Due to the unique properties of fluorine atom(s), the introduction of fluorinated functional groups into molecules has become one of the powerful strategies in the discovery of new pharmaceuticals, agrochemicals, and advanced functional materials. Consequently, considerable efforts have been made to develop new and efficient methods for preparing organofluorine compounds. Among the fluorine functionalities, the gem-difluoroallyl group represents one of the attractive moieties due to the unique properties of the difluoromethylene group (CF₂) and the synthetic versatility of the carbon-carbon double bond. Over the past decade, important progress has been made in the catalytic gem-difluoroallylation reactions. However, the efficient methods for the preparation of gem-difluoroallyl arenes remain limited despite their important applications in medicinal chemistry. Here, we report a palladium-catalyzed gem-difluoroallylation of heteroaryl bromides with gem-difluoroallylboronates. The reaction proceeds under mild conditions with high efficiency, high functional group tolerance, and excellent regioselectivity. A series of heteroaryl bromides are applicable to the reaction, providing facile access to gem-difluoroallyl heteroarenes of medicinal interest. A representative procedure for the palladium-catalyzed cross-coupling of heteroaryl bromides with gem-difluoroallylborons is as following: heteroaryl bromide (0.40 mmol, 1.0 equiv.) and (P(t-Bu)₂Ph)₂•PdCl₂ (3.0 mol%) were added to a 25 mL of Schlenck tube. The tube was then evacuated and backfilled with Ar (3 times). CsF (2.0 equiv.), gem-difluoroallylboron (0.44 mmol, 1.1 equiv.), and 1,4-dioxane (2.0 mL) were added under Ar. The tube was screw capped and put into a preheated oil bath (100 ℃). After stirring for 2 h, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (2.0 mL). The yield was determined by ¹⁹F NMR using fluorobenzene (1.0 equiv.) as an internal standard before working up. If necessary, the reaction mixture was diluted with EtOAc and filtered with a pad of cellite. The filtrate was concentrated, and the residue was purified with silica gel chromatography to give product 11.

Difluorocarbene has found widespread applications in the synthesis of fluorine-containing molecules. We have previously found that difluorocarbene can react with elemental sulfur to produce thiocarbonyl fluoride, which is of great value for the new discoveries of difluorocarbene chemistry and the investigations of synthetic utilities of thiocarbonyl fluoride. We have developed the transformation of difluorocarbene into thiocarbonyl fluoride as a synthetic tool to achieve trifluoromethylthiolation of terminal alkynes and alkyl halides. In continuation of our research interest in this chemistry, herein we further apply the difluorocarbene transformation to the trifluoromethylthiolation of aryl and alkenyl iodides. Trifluoromethylthiolation is an active research area in organofluorine chemistry, and the commonly used trifluoromethylthiolation methods usually require the use of expensive CF₃S-containing reagents. In contrast, in our protocol the CF₃S group is generated in situ from difluorocarbene, elemental sulfur and a fluoride anion, all of which are cheap and easily available reagents. The general experimental procedure is shown as follows. Into a 5 mL sealed tube were added 4-phenyl phenyl iodide (1a, 56.0 mg, 0.2 mmol), S (57.8 mg, 1.8 mmol), Ph₃P⁺CF₂CO₂^– (PDFA) (213.8 mg, 0.6 mmol), AgF (0.5 mmol, 63.4 mg), ligand L₁ (0.6 mmol, 158.9 mg), CuI (76.2 mg, 0.4 mmol), and dioxane (1.0 mL) under a N₂ atmosphere. The reaction mixture was stirred at 110 ℃ for 8 h. After the reaction system was cooled to room temperature, Et₃N (0.5 mL) was added to remove the excess elemental sulfur by a redox reaction (the final product would be contaminated by elemental sulfur if elemental sulfur was not removed). The mixture was diluted with 10 mL of saturated brine, and then the product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to 1 mL. The residue was subjected to flash column chromatography to afford the pure product.

