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Comprehensive Summary: Organofluorine compounds have attracted substantial interest in life and materials sciences due to the unique properties of fluorine atom(s) that often change the physicochemical and biological properties of organic molecules. Transition‐metal‐mediated cross‐electrophile coupling between carbon electrophiles and fluoroalkyl electrophiles has emerged as a straightforward and efficient route for the synthesis of a wide range of fluoroalkylated compounds because of its synthetic convenience without the tedious synthesis of organometallic reagents. Moreover, alkenes or alkynes‐involved three‐component cross‐electrophile couplings provide rapid and effective access to carbonfunctionalized fluoroalkylated alkanes and alkenes. Herein, we comprehensively summarize the transition‐metal‐mediated reductive fluoroalkylation of diverse carbon electrophiles through a historical perspective, including trifluoromethylation, difluoroalkylation, monofluoroalkylation, and so on. Different transition metals (Cu, Ni, etc.) and strategies are discussed, in which nickel‐catalyzed reductive fluoroalkylation reactions represent an attractive and efficient synthetic route to site‐selectively access organofluorine compounds. Key Scientists: As early as 1965, McLoughlin and Thrower finished the first stoichiometric copper‐mediated fluoroalkylation of aromatic iodides with fluoroalkyl iodides. However, excess aromatic iodides and elevated temperature were used for this method. In 1969, Kobayashi and Kumadaki reported studies on the copper‐mediated trifluoromethylation of aromatic halides with excess trifluoromethyl iodide. After more than four decades, the Zhang group developed a nickel‐catalyzed β‐fluorinated alkylation of (hetero)aryl iodides with fluoroalkylated secondary alkyl bromides in 2015, and a nickel‐catalyzed difluoromethylation of (hetero)aryl chlorides with chlorodifluoromethane ClCF2H in 2017. The Zhang group also developed enantioselective nickel‐catalyzed reductive alkyl‐arylation of 3,3,3‐trifluoropropene with (hetero)aryl and tertiary alkyl iodides. In 2018, the MacMillan group developed a novel copper/photoredox dual catalytic system for the trifluoromethylation of aryl bromides or alkyl bromides with (S)‐(trifluoromethyl) dimesitylsulfonium triflate in the presence of tris‐(trimethylsilyl) silanol. They also developed a nickel/photoredox catalyzed difluoromethylation of aryl bromides in the presence of silane. During this time, the Wang group reported a nickel‐catalyzed monofluoroalkylation of aryl halides with monofluoroalkyl halides. From 2021 to 2023, the same group further developed a series of enantioselective nickel‐catalyzed trifluoroalkylation of aryl, alkenyl, and acyl halides. Moreover, nonfluorinated alkenes or alkynes could also be used in three‐component cross‐electrophile couplings. In 2018, the Chu group reported a nickel‐catalyzed fluoroalkyl‐acylation of alkenes with acyl chlorides and fluoroalkyl iodides. Later, they developed a nickel‐catalyzed enantioselective fluoroalkyl‐arylation of unactivated alkenes tethering with a pendant chelating group. In 2019, the Chaładaj group reported a palladium‐catalyzed reductive perfluoroalkyl‐arylation of alkynes with perfluoroalkyl and aryl iodides. [ABSTRACT FROM AUTHOR]

β‐(Trifluoromethyl)styrenes are potentially useful building blocks for the synthesis of organofluorine compounds because their electron‐deficient C=C double bonds can undergo diverse transformations. One of the most practical methods for preparing β‐(trifluoromethyl)styrenes is the decarboxylative trifluoromethylation of readily available cinnamic acid derivatives using the Langlois reagent as a less expensive trifluoromethyl source. We revisited the electrochemical decarboxylative trifluoromethylation of cinnamic acid derivatives to identify modified conditions that reduce the loading of the Langlois reagent without additional additives. The reaction mechanism was computationally investigated to gain insight into the dependence of the product yields on the aryl terminal groups. The synthetic utility of the obtained β‐(trifluoromethyl)styrenes was demonstrated by their transformation into 4‐aryl‐3‐(trifluoromethyl)pyrrolidines. [ABSTRACT FROM AUTHOR]

Ideal pathways to synthesize fluorinated compounds were pursued for over 100 years, due to wide application of organofluorides in materials, agrochemicals and pharmaceuticals. In this regard, electro‐organic synthesis, evolved as a sustainable and scalable approach in various synthetic protocols, stands out as a promising strategy. As a result, many novel and attracting applications of introduction of fluorine items into organic compounds by direct and redox‐mediated electrochemical methods has been reported, especially in recent five years. In this review, we are aim to highlight the reaction scopes, reaction mechanism, the fundamental aspects and the fluorine source variation in electrochemcial fluoriation transformation. [ABSTRACT FROM AUTHOR]

