Electrochemical Cobalt-catalyzed C-H Amination And Radical Cyclization To Construct Nitrogen Heterocycles

Modern organic synthesis can construct a variety of high value-added functional molecules efficiently;developing more efficient and environmentally friendly synthetic methods is an important topic in the field of organic synthesis.As the widely existing hydrocarbon,C-H functionalization reaction is an important means to synthesize various functional molecules.The direct oxidative dehydrogenation coupling reaction of R~1-H/R~2-H is undoubtedly a very ideal reaction mode.Organic electrochemical synthesis can activate substrate molecules through redox process without adding external oxidants or reducing agents,which meet the requirements of atomic economy and green chemistry.In recent decades,a series of electrochemical C-H functionalization reactions have been developed to construct various functional molecules by combining the strategy of electrochemical anodization with modern organic synthesis methods.In transition-metal-catalyzed C-H functionalization reactions,the metal catalyst can realize the catalytic cycle by anodic oxidation.In addition,electrochemical oxidation-induced C-H functionalization can also construct C-C and C-X efficiently.Here are the main results as follows:(1)An environmentally-friendly electrochemical cobalt-catalyzed C-H amination of arenes has been developed,which provides a simple way for the synthesis of useful aromatic amines.In the cobalt-catalyzed C-H functionalization reaction,a lot of silver or manganese salts are needed to promote the dehydrogenation process of the reaction,which would cause serious metal residues.In divided cells,cobalt catalyst could be directly oxidized on the anode without using additional oxidant.In terms of substrates,varieties of aromatic and alkyl amine substrates could participate in this reaction to furnish C-N formation products with high atomic economy,avoiding the formation of other by-products.Importantly,the reaction could also be scaled up to gram level in good yield.Mechanistically,the intermolecular and intramolecular kinetic isotope effect experiments indicated that C-H bond cleavage might not be involved during the rate-limiting step.In addition,cyclic voltammetry experiments and chronoamperometric experiments also proved that cobalt catalyst was oxidized at the anode.(2)A green and efficient method for the synthesis of indole derivatives was developed by electrochemical intramolecular oxidative cyclization of N-aryl enamines.In the past,the intramolecular epoxidation of N-aryl enamines usually required the use of stoichiometric oxidants,such as copper(II)salt,high valent iodide reagent,N-bromosuccinimide(NBS)and oxygen to promote the reaction.From the point of view of atomic economy and sustainable chemistry,the direct dehydrocyclization of N-aryl enamines without external oxidants is more attractive.Herein,a simple method for the synthesis of indole was realized by electrochemical oxidation.The final target product could be obtained efficiently without the addition of external oxidants and transition metal catalysts.At the same time,N-pyridine enamine could also participate in this reaction to furnish imidazo pyridine derivatives through intramolecular C-N formation.Mechanistically,we confirmed that hyperiodide intermediate generated in situ by anodic oxidation was found to be the key for achieving this transformation.(3)A practical method for the synthesis of polysubstituted pyrrole was developed by electrochemical oxidation cyclization from amines and aldehydes or ketones.Well-documented classic Paal–Knorr reaction could synthesize susbstitued pyrroles via the condensation and cyclization between 1,4-diketones and primary amines.Transition-metal-catalyzed dehydrogenative annulation reaction was a general and practical strategy to synthesize various polysubstituted pyrroles.Under electrochemical conditions,?-substituted pyrrole was synthesized by using arylacetaldehyde and primary amine as substrates.Using imine intermediates as substrates,which were synthesized in situ via condensation between easily accessible ketones and amines,the final tetrasubstituted pyrrole derivatives,which were difficult to synthesize by traditional chemical methods,could be successfully obtained by anodic oxidation.In addition,this electrochemical reaction could be carried out with good functional group tolerance and scalability.The polysubstituted pyrrole products could also proceed later stage functionalization.