Studies On Iodine Pentoxide-Promoted Free Radical Trifluoromethylation Reactions

The recent advances in installation of fluorine atom and/or trifluoromethyl group into organic molecules have been summarized in this thesis first.And then a safe,green,efficient free radical trifluoromethylation of four catergories of organic compounds has been demonstrated.It includes the following five parts.In the first part,we summarized the importance of fluorinated drugs and the recent developments of trifluoromethylation reactions.Additionally,the previous strategies and its mechanisms have been discussed.And the possible improvement of these methods has also been proposed.In the second part,we demonstrated our strategy for highly efficient trifluoromethylation in details.By using this protocol,a wide range of alkenes including styrenes and unactivated olefins could all be iodotrifluoromethylated in good yields.In addition,the mechanism for this reaction has been extensively studied by using spin trapping technology with electron-spin-resnance(ESR),which clearly indicates a free radical process should be involved in this system.In the third part,we disclosed that terminal alkynes could be successfully iodotrifluoromethylated by using sodium sulfonate with iodinepentoxide.Further organic transformation could be carried out to synthesize fluorinated pharmaceuticals and pesticides with these products as valuable building blocks.In the fourth part,we depicted that introduction of trifluoromethyl group into heterocyclic compounds such as pyrroles,furans,thiophenes,benzofurans,and benzothiophenes etc could also be achieved by using sodium sulfonate with iodine pentoxide.This method could be used to prepare a variety of drugs with fluorinated heterocycles.In the last part,we discussed the radical addition/elimination reaction of cinnamic acids and its derivatives with sodium sulfonate and iodine pentoxide.A series of trifluoromethyl group substituted styrenes could be isolated in good yields and high stereo-selectivities by using this strategy.In summary,we have developed a valuable and highly efficient free radical trifluoromethylation method by using sodium trifluoromethanesulfinate and iodine pentoxide.Four representative organic molecules could be smoothly trifluoromethylated with this approach.Furthermore,this strategy features safe and low-cost starting materials,easy operation,andenvironmentally benign,which makes it very attractive for organic synthetic chemists.And it is believed to be widely used for drug synthesis in the nearly future.