Study On The Construction Of C(sp~3)-C(sp~2) Bond Based On Photocatalytic Debromination And Decarboxylation

In the research of organic synthesis,the modification of aromatic groups is generally made of Grignard reagents of aromatic halides,and then expanded,the conditions are severe,the technical difficulty is high,and it is not suitable for the research and application of small molecule drugs.However,photochemistry has obvious advantages:the reaction conditions are mild,the reaction process is a free radical reaction,and the operation is simple.It is very convenient for the synthesis of C(sp~3)-C(sp~2)bonds in conventional synthetic molecules.In recent years,the types of reactions involved in photocatalysis research have been increasing,and it is expected to develop into a practical method for organic synthesis,which has received more and more attention in organic synthesis methodology.Especially large-scale R&D companies often encounter various C-C bond construction problems during the heterocyclic carbon-carbon coupling reaction.Therefore,it is necessary to quickly build a photocatalytic coupling platform and introduce photocatalysis Chemical methods to reduce the cost of operating a photochemical platform and apply it to new drug development.It can not only reduce energy consumption,reduce the generation of waste materials of heat medium consumables,solve chemical problems such as environmental pollution,achieve optimized processes,improve the efficiency of new drug research and development,shorten the cycle of new drug research and development,and have a broad market value.In order to obtain the advantages of mild conditions,avoid pre-preparation,easy post-processing,and high selectivity,this subject uses the following photocatalytic methods to construct C(sp~3)-C(sp~2)bonds:1.We synthesize 4-(1-oxoisoindol-5-yl)piperidine-1-carboxylic acid tert from5-bromo-2,3-dihydroisoindol-1-one and 4-bromopiperidine as raw materials In the template reaction of butyl ester,the photocatalyst,alkali,temperature,solvent and other conditions were screened.At the same time,the substrate was also expanded,and a good reaction yield was obtained.By consulting the literature,we preliminarily speculated the reaction mechanism of visible light catalysis and nickel-catalyzed double catalysis.Finally,we clearly understand that aromatic bromine and alkyl bromide play a green,environmentally friendly,fast and effective role in the construction of the bond between C(sp~3)-C(sp~2).2.Synthesis of ethyl 4-(1-tert-butoxycarbonyl)(methyl)amino)ethyl)benzoate from ethyl 4-bromobenzoate and N-(tert-butoxycarbonyl)-N-methylalanine Study on the template reaction of esters,screening photocatalyst,alkali,temperature,solvent and other conditions.The expanded substrate gives a better reaction yield.At the same time,the possible mechanism of the reaction was preliminarily speculated,and the cooperative catalytic cooperation mechanism between photocatalytic reduction and nickel was obtained.Through the above photocatalytic methods,we have solved the problem of the bond construction between many heterocyclic compounds C(sp~3)-C(sp~2).