The Tetrafluoroethylene-Mediated Ring-Closing Metathesis: Enabling Unfavored Reactions.

While ring-closing metathesis (RCM) is a powerful method for constructing medium and large cyclic alkenes, its application to the synthesis of heterocycles faces considerable limitations. For instance, RCM of divinyloxyalkanes does not proceed under the conventional conditions of RCM. The challenge lies in the formation of stable Fischer-type carbene intermediates with heteroatom(s) bound to the carbene carbon, impeding subsequent metathesis.

Exceptionally Short Tetracoordinated Carbon-Halogen Bonds in Hexafluorodihalocubanes.

Molecules that contain bonds whose length significantly deviates from the average are of interest in the context of understanding the nature and limits of the chemical bonds. However, it is difficult to disentangle the individual contributions of the multiple factors that give rise to such bond-length deviations as reports on such molecules remain scarce. In the present study, we have succeeded in synthesizing hexafluorodihalocubanes of the type CFX () (X = Cl (), Br (), I ()), which represent a new series of molecules with unusual C(sp)-halogen bonds.

Fluoro-Crown Ether Phosphate as Efficient Cell-Permeable Drug Carrier by Disrupting Hydration Layer.

Fast and direct permeation of drug molecules is crucial for effective biotherapeutics. Inspired by a recent finding that fluorous compounds disrupt the hydrogen-bonded network of water, we developed fluoro-crown ether phosphate FP-X. This compound acts as a fast cell-permeating agent, enabling direct delivery of various bioactive cargos (X) into cancer cells without endocytic entrapment.

Fluorocarbon-DNA Conjugates for Enhanced Cellular Delivery: Formation of a Densely Packed DNA Nano-Assembly.

Forming nano-assemblies is essential for delivering DNA conjugates into cells, with the DNA density in the nano-assembly playing an important role in determining the uptake efficiency. In this study, we developed a strategy for the facile synthesis of DNA strands bearing perfluoroalkyl (R) groups (R-DNA conjugates) and investigated how they affect cellular uptake. An R-DNA conjugate bearing a long R group at the DNA terminus forms a nano-assembly with a high DNA density, which results in greatly enhanced cellular uptake.

Photo-on-Demand One-Pot Synthesis of Carbonate Esters from Tetrachloroethylene.

The present study reports a novel one-pot synthesis of carbonate esters with photo-oxidized tetrachloroethylene (TCE). Acyclic and cyclic alkyl carbonate esters could be synthesized through base-promoted condensation reactions of alcohols with the photo-oxidized TCE that was prepared by irradiation with UV-C or visible light under O or O/Cl (∼4%) bubbling, respectively. Cyclic carbonate esters could also be synthesized from a solution of TCE and the ethylene glycol derivative by irradiation of UV-C light under O bubbling.

Cellular Penetration and Intracellular Dynamics of Perfluorocarbon-Conjugated DNA/RNA as a Potential Means of Conditional Nucleic Acid Delivery.

Nucleic acid-based therapeutics represent a novel approach for controlling gene expression. However, a practical delivery system is required that overcomes the poor cellular permeability and intercellular instability of nucleic acids. Perfluorocarbons (PFCs) are highly stable structures that can readily traverse the lipid membrane of cells.

Fluoroalkylated hypervalent sulfur fluorides: radical addition of arylchlorotetrafluoro-λ-sulfanes to tetrafluoroethylene.

Fluorinated groups are essential hydrophobic groups in drug design. Combining a carbon-free tetrafluoro-λ-sulfanyl (SF) group with a polyfluoroalkyl group (R) provides SFR groups, exhibiting high hydrophobicity with a short carbon chain. In this study, various aryltetrafluoro(polyfluoroalkyl)-λ-sulfanes (ArSFR) were synthesized through the radical addition of arylchlorotetrafluoro-λ-sulfanes (ArSFCl) to tetrafluoroethylene.

Synthesis of Short Peptides with Perfluoroalkyl Side Chains and Evaluation of Their Cellular Uptake Efficiency.

With an increasing demand for macromolecular biotherapeutics, the issue of their poor cell-penetrating abilities requires viable and relevant solutions. Herein, we report tripeptides bearing an amino acid with a perfluoroalkyl (R ) group adjacent to the α-carbon. R -containing tripeptides were synthesized and evaluated for their ability to transport a conjugated hydrophilic dye (Alexa Fluor 647) into the cells.

