Study On The Fluoroalkylation Reactions Based On Noncovalent Interactions Between Solvent And Fluoroalkyl Iodide And Synthesis Of Fluorinated Homophenylalanines

The fluorine atom has the characteristics of small atomic radius,maximum electronegativity and strong C-F bond energy.It is these characteristics that enable fluorine atom or fluorine-containing groups to be introduced into organic molecules to significantly change the physicochemical and biological properties of the parent molecules.At present,fluorinated compounds have been widely applied in agriculture,medicine,materials and other fields.However,due to the scarcity of naturally occurring fluorinated organic compounds,it is critical for organic fluorine chemistry to develop efficient,concise,and environmentally friendly methods for synthesizing fluorinated compounds.Therefore,this paper is oriented to the synthesis of some important fluorinated organic compounds.Some methods are developed for direct coupling with alkenes,alkynes,aromatics,and amino acid zinc reagents by using cheap and easily available halogen(iodine/bromine/chlorine)substituted fluorinated reagents as raw materials.In addition,the reaction mechanisms involved were initially discussed.This dissertation mainly includes three parts:Part one: Fluoroalkylation reactions induced by noncovalent interactions between solvent and fluoroalkyl iodideDue to the unique properties of the fluoroalkylation reactions induced by noncovalent interactions(EDA complex or halogen bond),it is advantageous for the synthesis of certain fluorinated organic compounds.Previously,the electron donor was frequently an organic amine or the substrate itself.This chapter establishes for the first time that fluoroalkyl radical can be efficiently generated induced by the noncovalent interactions between solvent and fluoroalkyl iodide under visible light irradiation,allowing for the initiation of various fluoroalkylation reactions.Such as1,2-addition reaction of alkenes to alkynes and fluoroalkylation of arenes to heterocycles.Additionally,this discovery serves as a guide for the synthesis of fluorinated materials.Part two: Difluoroalkylative cyclization of alkenes induced by noncovalent interactionsBenzofurans and indolines are abundant in natural products and serve as important scaffolds for pharmaceutical active ingredients and the realization of fluoroalkylation of these compounds has aroused our research interest.In this chapter,we successfully developed that difluoroalkylative cyclization of alkenes induced by noncovalent interactions between organic bases and fluoroalkyl iodides.Starting from simple and readily available raw materials,the method provides a novel strategy for the synthesis of difluoroalkylated benzofurans and indolin derivatives.Mechanistic experiments further prove that the 1,2-addition product of alkene is the key intermediate of this reaction.Part three: Efficient synthesis of fluorinated homophenylalaninesThe acquisition of amino acids has always been one of the key problems to be solved in the synthesis of polypeptides.Amino acids with polyfluoroaromatic hydrocarbons play a very important role in the synthesis of polypeptides and the research of new medicines.However,the synthesis methods of such compounds are very limited,which seriously hinder the development in related fields.Therefore,the development of efficient and simple methods for the synthesis of these compounds is very important in the field of peptide chemistry.In this chapter,we used the cheap and readily available natural amino acid as the starting material,converted it into zinc reagent,and studied its coupling reaction with polyfluorobenzyl bromides/chlorines catalyzed by nickel.It was found that the reaction could be carried out well without the addition of ligands,and β-H elimination could also be inhibited for long chain alkyl bromines so as to obtain the target product with good yield.This method has the advantages of simple reaction system and good functional group tolerance.Mechanistic studies found that the addition of additional monodentate ligands had no effect on the reaction,while the addition of bidentate ligands inhibited the reaction.Therefore,we hypothesize that amino acids act not only as reactants but also as ligands.Further calculation indicated that amino acids may form a stable six-member ring transition state with Ni catalyst during the catalytic cycle.