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.

A rhodium-catalyzed rearrangement reaction of N-tosylhydrazones and 3,3-difluoroallyl sulfides was developed. This protocal provided a facile and efficient synthesis route to gem-difluoroallyl compounds with medium to excellent yield and good functional group tolerance. Moreover, the applicability of current method has been demonstrated by one-pot reaction, gram-scale synthesis and further transformations.

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.

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.

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.

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.

The biological significance of sp³-rich synthetic scaffolds with natural product like features yet distinct global frameworks is being increasingly recognized in medicinal chemistry and biochemistry. Herein, a fragment library consisting of 3D-shaped natural product fragments was assembled. Library construction was performed by photocatalytic amidofluorination of curcumol to incorporate amine and fluorine as potential binding groups and synthetic growth points. Through this strategy, a fragment library of 24 fragments was generated, which was demonstrate to have high three-dimensionality, natural product likeness and superior fragment-like properties, covering a novel chemical space in fragment based drug discovery.

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.

Based on the platform of boron-dipyrromethene (BODIPY) derivatives, a fluorescence turn-on probe BDP-2Z was rationally designed and synthesized with good water-solubility. With high sensitivity and selectivity for Cu^2＋ over other competitive ions, the reaction-based probe showed low detection limit and fast response in a wide pH range (pH=3.0~12.0). The contrast of color and fluorescence caused by Cu^2＋ was remarkable so much so that it was easily to distinguish Cu^2＋ from other ions with naked-eye detection. Along with adding of Cu^2＋, a blue shift of maximum absorption was observed from 548 nm to 496 nm, the corresponding solution color changed obviously from purple to light orange, and the fluorescence is enhanced by nearly 5-fold. Furthermore, the recognition mechanism was confirmed by UV-Vis, fluorescence spectra, and mass spectral analysis. The identified product of recognition process was even obtained by original silica gel column chromatography separation method. Also, the rapidly naked-eye application in real water samples provides an alternative to extension environmental detection.

A new shelf-stable and easily scalable monofluoromethylating reagent, fluoromethyl benzenesulfonate (PhSO₃CH₂F), was developed. This reagent is able to react with acetylacetone derivatives to afford corresponding O-monofluoromethylated products in high selectivity and good yields under mild conditions. Moreover, the method could be used in late-stage monofluoromethylation. This method provides more options for the synthesis of monofluoromethyl compounds.

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.

Sulfoximines derivatives are widely used in the field of pesticides and medicine due to its antimalarial, antibacterial and herbicidal properties. A concise and direct synthetic strategy for the construction of trifluoromethylated cyclicsulfoximines has been developed via [3+2] cycloaddition reaction of benzynes and trifluoromethyl α,β-unsaturated N-(S)-tert-butyl sulfinylketoimines. The reaction affords the cyclosulfoximines at room temperature in low to moderate yields (13%~57%) and KF as fluorinated reagent, 18-C-6 as additives, and acetonitrile and toluene as mixed solvent (V∶V=4∶1). The insecticidal activities against Aphis gossypii were determined by impregnation method. The results showed that 24-h median lethal concentrations (24 h LC₅₀) of (1R,3S)-1-(tert-butyl)-3-((E)-4-methylstyryl)-3-(trifluoromethyl)-3H-1λ⁴-benzo- [d]isothiazole 1-oxide) (3b) and (1R,3S)-1-(tert-butyl)-3-(trifluoromethyl)-3-((E)-4-(trifluoromethyl)styryl)-3H-1λ⁴-benzo[d]- isothiazole 1-oxide (3h) are lower than that of the positive control imidacolprid (0.0800 mg/L) and dinitraz (0.0532 mg/L). They can be used as new lead insecticidal compounds with further structure modification.

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 nickel-catalyzed aryl-difluoroalkylation of alkynes is developed. A series of trisubstituted fluoroalkenes can be obtained in a highly stereoselective manner by mixing of simple starting materials alkynes, ethyl bromodifluoroacetate, and arylboronic acids in the presence of nickel catalyst. This method features low-cost catalyst, mild reaction conditions, and excellent functional group compatibility.

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).

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.

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.

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.

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.

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.

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.

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 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 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.

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.

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.

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.