Electrophilic substitution in lndoles. Part 11. The mechanism of substitution in 5-methoxyindoles

Abstract

Deuterium labelling experiments show that the boron trifluoride-catalysed cyclisation at 90 °C of 4-(5-methoxyindol-3-yl)butanol (1e) to 6-methoxytetrahydrocarbazole (11a) occurs by two simultaneous pathways. The main route (83.5%) involves initial cyclisation at the 3-position of (1e) to give an intermediate spirocyclic indolenine which then rearranges to the tetrahydrocarbazole. The minor pathway (16.5%) involves direct attack at the 2-position. A similar duality of mechanism of substitution applies to the 6-methoxy-, 4,6-dimethoxy-, and 5,6-dimethoxy-indole analogues for which the extent of substitution at the 2-position can be correlated with the calculated change in π-electron density at the 2- and 3-positions for a series of methoxy-substituted 3-methylindoles. These calculations do not, however, fit the experimental findings for the 5-methoxy-derivative which appears to be anomalous, showing an unexpectedly high percentage of direct substitution at the 2-position. A possible explanation of this result is advanced.