Polyhalogenated molecules are often found as bioactive compounds in nature and are used as synthetic building blocks. Fluoroalkyl compounds hold promise for the development of novel pharmaceuticals and agrochemicals, as the introduction of fluoroalkyl groups is known to improve lipophilicity, membrane permeability, and metabolic stability. Three‐component 1,2‐halo‐halodifluoromethylation reactions of alkenes are useful for their synthesis. However, general methods enabling the introduction of halodifluoromethyl (CF2X) and halogen (X') groups in the desired combination of X and X' are lacking. To address this gap, for the first time, we report a three‐component halo‐halodifluoromethylation of alkenes and alkynes using combinations of commercially available fluorinated carboxylic anhydrides ((CF2XCO)2O, X=Cl and Br) and alkali metal halides (X'=Cl and Br). In situ prepared fluorinated diacyl peroxides were identified as important intermediates, and the use of appropriate bipyridyl‐based ligands and a copper catalyst was essential for achieving high product selectivity. The synthetic utility of the polyhalogenated products was demonstrated by exploiting differences in the reactivities of their C−X and C−X' bonds to achieve selective derivatization. Finally, the reaction mechanism and ligand effect were investigated using experimental and theoretical methods to provide important insights for the further development of catalytic reactions. [ABSTRACT FROM AUTHOR]

N-(2-(diphenylphosphino)ethyl)-4,6,7-trifluoro-2,1,3-benzothiadiazol-5-amine (Ph2PCH2CH2NH-btd-F3 (PCCN)) is prepared by the reaction of 4,5,6,7-tetrafluoro-2,1,3-benzothiadiazole (btd-F4) with 2-(diphenylphosphino)ethyl-1-amine (Ph2PCH2CH2NH2) leading to the nucleophilic substitution of F– by a phosphinamide fragment (Ph2PCH2CH2NH)– in btd-F4. Phase 1 (a product of cocrystallization of PCCN (85%) and its oxide Ph2P(O)CH2CH2NH–btd-F3 (POCCN, 15%)) is obtained by the separation of the mixture of products by thin-layer chromatography and subsequent evaporation of the solution. POCCN is obtained preparatively using the oxidation of PCCN by hydrogen peroxide. Phase 1, two polymorphs of POCCN (2 and 4), and the POCCN·C6H6 solvatomorph (3) are characterized by XRD. The P–C–C–N fragment in these phases adopts either a bent gauche-conformation with an intramolecular N–H⋯O hydrogen bond or an anti-conformation stabilized by a pair of intermolecular hydrogen bonds combining the molecules into a dimer. According to the DFT data, gauche-POCCN has a larger negative electrostatic potential at F and N than anti-POCCN, i.e. the btd-F3 fragment of the first conformation is more likely to participate in predominantly electrostatic intermolecular interactions. [ABSTRACT FROM AUTHOR]

Organofluorine compounds have consistently demonstrated practical applications in the life sciences due to the fascinating properties imparted by the fluorine substituents. In recent years, significant advancements have been made in the synthesis of N‐fluoroalkyl carbonyl and sulfonyl compounds. This review offers a current overview of the various synthetic routes for N‐fluoroalkyl amides/sulfonamides and their transformation to new unexplored N‐fluoroalkyl carbonyl/sulfonyl derivatives, categorized into three parts based on the different fluoroalkyl groups. [ABSTRACT FROM AUTHOR]

The formation of carbon‐fluorine (C−F) bonds is an important research field in organic synthesis because inserting a fluorine atom into an organic compound can alter its physicochemical properties, such as metabolic stability and permeability. Due to this unique property, organic fluorinated compounds, especially aryl fluorides, have a wide range of applications in various fields, including agrochemicals, pharmaceuticals, and materials science. Therefore, numerous metal‐ or metal‐free‐mediated fluorination reactions have been developed to synthesize aryl fluorides. In this mini‐review, we summarize recent ten years' advances in fluorination reactions for the synthesis of aryl fluorides. [ABSTRACT FROM AUTHOR]

The development of an efficient alternative to the widely employed Balz‐Schiemann deaminative fluorination method (i. e. without using aryl diazonium tetrafluoroborate salt) is a challenging task. Herein, we report a convenient one‐pot method for the FeCl3‐nanocellullose mediated mechanochemical synthesis of fluoroarenes through the selective substitution of an aromatic amino group by fluorine group using pyrylium tetrafluoroborate (Pyry‐BF4) and sodium fluoride (NaF) via in situ formation of pyridinium salt intermediate. The scope of the present protocol includes synthesis of thirty‐four organofluorine compounds with excellent yields via a selective substitution (SNAr) of an amino group by fluorine. The presented concise methodology opens a pathway to access new chemical spaces for the late‐stage functionalization in pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The primary objective of this work is to delve into the intricacies of allylic fluorination reactions through the application of density functional theory (DFT) calculations. These reactions hold significant importance in the realm of synthesizing organofluorine compounds. The specific focus lies on comprehending the interaction mechanisms when styrenes, a class of organic molecules, come in contact with an electrophilic fluorinating reagent known as Selectfluor. Notably, this interaction pathway demonstrates remarkable efficiency in yielding allylic fluoride products. The proposed mechanism for this transformation involves a sequential process. To unveil the microcosmic intricacies governing this reaction between the alkene substrate and Selectfluor, advanced computational methodologies are employed. The paper systematically outlines the computational strategies harnessed to probe the minute details of the reaction mechanism. The outcomes of these computations are subsequently subjected to thorough analysis, encompassing crucial facets such as transition states and energy barriers. This analytical depth enhances the fundamental understanding of the reaction mechanism and sheds light on the underlying factors influencing its feasibility and efficiency. In a broader context, the insights garnered from this study carry significant utility. They provide pivotal guidance for the optimization of reaction conditions, facilitating the fine-tuning of experimental setups. Moreover, the elucidated mechanism serves as a platform for the design of even more efficient and selective allylic fluorination reactions. This paper, by amalgamating theoretical insights with practical synthetic objectives, contributes to the broader advancement of organofluorine compound synthesis and allied fields. [ABSTRACT FROM AUTHOR]

