Study Of The Synthesis Of Fluoromethyl Compounds And Polyfluoroaryl Compounds

Fluorinated compounds are the least abundant natural organohalides,most terrestrial F is bound in insoluble form,hindering uptake by bioorganisms.Fluorine uniquely affects the properties of organic molecules through strong polar interactions due to the atom's high electronegativity and small size.For example,the introduction of fluorine into pharmaceuticals can make them more bioavailable,lipophilic and metabolically stable.With the increasingly wide application of fluorochemistry in pharmaceuticals and agrochemicals as well as in materials science,the development of efficient methods for the synthesis of fluorine-containing molecules has become a research hotspot in the field of organic synthesis.This thesis mainly focuses on the history and development of fluorination field,for the construction of C-F bond and the synthesis methods of fluorine-containing compounds.On the basis of previous work,the synthesis of fluoromethyl compounds and polyfluoroaryl compounds were studied in this article,the full text was divided into three parts:Firstly,the synthesis of monofluoromethyl compounds-the deoxyfluorination reactionof alcohols is introduced.The deoxyfluorination of alcohols was realized by in-situ formation of fluorine phosgene from triphosgene,18-crown-6-ether and potassium fluoride.The reaction has the advantages of cheap raw materials and wide range of substrates,not only the primary alcohol can be converted smoothly,but also the secondary alcohol can obtain the corresponding product with a moderate yield.In addition,amino acid derivatives are also tolerant to this system.Since the fluorine source of this reaction is potassium fluoride,it may be used for the synthesis of PET radioactive tracer in the later stage.Then we explored the synthesis of thiodifluoromethyl compounds-the selective activation reaction of trifluoromethyl aromatic hydrocarbons catalyzed by visible light.Single C(sp³)-F bond cleavage of Ar CF₃ is a challenging problem in organic synthesis,as the high bond dissociation energy makes C(sp³)-F bonds usually quite inert under various reaction conditions.Furthermore,the dissociation energy of the remaining C(sp³)-F bonds decreases after one C(sp³)-F bond in the trifluoromethyl group is cleaved,avoiding multiple defluorinations is rather difficult.The selective defluorination functionalization reaction of thiophenol(alcohol)and trifluoromethyl aromatic hydrocarbon was synergistically catalyzed by light and cuprous iodide and a series of derivatization containing the active structural unit SCF₂ were synthesized with moderate and excellent yields.This reaction is the first example of selective defluorination of trifluoromethyl aromatics by copper catalyst.The conditions are mild and the structure of the products are simple,which provides a new idea for the selective activation of trifluoromethyl aromatics.In addition,mechanistic studies have shown that the reaction has gone through a free radical path.Finally,the synthetic methods of polyfluoroaryl compounds were developed,and the simple synthesis of polyfluoroaryl compounds was realized through the synergistic cleavage of the C-B bond and C-F bond of B(C₆F₅)₃.B(C₆F₅)₃ is well known as a strong Lewis acid that has been extensively used as a catalyst in various reactions,there were only few studies reported on B(C₆F₅)₃,which has been used as a reagent involved in the reaction.This transition metal and ligand free method is well compatible with various oxygen-and sulfur-based nucleophiles and afforded the corresponding polyfluorinated aromatic ethers in good to high yields without the need for anhydrous and oxygen-free operation.Most importantly,this method provides a new strategy for B(C₆F₅)₃ as a reagent to participate in the reaction,which expands the utility of B(C₆F₅)₃ as building blocks in organic synthesis.