The fluorine-containing group has a significant effect on properties such as lipophilicity, permeability, and metabolic stability of compounds. Therefore, the efficient introduction of fluorine-containing groups into pharmaceutical and agrochemical compounds, as well as functional organic materials, has become an important research field of chemistry. Undoubtedly, new methodologies for the efficient and highly selective incorporation of fluorinated substituents into diverse molecular structures continue to be in strong demand. During the past few years, electrosynthesis has been considered to be a practical and environmentally friendly synthetic tool. The application of electrochemical anodic oxidation in synthetic organic chemistry has drawn increasing attention. Electrochemistry utilizes direct interaction of electrons from the anode and cathode with the nucleus, avoids using strong oxidants, and minimizes byproduct formation. Herein we describe an electrochemical synthesis of α-trifluoromethylated ketones from alkenes based on sodium trifluoromethanesulfinate. Sodium trifluoromethanesulfinate generates trifluoromethyl radicals through anodic oxidation to attack the carbon-carbon double bonds of alkenes, and then oxidized in air atmosphere to obtain the target compounds. The optimized reaction conditions of electrochemical synthesis of α-trifluoromethylated ketones are as follows: 1 equiv. of alkenes, 2 equiv. of sodium trifluoromethanesulfinate, a mixture of CH₃CN/H₂O (V∶V=2∶1) as the solvent, 2 equiv. of lithium perchlorate as electrolyte, CF₃COOH as the sacrificial oxidant, graphite as the anode and platinum as the cathode, react at room temperature for 6 h under a constant current of 20 mA and air atmosphere, giving the corresponding α-trifluoromethyl-substituted ketones in 66%~84% yields. The reaction substrate has good applicability, and the reaction conditions are mild. Compared with the traditional methods, the electrocatalytic process avoids the use of peroxidants or expensive photocatalysts. In addition, this reaction can be applied to the synthesis of α-difluoromethylated ketones when using sodium difluoromethanesulfinate instead of sodium trifluoromethanesulfinate.

Incorporation of fluorine has always been a conventional strategy for designing new drugs and materials because it can usually improve the physiochemical and physiological properties of organic molecules. Among various organofluorine compounds, α-fluoroalkyl alcohols are of particular importance and they are important skeletons of bioactive molecules. Herein, we report a three components olefin difunctionalization reaction for the synthesis of α-fluoroalkyl alcohols through manganese-catalyzed radical Brook rearrangement of α-fluoroalkyl-α-silyl methanols. The operationally simple reaction showed broad substrate scope, and the product could be prepared on gram scale. Twenty-five α-fluoroalkyl alcohols have been synthesized in 44%~86% yields. It is compatible with a variety of halogen substituents (F, Cl, Br), electron donating OMe and naphthalenyl groups and is also suitable for different symmetrical aryl olefins, asymmetric aryl olefins and alkoxyl olefins. The reaction is also compatible with different nucleophiles such as aryl carboxylic acids and anilines. Besides, the reaction is compatible with a α-alkyl alcohol which afford the desired olefin difunctionalization product in 36% yield. A representative procedure is described as follows. In the glovebox, α-difluoromethyl-α-dimethylphenylsilyl methanol (64.8 mg, 0.3 mmol), 1,1-stilbene (223 mg, 0.3 mmol), benzoic acid (110 mg, 0.9 mmol), Mn(OAc)₂ (2.6 mg, 0.015 mmol), tert-butyl peroxybenzoate (TBPB, 175 mg, 0.9 mmol), 4Å MS (30 mg) and dry dichloromethane (DCM, 0.5 mL) were added to a dry 10 mL reaction tube equipped with a magnetic agitator. The reaction mixture was then removed from the glove box, stirred at 70 ℃ for 1 h. Then tetrabutylammonium fluoride (TBAF, 0.36 mmol) was added at 0 ℃. After 30 min, the reaction mixture was quenched with saturated sodium bicarbonate aqueous solution (10 mL), extracted with ethyl acetate (10 mL×3). The organic phase was combined, washed with saturated NaCl aqueous solution and dried with anhydrous sodium sulfate and concentrated under vacuum. Then the crude product was purified by silica gel column chromatography to obtain corresponding target product.

