Boron dipyrromethene (BODIPY) dyes are widely used in the fields of life sciences, chemical analysis and optoelectronic materials due to its excellent photophysical properties, favorable biocompatibility, facile synthesis and modification etc. The synthesis and derivative strategies of BODIPY provide the basis for its wide application and have attracted great attention from researchers. In this review, the modification strategies for different reaction positions of BODIPY have been discussed, and Pd-catalyzed cross-coupling reactions and oxidative coupling reactions about BODIPY are discussed individually. Finallly, the development of this field is prospected.

gem-Difluoroalkenes are important fluorine-containing compounds with structural superiority in organic synthetic chemistry and medicinal chemistry. For instance, the gem-difluoroethylene moiety could be converted to monofluoroalkenyl, difluoroalkyl, trifluoromethyl moiety, and many other fluorine-containing structures conveniently. The gem-difluoroethylene moiety is also an ideal carbonyl group bioisostere and has already been widely used in drug design. Herein, a nickel-promoted electrochemical reductive cross-coupling to access functionalized and substituted gem-difluoroalkenes is reported. This reaction enables the combination of allylic defluorination of trifluoromethyl alkenes and decarboxylation of redox-active esters or dehalogenation of alkyl halides under mild electrochemical reduction conditions and in an undivided cell, therefore obviates the use of stoichiometric amount metal powder or organic reductants. Furthermore, this reaction provides efficient access to biologically interesting molecules containing gem-difluoroethylene moiety.

Synthesis of fluorine-containing compounds is greatly dependent upon the development and application of fluorinated reagents. Thanks to the unique fluorine effects, fluorinated reagents usually exhibit different properties and reaction profiles from those of the non-fluorinated analogues. Among various trifluoromethoxylation reagents, trifluoromethyl trifluoromethanesulfonate has drawn much attention in recent years because of its easy preparation, low cost and diverse reactivities. This reagent rapidly decomposes to form trifluoromethoxy anion in the presence of fluoride ion, thus regarded as a reservoir of trifluoromethoxy anion, and has been widely used in the nucleophilic trifluoromethoxylation reactions. Moreover, the trifluoromethoxy anion derived from trifluoromethyl trifluoromethanesulfonate and nucleophiles has poor thermal stability and tends to decompose at room temperature to afford fluorophosgene and fluorine anion, which can be used as a carbonylation reagent, a fluoroformylation reagent, a condensation agent or a nucleophilic fluorination reagent. The trifluoromethoxylation, carbonylation and fluorination reactions with trifluoromethyl trifluoromethanesulfonate as the reagent are reviewed.

The trifluoromethylselenylation reaction is another important research topic after trifluoromethylsulfanylation reaction in recent years. Because the trifluoromethylselenyl group contains two important chemical elements, fluorine and selenium, and the compounds containing trifluoromethyl selenide have important potential biological activities, more and more researchers begin to turn their attention to this new group in recent years. In this paper, according to the three reaction types of nucleophilic trifluoromethylselenylation reaction, electrophilic trifluoromethylselenylation reaction and radical trifluoromethylselenylation reaction, the research results of domestic and foreign scholars on direct trifluoromethylselenylation reaction in recent 6 years are comprehensively summarized, and some reaction mechanisms are discussed in detail. Finally, the direct trifluoromethylselenylation reaction is summarized and prospected.

Fluoro-containing heterocyclics play an important role in many fields, such as organic chemistry, pharmaceutical chemistry and material science due to their excellent physical and chemical properties. However, there are few natural fluoro-containing heterocyclics in nature, so it is particularly important to develop efficient synthesis methods of fluoro- containing heterocyclics. With the rapid development of transition metal catalyzed, photocatalyzed and electrocatalyzed radical reactions, radical chemistry has made a breakthrough in the field of synthesis and stimulated the interest of organic chemists in constructing fluoro-containing heterocyclics by using radical chemistry. In this paper, monofluoroalkylation, difluoroalkylation, trifluoromethylation, trifluoroalkoxy/sulfur/selenylation, perfluoroalkylation of unsaturated hydrocarbons and direct C—H fluoroalkylation of heterocycles are classified, and the construction of fluorine-containing side chain heterocycles mediated by free radicals is discussed from the aspects of transition metal catalysis, photocatalysis and electrocatalysis.