This article explores the incorporation of fluorine atoms into organic compounds and its potential impact on their chemical and biological properties. Specifically, it focuses on the gem-difluoromethylene functionality as a bioisostere of the methylene group, which has applications in drug discovery. The article presents a detailed synthetic method for introducing the gem-difluoromethylene group using a building block approach. The method involves the preparation of sulfonate esters from sulfonyl chlorides and bromodifluoroethanol, followed by a photochemical Smiles rearrangement to generate the desired compound. Additionally, the article describes a synthesis method for gem-difluorinated thiophene, a compound that can be used as a building block in medicinal chemistry. The synthesis involves a multicomponent cyclization and oxidative chlorination reaction, followed by a radical Smiles rearrangement mediated by visible light. The authors provide supporting information and acknowledge the assistance of others in the analysis. [Extracted from the article]

The distinctive properties of the fluorine atom confer significant advantages to organofluorine compounds in pharmaceuticals, agrochemicals, and materials science. A particularly promising approach for synthesizing these compounds involves atom-economical carbofluorination reactions. These reactions involve the activation of a carbon-fluorine (C–F) bond, then facilitating the incorporation of both a carbon-based fragment and a fluorine atom into an unsaturated system. The capacity to reintegrate the fluorine atom from the starting material into the final product, known as fluoride recycling via C–F bond reconstruction, is advantageous in terms of both atom and step economy. This review highlights recent advancements in catalytic C–F bond reconstruction, encompassing the background, chemical transformations, reaction scope, synthetic applications, mechanisms, and future research directions.

Perfluorocarbon-encapsulated silica nanoparticles possess attractive features such as biological inertness and favorable colloidal properties for bioimaging with fluorine magnetic resonance imaging (19F MRI). Herein, a series of elliptic shaped silica nanoparticles with perfluorocarbon liquid perfluoro-15-crown-5 ether as core (PFCE@SiO2) were synthesized using fluorinated surfactants N-(perfluorononylmethyl)-N,N,N-trimethylammonium chloride (C10-TAC) and N-(perfluoroheptylmethyl)-N,N,N-trimethylammonium chloride (C8-TAC). The nanoparticles are characterized to obtain elliptic core-shell structures. PFCE@ SiO2 showed strong 19F NMR signals of the encapsulated PFCE, indicating the potential as a highly sensitive 19F MRI probe. These elliptic PFCE@SiO2 nanoparticles provide a new option of 19F MRI probe with a morphology different from conventional nanospheres. [ABSTRACT FROM AUTHOR]

Photoinduced single‐electron reduction is an efficient method for the mono‐selective activation of the C−F bond on a trifluoromethyl group to construct a difluoroalkyl group. We have developed an electron‐donor‐acceptor (EDA) complex mediated single‐electron transfer (EDA‐SET) of α,α,α‐trifluoromethyl arenes in the presence of lithium salt to give α,α‐difluoroalkylarenes. The C−F bond reduction was realized by lithium iodide and triethylamine, two common feedstock reagents. Mechanistic studies revealed the generation of a α,α‐difluoromethyl radical by single‐electron reduction and defluorination, followed by the radical addition to alkenes. Lithium salt interacted with the fluorine atom to promote the photoinduced reduction mediated by the EDA complex. Computational studies indicated that the lithium‐assisted defluorination and the single‐electron reduction occurred concertedly. We call this phenomenon fluoride‐coupled electron transfer (FCET). FCET is a novel approach to C−F bond activation for the synthesis of organofluorine compounds. [ABSTRACT FROM AUTHOR]

Due 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. [ABSTRACT FROM AUTHOR]

Organofluorine compounds find extensive application in the fields of agrochemicals, pharmaceuticals, materials science, and molecular imaging. Introducing fluorine atoms can provide organic compounds with unique physicochemical properties or improve their biological activity. Although significant progress has been made in the chemical synthesis of fluorine‐containing compounds, achieving selective fluorination under mild conditions remains extremely challenging. Introducing biocatalytic approaches in organofluorine chemistry is an important strategy given their high efficiency, selectivity, and environmental friendliness. In this review, we present the discovery of fluorinated natural products and fluorinases, the crystal structure and the directed evolution of fluorinases, with a focus on recent advances in the enzymatic synthesis of fluorine‐containing compounds in recent years. It is hoped that this review will help to promote the field of biocatalytic organofluorine compound synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] Synthesis and electrochemical study of novel trifluorinated diethers, namely, α-methoxy-ω-(2,2,2-trifluoroethoxy)- alkanes, as potential candidates for new-generation electrolyte solvents for lithium-metal batteries are presented. The trifluoro diethers were tested in cell configurations implying cathodes with high nickel content and revealed Coulombic efficiencies exceeding 99.9% and specific discharge capacity retention up to 99% over 55 cycles for potentials up to 4.5 V. This study opens up new prospects in targeted design of organic ether molecules as lithium-metal batteries electrolyte components. [ABSTRACT FROM AUTHOR]

Acyl fluorides, carbamoyl fluorides and fluoroformates have been employed as efficient reagents in a number of organic syntheses. Their application in catalytic transformations, however, began to be explored in the early 2000s. Recently, these reagents have increasingly gained attention owing to their unique reactivity in diverse catalytic systems. This review aims to overview the advancements in the development of catalytic processes, including transition‐metal catalysis, organocatalysis, and cooperative NHC/photoredox catalysis, where these organofluorine compounds are employed as acyl, carbamoyl, and ester group donors. [ABSTRACT FROM AUTHOR]

The article focuses on the synthesis of organofluorine compounds with acylsilanes, summarizing investigations into their preparation pathways and reactivities, highlighting in situ generation and radical rearrangement processes. Topics include the major pathway for non-fluorinated acylsilanes, leading to the synthesis of various α,α-difluoroketones, and the selective control of reactivities for fluoroalkylacylsilanes.

