Organic fluorides play an indispensable role in medicine, agricultural chemistry and other fields, among them fluoromethyl functional groups have strong lipophilicity, which can greatly improve the pharmacokinetics properties of drug molecules. Therefore, it is of great value to develop various fluorination reactions, especially to introduce monofluoromethyl into molecules in fluorination chemistry. The research progress of the monofluoromethylation of different structural molecules is summarized according to the classification of fluoromethyl reagents, and the possible mechanism of some reactions is discussed.

Recently, transition metal-promoted trifluoromethylation has been developed rapidly. Starting with the types of transition metal that promote the trifluoromethylation reactions, the research progress of trifluoromethylation promoted by silver, iron, palladium, nickel, rhodium and cobalt in recent years is reviewed. Moreover, the possible mechanisms of some parts of reactions are also discussed.

Aggregation-induced emission (AIE) compounds have attracted much attention due to their important potential applications in biological and chemical sensing, luminescent materials, display and other areas. As an important class of functional molecules, organofluorine compounds have been widely studied in areas such as organic chemitry and materials chemistry. The organofluorine compounds with AIE properties are summarized and classified. The currently reported AIE organofluorine compounds include the fluorinated tetraphenylethene (TPE) derivatives, 9,10-distyrylanthracene (DSA) derivatives, cyanostilbene derivatives, distyrylbenzene derivatives, fluorinated polymers, carborane clusters, room temperature phosphorescent molecules, and some other fluorinated structures. With fluorine atoms in the structures, the stability of the resulting AIE compounds is generally improved, and fluorine atoms often participate in the intermolecular interactions leading to significant changes in the structure of the aggregation state, and hence changes in luminescence properties, for example, emission enhancement, bathochromism or hypsochromism of the emissions, improvement of the emission quantum yield and lifetime. The prospects of the future study are also discussed.

Trifluoromethyl is an important group, which is often used in pharmecuticals and agrochemicals. Quaternary carbon centers are widely existed in natural products and synthetic compounds. Recently, the construction of molecules containing trifluoromethylated quaternary carbon centers has been developed rapidly. Starting with direct trifluoromethylation, new synthons and new reactions, the research progress of the synthesis of trifluoromethylated quaternary carbon centers is reviewed.

Fluorine chemistry has been widely used in all walks of life, and the combination of fluorine chemistry and organic chemistry is blooming everywhere. Since the introduction of fluorine atoms or fluorine groups into drugs is of great significance, it is essential to seek an effective fluoroalkylation pathway. With the development of electrochemistry, people combine electrochemistry and fluoroalkylation reaction skillfully. In turn, a safer, more economical, environmentally friendly and efficient fluoroalkylation pathway is obtained. The fluoroalkylation reaction pathway under the guidance of electrochemistry has not only reformed the reaction method, but also has advantages in terms of substrate universality. Fluoroalkylation of unsaturated aliphatic compounds their derivatives and aromatic compounds under electrochemical catalysis has been reported. According to the nature of the substrate and its reaction mechanism, the progress of electrocatalytic fluoroalkylation methods is summarized.

Multi-component fluoroalkylation is a hot topic in organic fluorine chemistry. In the past few years, due to the development of new reagents and new methods, multi-component fluoroalkylation reactions have made great progress. It can not only introduce fluoroalkyl groups with other functional groups in one step economically and effectively, but also transform the starting materials into a variety of compounds with biological or pharmaceutical. The development of multi-component fluoroalkylation over the past decade is reviewed from seven parts: three-component difluoroalkylation reaction, three-component trifluoroalkylation reaction, three-component perfluoroalkylation reaction, three-component monofluoro- alkylation reaction, three-component fluorination and four-component fluoroalkylation and conclusion. At the same time, this kind of reaction is summarized and prospected.

In recent years, the field of organic fluorine chemistry has developed rapidly. Fluorination and fluorine-containing functionalization reactions have attracted extensive attention of organic chemists due to their special physical and chemical properties. The introduction of fluorine-containing group into drug molecules can improve the biological activity of drug molecules. Trifluoromethoxy group has strong electron absorption and high lipophilicity, compounds containing trifluoromethoxy play an important role in the fields of medicine, pesticides and materials. In recent years, some innovative strategies have been used to synthesize compounds containing trifluoromethoxy group. This account mainly focuses on the research of trifluoromethoxy reaction in our group, and some challenges faced by trifluoromethoxy reaction.