Trifluoromethyl group has strong electron-withdrawing ability and stable C—F bond, and its introduction into organic molecules could often significantly modify the acidity, dipole moment, lipophilicity and metabolic stability of parent compounds. Therefore, the incorporation of trifluoromethyl group into bioactive molecules has become a common strategy for drug development. Trifluoromethylated arene moiety is the important unit of many drugs and related candidates, such as Nilotinib, Radotinib, Ponatinib, Regorafenib, Pexidartinib, Bimiralisi, and Defactinib. Therefore, it is of great interest to design new compounds containing trifluoromethyl group and explore their potential applications in the development of protein kinase inhibitors. Imatinib is the first-generation tyrosine kinase inhibitor and the first small molecule targeting anti-tumor drug that inspires the synthesis of a large number of excellent anti-tumor drugs. Therefore, in this study, we aimed to design new trifluoromethyl-containing tyrosine kinase inhibitors via combining the aniline-pyrimidine structure of Imatinib with 1,2,4-triazines. In particular, we developed a one-pot [3＋3] cycloaddition sequence to construct a series of 3-ester-5-aryl-6- CF₃-1,2,4-triazines in good yields. Subsequently, a series of new compounds containing the trifluoromethyl 1,2,4-triazine skeleton were obtained via a sequence of hydrolysis, chlorination, and amidation reactions. Finally, a preliminary evaluation of biological activity was conducted and a hit compound 4a was found with good activity in promoting apoptosis protein Caspase 9. A representative procedure for the synthesis of model product 4a is described as following: Starting from trifluoroethylamine (9.91 g, 100 mmol), tert-butyl nitrite (11.34 g, 110 mmol) and AcOH (1.2 g, 20 mmol) were used to generate trifluorodiazoethane in situ in tetrahydrofuran (THF, 20 mL) at 55 ℃ for 30 min. Then the CF₃CHN₂ solution was added to the mixture of glycine imine 1 (50 mmol), silver fluoride catalyst (0.64 g, 5 mmol) and cesium carbonate (20.36 g, 62.5 mmol) in THF (80 mL), and the reaction mixture reacted at 0 ℃ for 24 h to give the corresponding 6-CF₃-tetrahydrotriazine 2. Afterwards, 2,3-dichloro-5,6-dicyanophenoquinone (DDQ) (2.72 g, 12 mmol) was used as oxidant for compound 2 (3 mmol) to produce the corresponding 3-ester-5-aryl-6-trifluoromethyl-1,2,4-triazine 3. The obtained trifluoromethyl-1,2,4-triazine 3 (3 mmol) was hydrolyzed under the promotion of lithium hydroxide (0.15 g, 3.6 mmol) in THF/H₂O (5 mL THF, 10 mL H₂O) at r.t. for 1 h to give the corresponding carboxylic acid. The carboxylic acid intermediate reacted with oxalyl chloride (0.31 mL, 3.6 mmol) under the catalysis of N,N-dimethylformamide (DMF, 1~2 drop) in CH₂Cl₂ at r.t. for 2 h to give the corresponding acyl chlorides. Finally, in a mixture of CH₂Cl₂ (5 mL) and DMF (2 mL), acyl chloride intermediates reacted with the corresponding aniline-pyrimidine intermediate (0.92 g, 3.3 mmol) to give the desired product 4.

Trifluoromethyl-containing organic compounds have found widespread applications in various areas such as pharmaceuticals, agrochemicals and materials science. Fluoroform is the cheapest and most atom-economical trifluoromethyl source, but chemically inert. The use of fluoroform in trifluoromethylation reactions remains a formidable challenge. In this work, with a trifluoromethylboron complex derived from fluoroform as the trifluoromethylating reagent, the hydrotrifluoromethylation of styrenes, acrylates and acrylamides is successfully accomplished under photoredox catalytic conditions. Thus, with potassium bis(trimethylsilyl)amide (KHMDS) as the base, the reaction of fluoroform with (4-methoxyphenyl)boronic acid pinacol ester at room temperature (r.t.) leads to the corresponding trifluoromethylboron complex in 59% yield as a white solid stable in air and moisture. With the ate complex as the trifluoromethylating reagent, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6- dicyanobenzene (4CzIPN) as the photocatalyst and benzoic acid as the proton source, the reaction of styrenes in N,N-dimethylacetamide (DMA) at r.t. under blue light irradiation provided the corresponding anti-Markovnikov hydrotrifluoromethylation products in satisfactory yields. The protocol is also applicable to various acrylates as well as acrylamides, furnishing the expected ꞵ-trifluoromethylated esters or amides. A wide functional group compatibility is observed. The reaction is efficient and highly regioselective. In addition, the pinacol boronate generated along with the hydrotrifluoromethylation products can be recovered and reused. A redox-neutral mechanism is proposed, which involves the oxidative generation of CF₃ radicals, addition to C=C bonds, subsequent single electron reduction and protonation.