Comprehensive Summary: Organofluorine compounds are central in synthetic chemistry, medicinal chemistry and material chemistry. In this review, we summarize the investigations on the synthesis of organofluorine compounds with acylsilanes. For the non‐fluorinated acylsilanes, the in situ generation of difluoroenoxysilanes from the reactions of the acylsilanes with trifluoromethylation reagents is the major pathway, leading to the facile preparation of various α,α‐difluoroketones. For the fluoroalkylacylsilanes, apart from the in situ generation of difluoroenoxysilanes through anion Brook rearrangement, radical Brook rearrangement of the photoexcited acylsilanes and the selective control of reactivities of the biradicals pave the way for the synthesis of a variety of organofluorine compounds. In general, most of these reactions gave racemic products, and the asymmetric synthesis of organofluorine compounds with acylsilanes is still rare, which would be a future direction of this field. Key Scientists: In 1957, the first acylsilane compound, triphenylsilyl phenyl ketone was reported by Brook group. In 1991, Portella and coworkers reported the reaction of non‐fluorinated acylsilanes and perfluoroorganometallic reagents without Brook rearrangement, resulting in the formation of alcohols as the products. In 1992, Xu and coworkers carried out the first investigation on fluoroalkylacylsilanes for the preparation of difluoroenoxysilanes through anion Brook rearrangement. In 1994, Portella group reported the synthesis of difluoroenoxysilanes with non‐fluorinated acylsilanes and Ruppert‐Prakash reagent. In 2009, Otaka and coworkers reported a NHC‐mediated intramolecular redox reaction to prepare (Z)‐fluoroalkene dipeptide isosteres (FADIs) from γ,γ‐difluoro‐α,β‐ enoylsilane. Until 2022, the application of radical Brook rearrangement of fluoroalkylacylsilanes for the generation of fluoroalkylsiloxycarbenes was achieved by Shen group, enabling the synthesis of fluoroalkylated cyclopropenols. In 2022, Shen and coworkers successfully achieved the trapping of biradical intermediates generated from fluorine‐containing acylsilanes, leading to the facile preparation of fused gem‐difluorooxetanes. In the same year, Shen group reported the first asymetric reactions of fluoroalkylacylsilanes to prepare enantiomerically enriched fluoroalkyl alcohols and difluoroenoxysilanes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Organofluorine compounds are central in synthetic chemistry, medicinal chemistry and material chemistry. In this review, we summarize the investigations on the synthesis of organofluorine compounds with acylsilanes. For the non‐fluorinated acylsilanes, the in situ generation of difluoroenoxysilanes from the reactions of the acylsilanes with trifluoromethylation reagents is the major pathway, leading to the facile preparation of various α,α‐difluoroketones. For the fluoroalkylacylsilanes, apart from the in situ generation of difluoroenoxysilanes through anion Brook rearrangement, radical Brook rearrangement of the photoexcited acylsilanes and the selective control of reactivities of the biradicals pave the way for the synthesis of a variety of organofluorine compounds. In general, most of these reactions gave racemic products, and the asymmetric synthesis of organofluorine compounds with acylsilanes is still rare, which would be a future direction of this field. Key Scientists: In 1957, the first acylsilane compound, triphenylsilyl phenyl ketone was reported by Brook group. In 1991, Portella and coworkers reported the reaction of non‐fluorinated acylsilanes and perfluoroorganometallic reagents without Brook rearrangement, resulting in the formation of alcohols as the products. In 1992, Xu and coworkers carried out the first investigation on fluoroalkylacylsilanes for the preparation of difluoroenoxysilanes through anion Brook rearrangement. In 1994, Portella group reported the synthesis of difluoroenoxysilanes with non‐fluorinated acylsilanes and Ruppert‐Prakash reagent. In 2009, Otaka and coworkers reported a NHC‐mediated intramolecular redox reaction to prepare (Z)‐fluoroalkene dipeptide isosteres (FADIs) from γ,γ‐difluoro‐α,β‐ enoylsilane. Until 2022, the application of radical Brook rearrangement of fluoroalkylacylsilanes for the generation of fluoroalkylsiloxycarbenes was achieved by Shen group, enabling the synthesis of fluoroalkylated cyclopropenols. In 2022, Shen and coworkers successfully achieved the trapping of biradical intermediates generated from fluorine‐containing acylsilanes, leading to the facile preparation of fused gem‐difluorooxetanes. In the same year, Shen group reported the first asymetric reactions of fluoroalkylacylsilanes to prepare enantiomerically enriched fluoroalkyl alcohols and difluoroenoxysilanes. [ABSTRACT FROM AUTHOR]

[Display omitted] A silver phosphine complex (XantPhos)AgBr proved to be a cheap and readily accessible catalyst for bromofluoro- cyclopropanation of electron-rich alkenes with CFBr 2 CO 2 Na. Ozonolysis followed by treatment with NaHSO 3 was shown to be an effective protocol to purify gem -bromofluoro- cyclopropanes from unreacted alkene precursors. [ABSTRACT FROM AUTHOR]

