Visible-Light-enabled Difluoroalkylation Of Hydrazones Under Eosin Y Catalysis

The introduction of a fluorine-containing group into an organic molecule enhances the metabolic stability,lipophilicity,and cell membrane permeability of the organic molecule,the target protein binding ability,and the bioavailability ratio.However,natural organic fluorine-containing compounds existing in nature are extremely rare,and therefore,the reaction of introducing a fluorine-containing group into an organic compound has been widely concerned by chemists.Due to the difluoroalkylation reaction of organic molecules,not only the fluorine-containing groups can be introduced into the organic molecules,but also other groups can be introduced into the organic molecules,which is more economical in the organic synthesis step.Hydrazones are an important class of organic synthesis intermediates,which have extremely important applications in the fields of medicine,pesticides and materials.The introduction of a difluoro group into the hydrazones enhances the metabolic stability,the esterophilicity and the reactivity of the steroid,so that it can act better on the organism.Therefore,the introduction of difluoro groups into hydrazones is of great significance for enhancing the applicability of hydrazones.In recent years,transition metal-catalyzed difluoroalkylation of hydrazones has made good progress.However,these reactions also have some limitations.For example,some of the transition metal catalysts used are expensive,which limits their further applications.The transition metals used are prone to residues in the product and remain in the waste liquid after the reaction.Transition metals can cause significant pollution to the environment.Therefore,the development of an efficient,green method to synthesize difluoroalkylated hydrazones still has potential application value.This paper reports the difluoroalkylation of hydrazones catalyzed by EosinY under visible light.In this paper,the coupling reaction of hydrazones with ethyl bromide difluoroacetate was catalyzed by Eosin Y under the action of visible light.In this paper,benzaldehyde and N-aminomorpholine synthesized hydrazone and ethyl bromodifluoroacetate were used as substrates for the model reaction.The reaction conditions were optimized.The types and amounts of high-valent iodine reagents,the types and amounts of catalysts were investigated,solvent,alkali effect on the reaction.The optimum conditions for the reaction were determined to be 0.2 mmol for hydrazone,0.3 mmol for ethyl dibromodifluoroacetate,and 0.4 mmol for BI-OH,the amount of i-Pr₂NEt is 2 times equivalent is 0.4 mmol,the amount of catalyst Eosin Y is 5 mol%,the amount of solvent t-BuOH is 2 mL,under room temperature conditions in argon atmosphere,at 15 W LED.The reaction was carried out for 12 h.On this basis,the substrate was expanded,and the yield of the substrate was 40%-89%.The free radical capture experiment demonstrated that the reaction involves a free radical process.And proposed the possible mechanism of the reaction.