An Efficient Sequential One-Pot Approach for the Synthesis of C3-Functionalized Imidazo[1,2-a]pyridines under Transition-Metal Free Conditions

A metal-free sequential one-pot three-component protocol is described for the synthesis of C3-functionalized imidazo[1,2-a]pyridines. A successive construction of imidazo[1,2-a]pyridine followed by iodine-catalysed sulfenylation has been achieved in a one-pot operation from readily available alpha-bromomethyl ketones, 2-aminopyridines and thiosulfonates. An immense array of 3-sulfenylimidazo[1,2-a]pyridines were obtained in good to high yields. Also, the method extended for the synthesis of C3-halogenated imidazo[1,2-a]pyridines using sodium halides in the presence of K2S2O8. Notably, the reaction between alpha-bromomethyl ketones and 2-aminopyridines in the presence of K2S2O8 to yield 3-bromo-2-aryl-imidazo[1,2-a]pyridines, thus implies alpha-bromomethyl ketones also served as brominating agent. Overall, the present sequential one-pot protocol is straightforward, operationally simple, tolerates a broad range of functional groups, and is reliable for gram-scale experiments.