[Display omitted] Polycondensation of perfluorobiphenyl with 1,4-dihydroxy- thioxanthen-9-one resulted in the title highly thermally stable polyether containing the thioxanthenone-type electron acceptor in-chain blocks in its structure. Model resistive memory devices based on it as the active medium exhibited a bipolar switching memristive effect with a 4-order difference in resistance between the low and high resistance states. The charge transport in this polyether is quantitatively described by the Nasyrov–Gritsenko model of phonon-assisted electron tunneling between traps. [ABSTRACT FROM AUTHOR]

[Display omitted] 1-Alkylsulfanyl-4-X-2,3,5,6-tetrafluorobenzenes (X = CF 3 , H; alkyl = Me, Bn, CHF 2) upon reactions with nitromethane in the presence of DBU undergo replacement of 2 or 3-positioned fluorine atoms by a nitromethyl group to afford the corresponding (nitromethyl)trifluoroarenes. The calculations of the transition states using the DFT method correctly predict the ratios of reaction products. In the cases of relative sulfones, only 2-positioned fluorine atom undergoes substitution; however, the sulfonyl group can also be displaced by a nitromethyl moiety. [ABSTRACT FROM AUTHOR]

This article explores the use of fluoroalkanesulfite derivatives in the direct fluoroalkylthiolation of organic compounds. The synthesis of fluoroalkylthiolated compounds through the reduction of these derivatives is discussed, along with innovative approaches for their formation. The article also includes examples of other researchers' work in this field and discusses the mechanism of these reactions. The research has important implications for the synthesis of biologically active compounds, although there are still challenges to overcome in certain areas. Ongoing research is being conducted to address these challenges and further advance the field. [Extracted from the article]

The increasing demand of organofluorine compounds in medicine, agriculture, and materials sciences makes sophisticated methods for their synthesis ever more necessary. Nowadays, not only the C−F bond formation but also the selective C−F bond cleavage of readily available poly‐ or perfluorine‐containing compounds have become powerful tools for the effective synthesis of organofluorine compounds. The defluorinative cross‐coupling of trifluoromethyl alkenes with various nucleophiles or radical precursors in an SN2' manner is a convergent route to access gem‐difluoroalkenes, which in turn react with nucleophiles or radical precursors via an SNV‐type reaction. If the SNV reactions occur intramolecularly, the dual C−F bond cleavage of trifluoromethyl alkenes allows facile assembly of monofluorinated cyclic skeletons with structural complexity and diversity. In this personal account, we summarized the advances in this field on the basis of coupling and cyclization partners, including binucleophiles, alkynes, diradical precursors and radical precursors bearing a nucleophilic site. Accordingly, the annulation reactions can be achieved by base‐mediated sequential SN2′/SNV reactions, transition metal catalyzed or mediated reactions, photoredox catalysis, and the combination of photocatalytic reactions with SNV reaction. In the context of seminal works of others in this field, a concise summary of the contributions of the authors is also offered. [ABSTRACT FROM AUTHOR]

[Display omitted] Isosteric replacement of the oxadiazole ring by amide bond in the structure of new non-β-lactam antibiotics led to compounds with higher activity against Gram-positive pathogens of ESKAPE panel. A series of 17 compounds were synthesized by acylation of 4-(4-fluorophenoxy)aniline with various amino acids. The spirocyclic derivative with 6-methylsulfonyl-2,6-diazaspiro[3.4]octane moiety showed excellent minimum inhibitory concentrations of 0.093–0.75 μg ml−1 against a number of methicillin-resistant Staphylococcus aureus strains. [ABSTRACT FROM AUTHOR]

Theoretical decomposition of "through space" spin–spin coupling constants (SSCCs) in organofluorine compounds signal that intramolecular hydrogen bonds (H-bonds) are not the primary mechanism of transmission for SSCCs. Increasing solvent polarity may disrupt H-bonds, but not necessarily the JFH SSCC. Substituent effects may drastically alter the SSCC transmission pathway. Accurate SSCC analysis requires benchmarking theoretical calculations to support experimental data interpretation. [ABSTRACT FROM AUTHOR]

The synthesis of monofluorinated compounds is of great interest because of the vast applications of organofluorine compounds. Recently, the introduction of monofluorocarbene synthons has emerged as an important strategy for the synthesis of fluorine‐containing products. In contrast to direct fluorination, in which C−F bonds are formed, the use of monofluorinated carbenes and related reactive species involves C−C or C−X bond formation while delivering valuable fluorine atoms into the target structure. Owing to increased knowledge on carbon‐carbon and carbon‐heteroatom bond formations, monofluorinated carbenes have enormous potential for the synthesis of organofluorine compounds, which, in our opinion, has not yet been fully exploited. This review summarizes the recent advances in the synthetic applications of monofluorinated carbenes, carbenoids, ylides, and related species. [ABSTRACT FROM AUTHOR]

