Copper-Catalyzed Double Thiolation To Access Sulfur-bridged Imidazopyridines

As a nitrogen-containing heterocyclic compound with a special structure,imidazo[1,2-α]pyridine compounds widely present in pharmaceutical intermediates,and their thioetherated derivatives have attracted much attention in recent years.A copper（I）-catalyzed sulfur-bridged dimerization of imidazopyridines has been developed using isothiocyanate as the sulfur source.This method enables a switchablesynthesisofbis（imidazo[1,2-a]pyridin-3-yl）sulfanesor bis（2-（imidazo[1,2-a]pyridin-2-yl）phenyl）sulfanesinthepresenceof4-dimethylaminopyridine（DMAP）or K₂CO₃ when different imidazopyridines were employed.Under the optimized conditions,a variety of sulfur-bridged imidazopyridines were obtained in good yields.Meanwhile,this protocol is featured with broad substrate scope,good functional group compatibility,and operational convenience.The discovery of isothiocyanate as sulfur source may promote the development of C-H thiolation.The main research contents are as follows:Thereactionof2-phenylimidazo[1,2-a]pyridine1aor2-（2-bromophenyl）-imidazo[1,2-a]pyridine 4a with phenyl isothionitrile 2 was usetiled as a model reaction.After screening the reaction conditions of catalyst,base,solvent and temperature etc,we obtained the optimal reaction conditions for synthesesofbis（imidazo[1,2-a]pyridine-3-yl）sulfaneor bis(2-（imidazo[1,2-a]pyridine-2-phenyl）-sulfane.Under the optimal conditions,the imidazo[1,2-α]pyridinesand2-bromo-2-phenylimidazo[1,2-α]pyridineswere separately extended,and the corresponding sulfide products were obtained in up to88%and 89%yields,respectively（Scheme 1）.In addition,a possible reaction mechanism was proposed according to experiments.