Visible-light-induced Selective Alkylation Of C-H Bond On Nitrogen-containing Heterocycles

The construction of C-C bond is an important research direction in organic synthesis.For small molecules of drugs,the introduction of alkyl groups can enhance their lipid solubility and stability,which is of great significance for enhancing the absorption and transport capacity of drugs in the human body.Visible light catalysis can realize single electron transfer,energy transfer or atom transfer between catalyst and substrate under mild conditions,and it is a green and efficient reaction method.In recent years,with the vigorous development of visible light catalysis,the construction of carbon-carbon bonds or carbon-hetero bonds through visible-light-catalyzed radical coupling reactions has become a research focus in the field of organic synthesis.This thesis focuses on the visible-light-induced selective alkylation of C-H bond on nitrogen-containing heterocycles.The specific content is mainly divided into the following three aspects:The first chapter introduces the research background of C-H bond alkylation.The alkyl radical precursor reagents developed in recent years were classified,and related research results were reviewed from the aspects of catalytic system,reaction yield,substrate practicality,and reaction mechanism.Chapter 2 introduces a visible-light-induced selective alkylation at the C-5position of imidazo[1,2-a]pyridines.This reaction system uses the cheap dye Eosin Y as a photocatalyst and N-hydroxyphthalimide?NHP?ester as an alkylating reagent,and a new method for constructing C?sp²?-C?sp³?bond has been developed.Through the screening of photocatalysts,light sources,acid additives,solvents,and comparative studies,optimal reaction conditions were obtained,and 30 examples of C-5 alkyl-substituted imidazo[1,2-a]pyridine compounds were synthesized in a medium to excellent yield?38%to 86%?.This reaction has good substrate applicability to a variety of primary,secondary or tertiary alkyl-substituted NHP esters.The Stern-Volmer fluorescence quenching and free radical intermediate capture experiments were performed to verify the visible-light-induced free radical decarboxylation coupling mechanism.The advantages of this method involve environmental friendliness,the avoidance of transition-metal and stoichiometric oxidants,and mild conditions.The target compound could also be obtained in a good yield when the reaction was scaled up to the gram level.Chapter 3 introduces the selective alkylation of 2H-indazoles under visible-light catalysis using aliphatic carboxylic acid active ester?NHP ester?as the alkyl source.In the experiment,the optimal conditions for the reaction were determined through the screening of photocatalysts,additives,solvents,light sources,and reaction time.At the same time,the application of the NHP ester substrate was studied.Under the optimal reaction conditions,employing fac-Ir?ppy?₃ as a photocatalyst,8 examples of C-3 alkyl-substituted 2H-indazole compounds were synthesized in a medium to excellent yield?44%to 83%?.The experimental results showed that the reaction was well tolerated to primary,secondary or tertiary alkyl-substituted NHP esters.Due to the epidemic situation,follow-up work such as Stern-Volmer fluorescence quenching,intermediate capture and other mechanism verification experiments will be carried out in due course after the epidemic.