The design and synthesis of three kinds of arylamide molecules (compounds 1~3) containing halogen bonding donor and acceptor fragments, and the exploration and analyzation of different action modes of halogen bonding in solid phase were reported. Compounds 1 and 2 contain two tetrafluoroiodobenzene fragments, and compound 1 also contains a halogen receptor fragment—pyridine group. Isobutyl groups are introduced into the molecule to increase its solubility and crystallinity. And a pyrimidine fragment was introduced into compound 3, which has more aromatic rings. The two N atoms of the pyrimidine fragment can theoretically form intramolecular hydrogen bonds with the adjacent amide hydrogen atoms (—C(=O)NH), so that the whole molecule has the properties of hydrogen-bonded arylamide foldamer. Moreover, trifluorobenzene fragments were selected in compound 3 to eliminate the repulsion between excess fluorine atoms and carbonyls. The crystal structures reveal that the three aromatic rings in compound 1 are twisted with each other for there is no intramolecular hydrogen bond, and a supramolecular DNA-like double helix was assembled controlled by intermolecular N···I and O···I halogen bonds arranged alternately. Compound 2 failed to form an intramolecular three-center hydrogen bonding due to the repulsion between the amide carbonyl groups and the two fluorine atoms in close proximity. As expected, in the solid phase of compound 3, an effective three-center hydrogen bond is formed between the terminal trifluoroiodobenzene and the benzene ring attached to it. Moreover, the two N—H bonds connected to the pyrimidine ring also form two effective three-center hydrogen bonds. The difference is that the participants of these two groups of three-center hydrogen bonds include two N atoms in the pyrimidine ring. The four aromatic rings in compound 3 are nearly coplanar driven by these intramolecular three-center hydrogen bonds. Two sets of strong intermolecular (pyridine ring) N···I halogen bonds control the formation of [1+1] bimolecular supramolecular macrocycles with inner diameters of 1.36 nm and 1.07 nm in length and width. Moreover, the supramolecular macrocycle is near-planar due to the introduction of pyrimidine ring.

The synthesis of organosilicon compounds has attracted considerable interest, especially the allyl silanes, which are regarded as ideal building blocks in the synthesis of small molecules and polymers. The traditional synthetic method for allyl silanes relies on the cross-coupling of Grignard reagent and chlorosilane (Silyl-Kumada reaction), transition metal catalyzed silylation of allylic alcohols with disilanes or silylboranes, and regioselective silylation of conjugated alkenes or allenes. Although some other methods were also developed, the using of transition metal catalysts has resulted in disadvantages such as contamination of desired allyl silanes and high production costs. Therefore, a mild and metal-free practical method is highly desired. We herein describe a metal-free difluoroallylation of silanes with α-trifluoromethyl alkenes in the presence of quinuclidine as hydrogen atom transfer (HAT) reagent under the irradiation of 30 W blue light-emitting diode (LED) (460~470 nm) at room temperature. To an oven dried Schlenk-tube, trifluoromethylpropene (0.1 mmol), silane (0.3 mmol), KHCO₃ (0.1 mmol), 4-CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) (0.002 mmol) and MeCN (1 mL) were added under argon atmosphere. The reaction mixture was stirred under the irradiation of 30 W blue LED (460~470 nm) at room temperature. After completion of the reaction, the reaction solution was removed by reduced pressure and the residue was purified by silica gel chromatographic column to obtain gem-difluoroallylation products. A wide range of aromatic and heterocyclic α-trifluoromethyl alkenes were successfully applied in the difluoroallylation of silanes to afford difluoroallylsilanes. And all of the tested silanes, including trimethylsilane, sterically more demanding silanes as well as dimethylphenylsilane all participated in the present transformation readily to afford the corresponding difluoroallylsilanes in excellent yields. The present methodology has provided an efficient and cost-effective gram scale synthetic method for the preparation of difluoroallylsilanes under blue light irradiation in the presence of 4-CzIPN as organic photosensitizer. The scalability in large scale and excellent functional group compatibility of this transformation ensures broad applicability to a variety of difluoroallylsilanes. The proposed reaction mechanism showed that the reaction proceeded through the radical addition of α-trifluoromethyl alkene with silane free radical and subsequent β-fluoride elimination.

