Neighboring Group Participation in the Pyrrole Series

With use of proton and carbon-13 NMR spectroscopy of deuterium- and carbon-13-labeled substrates, the transformation of certain (2-hydroxyethyl)pyrroles (4,18, 21) into the corresponding (2-haloethyl)pyrroles (using thionyl chloride/pyridine or triphenylphosphine/carbon tetrabromide) is shown to proceed with scrambling of the two carbons in the side chain. The mechanism is proposed to involve neighboring group participation by the pyrrole nucleus to give an ethylenepyrrolonium ion, 17. When a nuclear ester is conjugated with the carbon bearing the hydroxyethyl side chain and the adjacent peripheral β position is unsubstituted (e.g., pyrrole 25), the transformation into (2-chloroethyl)pyrrole 26 proceeds without scrambling. In contrast, the β-methylpyrrole 21 was transformed into a mixture of (2-chloroethyl)pyrroles (33 and 34) when treated with thionyl chloride/pyridine. Using carbon-13-enriched porphyrins, conversion of (2-hydroxyethyl)porphyrins into the corresponding 2-chloroethyl derivatives is shown to take place without scrambling of the side-chain carbons and therefore without anchimeric assistance by the porphyrin nucleus.