Visible-Light-Induced Reactions Of Acyl Radical For The Construction Of Acylated Heterocycles

As the crucial structural scaffolds in organic synthesis,ketone derivatives are widely present in pesticides,biologically active natural products and various drug molecules.Recently,the research based on the preparation of ketone derivatives has received extensive attention from organic synthesis workers.There is no doubt that the construction of complex ketone compounds based on the addition tandem cyclization reaction efficiently generates acyl radicals is an efficient synthetic route,showing high atom and step economy.As a special kind of carboxylic acid,α-keto acid has the advantages of simple preparation,high stability,easy storage and high reactivity,which is often used as the starting material in organic synthesis.At the same time,α-keto acid can be used as an acylating reagent in acylation reactions,and the carbon dioxide(CO2)release during decarboxylation process is non-toxic and harmless.In recent years,with the development of ruthenium,iridium and other precious metal complexes and various inexpensive and easy-to-obtain organic dye photocatalysts,visible-light-catalyzed green synthesis strategies have become a pivotal existence in organic synthesis.However,the traditional strategies often use transition metal catalysts,high temperatures and stoichiometric amounts of alkaline agents,which run counter to the concept of green synthesis advocated in the modern synthesis field.In this paper,a novel visible-light-mediated strategy for the efficient and mild synthesis of a series of acylated heterocyclic derivatives using α-keto acid derivatives as acyl radical precursors was developed.The research contents are outlined as follow s:A novel metal-free visible-light-promoted decarboxylative arylation procedure ofα-keto acids for the construction of acylated heterocyclic derivatives:(1)By employing α-keto acids and N-acryloyl-2-phenylbenzimidazole/indole with different substituents as reaction substrates,4CzIPN as a photocatalyst,dimethyl carbonate(DMC)as a green solvent at room temperature under the irradiation of a blue LED(5 W),the corresponding cyclization products benzimidazo/indolo[2,1a]isoquinolin-6(5H)-ones were obtained.On the basis of 2,2,6,6-tetramethylpiperidine oxide(TEMPO)and 2,6-di-tert-butyl-p-cresol(BHT)radical capture experiments,fluorescence quenching experiments and other related control experiments,we proposed a plausible reaction mechanism on the example reaction of benzoyl formic acid 2a and N-methacryloyl-2-phenylbenzoimidazole 1a.(2)By employing a-keto acids and N-arylpropynamides(2-methylthioalkynones)as reaction substrates,4CzIPN as a photocatalyst,acetonitrile(MeCN)as a reaction solvent at room temperature under the irradiation of a blue LED(10 W),the corresponding cyclization products 3-acylazaspiro[4.5]trienones(3-acylthioflavones)could be obtained under a nitrogen atmosphere.(3)By employing α-keto acids and heterocyclic compounds(quinoxaline-2(1H)-one,quinoline,isoquinoline,etc.)as reaction substrates,4CzIPN as a photocatalyst,dimethyl carbonate(DMC)as a green solvent at room temperature under the irradiation of a blue LED(5 W),the corresponding acylated heterocyclic products could be obtained.