In 1989, Qing-Yun Chen’s research group at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences reported the development of methyl fluorosulfonyldifluoroacetate (FSO₂CF₂CO₂Me or MFSDA) as trifluoromethylation reagent. This reagent is now known as Chen’s reagent, which is perhaps the first well-recognized and widely used trifluoromethylation reagent originate from China. Despite the widespread use of Chen’s reagent in both academia and industry, the detailed mechanism underlying the conversion of Chen’s reagent into a trifluoromethyl source has remained elusive. In this contribution, we conducted a thorough investigation into the reaction mechanism, employing density functional theory (DFT) calculations. Geometry optimizations and frequency analyses were performed using the PBE0/def2-SVP level of theory. To ensure accurate electronic energy calculations, single-point energy calculations were conducted at the ωB97X-D/def2-TZVPP level of theory. The solvent effects were considered using the solvation model density (SMD) model during both geometry optimizations and single-point energy calculations. Furthermore, Gibbs free energies were corrected with GoodVibes, employing Truhlar et al.’s quasi-harmonic treatment by setting all positive frequencies less than 100 to 100 cm^–1. Concentration corrections were applied from 1 atm to 1 mol/L. Our calculations reveal the detailed mechanism governing the generation of copper(I) trifluoromethyl from Chen’s reagent in the presence of a CuI catalyst. An in-depth understanding of such mechanistic details would be helpful for future development of new reaction and application with Chen’s reagent.

Fluoropolymers exhibit unique properties, such as outstanding thermal stability and chemical inertness, ultralow surface energy, and have found broad applications in lots of areas. Many fluoropolymers show high crystallinity and low solubility, restricting their practical usage through melting and solution processing. To address such issues, copolymerization of fluoroalkenes and comonomers have been developed to prepare fluorinated copolymers that retain fluoroalkyl characteristics and good processibility, bringing many important commercial products, for example, copolymers of chlorotrifluoroethylene (CTFE) and vinyl ethers. However, such copolymers could possess low glass transition temperature (T_g), which is a key property to influence the applicable scope. In this work, we report copolymerization of CTFE and methyl isopropenyl ether (MIE) for the first time, which have enabled the synthesis of novel fluorinated copolymers under LED (light emitting diode) light irradiation conditions by merging an organic thermally activated delayed fluorescence catalyst and a redox active organic amine via a redox-relay catalysis. In comparison to conventional free radical (co)polymerization of fluoroalkenes, this method not only provides main-chain fluoropolymers of readily tunable molecular weights as evidenced by gel permeation chromatography (GPC) and multi-angle light scattering detection coupled with GPC (GPC-MALS), but also allows smooth transformation of fluoroalkene feedstock at ambient pressure using common Schlenk glassware without needing high-pressure metallic vessels. Although the obtained CTFE-MIE copolymers exhibited less controlled molecular weight distributions (MWDs) and limited chain-end fidelity as confirmed by chain-extension polymerization and GPC analysis, the chain-growth process presents first-order kinetics as validated by monitoring the monomer consumption, and follows alternating copolymerization as supported by the variation of degrees of polymerization (DPs) of both vinyl compounds along the light irradiation time, presenting improved chain-growth control as compared to conventional free radical transformation. Notably, as analyzed by differential scanning calorimetry (DSC), in contrast to copolymers of CTFE and ethyl vinyl ether (EVE), the CTFE-MIE copolymers with similar molecular weights exhibit clearly improved T_g of about 50 ℃ via simply introducing methyl substituents on the polymer backbone. Given the broad interests in fluoropolymers and established applications of fluoroalkene-vinyl ether copolymers, we believe that this work should be informative to the rational design of novel fluoropolymers and attractive for material engineering with improved thermal stability.

