Intramolecular reactions. Part 12. Ring size and leaving group effects on inter- and intra-molecular nucleophilic substitution by carbanions

Abstract

In cyclisations of aryl ω-halogenoalkyl ketones to aryl cycloalkyl ketones with base, cyclopropanes are formed up to 23 000 times faster than cyclopentanes. Hydrogen–deuterium exchange experiments and very low bromidechloride ratios (1.9) for three-membered ring formation are consistent with rate-determining deprotonation of the ketone. By contrast, in five-membered ring formation, hydrogen–deuterium exchange adjacent to the carbonyl group occurs much faster than cyclisation and the chloride–bromide ratio is ‘normal’ at 99. In formation of arylsulphonylcyclopropanes from arylsulphonylpropyl arenesulphonates, the Hammett ρ value for the leaving group is +1.7, and for intermolecular substitution by bis-sulphonyl stabilised carbanions, +1.2. Attempts to obtain ρ_LG values for five-membered ring formation were frustrated by competing intermolecular reactions. The results are discussed against the background of previous work on ring formation by intramolecular nucleophilic substitution.