Research progress in nucleophilic fluorination reaction
In recent years, more and more attention has been paid to the study of Organofluorine chemistry by organic chemists, whose main driving force is that organic fluoride has shown more and more extensive applications in medicine , pesticides , materials  and other fields. Fluorine is a Electronegativity element in nature, and its Atomic radius is close to that of hydrogen [4,5]. Therefore, in Drug design, the Electronic effect, blocking effect, pseudo effect, permeation effect, etc. of fluorine atoms and fluorine containing substituents are often used to design and modify drugs. Studies have found that the introduction of fluorine atoms into drug molecules can often enhance drug binding, change physical and chemical properties, improve drug metabolic stability and selectivity, and thus improve drug efficacy .
Because organic Fluorine compounds have extensive application value, how to obtain organic Fluorine compounds is very important. However, there are very few organic Fluorine compounds provided by nature. At present, only 12 organic Fluorine compounds are obtained from Natural product , so a large number of organic Fluorine compounds needed can only be obtained through artificial synthesis.
At present, the main methods for directly introducing fluorine atoms into organic molecules include electrophilic fluorination and nucleophilic fluorination . Among them, electrophilic fluorination has been widely used in fluorination reactions, mainly due to the emergence of efficient electrophilic fluorination reagents in recent years, such as DesMarteau reagent , perfluoroquidine , Umist reagent , Umemoto reagent , NF-TEDA reagent (Selectfluoror) , etc. Due to the emergence of these electrophilic fluorination reagents, electrophilic fluorination has developed rapidly, but most electrophilic fluorination reagents are relatively expensive and not conducive to large-scale industrial applications. The slow development of nucleophilic fluorination is mainly due to the strong Electronegativity of fluorine itself, which requires high energy for the formation of C-F bond. Secondly, fluoride is prone to form hydrogen bonds, which weakens the nucleophilicity of fluorinated reagents and greatly enhances their alkalinity, leading to the elimination of side reactions .
Based on the advantages of nucleophilic fluorination reagents (such as NaF, KF) being very cheap and easily available in industry, people have been researching the use of them as a fluorine source to introduce fluorine atoms into organic molecules, and have made certain progress. This article mainly introduces the development of nucleophilic fluorination in recent years based on the types of nucleophilic fluorination reagents.