Study On Photocatalytic Fluoroalkylation Of Aromatics Or Olefins

The introduction of fluorine-containing functional groups into the parent molecules can significantly improve their conformational stability,lipophilicity and biological activity.Difluoroalkyl or trifluoromethylcyclopropyl are the most common fluorine-containing group,is widely used in the fields of pharmaceuticals,dyes and materials.Difluoroalkyl groups are usually selectively introduced into the benzene ring structure by means of pre-installed or transient guiding groups.The para-selective C-H difluoroalkyl of substituted aromatic hydrocarbons is less explored.This may be due to the long distance between the para-C-H bond and directing groups,which makes it difficult to form a cyclic metal chelate with metal catalysts.The cycloaddition reaction of trifluoroethylcarbin with olefins was usually used to introduce trifluoromethylcyclopropyl into organic molecules,but the raw materials required for this method are less stable diazo compounds,which have certain dangers.In recent years,visible light-catalyzed organic reactions have become a reliable and effective method of synthesis in organic chemistry because of their good selectivity,mild conditions,safety,high efficiency and low energy consumption.In this thesis,the photocatalytic difluoroalkylation or trifluoromethyl cyclopropylation of aromatic hydrocarbons or olefin derivatives were developed from commercial available,stable and safe raw materials.This dissertation mainly includes three parts:Part I:A new method for efficient and practical aromatic aldehyde ortho-and para-selective C-H bond difluoroalkylation.has been developed based on the study of photocatalytic site-selective C-H difluoroalkylation of aromatic aldehydes.The reaction of the fluoroalkylation reagent ethyl difluorobromoacetate with benzaldehyde catalyzed by fac-Ir(ppy)₃ under blue light radiation conditions afforded highly para-selective substituted 4-difluoroacetate benzaldehyde products.The reaction substrates were widely applicable and has good functional group compatibility,and was suitable for regardless of the substitution pattern on the aromatic ring(ortho-or meta-substituted benzaldehyde)to obtain aromatic aldehyde difluoroalkylation products in good yields(up to 80%)and high para-selectivity.Additionally,when using various para-substituted(electron-rich and electron-deficient)benzaldehydes,as a substrate,the ortho-preferred difluoroalkylated products can also be synthesized in good yield and with excellent o-position selectivity.The mechanism study shows that under visible light excitation,fac-Ir(ppy)₃ promotes the formation of fluorine-containing radical intermediates from ethyl difluorobromoacetate through single electron transfer,and radical substitution occurs at the para-(ortho-)position of aromatic aldehydes to produce para-(ortho-)substituted difluoroalkylbenzaldehydes.The selective C-H bond difluoroalkylation of aromatic aldehydes was realized directly through the radical pathway without the assistance of additional directing groups,which expands the photocatalytic selective C-H bond fluoroalkylation reaction with certain theoretical significance and potential applications.Part II:The trifluoromethylcyclopropylation of aryl olefins was achieved by decarboxylation coupling reaction with N-hydroxyphthalimide trifluoromethyl cyclopropane carboxylate as fluorination reagent and catalytic amount of fac-Ir(ppy)₃as photosensitizer under blue light radiation conditions.Aromatic olefins with different substituents(electron-rich and electron-deficient)on the aromatic ring can obtain E-configuration products with good yield and excellent stereoselectivity under mild and safe reaction conditions.A series of trifluoromethylisopropyl-substituted olefin derivatives with potential application value and excellent stereoselectivity(E/Z up to99:1)were synthesized in this reaction system,and also shows good functional group compatibility with aryl olefin substrates.Through the radical inhibition experiment,we speculated that the reaction proceeds via a radical pathway.A novel and efficient method for the synthesis of allyl trifluoromethylcyclopropane and allyl trifluoromethylisopropane compounds has been discovered,expanding the research field of aromatic olefins containing fluorine compounds.Part III:A series of aryl trifluoromethylcyclopropane carboxylates with important applications were synthesized in high yields(up to 90%)by the coupling reaction of aryl bromides with 1-trifluoromethylcyclopropanecarboxylic acid under the conditions of blue light radiation through the optimization of conditions and the expansion of reaction substrates,using Ni Br₂·DME or Ni Cl₂·DME as catalysts and fac-Ir(ppy)₃ as photosensitizer.The reaction mechanism may involve the energy transfer from the excited state of[Ir(ppy)₃]^*to the carboxylic acid-Ni^II-aryl complexes to achieve a direct coupling reaction between aryl bromides and 1-trifluoromethylcyclopropanecarboxylic acid by nickel-catalyzed.A novel synthetic route to aryl trifluoromethylcyclopropane carboxylates has been developed and can be smoothly scaled up to gram-scale reactions with potential industrial applications.