Amphoteric phosphocholine as a family of mild surfactants are widely used in biology due to their phosphate structure related to naturally occurring membrane lipids. Changing its hydrophobic part to the fluorocarbon counterparts, it was found that the interfacial properties of phosphocholine surfactants exhibit significant differences. Currently, the research on fluorinated phosphocholine surfactants is limited and lacks types of fluorinated hydrophobic structures. We found that oxygen atoms exhibit specificity in fluorinated surfactants in our previous works. In this work, a kind of phosphocholine containing a fluoroether hydrophobic chain was synthesized, and its interfacial properties, foam properties, and wetting properties were studied. At the beginning, we conducted a substitution reaction using fluoroether alcohols and 2-chloro-2-oxo-1,3,2-dioxaphospholane as raw materials, triethylamine as a base, and tetrahydrofuran (THF) as a solvent under ice bath. Then, the intermediate C72-P is obtained through distillation, which is a transparent viscous liquid with a yield of 70%. The next step is to dissolve the C72-P with trimethylamine (2 mol/L in THF) in acetonitrile at 70 ℃ for 48 h. Finally, a fluoroether phosphocholine surfactant was obtained and purified through column chromatography to give C72-MPB in 90% yield. Under the same conditions, a fluorinated linear phosphocholine surfactant 6:2-MPB was prepared using perfluorohexyl ethanol, which is a white solid with a overall yield of 60%. The phosphocholine fluorinated surfactants C72-MPB and 6:2-MPB were diluted with distilled water to obtain various concentrations of solutions, the surface properties were measured by surface tension instrument Krüss K100C, and the surface tension was measured by Wilhelmy platinum plate method. On the other hand, the performance of foam under two different concentrations of C72-MPB was tested by bubbling method, and the morphology of foam was observed. C72-MPB solution was dropped onto the surface of polytetrafluoroethylene (PTFE), contact angle on PTFE was measured, and its wettability at different time was recorded. The results show that the new fluoroether phosphocholine surfactant has good solubility, low surface tension, good wettability, good foam stability. Fluoroether phosphocholine surfactants have potential utility value in the field of life sciences and medicine. It is a kind of surfactant with excellent application prospects.

In this work, a borondipyrromethene (BODIPY)-based activatable photosensitizer FP-IBDP was designed and synthesized, which has absorption and emission wavelengths in the near infrared (NIR) region. The maximum absorption and emission of FP-IBDP are 681 nm and 740 nm in acetonitrile. The fluorescence quantum yield and singlet oxygen yield of FP-IBDP is 0.01 and 0.09, respectively. After activated by H₂O₂, FP-IBDP was transformed to photosensitizer IBDP, which has maximum absorption and emission peak at 661 nm and 701 nm in acetonitrile. Compared with FP-IBDP, the fluorescence quantum yield and singlet oxygen yield of IBDP are much increased, up to 0.11 and 0.48 respectively. It is demonstrated that FP-IBDP can respond H₂O₂ sensitively in cancer cells and has the ability to distinguish cancer cells from normal cells by a fluorescence enhancement way. Reactive oxygen species (ROS) detection indicated that FP-IBDP could be activated by the endogenous H₂O₂ in cancer cells and produce highly toxic singlet oxygen under 660 nm light excitation with dichlorodihydrofluorescein diacetate (DCFH-DA) as ROS indicator. Tetrazolium (MTT) assay indicated that FP-IBDP has good biocompatibility and low dark toxicity to both cancer cells and normal cells, while phototoxicity test and living/dead cell double staining experiment proved that FP-IBDP has higher phototoxicity to cancer cells than to normal cells. Besides, wounding healing assay confirmed its good ability to inhibit cancer cell proliferation. Fluorescence localization and lysosome disruption assays further indicated that FP-IBDP was specifically located in lysosomes of living cells and the produced singlet oxygen could induce cancer cell death in a lysosome disruption associated pathway. These features are expected to lay good foundation for the application of FP-IBDP in imaging guided photodynamic therapy under NIR excitation.

Olefin polymerization is one of the most important chemical reactions in industry. Transition metal catalysts are the key to the development of olefin polymerization. Neutral salicylaldiminato nickel catalyst stands out due to the nature of both functional-group tolerance and cocatalyst-free. Either sterically hindered effect or fluorine effect has extensively been reported over the past decades to improve properties of neutral and single-component salicylaldiminato nickel catalyst; however, combination of these two effects to generate a concerted strategy is much less studied. In this work, both para-sterically hindered substituents including phenyl, 1-naphthyl or 9-anthracenyl group and ortho-fluorine substituents are concurrently installed into salicylaldimine ligands, and thus five salicylaldiminato nickel catalysts have been synthesized and fully identified by ¹H and ¹³C NMR spectroscopy, elemental analysis and X-ray diffraction technique if possible. Without the addition of any activator, these single-component nickel catalysts are used to ethylene polymerization. Influence of sterically hindered effect, fluorine effect, reaction temperature and reaction time on catalytic activity, polymer molecular weight, and branching density of polymer is comprehensively investigated. ortho-Fluorine substituents particularly elevate catalytic activity, lifetime of catalyst species, and polymer molecular weight, while decreases branching density of polymer. Enhancement of catalytic activity and polymer molecular weight reaches two orders of magnitude and 36 times, respectively; and linear structure (5 branches/1000 carbon) of polyethylene can be accessible. This should originate from the inhibition of both chain transfer and chain walking pathways. The bulk of para-sterically hindered substituents can be designed according to the required catalytic activity and molecular weight, and notably it has a minor influence on branching density of polymer. The concerted combination of fluorine effect and steric shielding effect enables the formation of linear ultrahigh molecular weight polyethylene (UHMWPE). This work develops a new strategy for the efficient design of salicylaldiminato nickel olefin polymerization catalyst.