Fluoroalkyl groups play a vital role in pharmaceutical products and agrochemicals, where their installation onto aryl and heterocyclic rings can often lead to enhanced physicochemical and biological properties. Among them, heterocycles containing monofluoromethyl groups are an appealing but scarcely investigated class of organofluorine compounds with potential applications in medicinal chemistry. Here we report that an iodine(III) reagent containing monofluoroacetoxy ligands can be used to transfer monofluoromethyl radicals to heterocycles via visible-light photoredox catalysis, allowing for the mild, direct, and operationally simple modification of medicinally relevant heterocycles through a Minisci-like C–H functionalization process. This approach enriches the synthesis of a structurally diverse set of heteroaromatics incorporating monofluoromethyl groups in moderate to excellent yields. The practicability of direct C–H radical monofluoromethylation for late-stage modifications of medicinally relevant biomolecules and drugs is also demonstrated. Moreover, the monofluoromethylated heterocyclic compounds exhibit promising antimicrobial and anticancer activities, indicating that this methodology might assist in drug discovery as a dependable tool for lead drug modification in the development of new small-molecule drugs. [ABSTRACT FROM AUTHOR]

In this work, we have developed selective methods for the synthesis of quinoline‐2‐carboxylates and quinoline‐3‐carboxylates as well as (indolin‐2‐ylidene)acetates through copper‐, silver‐, or phosphine‐catalyzed reaction of propiolates with 2′‐amino‐2,2,2‐trifluoroacetophenones. The approaches proposed ensure synthesis of substituted quinoline carboxylates and (indolin‐2‐ylidene)acetates in good yields. Introduction of alkynones into the reaction with 2′‐amino‐2,2,2‐trifluoroacetophenones gives acyl substituted derivatives in good yields. [ABSTRACT FROM AUTHOR]

The C-F bonds, due to their many unique features, have been incorporated into numerous compounds in countless products and applications. These fluorinated compounds eventually are disposed of and released into the environment through different pathways. In this review, we analyzed the occurrence of these fluorinated compounds in seven types of products (i.e., refrigerants/propellants, aqueous film-forming foam, cosmetics, food packaging, agrochemicals, pharmaceuticals, coating materials) and discussed their fate in the environment. This is followed by describing the quantity of fluorinated compounds from each source based on available data. Total on- and off-site disposal or other releases of 536 fluorinated compounds in 2021 were analyzed using the data sourced from the U.S. EPA Toxics Release Inventory (TRI). Among the chemicals examined, chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) were the primary contributors in terms of total mass. Upon examining the seven sources of fluorinated compounds, it became evident that additional contributors are also responsible for the presence of organofluorine compounds in the environment. Although various toxic degradation products of fluorinated compounds could form in the environment, trifluoroacetic acid (TFA) was specifically highlighted in this review given the fact that it is a common dead-end degradation product of > 1 million chemicals. This paper ended with a discussion of several questions raised from this study. The path forward was elaborated as well for the purpose of protecting the environment and human health. [ABSTRACT FROM AUTHOR]

The electrophilic cyclization via the boronate complex between various homoallylic boronates and Selectfluor® is reported. This reaction provides a fluoromethylated cyclopropane ring that was difficult to synthesize by previous methods. The use of phenyl lithium, which activates the homoallylic boronate, is important for the reaction. The intermediate boronate species in this reaction was observed through 11B{1H} NMR experiments. We also demonstrate the synthesis of a building block, including fluoromethyl‐substituted cyclopropane for a bioactive compound. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cyano-modified graphitic carbon nitride (g-NCNCN x) was developed for photocatalytic perfluoroalkylation reactions.. • Photocatalytic addition or coupling reaction can be achieved selectively and effectively with a broad substrate scope. • g-NCNCN x exhibits excellent photocatalytic activity for at least five catalytic cycles. • More photoelectrons of g-NCNCN x generated after light irradiation, improving the photocatalytic performance, comparing to pristine g-CN x. Photocatalytic radical fluoroalkylation has become an important approach to prepare valuable organofluorine compounds under mild conditions. Compared to the homogenous photocatalytic fluoroalkylation reactions based on the precious metal complexes or organic dyes, heterogeneous photocatalysis using metal-free carbon nitride catalyst shows cost-effective, easier separation and excellent recyclability. In this work, we report the visible-light-induced photocatalytic perfluoroalkylation of alkynes with perfluoroalkyl iodides (R f I) using heterogeneous cyano-modified graphitic carbon nitride (g-NCNCNx) as the photocatalyst. The mechanism proposed by the experimental and computational studies reveals that the long-lived triplet excited states in photoinduced g-NCNCNx are involved in the initial bimolecular electron transfer process, resulting in the effective activation of R f I and the improvement of sequential photocatalytic reactions. Moreover, the stronger interaction between the substate and surface of catalyst g-NCNCNx can further improve the photocatalytic activity, comparing to the pristine carbon nitride (g-CNx). Through simple variation of the reaction conditions, the photocatalytic addition or coupling reaction can be achieved effectively and selectively. Importantly, the heterogeneous g-NCNCNx photocatalyst can not only show high performance with a wide reaction scope, but also be readily recovered and reused for at least five catalytic cycles with high photocatalytic activity. This work provides a sustainable alternative to the conventional metal-based photocatalysts for organofluorine synthesis. [ABSTRACT FROM AUTHOR]

Keywords: photocatalysis; organocatalysis; aryldifluoromethyl compounds; late-stage functionalization; C-F bond cleavage; radical-polar crossover reaction EN photocatalysis organocatalysis aryldifluoromethyl compounds late-stage functionalization C-F bond cleavage radical-polar crossover reaction 1747 1751 5 08/29/23 20230915 NES 230915 Graph Organofluorine compounds are important in agrochemistry and medicinal chemistry due to their special chemical and biological properties. [5] However, the high bond-dissociation energy of the C-F bond and the fact that the bond-dissociation energy decreases when the carbon has fewer C-F bonds makes selective C-F bond functionalization challenging. Photocatalysis, organocatalysis, aryldifluoromethyl compounds, C-F bond cleavage, radical-polar crossover reaction, late-stage functionalization. [Extracted from the article]

