The Research On Transition Metal-free Trifluoromethylselenolation And Difluoromethylselenolation

In recent decades,more and more organic fluorides have been applied to various fields such as medicines,pesticides,and materials.Although fluorine-containing organic molecules are so useful,natural fluorine-containing organic molecules are too rare to be utilized.Therefore,the methods of introducing a fluorine atom or a fluorine-containing functional group into a molecule are of great significant.Trifluoromethylselenyl and difluoromethylselenyl are a special class of fluorine-containing functional groups,which not only increase lipophilicity and membrane permeability of target molecules,but also play an important role in anticancer and antiviral fields.These two types of compounds are novel selenium-containing compounds,who have potential applications in pharmaceutical and selenium-enriched products.This thesis mainly studies the trifluoromethylselenolation and difluoromethylselenolation methods in a translation-metal-free protocol,allowing a mild and straightforward synthesis of various trifluoromethyl selenoethers and difluoromethyl selenoethers in a greener and more efficient way.In the first part of this work,we found that tetramethylammonium trifluoromethylselenate（[Me₄N][SeCF₃]）as a cheap,readily available and thermally stable trifluoromethylselenolation reagent,can be used without the present of metals and additives.Trifluoromethylselenolation of a series of electrophiles such as alkyl halides,electron-deficient aryl halides,diaryliodonium triflates,aryldiazonium tetrafluoroborates,andα-diazo carbonyls are directly achieved under the mild conditions.Compared to the known means,advantages of this method include simplicity,sustainability,high speed,low reaction temperatures,mild reaction conditions,a wide range of substrates,and good functional group tolerance.What is more,the reaction conditions we developed for the alkyl halides,reacted for 0.5 h at room temperature,are mild and have comparative yields.In addition,we confirmed that aryldiazonium tetrafluoroborates can also react with[Me4N][SeCF3]and give birth to various trifluoromethyl selenoethers without using any catalyst or additive,and the yields of some products are comparable with those of the early reports employing copper catalysts.In the second part of the work,an efficient and transition metal-free method for the synthesis of aryl or alkyl difluoromethyl selenides（RSeCF₂H）from the corresponding selenocyanates（RSeCN）and TMSCF₂H/t-BuOK is described.Performing the reaction in THF at 0 ^oC for 24 h or at room temperature for 6 h,various types of difluoromethylselenoether compounds were obtained in good to excellent yield.The successful preparation of difluoromethylselenolated sulfadimethoxine derivative and the gram-scale synthesis of1-benzyl-5-（（difluoromethyl）selanyl）indoline,as examples,suggested good practicability of this method.Advantages of the reaction include mild reaction conditions,good functional group tolerance,a wide range of substrates,and high efficiency.Prior to this,the difluoromethylselenolation reactions have not been systematically studied,and the method of synthesizing difluoromethyl selenoethers is very limited.This part of the work offered a number of novel difluoromethyl selenoethers,which would accelerate use of such compounds in the areas of life science.In summary,using[Me₄N][SeCF₃]as trifluoromethylselenolation reagent,trifluoromethylselenolation of a series of electrophiles have been successfully achieved without the present of metals and additives,confirming that transition-metal is not necessary in this kind of transformation.Similarly,in the absence of transition-metal,we synthesized a variety of difluoromethyl selenoethers,which would accelerate use of such compounds in the areas of life science.