Organofluorine compounds have been widely applied in various fields ranging from drug discovery, clinical medicines, agrochemistry, and materials science to organic synthesis, due to their special chemical and physical properties when compared with nonfluorinated analogs. In the past decades, significant progress has been made in the development of selective fluorination and fluoroalkylation for the synthesis of structurally diverse fluorine-containing molecules. Among them, the α-fluoroalkylated carbonyl group represents an important class of scaffold components in biologically active and druglike compounds. In this context, based on the use of difluorinated silyl enol ether (DFSEE) as a unique fluoroaklylating reagent, a variety of methods for the incorporation of gem-difluoroalkylated carbonyl moiety have been achieved, including aldol, Mannich, arylation, allylation, protonation, halogenation, conjugate addition, and olefination reactions. On the other hand, DFSEEs could also merge with new types of reactions such as radical-type difluoroalkylation and cascade reaction by virtue of their incredible reactive flexibility. In addition, the O-site selective addition of DFSEEs was also reported, enabling the construction of versatile gem-difluoroalkenes. Given the importance of organofluorine compounds and the synthetic potential of these avenues, herein, we highlight the recent advances in the functionalization of gem-difluorinated silyl enol ethers, which serve as key fluorine-containing building blocks for the synthesis of organofluorine compounds.

Photocatalytic heterogeneous chlorotrifluoromethylation and iodoperfluoroalkylation of unactivated terminal alkenes have been achieved under the catalysis of phenylphenothiazine-based porous organic polymer (PTH-POP). This method offers a transition-metal-free and recyclable platform to access valuable perfluoroalkylated compounds in a highly efficient fashion.

Organoselenium compounds have great application value in the fields of medicine, pesticide, synthesis and materials, and play a particularly prominent role in anti-cancer and anti-inflammatory. Therefore, the synthesis of organoselenium compounds is particularly important in organic synthesis. The traditional methods of synthesizing organoselenium compounds were using selenol or selenium ether react with alkylation or arylation reagents. Various direct alkyl- and aryl-selenylation reagents were also developed in recent years. Moreover, there are few studies on fluoroalkylselenylation. Thus, it is still highly desirable to develop new methods for alkyl-, aryl- and fluoro-alkylselenylation as well as new types of corresponding selenylation reagents. The recent development of alkyl-, aryl- and fluoro-alkylselenylation is summarized, and part of their mechanisms are also discussed.

The unique properties of difluorinated compounds have attracted widespread attention in the fields of medicine and material sciences. The conversion of inexpensive and easily available trifluoromethyl groups into difluoro groups is of great importance in organic synthesis. However, there still exist great challenges in the selective cleavage of C—F bonds, because the dissociation energy of single C—F bond in trifluoromethyl group is much higher than that of the C—F bond in the difluoro unit of the generated product. Thus, the selective cleavage of C—F bond is difficult to control, which can easily lead to excessive defluorination. Compared with the traditional thermal reaction, the visible-light irradiated reaction provides an alternative pathway to achieve C—F cleavage more efficiently and selectively. The research progress on the selective cleavage of C—F bonds mediated by visible light in the past three years is summarized and its future perspective is prospected.

Bromodifluoromethyl trimethylsilane (TMSCF₂Br) has proved to be an important difluoromethyl(alkyl)ation reagent that is widely applied in organic synthesis over the past decade, since it was used as a difluorocarbene precursor in 2011. This review aims to provide a briefly summary for the synthesis of TMSCF₂Br, and to introduce the recent advances in the applications of TMSCF₂Br as a difluorocarbene or trimethylsilyldifluoromethyl radical precursor for developing various difluoromethyl(alkyl)ations of different kinds of substrates. Meanwhile, the activation ways of TMSCF₂Br and the possible mechanism, as well as its advantages and disadvantages in each kind of reactions are detailedly disccussed, which might provide some references and inspiration for researchers engaged in organic synthesis and organic fluorine chemistry.

Selective C-F bond activation of the trifluoromethyl group is an important approach for the synthesis of gem-difluoro compounds. Given the importance of trifluoromethyl alkenes in synthetic chemistry as well as their diversity in selectivity, the research on selective C-F bond activation of these compounds has received considerable interest. To this end, The research progress is summarized, including nucleophilic addition/defluorination (S_N2' type), acid-promoted defluorinative Friedel-Crafts arylation, (formal) ipso-defluorinative functionalization, and transition-metal-catalyzed migratory insertion/ defluorination.

