Fluorinating Reagent Research Articles

Development of SF6 as a Formal Electrophilic Fluorinating Reagent for Photocatalyzed Oxidative Fluorination of Phosphine Oxides.

Organophosphorus-fluorine compounds are of significant utility across biology, pharmacy, and chemical synthesis. Here, we introduce a photocatalyzed oxidative-fluorination approach employing SF6 as a formal electrophilic fluorinating reagent. It offers an innovative pathway to forge P(O)-F bonds. Notably, sulfur hexafluoride plays a dual role as both the oxidant and the fluorinating reagent under mild conditions in this transformation. Meanwhile, this method contributes to environmental sustainability by consuming a notorious greenhouse gas, underscoring the ecological benefits of our approach.

Decarboxylative Nucleophilic Fluorination of Aliphatic Carboxylic Acids.

Herein, we present a decarboxylative nucleophilic fluorination of carboxylic acids with a silver catalyst. This strategy enables the synthesis of a myriad of diverse and valuable fluorinated motifs under mild conditions, demonstrating good functional-group tolerance and utility in late-stage functionalization. In contrast to traditional electrophilic fluorination, this nucleophilic method utilizes a more readily available nucleophilic fluorinating reagent, providing substantial advantages in terms of cost efficiency, broad substrate scope, and functional-group compatibility.

Ligand-Enabled Oxidative Fluorination of Gold(I) and Light-Induced Aryl-F Coupling at Gold(III).

MeDalphos Au(I) complexes featuring aryl, alkynyl, and alkyl groups readily react with electrophilic fluorinating reagents such as N-fluorobenzenesulfonimide and Selectfluor. The ensuing [(MeDalphos)Au(R)F]+ complexes have been isolated and characterized by multinuclear NMR spectroscopy as well as X-ray diffraction. They adopt a square-planar contra-thermodynamic structure, with F trans to N. DFT/IBO calculations show that the N lone pair of MeDalphos assists and directs the transfer of F+ to gold. The [(MeDalphos)Au(Ar)F]+ (Ar = Mes, 2,6-F2Ph) complexes smoothly engage in C-C cross-coupling with PhCCSiMe3 and Me3SiCN, providing direct evidence for the oxidative fluorination/transmetalation/reductive elimination sequence proposed for F+-promoted gold-catalyzed transformations. Moreover, direct reductive elimination to forge a C-F bond at Au(III) was explored and substantiated. Thermal means proved unsuccessful, leading mostly to decomposition, but irradiation with UV-visible light enabled efficient promotion of aryl-F coupling (up to 90% yield). The light-induced reductive elimination proceeds under mild conditions; it works even with the electron-deprived 2,6-difluorophenyl group, and it is not limited to the contra-thermodynamic form of the aryl Au(III) fluoride complexes.

Design of fluorine-free superhydrophobic silk fabrics with mechanical durability and self-cleaning properties for oil-water separation

The separation of oil and water can be effectively addressed through the application of superhydrophobic coatings. This method, known for enhancing the self-cleaning, anti-corrosive, and friction-reducing properties of materials, typically employs fluorine reagents to ensure the durability of the coating nanostructure. However, the use of fluorine reagents raises concerns related to health and the environment. We present a straightforward and efficient approach to fabricate a robust, fluorine-free superhydrophobic composite coating. The coating solution, comprised of hydrophobic silica nanoparticles and polydimethylsiloxane (PDMS), is formed through sonication. The resulting superhydrophobic coating is effortlessly applied to silk fabric through immersion and subsequent drying/curing. micrograph confirms the creation of porous micro/nanostructures on the silk fabric's surface. Exceptional superhydrophobicity is demonstrated with a water contact angle (WCA) of 161 °±1.5 ° and a small sliding angle (SA) of 5 °±0.5 °. The coating's firmness, durability, and UV resistance are assessed through 20 cycles of sandpaper friction (load 200 g) and repeated tape peeling tests. Furthermore, the modified silk fabrics exhibit excellent capabilities in oil-water separation. This fluorine-free superhydrophobic coating, characterized by its robustness, environmental friendliness, and ease of manufacture, holds promising applications in the textile industry.

