Electron-withdrawing group effect in aryl group of allyl bromides for the successful synthesis of indolizines via a novel [3+3] annulation approach

A new synthetic approach to 6,7-disubstituted indolizines has been developed from pyrrole-2-carboxaldehydes and allyl bromides via two successive base-mediated reactions. As three-carbon units for formation of pyridine moiety of indolizines, allyl bromides easily derived from Morita-Baylis-Hillman (MBH) adducts were employed. We found that positioning electron-withdrawing group(s) at the aromatic ring of allyl bromides was a key to successful ring closure to allow access to indolizines with unique substitution style. Structurally relevant imidazo[1,2-a]pyridine and pyrido[1,2-a]indole were assembled by this method as well.