Compounds bearing difluoromethylthio (SCF₂H) and monofluoromethylthio (SCFH₂) groups are potentially important targets in the pharmaceutical and agrochemical fields due to their unique physical and chemical properties. The traditional methods of synthesizing these two kinds of compounds are difluoromethylation and monofluoromethylation of sulfhydryl substrates. However, the limitation of sulfhydryl substrates also limited the application and development of such compounds. Thus, it is still highly desirable to develop new methods for difluoromethylthiolation and monofluoromethylthiolation as well as new types of difluoromethylthiolation and monofluoromethylthiolation reagents. The recent development of direct difluoromethylthiolation and monofluoromethylthiolation reactions is summarized, and the related mechanism are also discussed.

Organic molecules containing trifluoromethyl groups often exhibit unique physical and chemical properties, and have found extensive applications. Trifluoroacetic acid and its derivatives have advantages including low cost, ready availability and high stability. Furthermore, CO₂ is the byproduct. Therefore, trifluoroacetic acid and its derivatives are ideal trifluoromethylating reagents, and have great application potentials. The progress of trifluoromethylation reactions using trifluoroacetic acid and its derivatives as CF₃-sources is reviewed, including the reactions of C-X (X=Br and I), C-H, and C=X (X=C, O). The mechanisms are also introduced.

Transition metal-free and metal-catalyzed reactions using aryl(trifluoroethyl)iodonium salts as the trifluoroethylation reagents are summarized in this review. A large number of different types of N-, O-, S-, and C-nucleophiles were readily trifluoroethylated in these reactions under mild conditions. The results revealed that aryl(trifluoroethyl)iodonium salts possess much higher electrophilic reactivity than the other CH₂CF₃ sources. Especially, aryl(trifluoroethyl)iodonium bis(trifluoromethanesulfonyl)amides are stable and slightly soluble in water, which were successfully applied in the aqueous trifluoroethylation of amino acid derivatives and peptides. The utilization of aryl(trifluoroethyl)iodonium salts for aromatic trifluoroethylation has promisingly solved the problems that arise from the other reagents. These achievements have also demonstrated the synthetic possibilities of direct trifluoroethylation using aryl(trifluoroethyl)iodonium salts under transition-metal catalysis.

Allylation reactions of trifluoromethylated acylhydrazones with allyltrimethylsilane or pinacolyl allylboronate were found to proceed smoothly in the presence of Lewis acid to afford a series of trifluoromethylated homoallylic N-acylhydrazines with high yields. The results showed that the activity of pinacolyl allylboronate was higher than that of allyltrimethylsilane in allylation of trifluoromethylated acylhydrazones.

A green and efficient nucleophilic addition reaction of trifluoromethyl ketone with pyrazolone was developed under "on water" conditions, affording pyrazolone substituted tertiary trifluoromethyl alcohols in high yields. The advantages of being catalyst-free, column chromatography-free, environmentally benign and easy workup make it a promising method for preparation of a variety of pyrazolone substituted tertiary trifluoromethyl alcohols.

The CHF₂ moiety has been widely utilized in the design of pharmaceuticals and agrochemicals, because this group can act as hydrogen-bonding donor to improve the binding selectivity of biologically active compounds, as a bioisostere to substitute for methyl, methoxy, hydroxy, amino and thiol groups, and as a lipophilic regulator to improve the liposolubility of the active compounds. For example, 3-difluoromethylpyrazole scaffolds are present in many organic compounds that exhibit important biological activities. In this content, there are nearly ten kinds of pesticide molecules on the market that contain 3,4-disubstituted-3-(difluoromethyl)pyrazole units, with annual sales of up to one billion dollars. In this review, the methods of construction of 3,4-disubstituted 3-difluoromethylpyrazoles will been briefly summarized that have been reported so far. Four different strategies including using fluorinated reagents as substrates, difluoroacetic acid and its derivatives as fluorine building blocks, difluorodiazonium and others as fluorine building blocks will be introduced.

