Synthesis Of Imidazo [1,2-a] Pyridine Derivatives Through Cu-Catalyzed C-H Bond Activation

Imidazo[1,2-a]pyridines which exhibit a wide range of biological activities,such as sedative-hypnotic,antineoplastic and antibacterial,are core skeletons of many drug molecures.The objects of this thesis are synthesis of imidazo[1,2-a]pyridine derivatives through Cu-catalyzed C-H bond activation.Three carbonylation reactions and one homocoupling reaction of imidazo[1,2-a]pyridine were developed through regioselective C-H activation at C-3,which enriched the synthetic methods and the diversity of imidazo[1,2-a]pyridines.The details are as follows:In chapter 1,recent progress of imidazo[1,2-a]pyridines was summarized in two aspects which are biological activity and synthetic method study.The contents and ideas of this thesis were also described.In chapter 2,an efficient copper-catalyzed oxidative cross-coupling of imidazo[1,2-a]pyridines with methyl ketones to directly generate 1,2-dicarbonyl imidazo[1,2-a]pyridine derivatives has been described.Dioxygen was used as the oxidant.18O-labelling experiments indicated that the oxygen of the dicarbonyl products originated from dioxygen rather than from water.A series of compounds with Hela cell inhibitory activity was identified through Antitumor activity experiments.In chapter 3,an efficient regioselective Cu-catalyzed C3-formylation reaction of imidazo[1,2-a]pyridines has been developed.Widely available DMSO was used as the ‘C' source and dioxygen was used as the oxidant.This method shows high practicality as the products was generated in good yields with mild reaction conditions.In chapter 4,an efficient copper-catalyzed selective cross-coupling of imidazo[1,2-a]pyridines with methyl heteroarenes has been reported.This transformation showed a new route to synthesize the C-3 carbonyl imidazo[1,2-a]pyridine derivatives without any directing groups.Dioxygen was used as the oxidant and 18O-labelling experiments indicated that the oxygen source of the products was originated from O₂.In chapter 5,a facile and efficient copper?I?-catalyzed intermolecular directly C-H homocoupling of imidazo[1,2-a]pyridines with excellent C-3 regioselectivity has been developed.This transformation provides a straightforward and operationally simple route for the preparation of biimidazo[1,2-a]pyridines.The application prospect of this strategy is positive since the important roles played by biheteroaryls in synthetic chemistry.