An efficient electrochemical oxidative trifluoromethylation of α-oxoketene dithioacetals with CF₃SO₂Na is developed without the usage of transition-metal catalysts and external oxidants. This protocol features mild reaction conditions and wide functionality tolerance. Mechanistic insights indicate that the reaction proceeded via radical mechanism.

Decarboxylation of fluoroalkyl carboxylic acid derivatives is an effective way to obtain fluoroalkyl radicals, which subsequently participates in the tandem and addition reactions of olefins, isonitriles and aromatic (hetero) rings, providing an important method to obtain divegent fluorine-containing molecules. A variety of fluoroalkyl cyclic compounds such as phenanthridines, dihydroflavonoid, quinolinones and indolones could be constructed using the tandem reaction initiated by fluoroalkyl radicals generated from fluoroalkyl carboxylic acids. The research progress of radical reactions induced by decarboxylation of fluoroalkyl carboxylic acids in recent years is summarized, which includes reaction design, reaction mechanism and outlook.

Trifluoromethylation reaction is a critical method to install fluorine atom into organic molecules. The recent advances in trifluoromethylation with CF₃Br as trifluoromethyl source are summarized. Various trifluoromethylation methods involving CF₃Br are presented. Their characteristics, scope and limitations as well as the reaction mechanism are discussed in detail, and a perspective on the further development by using CF₃Br as trifluoromethyl source is put forward.

Fluorinated compounds have been widely used in pharmaceuticals, pesticides and other disciplines due to their special physical and chemical properties, which motivates the frequent introduction of fluorinated functionalities into lead compounds to improve their physical and chemical properties. The trifluoromethylthio (SCF₃) group with high electronegativity and special lipophilicity plays an important role in a multitude of fluorinated compounds. The recent progress in the field of cascade reaction of unsaturated hydrocarbon initiated by SCF₃ radical, including reaction design, reaction mechanism and outlook, is summarized.

A practical Ag-catalyzed trifluoromethylthiolation cyclization reaction was developed. Various structurally diverse CF₃S-containing benzimidazo[2,1-a]isoquinolines were obtained for the first time in moderate to good yields. Mechanistic studies suggested that the catalytic reaction proceeds via a CF₃S-radical-triggered cascade cyclization pathway.

A photosensitizer-free visible-light-promoted method for site-selective trifluoromethylation of tryptophan- containing oligopeptides using YlideFluor as the trifluoromethyl radical source under mild conditions was developed. Mechanistic studies showed that a donor-acceptor between 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and YlideFluor is generated. Upon irradiation with blue LEDs, the S—CF₃ bond in the adduct undergoes homolytic cleavage to give trifluoromethyl radical, which attacks the electron-rich C-2 position of the indole moiety in the tryptophan-containing oligopeptide.

Fluoride ion is closely related to human life activities. Excessive or too little fluoride ions in human body will cause pathological changes. Therefore, it is necessary to develop appropriate measures to detect the fluoride ion content in human body and environment. Colorimetry and fluorescence detection have attracted much attention due to their high selectivity, high sensitivity and fast response. Herein, reaction-based fluoride ion probes are introduced. According to the reaction mechanisms, these probes can be divided into five types: interactions between fluoride ion and boronic acid derivatives, fluoride ion-promoted cleavage of Si—C bond, fluoride ion-promoted cleavage of Si—O bond, fluoride ion-induced dehydrogenation, fluoride ion-promoted cleavage of P—O bond. Not only the detection method of the probe is introduced, but also the action mechanism of some examples is described.

Laccase is a potential target and has important physiological functions in micro organisms. In order to find compounds with high laccase inhibitory activity, 15 cinnamaldehyde hydrazide derivatives containing difluoromethylpyrazole were designed and synthesized by using the principle of active substructure splicing with 4-chlorocinnamaldehyde thiosemicarbazone (PMDD-5Y) as the lead compound. The structures of the compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The results of laccase inhibitory activity test showed that all the prepared compounds have good activity, and N'- ((Z)-3-(3,4-dichlorophenyl)-3-phenylallylidene)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbohydrazide (5l) and N'-((Z)- 3-(2-chlorophenyl)-3-(4-chlorophenyl)allylidene)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbohydrazide (5m) had the half-maximal inhibiting concentration (IC₅₀) values of 0.069 and 0.063 mmol/L, respectively, which were significantly better than that of lead compound PMDD-5Y (IC₅₀=0.553 mmol/L) and positive control cysteine (IC₅₀=0.298 mmol/L). The in vitro bioassay showed that the compounds with good laccase inhibitory activity showed certain fungicidal activity against V. mali, F. graminearum and M. grisea at a concentration of 50 μg/mL. In vivo trials against M. grisea demonstrated that compound 5l was effective with curative activity of 78.55% at a concentration of 200 μg/mL, which showed a certain control efficiency in vivo. Further molecular docking study revealed that compound 5l with high laccase inhibitory activity had a good protein binding mode with laccase protein.

