Radical-based Trifluoromethylation

During the past serval years,radical based trifluoromethylation of diverse molecular architectures has become an important research topic in synthetic organic chemistry due to the specific advantages of radical reactions,such as milder reaction conditions,broader substrate scope and so on.Firstly,this thesis expatiates the nature of fluorine and the significance of trifluoromethyl-containing compounds,summarizes the history and status of trifluoromethylation,classifies and lists the recent reports about radical based trifluoromethylation according to property of trifluoromethyl reagents,concludes some common conditions for generating trifluoromethyl radical.On the basis of previous work,we focus on developing novel methods for initiating CF3 radical and applying to the reactions which can not be achieved by existing methodologies.The main contents include six parts:The chapter 2 introduced the initiating manner by heating.Despite its stability relatively,Umemoto's reagent could produce CF3 radical when heated.6-trifluoromethylated phenanthridine derivatives could be de novo synthesized by taking advantage of isocyanide insertion and modified the natural products and alkaloids on position 6.This metal-free method shows good functional group compatibility,broad substrate scope,mild reaction conditions and simple operation.The chapter 3 presented initiating manner by photoredox catalyst.Herein,1-trifluoromethylisoquinolines were attained regiospecifically by using photoredox vinyl isocyanide insertion for the first time.The regiospecific synthesis of I-trifluoromethylisoquinoline proceeds under mild conditions in good-to-excellent chemical yields.A detailed mechanism is proposed,which is supported by experiments and theoretical calculations.The chapter 4 developed one novel initiating manner,that is,EDA complex formed between Umemoto's reagent and a tertiary amine activated thermally to generate CF3 radical through SET.Some experiments and theoretical calculations were furnished to support the EDA complex,which was applied to C-H direct trifluoromethylation of arenes.Transition-metal catalysts,directing groups and external oxidants can be avoided.The methodology allows to access highly-functionalized CF3-containing indoles,pyrroles,benzofurans and electron-rich benzenes in good chemical yields.The chapter 5 enriched the application of EDA complex in organic chemistry.We found that Togni's reagent and a tertiary amine could form EDA complex,which was applied to more challenging reactions-hydrotrifluoromethylation of unactivated aliphatic alkenes and alkynes.This strategy featured by broad substrate scope due to the mild reaction conditions.The chapter 6 does business within CF3 radical generated from Umemoto's reagent by being reduced with PPh3.Solvent-controlled oxytrifluoromethylation and hydroxytrifluoromethylation of alkenes were achieved from the same starting material.This method shows simple operation,broad substrate scope which can not be obtained by existing methods,mild reaction conditions and excellent selectivity controlled just by changing solvent.Taking advantage of this strategy,the first hydrotrifluoromethylation of unactivated aliphatic alkenes has been developed.The isotope-labeling studies clearly demonstrate that the oxygen of the newly formed carbonyl and hydroxyl groups of the products were wholly from oxygen molecular,not water.