As aryl triflates are widely used in organic synthesis and medicinal chemistry, significant efforts have been directed towards the development of efficient methods for their synthesis. It was found that trifluoromethanesulfonyl pyridinium salt (C₅H₅N⁺SO₂CF₃·CF₃SO^-₃) was able to act as a mild trifluoromethanesulfonylation reagent to convert phenols into aryl triflates. All aryl triflate products could be purified simply by washing, and tedious chromatography operations were avoided. Besides aryl triflates, vinyl triflates could also be synthesized by using this pyridinium salt as reagent. The pyridinium salt could be easily prepared and purified, is stable under dry atmosphere, and thus may become an easy-to-handle reagent.

The Lewis acid catalyzed 1,2-addition reaction of trifluoromethylated acylhydrazones with trimethylsilyl cyanide was investigated, and a series of cyanohydrazide compounds containing trifluoromethyl group were afforded in high yield. The method could be easily operated in mild reaction conditions, which provides an efficient method for the synthesis of trifluoromethylated hydrazides with structural diversity.

The C(5) C-H fluorination of 8-aminoqunolines has attracted much attention recently. However, transition-metal catalyst and electrophilic fluorination reagents were required in most of these reactions. Transition-metal catalyst free C(5) C-H nucleophilic fluorination of 8-aminoqunolines was reviewed. This reaction was mediated by a hypervalent iodine reagent and employed cheap, safe and stable silver fluoride as the nucleophilic fluorination reagent. The reaction proceeded without inert gas protection. It possess the merits of simple and mild reaction conditions, easy operation, high regioselectivity and wide substrate scope and provides a novel method for fluorination of quinolines with potential application value.

Herein, a nucleophilic fluorination reaction to construct fluorine-containing β-ketoesters and β-ketoamides is reported. The reaction uses PhI(OAc)₂ as oxidant and 3HF·Et₃N as fluorinating reagent. It can effectively build a series of fluorochemical compounds containing quaternary carbon center under room temperature reaction conditions for 30 min. Compared with the traditional electrophilic fluorination reaction, this method has the advantages of no metal participation, short reaction time, simple reaction conditions and high reaction yield.

Trifluoromethylation using Togni reagents usually releases one equivalent of iodobenzoats as wasteful byproducts. A visible-light-mediated, atom-and step-economical hydrotrifluoromethylation of aromatic alkynes and remote benzoyl-oxylation of α-C(sp³)-H bond of ether with Togni reagent as a bifunctional reagent by means of hydrogen atom transfer strategy was disclosed. The combination of two organic transformations into one reaction not only brings 100% atom economy but also addresses the challenge of stereoselective hydrotrifluoromethylation of aromatic alkynes. This unprecedented protocol offers an important access to a wide range of highly functionalized CF₃-containing alkenes with great potential for post-modification.

Due to the uniqueness of fluorine atom and C—F bond, difluoromethylene has special properties. As a bioisostere of an oxygen or a carbonyl group, it plays an important role in medicines, pesticides and materials. Difluoromethyl heteroaryl sulfones, represented by 2-PySO₂CF₂H (Hu reagent), have been developed recently as difluoromethylation reagents, and widely recognized by synthetic chemists for their ease of preparation, good functional group tolerance and universal applicability to a wide range of carbonyl compounds. Through different types of reactions such as nucleophilic substitution, nucleophilic addition, Julia-Kocienski olefination reaction, and radical-mediated difunctionalization, they introduced difluoromethyl, difluoromethylene, gem-difluoroalkene and other fluorine-containing groups into aldehydes, ketones, and heterocyclic compounds. For the first time, the synthesis of fluorine-containing organic compounds involved in various difluoromethyl heteroaryl sulfones in the past decade is reviewed from the perspective of reaction types and their application studies.

Wittig gem-difluoroolefination of aldehydes with difluoromethyl phosphonium salt (Ph₃P⁺CF₂H·Br^-) by using zinc oxide as a base is described. Although the proton in the CF₂H group is acidic and a base could easily lead to its deprotonation to form ylide (Ph₃P⁺CF₂^-), the attack of the base at the positive phosphorus atom may also take place to produce a nucleophilic [HCF₂^-] equivalent, and then nucleophilic difluoromethylation instead of Wittig reaction would occur. The use of ZnO as the base favored the Wittig reaction and the nucleophilic difluoromethylation was not observed. Furthermore, the excessive ZnO and Zn^Ⅱ salts produced from ZnO could be easily removed by filtration, which may be convenient for the purification process.