Polycyclic indoles are widely found in natural products and pharmaceutical molecules, and have a wide range of applications in the pharmaceutical, pesticide and dye industries. Although considerable development has been made in the synthesis of indole polycycles, it is still of great scientific interest and value to explore more efficient and milder experimental strategies for the synthesis of highly-functionalized polycyclic indoles. Herein, a one-step radical tandem cyclization reaction to synthesize difluoroalkylindoles with quaternary carbon centers by using difluorobromoesters as the fluorine source and 3-alkenyl indoles as the substrates under visible light-catalyzed conditions was developed. The method is easy-to-operate and mild in conditions, with a wide range of substrate adaptability and good yields, providing a green and efficient synthetic route for fluorine-containing polycyclic indoles.

A convenient approach to pyridine quaternary ammonium salts containing enamine fragment has been developed, which features a trifluoromethyl sulfonic anhydride mediated regioselective addition process of pyridine with ynamides. Using this method, a variety of substituted pyridine quaternary ammonium salts containing enamine fragment 3a~3m were prepared in moderate to excellent yields with high regioselectivities (Z:E up to 20:1).

The biaryl frameworks are momentous organic backbones that are commonly occurred in pharmaceutical, functional materials and natural products. By virtue of the distinctive reactivity through state-of-the-art process, decarbonylative couplings, which have bypassed the restriction to specifically substituted (hetero)aryl carboxylic acids of decarboxylative couplings, gradually become unneglected methods in the conversion of carboxylic acid derivatives. Herein, a rhodium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling via in-situ generation strategy of acyl fluorides from carboxylic acids was developed. This protocol shows eminent functional group tolerance with arrays of combinations between carboxylic acid and boronic acid. Furthermore, the reaction offers a new access to those conventionally unattainable biaryl motifs, including natural product and modified drugs.

In this study, a visible-light photoredox-catalyzed difluoroalkylation of newly designed functionalized aromatic isocyanides with commercially available CF₂ precursors was reported. A series of CF₂-containing indole-1,2-fused diazepanones were constructed in cascade reaction through a sequence of radical addition/cyclization processes under mild conditions. This reaction not only generated a class of polycyclic indole fused seven-membered nitrogen heterocycles but also expanded the reactions of functionalized isocyanides.

Difluoroethyl products have a wide range of applications in the fields of biomedicine and materials, and it is important to develop new method to synthesize difluoroethyl compounds. Herein, a palladium-catalyzed chlorodifluoroethylation was disclosed via ortho-C—H activation of acetanilide, using chlorodifluoroethyl(mesityl) hypervalent iodine reagent as the source of CH₂CF₂Cl. Moreover, adding organic base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to the above system, the difluorovinylated acetanilide products were obtained via an elimination reaction.

Photoredox-catalyzed 2∶2 coupling of styrene and BrCF₂CO₂Me is reported, which undergoes a homo-coupling of in situ generated β-CF₂CO₂Me substituted benzyl radical. The reaction features a wide substrate scope and functional group tolerance to afford bis-difluoroacetylated hexestrol derivatives with high yields.

A supporting electrolyte-free method for the electrochemical synthesis of trifluoromethylated oxindoles in conti- nuous flow was developed. Various N-arylacrylamides reacted with CF₃SO₂NHNHBoc smoothly to provide the corresponding products in moderate yields. The reaction scale-up was easily realized without changing the reaction conditions, which showed the application potential of continuous flow electrochemical synthesis.

In the presence of cerium ammonium nitrate, the β-H radical sulfonation reaction of aryl ethylene with sodium trifluoromethanesulfinate was reported to give highly regioselective trans-alkene. The advantages of this method were cheap and easy to obtain reaction reagents, mild reaction conditions and simple operation. Moreover, the reaction had a high regioselective and configurational selectivity.

N-Fluoroallyl hydrazones with four-ring structure were effectively synthesized using cyclobutanone hydrazones and gem-difluorocyclopropanes as raw materials through palladium catalyzed ring opening of difluorocyclopropanes and nucleophilic capture process of nitrogen nucleophile. This protocol shows broad substrate scope and good functional group tolerance, which can be applied for gram-scale preparation.

