Iron-Catalyzed Trifluoroethylation Of Amines

Modification of organic molecules compounds with fluorine and fluoroalkyl groups is arguably one of the most successful additions to the drug discovery toolkit in the last several decades,for example,bioactive compounds containin?-fluoroalkylamine,which are much less basic than their hydrocarbon counterparts?pKaH 10.7 for CH₃CH₂NH₂,5.7 for CF₃CH₂NH₂?and often exhibit decreased acute toxicity and increased metabolic stability.Among them,the N-H bond insertion reaction of amine is one of the most effective methods to construct fluoroalkylamine molecules,but most of them are limited to arylamine substrates.In this thesis,a method of N-H insertion of alkyl secondary amines with trifluoromethyl diazomethane to realize trifluoroethylation of alkylamines is introduced.The optimal reaction conditions for the secondary alkylamine insertion reaction are:2 mol%FeTPPCl catalyst,1.2 equivalents of trifluoromethyldiazomethane,toluene as a solvent.series of trifluoroethylated compounds can be obtained by reaction at room temperature.The reaction has the advantages of mild conditions,wide substrate range,high yield,and good chemoselectivity.Similar conditions are also suitable for aryl secondary amine compounds.In addition,we use this method for the late-stage modification of some drugs molecules.