Two electrophilic pentafluoroethylating reagents of pentafluoroethyl(p-methylphenyl)sulfonium bis(carbometh- oxy)methylide (4a) and pentafluoroethyl(4-nitrophenyl)sulfonium bis(carbomethoxy)methylide (4b), and their reactions under mild conditions with β-ketoesters, aryl iodides and heteroaromatics are described.

An efficient method for the synthesis of various Z-fluorostyrene derivatives via nickel-catalyzed cross-coupling of gem-difluorostyrenes with organozinc reagents with the assistance of LiCl was developed. The reaction proceeds efficiently under mild condition, affording monofluoroalkenes in moderate to good yields. This novel method exhibits good functional group compatibility and excellent stereoselectivity.

Trifluoromethylthiolation/oxidation of styrenes with easiy-handling AgSCF₃ used as the trifluoromethylthiolating reagent has been described, which furnished a series of α-trifluoromethylthio acetophenons. A variety of substituted styrene could be bifunctionalized via radical process in a mixed solvent of dimethyl sulfoxide (DMSO) and CHCl₃, with potassium persulfate used as the oxidant under mild conditions. A simple and efficent method for the facile construction of various α-trifluoromethylthio acetophenons is thus demonstrated.

A nickel-catalyzed direct difluoromethylation of (hetero)aryl bromides with bromodifluoromethane (BrCF₂H) is described. This reaction features high efficiency, broad substrate scope and high functional group tolerance, providing a cost-efficient and straightforward route for applications in medicinal chemistry. Preliminary mechanistic studies reveal that a nickel-based, reductive cross-coupling catalytic cycle is involved in the reaction.

An efficient protocol for facile access to trifluoromethylated tetrahydrofuran and tetrahydropyran has been developed under visible light irradiation conditions via radical 1,2-alkoxyl-trifluoromethylation of unactivated alkene. It features the use of readily commercially available and operatively simple trifluoromethanesulfonyl chloride as a trifluoro- methyl radical source, thus making the protocol potentially appealing for practical preparation.

The addition reaction of perfluoroalkanesulfenic acids, in-situ formed from imines, to alkynes and allenes were investigated. A series of perfluoroalkyl alkenyl sulfoxides were synthesized. Markovnikov adducts were obtained in good to excellent yields from the reactions of aryl or alkyl-substituted alkynes with perfluoroalkanesulfenic acids under mild conditions. However, the reaction of terminal alkynes containing an electron-withdrawing group afforded Michael-type adducts in good yields. The addition reaction of electron-rich allenes took place at the double bond with less steric hindrance, while the double bond connecting an electron-withdrawing group was the prior reaction site in the case of electron-deficient allenes.

Recently, the preparation of fluorinated compounds through difunctionalization strategies has become a hot research area in fluorine chemistry. In this work, a copper-catalyzed hydroxytrifluoromethylthiolation of arylpropynones for the synthesis of the corresponding trifluoromethylthiolated enols was developed. The copper salt and solvent are crucial to the yields of this reaction. Under optimized reaction conditions, a series of trifluoromethylthiolated enols were obtained in moderate to good yields.

Fluorination on conjugated components is one of popular strategies to modify organic optoelectronic materials. Following the research of a benzodithiophene/benzothiadiazole ADA-type optoelectronic molecule, two benzothiadiazole (BT) units were fluorinated with different numbers and positions, and the change in basic properties and performances for field-effect transistors and organic solar cells was investigated. It was found that when the F-substitution number increases, the molecule enhances thermal stability, decreases solubility, lowers HOMO and LUMO energy levels, but almost does not alter light absorption range. Furthermore, investigations on organic field-effect transistors found the molecular hole mobility reduces with only one F-substituent at outer position of BT units, while increases up to 0.27 cm²·V^-1·s^-1 with two F substituents on BT units. However, when these materials are applied in organic solar cells, the fluorinated ones enhance open-circuit voltage, but deteriorate active layer morphology, finally leading to decrease in short-circuit current and device efficiency.

A novel palladium-catalyzed intramolecular fluoroarylation of alkenes has been developed, in which ArIF₂ was employed as fluorine source as well as I(Ⅲ) reagent to activate olefin, to deliver the fluoroarylation products from 4-aryl- 1-olefins in moderate to good yields. The current transformation presents a convenient method to provide fluorotetralins and fluorochromanes under mild conditions from alkenes tethered arenes.

