Study On The Application Of Visible-Light Catalytic Free Radical Reaction In The Synthesis Of Pharmaceutical Active Intermediates

Using visible-light catalytic technology,we can directly convert solar radiation energy into chemical energy.With the development of metal coordination chemistry,researchers have broken through the bottleneck of low-efficiency visible light catalysts.In recent years,visible light catalytic technology has made rapid progress in the application of organic synthesis.A large number of reaction examples also show that visible light catalytic technology can be used to synthesize some molecules that cannot be constructed by traditional organic synthesis means.Under the action of photocatalysis,the disconnection and linkage of organic molecular bonds can produce unique and diverse types to produce a variety of active intermediates.Thus,it provides a more effective route for the organic synthesis of drugs.Visible light catalysis-mediated organic synthesis is highly innovative and has a very broad application prospect.This project established three reaction systems using visible-light catalysis.(1)Directly trifluoroethylation of alkynoate with visible-light catalysis to synthesize coumarin trifluoroethylated derivativesThe fluorine-containing group can significantly improve the physicochemical properties and biological activity of drug molecules,and is widely used in the field of medicine.However,the study of direct trifluoroethylation of the substrate has been limited.Here,using propylic acid ester and trifluoroiodoethane as raw materials,tris(bipyridyl)phosphonium dichloride as the photocatalyst and irradiated with a 5W blue LED bulb(400-450 nm),we successfully achieved the trifluoroethylation of alkynoesters.The conditions are mild with a simple operation and good yields of 21-74%.We synthesized 25 trifluoroethylated coumarin derivatives,which enriched the library of coumarin compounds,and provided synthesis methods for the coumarins in the anti-tumor,anticoagulant and other medicinal activities.(2)Heterocyclic ?-arylation with visible-light catalysisMany natural compounds and drug molecules contain a heterocyclic aryl skeleton.How to construct such structures simply and efficiently is an important issue.The unique chemical structure of aryl diazonium salt makes it easy to form aryl radicals,can react with many types of compounds,and can be used as a good source of arylation reagents.In this topic,we chose aryl diazonium salt as the arylation reagent,and tris(bipyridyl)ruthenium as the catalyst,successfully achieved the ?-arylation of furan and thiophene with a 5W blue LED bulb(400-450 nm)irradiating.And 30 arylation products were synthesized with a moderate yield of 43-70%.This method is simple and efficient.It does not need to pre-activate the substrate and subtly avoids the self-coupling phenomenon of the substrate in the reaction.(3)Ring-opening of epoxy with visible-light catalysis to produce ?-alcohol compoundsVinyl epoxides are molecules that are rich in chemical properties because the large-tension three-membered ring and the carbon-carbon double bond are close in nature and are prone to ring-opening reactions.We selected chalcone vinyl epoxy compounds as substrates,metal-free organic dye compound Eosin Y as the catalyst,and Hantzsch esters as hydrogen sources,successfully achieve the ring-opening reaction of chalcone epoxy compounds.Eleven ?-hydroxy chalcone compounds were synthesized in a yield of 38-73%.The photocatalyst we used does not contain metallic elements,is clean and environmentally friendly,meeting the requirements of green chemistry.