Fluorine-containing compounds have a wide range of applications in the fields of biomedicine and materials, and the development of synthetic methodology for fluorine-containing compounds is very important. Using fac-Ir(ppy)₃ as catalyst, a wide variety of amides containing fluoroalkyl substituted α-quaternary carbon center were prepared with N-aryl-N-(aryl- sulfonyl)-2-methyl acrylamides as starting materials by visible light induced cascade fluoroalkyl radical addition, aryl migration and desulfonylation. The reaction conditions are mild, and possess good functional group compatibility.

Visible light-mediated 1,5-hydrogen atom transfer and radical coupling reactions have been accomplished using N-fluoro-substituted benzamides. This method exhibits a broad substrate scope and high functional group tolerance, giving the corresponding bibenzyl products with generally good yields. Furthermore, this strategy could also be used to N-fluoro-substi- tuted aliphatic amides.

Herein, a practical formal silver-mediated trifluoromethylthiolation cyclization hydrolysis protocol was developed with the cyano group as a radical acceptor. Various structurally diverse F₃CS-substituted quinolinones were obtained in moderate to high yields. Easy scale-up operation and the potential for product derivatization make this method attractive for the preparation of other valuable F₃CS-containing N-heterocycles. Mechanistic studies suggest that the catalytic system involves a radical pathway and H₂O plays an indispensable role in the hydrolysis process.

Deuterated mono- and difluoroalkyl groups have attracted increasing attention in medicinal and biological studies. Controllable snipping one or two fluorine atoms from widely accessible trifluoromethyl groups followed by deuteration is an attractive method to access these molecules, whereas this has been hindered by the challenges associated with the chemoselectivity control during the defluoriantion process. Herein, a strategy for chemoselective deuterodefluorination reaction of trifluoro- and difluoroalkylacetamides via spin-center shifts is reported. The reaction starts with the attack of a deuterated 4-dimethylaminopyridine-boryl radical (DMAP-BD₂) to the amide oxygen atom, followed by a spin-center shift process to trigger the C—F bond scission. The resulting α,α-difluorocarbonyl radicals undergo deuterium atom transfer to afford the CF₂D-products in high yields and high levels of D-incorporation. Notably, increasing the amount of DMAP-BD₃ enables the selective cleavage of the two C—F bonds, leading to CFD₂-products in good yields meanwhile maintaining good levels of D-incorporation.

The silver salt catalyzed [3+2] cycloaddition reaction of trifluoromethylated N-acylhydrazones and ethyl isocyanoacetate was investigated. The reaction proceeds quickly to produce a series of trifluoromethylated 2-imidazoline compounds in high yields with excellent stereoselectivity, which provides a novel and efficient method for the synthesis of trifluoromethylated 2-imidazoline compounds.

An operationally simple electrochemical oxidative C—H trifluoromethylation of quinoxalin-2(1H)-ones was achieved by employing the inexpensive, readily available and easy processing CF₃SO₂Na as CF₃ source. In the absence of any catalysts or oxidant reagents, this method is more in line with the requirements of green and sustainable development. Most importantly, “electric-descriptor-diagram” was used to evaluate the reaction substrates. The reactive/non-reactive boundary and the trend of yield change can been clearly seen.

A novel transition-metal-free protocol for the synthesis of 1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones is developed. This work reveals that oxoindole skeletons can be directly constructed from ortho-vinylanilines and commercially available halogenated difluoroalkyl reagents via a C—N cleavage/new C—N bonds and C—C bond formation cascade. This reaction portrays high efficiency and excellent functional group compatibility, and has great potential in the late-stage modifications of pharmaceutical molecules and natural products.

In order to find efficient and low toxicity antitumor drugs, a series of novel 2,4,6-trisubstituted quinazoline derivatives containing trifluoromethyl were synthesized and evaluated for their antitumor activities against human cancer cell lines (PC-3, MCF-7, Eca-109, MGC-803, HGC-27, A549, H1975) by using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds exerted moderate to excellent antitumor activity against seven human cancer cells. Among them, N-(3-bromophenyl)-6-methoxy-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine (16l) showed the best antitumor activity against PC-3 cancer cell line, with the IC₅₀ values of (2.22±0.15) μmol/L, which was better than the positive control of gefitinib. At the same time, and compound 16l could dose-dependently and time-dependently induce PC-3 cells apoptosis.