Copper(Ⅰ)-mediated C(sp~3)-F Bonds Formation

Fluorine is the first element in halogens with small size, high electronegativity and low polarizability. Incorporation of fluorine atom(s) into an organic molecule often improves its physical, chemical and biological properties. Nowadays, organofluorine compounds are widely used in pharmaceuticals, agrochemicals, dyes, functional materials, positron emission tomography (PET) imaging agents and other fields. So more and more researchers devote themselves to synthetic fluorine chemistry. Among the numerous synthetic methods, the trasition-metal-mediated C-F bond construction has emerged as an area of extensive research. Currently, metal-mediated C-F bond construction mainly focused on the formation of aromatic C(sp2)-F bonds. However, the methods for site-specific formation of C(sp3)-F bonds remain rather limited. Therefore, exploring economical, environmentally friendly and efficient metal fluorinated reagents for the formation of C-F bonds has certain significance.This thesis mainly studies the synthesis of copper(Ⅰ) fluoride compounds for mediated C(sp3)-F bond construction, and three parts are contained in this thesis:Part I:The synthesis of metal fluorinated reagents. We used CuCl, NaO’Bu,2,9-dimethyl-1,10-phenanthroline,2,9-di-tert-butyl-1,10-phenanthroline and (HF)3-NEt3 as starting materials, and synthetized two copper(Ⅰ) fluoride compounds (Ligand-CuF) which are (Me2phen)2Cu(HF2) and (’Bu2Phen)CuF respectively.Part Ⅱ:Research on the reactivity of copper(Ⅰ) fluoride reagents. We found that copper(Ⅰ) fluoride reagents can react with alkyl halides to form C(sp3)-F bonds. After a series of optimization on the reaction conditions, we ultimately found that (Me2phen)2Cu(HF2) was the best fluorinated reagent. Under the best reaction condition, the substrate scope of the fluorination was wide. (Me2phen)2Cu(HF2) could react not only with benzylic halides and primary alkyl halides, but also with secondly alkyl halides. Moreover, a variety of useful founctional groups can be well tolerated in the reaction.Part III:Research on the reaction mechanism of the fluorination. For the reaction of (Me2phen)2Cu(HF2) with alkyl halides, We proposed two possible mechanisms which were radical mechanism and nucleophilic substitution mechanism. A series of experiments suggest that a radical mechanism is unlikely, and the fluorination proceeds through a bimolecular nucleophilic substitution (SN2) mechanism.