C-1 and C-3 protonation of indolizines

The structures of 3-methyl-, 3,7-dimethyl-, 2,3,6-trimethyl-, and 2,3,7-trimethyl-indolizinium perchlorates in trifluoroacetic acid were determined by proton magnetic resonance and shown to be protonated preferentially on C-1. These cations in dilute aqueous hydrochloric acid, however, were shown to be mixtures of C-1 and C-3 protonated species. The cations of seven indolizines lacking a 3-methyl group consisted almost entirely of C-3 protonated species in both solvents. Steric hindrance by a methyl group to protonation on C-3 in some 3-methyl-substituted indolizines is invoked.