Interaction of enol ethers enol acetates, enamides and enamines with fluorinated reagents may be considered as a reliable method for the synthesis of organofluorine compounds. While classic nucleophile/electrophile substitution or addition mechanisms cannot be realized for coupling of these components, their intrinsic reactivities are revealed with the aid of photoredox catalysis. A combination of these electron donating and accepting components provides a perfect balance needed for individual redox steps, which in some cases may proceed even without a photocatalyst. The same electronic factors also support the key C,C‐bond forming event involving addition of fluorinated radical at the electron rich double bond. [ABSTRACT FROM AUTHOR]

The incorporation of fluorine atoms into an organic compound can alter the chemical reactivity or biological activity of the resulting compound due to the strong electron withdrawing nature of the fluorine atom. We have synthesized many original gem‐difluorinated compounds and described the results in four sections. The first section describes the synthesis of optically active‐gem‐difluorocyclopropanes via the chemo‐enzymatic reaction; we applied these compounds to liquid crystalline molecules, then further discovered a potent DNA cleavage activity for the gem‐difluorocyclopropane derivatives. The second section describes the synthesis of selectively gem‐difluorinated compounds via a radical reaction; we synthesized fluorinated analogues of a sex pheromone of the male African sugarcane borer, Eldana saccharina, and used the compounds as proof for investigating the origin of pheromone molecule recognition on the receptor protein. The third involves the synthesis of 2,2‐difluorinated‐esters by visible light‐driven radical addition of 2,2‐difluoroacetate with alkenes or alkynes in the presence of an organic pigment. The last section describes the synthesis of gem‐difluorinated compounds via the ring‐opening of gem‐difluorocyclopropanes. We further developed a novel method of synthesizing gem‐difluorohomoallylic alcohols via the ring‐opening of gem‐difluorocyclopropane and aerobic oxidation by photo‐irradiation in the presence of an organic pigment. Since gem‐difluorinated compounds that were prepared by the present method have two olefinic moieties with a different reactivity at the terminal position, we accomplished the synthesis of four types of gem‐difluorinated cyclic alkenols via the ring‐closing‐metathesis (RCM) reaction. [ABSTRACT FROM AUTHOR]

This account describes the evolution of a research programme that started by linking fluoromethylene (−CHF−) groups along aliphatic chains and then progressing to alicyclic rings with contiguous fluorine atoms. Different stereoisomers of aliphatic chains tend to adopt low polarity conformations. In order to force polar conformations, the programme began to address ring systems and in particular cyclohexanes, to restrain conformational freedom and co‐aligned C−F bonds. The flagship molecule, all‐cis‐1,2,3,4,5,6‐hexafluorocyclohexane 7, emerged to be the most polar aliphatic compound recorded. The polarity arises because there are three co‐aligned triaxial C−F bonds and the six fluorines occupy one face of the ring. Conversely the electropositive hydrogens occupy the other face. These have been termed Janus face cyclohexanes after the Roman god with two faces. The review outlines progress by our group and others in preparing derivatives of the parent cyclohexane 7, in order to explore properties and potential applications of these Janus cyclohexanes. [ABSTRACT FROM AUTHOR]

The fluorinated building block strategy and the direct fluorination strategy are of great importance for the synthesis of new fluorinated molecules. These strategies complement each other and can be combined to develop a new methodology for the construction of a wide variety of fascinating organofluorine compounds. In our opinion, the versatile building blocks used in this method should satisfy the following conditions: 1) readily prepared from commercially available reagents; 2) easy to handle; 3) storage under ordinary conditions without noticeable decomposition; 4) wide applicability. Based on the aforementioned requirements, we focused on the use of vinyl sulfonium salts. This brief review describes the synthesis of five types of fluorinated vinyl sulfonium salts and their reactions. Especially, we featured typical fluorinated groups containing trifluoromethyl (CF3), difluoromethyl (CF2H), monofluoromethyl (CFH2), monofluoro (F) or β‐bromotetrafluoroethyl (BrCF2CF2) moieties in combination with vinyl sulfonium salts. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus (HSV) 1 and 2 are persistent infections that affect a significant percentage of United States (US) adults, with 48% having HSV-1 and 12% having HSV-2. Using data stratified by HSV-1 and HSV-2 exposures, this study investigated the association of per- and polyfluoroalkyl substances (PFAS), a group of toxic synthetic organofluorine chemical compounds found in environmental, occupational, and home settings, with allostatic load (AL), an index of chronic physiological stress. Descriptive statistics, multivariable logistic regression, and Bayesian Kernel Machine Regression (BKMR) modeling were used to assess the effects of multi-PFAS exposures on AL using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. Results indicated participants not exposed to PFAS exhibited 77% to 97% lower odds of higher AL (p < 0.001). For example, PFOS per unit increase brought forth a 2% odds increase in higher AL (OR: 1.02; 95% CI: 1.00, 1.05; p < 0.05). Participants exposed to PFAS had reduced odds of higher AL (77%–79%), regardless of their HSV-1 and HSV-2 status. PFAS exposure was more prevalent in those with HSV-1 (60%) than in those with HSV-2 (20%) infection, while AL levels were comparable in both groups (17%). BKMR revealed a nonlinear PFAS-AL association and confirmed interactions among PFAS. In summary, PFAS exposure increased the likelihood of higher AL among those with persistent HSV infections. Our study enhances the current understanding of the complex dynamics involving PFAS, persistent infections, and AL, which hold significant implications for public health and clinical intervention strategies. [ABSTRACT FROM AUTHOR]

