar effects are involved in these radical substitution reactions. The transition state is thought to involve a charge-transfer process from the radical (electron donor) to the pyridinium ion (electron acceptor) [114]. In this respect, frontier molecular orbital (FMO) theory [115] has been applied to explain the reactivity differences that have been observed upon varying the substituents at the pyridinium ion and upon altering the nucleophihc-ity of the attacking radical. FMO can also be used to explain the regioselectivities obtained in these homolytic aromatic substitutions. Here, the LUMO of the substituted pyridinium cation has the highest coefficients at carbon atoms 2 and 4 

---