Fabrication of robust superhydrophobic surface on TC4 alloy by wire electrical discharge machining

Superhydrophobic metal surfaces have significant applications in various areas such as surface self-cleaning, resistance reduction, anti-corrosion, etc. However, inexpensive preparation methods for superhydrophobic surfaces with a good mechanical stability are still to be developed. In this study, microarray structures on TC4 alloy were readily fabricated using a wire electrical discharge machining technology. Following the treatment with a fluorinating reagent, the microarray surface exhibited excellent superhydrophobic properties, where the largest contact angle and the smallest sliding angle reached 159° and 3°, respectively. Influences of the dimensions of microarray structure on the TC4 alloy surface wettability were also investigated in this study. Experiments show that this superhydrophobic surface possesses favorable self-cleaning, good mechanical stability, and promising anti-corrosion properties. In addition, by controlling the dimensions of the microstructure a superhydrophobic surface with a gradient wettability was also fabricated, which exhibits the property of doing nondestructive transportation of liquids.

Where do the Fluorine Atoms Go in Inorganic‐Oxide Fluorinations? A Fluorooxoborate Illustration under Terahertz Light

AbstractThe substitution of fluorine atoms for oxygen atoms/hydroxyl groups has emerged as a promising strategy to enhance the physical and chemical properties of oxides/hydroxides in fluorine chemistry. However, distinguishing fluorine from oxygen/hydroxyl in the reaction products poses a significant challenge in existing characterization methods. In this study, we illustrate that terahertz (THz) spectroscopy provides a powerful tool for addressing this challenge. To this end, we investigated two fluorination reactions of boric acid, utilizing MHF2 (M=Na, C(NH2)3) as fluorine reagents. Through an interplay between THz spectroscopy and solid‐state density functional theory, we have conclusively demonstrated that fluorine atoms exclusively bind with the sp3‐boron but not with the sp2‐boron in the reaction products of Na[B(OH)3][B3O3F2(OH)2] (NaBOFH) and [C(NH2)3]2B3O3F4OH (GBF2). Based on this evidence, we have proposed a reaction pathway for the fluorinations under investigation, a process previously hindered due to structural ambiguity. This work represents a step forward in gaining a deeper understanding of the precise structures and reaction mechanisms involved in the fluorination of oxides/hydroxides, illuminated by the insights provided by THz spectroscopy.

Where do the Fluorine Atoms Go in Inorganic-Oxide Fluorinations? A Fluorooxoborate Illustration under Terahertz Light.

The substitution of fluorine atoms for oxygen atoms/hydroxyl groups has emerged as a promising strategy to enhance the physical and chemical properties of oxides/hydroxides in fluorine chemistry. However, distinguishing fluorine from oxygen/hydroxyl in the reaction products poses a significant challenge in existing characterization methods. In this study, we illustrate that terahertz (THz) spectroscopy provides a powerful tool for addressing this challenge. To this end, we investigated two fluorination reactions of boric acid, utilizing MHF2 (M=Na, C(NH2)3) as fluorine reagents. Through an interplay between THz spectroscopy and solid-state density functional theory, we have conclusively demonstrated that fluorine atoms exclusively bind with the sp3-boron but not with the sp2-boron in the reaction products of Na[B(OH)3][B3O3F2(OH)2] (NaBOFH) and [C(NH2)3]2B3O3F4OH (GBF2). Based on this evidence, we have proposed a reaction pathway for the fluorinations under investigation, a process previously hindered due to structural ambiguity. This work represents a step forward in gaining a deeper understanding of the precise structures and reaction mechanisms involved in the fluorination of oxides/hydroxides, illuminated by the insights provided by THz spectroscopy.