Introduction of fluorine into organic molecules often causes significant changes in their physical, chemical and biological properties, which result in the wide application of fluorine-containing compounds in many fields of chemistry such as drug discovery, agrochemical development and material science. As a consequence, rapid assembly of fluorinated structures has become one of the most popular research topics in the past decade, which also propelled eminent breakthroughs in related areas. Generally, fluorination methods could be divided into two types according to the fluorinating reagent used, i.e., electrophilic fluorination and nucleophilic fluorination. Compared with electrophilic fluorination, the reagents used in nucleophilic fluorination are usually advantageous in economy and availability. In addition, mild conditions employed in nucleophilic fluorination also result in wide substrate scope and excellent functional group compatibility. By resorting to transition- metal and photoredox catalysis, as well as visible light promoted reactions, the authors’ research group has recently established a series of selective fluorofunctionalization of unsaturated carbon-carbon bonds with nucleophilic fluorine sources, affording a panel of structurally novel fluorine(s)-embedded molecules. In this account, the authors have systematically summarized their recent work in this area, challenges and directions which deserve future endeavors in this field are also discussed.

In recent years, organic reactions involving difluorocyclopropenes have attracted the attention of organic chemists and have made great progress. The reactions mainly include: (1) cyclization: a) transition-metal catalyzed C—H bond activation cyclization with directing groups; b) cyclization reactions with non-directing groups; (2) hydrogenation reduction; (3) fluorination as “F” source reagents. In this paper, the synthesis methods and applications of difluorocyclopropenes in past 10 years are summarized. The conversion reactions of difluorocyclopropenes are emphasized. Additionally, difluorocyclopropenes have aroused considerable interests both from a structural standpoint and their participation in various ring-opening reactions. Given the increasing application of cyclopropyl skeleton in the development of drugs and unarguable importance of fluorinated compounds in medicinal chemistry and agrochemistry, it is no doubt that difluorocyclopropenes are encountered into bioactive molecular and at present lie among “emerging fluorinated motifs”. Although the synthesis and application of structurally diverse difluorocyclopropenes have been witnessed in the past decade, the most widely used methods for the preparation of these compounds include difluoromethylenation of alkynes and difluoromethylation of heteroatom nucleophiles (such as NaF, NaI, ⁿBuN₄X, etc.) with a difluorocarbene reagent, which can be generated from various precursors (such as TMSCF₃, TMSCF₂X, Ph₃P^＋CF₂CO₂^-, TFDA, etc.). For the transition metal-catalyzed cyclization of difluorocyclopropenes, some common metal salts (such as rhodium, ruthenium, copper, palladium, silver) are used as catalysts. Moreover, the metallic hydrogen (M—H) reduction strategy is a simple and efficient method for the hydrogenation reduction of difluorocyclopropenes leading to difluorocyclopropanes, and the asymmetric hydrogenation reduction of difluorocyclopropenes can be achieved in the presence of chiral ligands. In fluorination reactions, difluorocyclopropenes have some advantages that cannot be achieved by traditional fluorination reagents for the direct fluorination and functionalization of hydroxyl groups (such as fluorination of polyhydroxyl alcohols). Of course, the biggest disadvantage of difluorocyclopropene as a fluorine source lies in its poor atomic economy, which has been criticized. Despite the remarkable achievements in the reactions of difluorocyclopropenes, there are still many issues that need to be addressed. For instance, difluorocyclopropenes are rarely applied in traditional radical reactions, photocatalysis, electrocatalysis and flow chemistry. Hopefully, difluorocyclopropenes can gradually appear in photo- and electro-catalyzed radical chemistry, and the related asymmetric reactions will also get more attention and development in the near future.