Trifluoromethylated triazoles and tetrazoles have emerged as increasingly important heterocycles in pharmaceuticals, agrochemicals, catalysis, and materials. As a consequence, great attention has been paid to the efficient synthesis of these valuable CF₃-containing molecules. Herein, the advances in the past decade towards the synthesis of CF₃-substituted triazoles and tetrazoles are summarized. The remarkable progress in the utilization of versatile CF₃-functionalized building blocks including CF₃-containing alkynes, CF₃-containing carbonyl compounds, CF₃-containing pyrones and trifluorodiazoethane (CF₃CHN₂) is demonstrated accordingly.

Aryl trifluoromethyl ketone is a very important intermediate in the organic synthesis. Much attention has been attracted from researchers, due to its potential bioactivity. In this paper, the recent progress in the synthesis of aryl trifluoromethyl ketone is reviewed, including the oxidant of α-trifluoromethyl alcohols, trifluoromethylation of carboxylic acid derivatives, trifluoroacetylation of organometallic reagents, electron-rich aromatics, aryl halides and aryl diazonium salts, and the reaction mechanisms are also discussed.

Organic fluorine chemistry has attracted considerable attention due to its unique character in the field of materials science, catalytic chemistry, medicine, fine chemicals and biochemistry, which majorly focus on the construction and cleavage of carbon-fluorine bonds. The transition metals are introduced to allow new possibilities for activating carbon-fluorine bonds and are gradually becoming an alternative way to synthesize numerous complex organics containing fluorine. In this review, the recent works on the theoretical mechanistic study for transition metals mediated carbon-fluorine bonds activation and cleavage are summarized. Meanwhile, the general modes of carbon-fluorine bonds activation have been concluded systematically, including the oxidative addition of carbon-fluorine bonds to transition metals, transition-metal-activated nucleophilic substitution, S_N2 type activation of carbon(sp³)-fluorine bonds and β-fluorine elimination, etc. The theoretical calculation shows that the reaction could be proceed by an oxidation addition mode, when the zero-valent nickel catalyst with strong reducibility is employed. However, if a zero-valent platinum catalyst is used, oxidation addition only occurs at extra activated carbon-fluorine bonds. In the reduction of polyfluorinated aromatic hydrocarbons by hydrogenated metal species, aromatic nucleophilic substitution between hydride and polyfluorinated aromatic hydrocarbons could occur to realize the activation of carbon-fluoride bonds. For carbon(sp³)-fluorine bonds, if “hard” Lewis base such as lithium or magnesium salt is employed, the carbon(sp³)-fluorine bonds can be activated via bimolecular nucleophilic substitution (S_N2). In addition, β-fluoride elimination is also frequently proposed in transition metal-catalyzed C—F functionalizations.

This review summarizes studies on halogen bonding of fluorine-containing alkyl and aryl iodides in China. From 1987 to 1993, Chen et al. found that there existed donor-acceptor interaction between fluorinated organic (di)iodides, as Lewis acids, and organic Lewis bases such as amines and ethers, which represented early important advances for the research on the non-covalent force currently called as halogen bonding. From 2001 to now, several groups have used halogen bonding as driving force to conduct researches on crystal engineering. In this catogery, Zhu et al. investigated the one-dimensional self-assembly between perfluoro-α,?-diioodalkanes and amines, ethers, and hexamethylphosphamide. Jin et al. studied the complexation between fluorinated aryl iodides and various N-heterocycles, whereas Zhang and Li et al. constructed supramolecular double and quadruple helices from one or two molecular components. Jin et al. conducted extensive studies on C—I…p halogen bonding and its applications in crystal engineering. Wang and Wan et al. utilized halogen bonding to induce trianglular aromatic molecules to co-assemble into two-dimensional honeycomb arrays on surface, whereas Wang et al. utilized halogen bond to induce mono-layer and layer-by-layer self-assembly of two polymers or organic molecules. Zhao and Li et al. developed the applications of halogen bonding in solution-phase multi-site molecular recognition of foldamer receptors for ICF₂-incorporated tri-armed guests. Hu, Gong, Liao et al. utilized halogen bonding to improve the material properties of a variety of organic aromatic molecules. Several groups have also used halogen bonding to increase the selectivity of a number of organic reactions. Representative examples are described, which highlight the utility of halogen bonding.