Recent Advances in C—F Bond Formation from Carbon‐Centered Radicals

Comprehensive SummaryConstruction of C—F bonds is a direct and efficient method for introducing fluorine into pharmaceuticals, agrochemicals, and materials. Strategies such as nucleophilic, electrophilic, radical, and transition‐metal catalyzed fluorination have been developed to meet the demand of diverse C—F bond formation. Among them, radical fluorination has been witnessed with substantial advancement in a recent decade. Herein, we reviewed methods for formation of C—F bonds with carbon‐centered radicals as key intermediates, especially in recent five years. We introduce in the paper with different fluorinating reagents, strategies for radical generation, and application in late‐stage functionalization and synthesis of PET tracers. We also indicate the current limitations and propose the direction of the field for the future development. Key ScientistsRadical fluorination was recognized as an old and uncontrolled reaction that may date back to the time when element fluorine was first mixed with organic compounds by Henri Moissan in 1891. The development of the field was slow in combination with discovery of new fluorinating reagents. Substantial changes took place in 2012, when the first example of carbon radical fluorination with robust and mild fluorinating reagents, such as NFSI and Selectfluor, was reported by the Sammis group. In the same year, Groves, Lectka, Li, and Boger led the pioneering works on aliphatic C—H fluorination, decarboxylative fluorination, and fluorofunctionalization of alkenes in a radical manner. Photoredox catalysis was introduced to radical fluorination in 2013 by the Chen group, which opens up a new avenue for diverse fluorinative transformations. Most of the previous works focus on radical fluorination to form C(sp3)–F bonds. In 2018, the challenging non‐directed aromatic C—H fluorination was solved by Ritter and coworkers. Direct arene fluorination with fluoride ion was later disclosed by the Nicewicz group in 2019. There are many other scientists that have also made tremendous contribution to the development of radical fluorination, with too limited space to list them all. We only list those with first discoveries that may point to the new direction of radical fluorination.

Visible light-induced photocatalytic deoxyfluorination of benzyl alcohol using SF6 as a fluorinating reagent

Synthesis of benzyl fluorides via visible-light-induced fluorination using SF6 has been established, exhibiting a broad substrate scope and high efficiency.

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides.

The ability to investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V) fluorides in good isolated yields (72-90%). Stability studies revealed that bicyclic difluoro(aryl)-λ5-iodane 6 was much more stable in acetonitrile-d 3 than in chloroform-d 1, presumably due to acetonitrile coordinating to the iodine(V) centre and stabilising it via halogen bonding.

An N-heterocyclic carbene-based pincer system of palladium and its versatile reactivity under oxidizing conditions.

NHC-based pincers (NHC = N-heterocyclic carbene) have been broadly employed as supporting platforms, and their palladium complexes have found many synthetic applications. However, previous studies mainly focused on the NHC pincers of palladium featuring an oxidation number of +II. In contrast, oxidation of these well-defined Pd(II) species and the study of their fundamental high-valent Pd chemistry remain largely undeveloped. In addition, from a perspective of PdII/PdIV catalysis, the reactivity and degradation of NHC pincers in catalytically relevant reactions have not been well understood. In this work, a series of Pd(II) complexes supported by a well-known NHC^Aryl^NHC pincer platform have been prepared. Their reactivity towards various oxidizing reagents, including halogen surrogates, electrophilic fluorine reagents, and alkyl/aryl halides, has been examined. In some cases, ambient-characterizable high-valent Pd NHCs, which have been scarcely reported, were obtained. The carbenes incorporated into the pincer framework proved to be effective spectator donors. In contrast, the central aryl moiety exhibits versatile reactivity and collapse pathways, allowing it to function either as a spectator or a non-innocent actor.

Quaternary ammonium fluorides and difluorosilicates as nucleophilic fluorination reagents.

TBAT (tetrabutylammonium difluorotriphenylsilicate) is an excellent homogeneous nucleophilic fluorination reagent, but a high excess of the reagent was reported to be essential. We hence optimized the reaction conditions and compared its nucleophilic fluorination reactivity with that of other common commercial nucleophilic fluorination reagents, such as anhydrous TBAF and TASF (tris(dimethylamino)sulfonium difluorotrimethylsilicate). As the substrates, we employed a standard set of primary and secondary octyl substrates under identical conditions. To eliminate the possibility of hydrogen fluoride elimination in the above reagents, we prepared four quaternary ammonium fluorides lacking β-elimination possibility in the hydrocarbon chain, transformed them to the corresponding difluorotriphenylsilicates, and compared their reactivity with that of the commercial reagents. Furthermore, attempts to isolate analogous tetrabutylammonium difluoromethyldiphenylsilicate or difluorodimethylphenylsilicate failed, as was confirmed by comparison of the published experimental data with computed 19F NMR spectra. Finally, we studied the transition states of decomposition of various tetramethylammonium methylphenyldifluorosilicates by DFT methods and found that their relative energies increase with an increasing number of phenyl groups. The formation of difluorosilicates is a nearly barrierless process.

