Scalable Synthesis And Application Of Complexes Of Fluorosulfonyldifluoroacetic Acid Copper(Ⅱ) And Difluoromethioethyl Benzene Sulfonate

Due to their unique physical and chemical properties,fluorinated compounds are widely used in medicine,pesticides,materials science,and other fields.How to efficiently introduce fluorinated groups into molecules has always been an important research topic in organic fluorine chemistry.Compared with harder fluorine atom,sulfur atom,as a softer atom,has many applications in organic chemistry.The combination of the two elements can produce many useful fluoroalkylation reagents for the synthesis of various fluorinated compounds.Fluorosulfonyldifluoroacetic acid copper（II）salt（Cu（O₂CCF₂SO₂F）₂）derived from Chen’s reagent（FSO₂CF₂CO₂Me）is a diverse fluoroalkylation reagent that can be used as both a nucleophilic trifluoromethylation reagent and a deoxyfluorination reagent.However,due to its own structural characteristics,it is very easy to coordinate with water,making it difficult to obtain corresponding anhydrous salts.Once the water is coordinated,the reaction efficiency and yield will be greatly reduced.Anhydrous Cu（O₂CCF₂SO₂F）₂ is obtained on a small scale by long-time vacuum heating and drying,which is not practical to scale-up production.Therefore,how to obtain anhydrous Cu（O₂CCF₂SO₂F）₂ has a significant impact on its application,and is also one of the key factors for its successful application.At the same time,if new fluoroalkylation methods can be developed based on Cu（O₂CCF₂SO₂F）₂,it will further expand its application range and effectively promote its practical application.In addition,due to the importance of difluoromethylthio groups,the scale-up synthesis process of an excellent free radical difluoromethylthio reagent,benzenesulfonic acid difluoromethylthio ester（Ph SO₂SCF₂H）,has also been studied.The main work of this paper is as follows:（1）Study on the preparation and reaction of（bpy）Cu（O₂CCF₂SO₂F）₂.By adding2,2’-bipyridine as a ligand to the in-situ prepared Cu（O₂CCF₂SO₂F）₂ reaction mixture,the water molecules previously coordinated with Cu（O₂CCF₂SO₂F）₂ can be"squeezed out",and the corresponding（bpy）Cu（O₂CCF₂SO₂F）₂ can be conveniently prepared in large quantities.The complex does not absorb water in the air and is convenient for use and operation.Next,we studied the nucleophilic trifluoromethylation reactions of this complex with various aryl iodides,and compared the trifluoromethylation reactions with those of corresponding Cu（O₂CCF₂SO₂F）₂ and FSO₂CF₂CO₂Me.The decomposition of this complex in large polar solvents was also studied and it was found that（bpy）Cu（CF₃）₃ intermediates can be produced in situ.Using this property,we have also preliminarily achieved direct radical trifluoromethylation of the C-H bond of saturated alkanes,but further research is still needed to improve the reaction yield.（2）Study on the scalable synthesis and application of Ph SO₂SCF₂H.The reaction conditions for the synthesis of Ph SO₂SCF₂H were studied and optimized in detail.The reagent was synthesized on 500 g scale,and its stability was analyzed.Several gram scale reactions of small molecules containing SCF₂H were also carried out using the reagent.