Investigation Of New Fluorinated Building Block Reagents And Related Reactions Based On Fluorinated 1,3-Dicarbonyl Compounds

Nucleophilic fluoroalkylation reaction is one of the important methods to introduce fluorinated group into organic molecules.However,the introduction of fluorine poses a negative effect on the thermal stability of many a-fluoro carbon anion and corresponding nucleophilic fluoroalkylation reactions.This dissertation mainly focuses on the investigation of the thermal stability of ?-fluoro carbon anion in carbonyl group mediated nucleophilic fluoroalkylation reactions.Therefore,investigating the fluorinated 1,3-dicarbonyl compounds,a new type of fluorine-containing building-block,which participate in some of the fluoroalkylation reactions and applicate in some highly stereoselective and multicomponent reaction systems to obtain some structure which is unable or difficult to obtain by directly fluoroalkylation raction.First of all,it was found that 2-fluoro-1,3-dicarbonyl compounds could react with aldehyde in a similarly Wittig raction process to produce a-fluorine-?,? unsaturated carbonyl compounds in alkaline and mild reaction conditions.Fortunately,we achieved high Z/E value and excellent yield through regulation of base species and proper temperature oweing to the high thermal stability of a-fluoro carbon anion.Compared with the fluorinated Wittig reagent used in traditional method,the advantage of this new building-block is that the stating material is easy to obtain and stable during storage due to its excellent physicochemical properties,also the reaction shows high stereoselectivity and excellent yield in mild reaction conditions wiyhout metal catalytic.In addition,we found that the substrate of the reaction is also very wide,especially for ester carbonyl,ketone carbonyl and amide carbonyl with which the reaction yields are relatively higher and Z/E value is above 95%.Secondly,we investigated the synthesis of 3,5-disubstituted phenols from a-fluoro-?-ketoesters and ?,?-unsaturated ketones in high temperature with cesium carbonate which involved the reaction mechanisms of Michael addition,Robinson annulation,dehydrofluorination,aromatization and decarboxylation.According to the further study,we found that this reaction process can be controled by the amount of cesium carbonate and the reaction temperature,which would determine the production of the corresponding 2-ester phenol and phenol before or after decarboxylation.Through this new reaction strategy,we could easily synthetic 3,5-disubstituted phenols which was difficult to obtain in traditional methods,also via the expansion of the substrate,we successfully synthesized 4-fluoro-3,5-disubstituted phenols using a-fluorine-?,?-unsaturated carbonyl compound instead of chalcone.Furthermore,we also successfully synthesized Polysubstituted Phenols by changing the starting material.Finally,we found that 2,2-difluoro-1,3-dicarbonyl compounds can produce decarbonylation with existence of base in mild condition to generate ?,?-difluoroenolates anion which showed high activity.The reaction substrate fixed to the chical catalyst in a special space location by forming a strong intermolecular ionic bonds between tertiary amine nitrogen ions(bifunctional thiourea derived from a cinchona alkaloid)and the fluorine enol oxygen anion(?,?-difluoroenolates),and N-substituted isatins fixed to the chical catalyst by forming ntermolecular hydrogen bonds.After that Aldol reaction occurred between the two molecular to synthesis(S)-3-hydroxy-3-substituted oxindoles.This reaction showed satisfactory results with substantial ee values up to 98%and high yields of more than 80%.As known to all,Cvinyl-CF2H is a huge challenge to establishment.After further research,we found that,under high temperature and presence of cesium carbonate a,a-difluoroenolates anion could react with acetonitrile to generate?-difluoromethyl-acrylonitrile through Knoevenagel condensation.This strategy is promising in construction of Cvinyl-CF2H bonds which utilizes simple procedures and non-metal catalytic and the reaction substrates is easy to obtain,stable during storage with excellent physicochemical properties.Since the new kind of fluorinated 1,3-dicarbonyl compounds shows many advantages and a promising prospect as fluorine-containing building-block in the synthesis of fluorinated molecule,development of this new series of compounds presents potential application value for the discovery and development of new drugs.In addition,as this new kind of fluorinated building-blocks are easy to synthesis,separation,purification,storage and transportation,the application in industrial production appears promising.