Novel Fluoroalkylated Reaction Based On CF₃SO₂-Type Reagents

Organofluorine compounds are frequently found in the areas of pharmaceuticals and argochemicals,as well as in materials science,the increasing interest on fluorinated compounds has prompted the development of various methods for introducing fluorine atoms or fluorinated functional groups into organic frameworks.Sodium trifluoromethanesulfinate and trifluoromethanesulfonyl chloride are both commercially available cheap fluorination reagents and have been widely used in various fluoroalkylation reactions,the development of their new applications in fluoroalkylation is not only of academic significance but also of high practical value.In this thesis,we have developed a few methods for the introduction of various fluorine-containing groups to amines and alkenes using sodium trifluoromethanesulfinate and trifluoromethanesulfonyl chloride.First,we have developed a practical and convenient method for the preparation of trifluoromethyl amines with sodium trifluoromethanesulfinate,by using triphenylphosphine as the reducing agent and silver fluoride as the fluorination agent,the trifluoromethylation of the amines can be achieved by a one-pot two-step method at room temperature.The main advantages of this synthetic method include mild conditions,high functional group tolerance and good yields（up to 90%）,the trifluoromethylation modification of bioactive complex molecules can also successfully obtain the corresponding products with a yield of 61%-82%.This method can also be used to synthesize perfluoroalkyl amines using Rf SO₂Na,which provides a practical method for the synthesis of perfluoroalkyl amines.Mechanistic studies reveal that the in situ generated thiocarbonyl fluoride or its perfluoro analogues were the key intermediates in the reaction.Next,we have developed an efficient method for the synthesis of thiocarbamoyl fluorides and isothiocyanates using trifluoromethanesulfonyl chloride with simple reaction conditions,broad substrate applicability and good functional group compatibility,drug-like molecules can also be converted to the corresponding products in good yield（69%-74%）under this condition,the reaction system can also be scaled up to gram scale,showing good application potential.The active intermediate of thiocarbonyl fluoride produced by the reduction of trifluoromethanesulfonyl chloride was captured by controlled experiments and a reasonable reaction route was proposed.Finally,a novel photocatalyzed trifluoromethylthio-trifluoromethylation of alkenes has been developed,using sodium trifluoromethanesulfinate as both CF₃ and SCF₃ source.The reaction is simple to operate,proceeds under mild conditions,and exhibits excellent substrate versatility and functional group compatibility.Various alkenes,including 1,1-disubstituted,1,2-disubstituted and trisubstituted alkenes,were successfully converted into the corresponding product,late-stage modification based on this new method was also proved to be feasible.Furthermore,the mechanistic investigations indicated that a photocatalyzed dual-oxidative process was involved in the reaction,and this method takes advantage of visible-light photocatalysis to generate the trifluoromethyl radical combined with copper-promoted trifluoromethylthiolating process to generate the product.In conclusion,we have found new reactivity of sodium trifluoromethanesulfinate and trifluoromethanesulfonyl chloride and provided theoretical explanation for the corresponding reactions,which will further promote the development and application of CF₃SO₂-type reagents.