Green Synthesis Of Isoindolinone Compounds And Base-catalyzed Isomerization Of Electron-deficient N-allylamides

The thesis contains two sections:Section one:Isoindolinone moiety is ubiquitous in many natural products and pharmaceuticals,which exhibit a wide range of biological activities such as antipsychotic,antihypertensive,anti-inflammatory,antiviral,antileukemic.Among the numerous approaches for the synthesis of isoindolinones,transition metal-catalyzed methods play an important role.However,for green chemistry,these may not be the best choice due to the probable heavy metal contamination for the environment.In this thesis,we have developed a green and facile approach to straightforward installation of isoindolinone skeletons via a tandem reaction of 2-cyanobenzaldehydes and ?,?-unsaturated ketones/esters.In the presence of catalytic amounts of organocatalyst,fluorous phosphine,in green solvents at rt,a variety of isoindolinones were obtained in good to excellent yields without tedious column chromatography.Moreover,both the catalyst and the solvent could be recycled,which greatly reduced the consumption and waste of resource.The main contents of this paper include:1.Green synthesis of isoindolinones.By employing recyclable phosphine(?)compounds as catalysts and ethyl acetate,isopropanol,etc.as green solvents,we realized the green and efficient synthesis of isoindolinones at room temperature.2.Efficient separation of product.Pure products can be obtained through filtration instead of tedious column chromatography.3.Resource recycling.By employing fluorous solid-phase extraction(F-SPE),the fluorous phosphine catalyst could be recycled.Besides,the solvents could be reused by directly adding substrates to the filtrate obtained from the seperation process of reaction mixture.Enamides are not only very useful synthetic intermediates for organic synthesis,but they are also widespread in many bioactive natural products and pharmaceuticals.In recent years,many metal-catalyzed methods for the preparation of enamides from the direct alkene isomerization of allyl amides have been developed,which mainly obtains thermodynamically stable E-enamides.However,metal-free methods for the isomerization of allylamide to form enamide is rarely reported in the literature.Section two:In this paper,a base-catalyzed method for the isomerization of electron-deficient N-allylamide to form Z and E enamides is described.Methyl-2(3-oxo-2,3-dihydro-1H-isoindol-1-yl)acrylate,synthesized from our previous work,was used as substrate and triphenylphosphine or DBU were used as organic base,the Z-and E-methyl-2-(3-oxoisoindolin-1-ylidene)propanoate were produced respectively in protic and aprotic solvents.Besides,the mechanism of the reaction was studied as well.The main contents of this paper include:1.Explore the effect of different bases on the conversion rate and selectivity of the reaction.2.Study on the isomerization reaction in protic and aprotic solvents3.By changing solvents and controlling the reaction temperature,Z-product and E-product are obtained respectively.4.Exploration of the possible mechanism.