Gold-catalyzed fluorination of alkynes/allenes: mechanistic explanations and reaction scope.

Since the beginning of this century, there has been a great deal of research on homogeneous gold-catalyzed alkyne fluorination due to the precious values of fluorinated scaffolds in many bioactive natural products, drugs, and agrochemicals. This area of research, which originally took advantage of gold's mild Lewis acidity and tendency to form π-complexes with alkynes, has gained new momentum after Sadighi's discovery in 2007 of Au-catalyzed hydrofluorination of internal alkynes. The methods have enabled direct access to valuable fluoroalkanes, fluoroalkenes, α-fluorocarbonyls, and fluorinated carbo- and hetero-cycles in one pot from readily available alkyne precursors. Both nucleophilic and electrophilic fluorination modes with versatile reactivity have been used to achieve several new cascade reactions. This study covers the literature reports published since 2007 and provides a comprehensive summary of the methods, applications, and mechanistic insights into gold-catalyzed alkyne fluorination using electrophilic and nucleophilic fluorinating reagents.

Hydrophobic modification of polyvinylidene fluoride membranes in supercritical carbon dioxide fluids

Polyvinylidene fluoride (PVDF) membranes exhibit exceptional chemical stability and find applications in various fields, including building membranes, flexible sensors, blood purification, and seawater desalination. Nevertheless, the hydrophobic performance of PVDF membranes in these applications is subpar and requires enhancement. Supercritical carbon dioxide (scCO2) fluid demonstrates a beneficial expansion effect on PVDF membranes and exhibits good solubility with fluorine reagents. This study employs scCO2 as a medium to introduce a fluorine reagent onto the surface of PVDF membranes, forming a layer of low surface energy substance that significantly improves the membrane's hydrophobicity. The results indicate the feasibility of hydrophobic modification of PVDF membranes using scCO2 as a medium, leading to improved hydrophobic properties. When using a fluorine reagent with a relatively large molecular weight, PVDF membranes in scCO2 fluid at 110 °C and 20–25 MPa for 4 h results in a substantial improvement in the hydrophobicity of the PVDF membrane, with the contact angle reaching 117.2° (compared to the primitive membrane's 80°). Scanning electron microscopy (SEM) analysis confirms the presence of a layer of low surface energy material on the modified PVDF membrane surface. Thermogravimetric (TG) and differential thermogravimetric (DTG) analyses demonstrate that the hydrophobic modification using scCO2 enhances the crystallinity and thermal stability of the PVDF membrane, raising the thermal cracking temperature from 425.3 °C to 450.5 °C. Fourier-transform infrared spectroscopy (FT-IR) reveals clear absorption peaks of the fluorine reagent at 1740 cm−1 and 1211 cm−1. Nuclear magnetic resonance (NMR) confirms the presence of characteristic peaks of hydrogen on the fluorine reagent, confirming the embedding of the hydrophobic reagent onto the PVDF membrane surface. This modification method holds significant potential for guiding the development of hydrophobic surfaces, contributing to carbon neutrality, and meeting environmental sustainability goals.

Advances in Continuous Flow Fluorination Reactions.

Fluorination reactions are important in constructing organofluorine motifs, which contribute to favorable biological properties in pharmaceuticals and agrochemicals. However, fluorination reagents and reactions are associated with various problems, such as their hazardous nature, high exothermicity, and poor selectivity and scalability. Continuous flow has emerged as a transformative technology to provide many advantages relative to batch syntheses. This review article summarizes recent continuous flow techniques that address the limitations and challenges of fluorination reactions. Approaches based on different flow techniques are discussed, including gas-liquid reactions, packed-bed reactors, in-line purifications, streamlined multistep synthesis, large-scale reactions well as flow photoredox- and electrocatalysis.