In this paper, two novel thienyl boron dipyrromethene (thienyl-BODIPY) near infrared (NIR) photosensitive dyes, ITBDP-1 and ITBDP-2 were designed and synthesized. The absorption and emission wavelengths of two photosensitizers reach near infrared region. The absorption and emission peaks of ITBDP-1 are 617 and 650 nm while the absorption and emission peaks of ITBDP-2 are 687 and 731 nm respectively. The singlet oxygen yields (Φ_Δ) of photosensitizers were determined using 1,3-diphenyliso- benzofuran (DPBF) as singlet oxygen scavenger. The results turned out that two photosensitizers both could generate singlet oxygen under 660 nm light irradiation, and the absorption of DPBF decreased over 50% within 1 min. Φ_Δ of ITBDP-1 and ITBDP-2 are 51% and 24% respectively. Excited state energy level of photosensitizers were studied by density functional theory (DFT) calculation. Theoretical calculation indicates that ITBDP-1 and ITBDP-2 can reach triplet state through intersystem crossing (ISC) after being excited to singlet state, thus improving singlet oxygen yield. ITBDP-1 and ITBDP-2 showed satisfying imaging effect in A549 cells, and ITBDP-1 could show distinct two-photon fluorescence in zebrafish under 900 nm excitation. Apart from good cell imaging effect, these two photosensitizers showed abilities to generate reactive oxygen species (ROS) in tumor cells as well. It can be proved that photosensitizers could produce singlet oxygen in tumor cells and zebrafish under light excitation with dichlorodihydrofluorescein diacetate (DCFH-DA) as ROS indicator. Besides, ITBDP-1 and ITBDP-2 also presented high cytotoxicity under 660 nm light irradiation. In the tetrazolium (MTT) experiment, the maximum half inhibitory concentration (IC₅₀) of ITBDP-1 and TBDP-2 were 2.22 and 2.86 μmol•L^-1 respectively, and the cell viability was over 80% without irradiation, which proved that both photosensitizers possess high phototoxicity and good biocompatibility. ITBDP-1 and ITBDP-2 could realize imaging-guided photodynamic therapy under excitation of NIR light in tumor cells, and displayed two-photon fluorescence imaging in vivo. Photosensitizers ITBDP-1 and ITBDP-2 are excepted to lay good foundation for the application of thienyl-BODIPY photosensitizers in two-photon photodynamic therapy under NIR excitation.

Organic small molecules of low LUMO/HOMO (lowest unoccupied molecular orbital/highest occupied molecular orbital) energy levels are in shortage in terms of both variety and quantity. Their design and synthesis have important scientific and application value. The traditional strategy for designing organic small molecules of ultra-low LUMO/HOMO energy levels is to introduce multiple cyano groups into the molecules. In this work, a polycyclic aromatic hydrocarbon molecule containing four boron and nitrogen coordination bonds and two imide groups is designed and synthesized, without involving any cyano groups. The cyclic voltammetry examination with 0.1 mol•L⁻¹ tetrabutylammonium hexafluorophosphate solution in dichloromethane as the electrolyte solution and ferrocene as the internal standard indicates that the molecule has a low LUMO and HOMO energy level of －4.77 eV and －6.39 eV, respectively. These values are the lowest for the reported fused-ring small molecules with boron and nitrogen coordination bonds and comparable to those of the reported organic small molecules with cyano groups. The density functional theory calculation results at the B3LYP/6-31G(d,p) theoretical level show that the molecule has a curved configuration and its conjugate skeleton has a dihedral angle of 23.6°. Both LUMO and HOMO are uniformly delocalized on the linear benzoid skeleton. It shows obvious near-infrared absorption in both solution and thin film state, with maximum absorption at 768 nm in film. The molecule can be used as a p-type dopant. After its blend doping, the electrical conductivity of the film of a typical p-type polymer P3HT is improved by 3 orders of magnitude. The doping behavior is also confirmed by UV-Vis absorption spectroscopy and electron paramagnetic resonance spectroscopy. This work develops a new strategy to achieve ultra-low LUMO energy level for organic small molecules without using cyano groups.