Organofluorine compounds have been widely used in pharmaceutical, agrochemical, and material sciences. Reported herein are divergent fluorination reactions of vinylcyclopropanes with different electrophiles, which allow the facile synthesis of homoallylic monofluorides and vicinal‐difluorides through ring‐opening 1,5‐hydrofluorination and ring‐retaining 1,2‐difluorination, respectively. Both protocols feature mild conditions, simple operations, good functional group tolerance, and generally good yields. The practicality of these reactions is demonstrated by their scalability, as well as the successful conversion of the formed homoallylic monofluorides into other complex fluorinated molecules. [ABSTRACT FROM AUTHOR]

Michael addition reaction, known since the 19th century, appeared as a relevant method with a great potential to design new organofluorinated fine chemicals and enlarged their structural diversity. In the Michael addition reaction for the synthesis of organofluorine compounds, the fluorinated blocks can be both used as the Michael donors and acceptors, but the latter is relatively rare. This review aims to provide a comprehensive summary of the use of fluorinated substrates as Michael acceptors in Michael reactions. [ABSTRACT FROM AUTHOR]

The development of novel synthetic methodologies to incorporate fluorine/s or fluoroalkyl group/s into the frameworks of organic molecules has become a highly prioritized research area because such modifications can tune their physiochemical and biological properties. In recent years, nucleophilic phosphine catalysis has been extensively explored to achieve this goal, and significant progress has been made. This review summarizes the methodological advancements of cycloaddition, addition and coupling reactions employing fluorinated building blocks as electrophilic and/or nucleophilic reaction partners under phosphine catalysis to construct structurally and synthetically valuable organofluorine compounds, with special emphasis on the synthetic strategies, proposed reaction mechanisms and synthetic utilities. [ABSTRACT FROM AUTHOR]

A simple convenient one-pot protocol for the synthesis of 5-alkyl/hetaryl-4-amino-3-(polyfluoroalkyl)pyrazoles (4-aminopyrazoles) has been suggested. The method is based on using readily available lithium 3-polyfluoroalkyl-1,3-diketonates and sodium nitrite as starting materials and hydrazine hydrate for cyclization into 4-nitroso-3-(polyfluoroalkyl)pyrazoles, followed by reduction of the latter into target products. Molecular structures of 5-methyl-, 5-(thiophen-2-yl)-, 5-(4-methylphenyl)-, and 5-(pyridin-2-yl)-substituted 3-trifluoromethyl-1H-pyrazol-4-amines have been established by X-ray analysis. [ABSTRACT FROM AUTHOR]

Despite the growing importance of fluorinated organic compounds in pharmaceuticals, agrochemicals, and materials science, the introduction of fluorine into organic molecules is still a challenge, and no catalytic fluorocarbonylation of aryl/alkyl boron compounds has been reported to date. Herein, we present the development of palladium and phosphine synergistic redox catalysis of fluorocarbonylation of potassium aryl/alkyl trifluoroborate. Trifluoromethyl arylsulfonate (TFMS), which was used as a trifluoromethoxylation reagent, an easily handled and bench-scale reagent, has been employed as an efficient source of COF2. The reaction operates under mild conditions with good to excellent yields and tolerates diverse complex scaffolds, which allows efficient late-stage fluorocarbonylation of marked small-molecule drugs. Mechanistically, the key intermediates of labile Brettphos-Pd(II)-OCF3 complex and difluoro-Brettphos were synthesized and spectroscopically characterized, including X-ray crystallography. A detailed reaction mechanism involving the synergistic redox catalytic cycles Pd(II)/(0) and P(III)/(V) was proposed, and multifunction of phosphine ligand was identified based on 19F NMR, isotope tracing, synthetic, and computational studies. Despite the growing importance of fluorinated organic compounds introduction of fluorine into organic molecules is still challenging. Here, the authors present the development of palladium and phosphine synergistic redox catalysis of fluorocarbonylation of potassium aryl/alkyl trifluoroborate. [ABSTRACT FROM AUTHOR]

Keywords: fluoroalkyl substituents; carboxylic acid anhydrides; N -propargylic amides; oxazoles; cyclization EN fluoroalkyl substituents carboxylic acid anhydrides N -propargylic amides oxazoles cyclization 1984 1995 12 06/16/23 20230704 NES 230704 Because of the unique properties of fluorine atoms, organic fluorine-containing compounds have been applied to various medicines and pesticides. [23] In the transformation of 4,5-disubstituted I N i H-1,2,3-triazoles with fluorinated acid anhydrides, the cyclization of -acyloxy enamide intermediates occurred after elimination of a nitrogen molecule under heating conditions, leading to fluoroalkylated oxazoles (Scheme 1c). The optimized reaction conditions with propargylic amide B 1a b was applied to the cyclization of propargylic amide B 1b b , which has a biphenyl group at the propargylic position, and the corresponding trifluoromethylated oxazole was generated in 98% yield (entry 7). [Extracted from the article]