Pyrrole 1-methyl-, radical substitution

Radical benzylation of pyrrole produces 2-benzylpyrrole (B-77MI30500), whilst indoles react to give low yields of the 1- and 3-mono-, together with the 1,3- and 2,3-di-benzylated indoles (65JCS4253). Similarly, radical methylation of 2-nitropyrrole (B-77MI30500) has been reported to yield C-substitution products, whereas, in contrast, 2,5-bis(triphenylmethyl)-A3-pyrroline is obtained from the addition of triphenylmethyl radicals to pyrrole. 

The pyrrole and indole rings are readily attacked by a range of electrophilic radicals, generated in various ways. The reaction of alkyl iodides with a combination of iron(II) sulfate and hydrogen peroxide generates alkyl radicals, which give 2-substitution products with pyrrole and 1-methyl-... 

Radical bromination of pyrrole and indole methyl substituents continues to be investigated, as does the substitution of the resulting bromo compound. Selective bromination of the 2-methyl group in 1-acetyl-2,3-dimethylindole can be achieved and the bromide ion displaced by malonate <85TL5253>. A recent example of an effective sequence of bromination and substitution is shown in Scheme 116 <928743, 930PP249,93TL3215>. 

N-methyl-2-formylpyrrole and subsequent H-abstraction by radical R eventually delivers the substituted pyrrole 79. 

Particularly, the book deals with regioselectivity of the reaction between asymmetric methyl alkyl ketoximes and acetylenes involving the construction of the pyrrole ring preferably via the methylene group of the alkyl radical. Also, the reasons of the process selectivity violation at the elevated temperature are discussed. It is shown that the latter phenomenon can be used for the preparation of not only 2,3-dialkyl substituted but also 2-alkyl substituted N-vinylpyrroles. 

---