SO2F2-Mediated Fluorination of P(O)-H and P(O)-OH Compounds under Mild Conditions.

With the increasing relevance of organophosphorus fluorine compounds in the pharmaceutical industry, their synthesis has attracted great attention. Herein, we report an efficient fluorination strategy for P(O)-H and P(O)-OH compounds using sulfuryl fluoride as the fluorination reagent. Avoiding the use of expensive or complex prepreparation reagents for fluoridation, this strategy could conveniently construct a variety of fluorophosphonates and phosphonofluoridates under mild conditions and without additional oxidants.

Fluorination strategy on π-bridge of polymer donor for efficient photovoltaic performance

Although fluorine-contained polymers have been adopted in efficient polymer solar cells, complicated reaction methods and costly fluorination reagents have impeded large-scale application. Here, a novel fluorinated polymer donor, PM6-F, was designed and synthesized via a newly developed 3-fluoro-2-iodithiophene to simplify synthesis procedures and minimise reaction costs from modest raw materials. Compared with the polymer analogue PM6 without any fluorine substituent on the main chain, it was found that PM6-F with a better configuration exhibited more orderly molecular packing, stronger and broader absorption, a narrower optical band gap, and a lower-lying HOMO energy level. The PM6-F:IT-4F-based PSCs obtained an excellent PCE of 14.90% with a VOC of 0.91 V, a JSC of 23.25 mA cm−2, and an FF of 70.42%. Notably, the value of 14.90% was among the highest recorded in the literature for IT-4F-based PSCs. This research demonstrated that modifying π-bridges with fluorine is a promising strategy for developing high-efficiency polymer donors.

Gold-catalyzed four-component multifunctionalization of alkynes

The alkyne unit is a versatile building block in organic synthesis and the development of selective multifunctionalization of alkynes is an important object of research in this field. Herein, we report an interesting gold-catalyzed, four-component reaction that achieves the oxo-arylfluorination or oxo-arylalkenylation of internal aromatic or aliphatic alkynes, efficiently breaking a carbon-carbon triple bond and forming four new chemical bonds. The reaction divergence can be controlled by site-directing functional groups in the alkynes; the presence of a phosphonate unit favors the oxo-arylfluorination, while the carboxylate motif benefits oxo-arylalkenylation. This reaction is enabled by an Au(I)/Au(III) redox coupling process using Selectfluor as both an oxidant and a fluorinating reagent. A wide range of structurally diverse α,α-disubstituted ketones, and tri- or tetra-substituted unsaturated ketones have been prepared in synthetically valuable yields and with excellent chemo-, regio- and stereoselectivity. The gram-scale preparation and late-stage application of complex alkynes have further enhanced their synthetic value.

Photoinduced Copper-Catalyzed Monofluoroalkylation of Terminal Alkynes to Propargylic Fluorides.

A photoinduced copper-catalyzed strategy for the monofluoroalkylation of alkynes with readily available monofluoroalkyl triflates was developed. It provides a new protocol to access valuable propargyl fluoride compounds via C-C bond formation by avoiding the use of highly toxic fluorination reagents. This reaction proceeded under mild conditions to afford propargyl monofluorides in moderate to high yields. Preliminary mechanistic studies reveal that a ligand-matched alkynyl copper complex might be the key photoactive substance.

Carbofluorination of π‐Bonds and Related Reactions Involving Tandem C−C/C−F Bond Formation

AbstractDue to the unique properties of C−F bonds, organofluorine compounds occupy a privileged space in the pharmaceutical, agrochemical, and polymer industries. Carbofluorination reactions involve the formation of a C−C and a C−F bond, typically across a π‐bond or another unsaturated functionality that is revealed upon in situ activation. The design of tailored substrates and new catalyst systems has enabled carbofluorination chemistry to emerge as a promising manifold for the synthesis of unique fluorinated scaffolds. This review covers the application of nucleophilic and electrophilic fluorinating reagents in this chemistry, in addition to recently developed atom‐economical carbofluorination reactions using organofluorine compounds as dual reagents.