-Fluorobenzenesulfonimide (NFSI) analogs with deprotectable substituents: synthesis of β-fluoroamines catalytic aminofluorination of styrenes.

The palladium-catalyzed aminofluorination of styrenes using novel -fluorobenzenesulfonimide (NFSI) derivatives with deprotectable substituents, and the selective deprotection and transformation of the resulting products into amines under mild reaction conditions are herein disclosed.

The Fluorocarbene Exploit: Enforcing Alternation in Ring-Opening Metathesis Polymerization.

Fluoroalkenes are known to be notoriously reluctant substrates for olefin metathesis due to the generation of thermodynamically stable Fischer-type fluorocarbene intermediates, which invariably fail to undergo further reaction. In the present disclosure, we find that fluorine substitution on the sp carbon also strictly suppresses homopolymerization of norbornene derivatives (NBEs), and this can be harnessed to achieve alternating ring-opening metathesis polymerization (ROMP) with an appropriately electron-rich comonomer. Dihydrofuran (DHF) is thereby shown to undergo alternating ROMP with fluorinated norbornenes, the perfectly alternating structure of the resulting copolymer having been unambiguously elucidated by H, F, and C NMR analyses.

Photo-on-Demand In Situ Synthesis of N-Substituted Trichloroacetamides with Tetrachloroethylene and Their Conversions to Ureas, Carbamates, and Polyurethanes.

N-substituted trichloroacetamides (NTCAs), which serve as blocked isocyanates, were synthesized in ∼97% yields by in situ photo-on-demand trichloroacetylation of amines with tetrachloroethylene (TCE). The reactions were performed by photo-irradiation of TCE solutions containing an amine under O bubbling over 70 °C with a low-pressure mercury lamp. TCE underwent photochemical oxidation to afford trichloroacetyl chloride having high toxicity and corrosivity, which then reacts in situ with the amine to afford NTCA.

Reactivity and Product Selectivity of Fluoroalkyl Carbonates in Substitution Reactions with Primary Alcohols and Amines.

The present study reports a systematic investigation of the substitution reactions of a series of symmetric and unsymmetric fluoroalkyl carbonates with primary alcohols or amines. The reactivity of the haloalkyl carbonate depends mainly on the electrophilicity and steric crowdedness of the carbonyl group and the leaving ability of the haloalkyl alcohols. Diethyl carbonate as a reference substrate showed no reaction with the alcohol or amine.

Electron in a cube: Synthesis and characterization of perfluorocubane as an electron acceptor.

Fluorinated analogs of polyhedral hydrocarbons have been predicted to localize an electron within their cages upon reduction. Here, we report the synthesis and characterization of perfluorocubane, a stable polyhedral fluorocarbon. The key to the successful synthesis was the efficient introduction of multiple fluorine atoms to cubane by liquid-phase reaction with fluorine gas.

Synthesis of Crystalline CF -Rich Perfluoropolyethers from Hexafluoropropylene Oxide and (Trifluoromethyl)Trimethylsilane.

The synthesis of a CF -rich perfluoropolyether (PFPE) is achieved via the fluoride-catalyzed reaction of hexafluoropropylene oxide (HFPO) with (trifluoromethyl)trimethylsilane (TMSCF , so-called Ruppert-Prakash reagent). Nucleophilic addition of a CF anion to HFPO affords an acyl fluoride via the ring-opening of HFPO, followed by fluoride elimination. Further addition of CF anions to the acyl fluoride gives tertiary perfluoroalkoxide, which attacks HFPO to regenerate an acyl fluoride.

Photo-on-Demand Phosgenation Reactions with Chloroform for Selective Syntheses of N-Substituted Ureas and Isocyanates.

Two new reaction processes involving the oxidative photochemical conversion of CHCl to COCl allowed selective syntheses of N-substituted ureas and isocyanates from amines. (I) A CHCl solution containing an amine and an organic base under O bubbling provided the urea derivative under exposure to UV light generated from a low-pressure mercury lamp at 20-40 °C. (II) A two-step reaction involving the oxidative photodecomposition of CHCl at lower temperatures and subsequent sequential injections of an amine and organic base into the sample solution provided the isocyanate in high yield.

An -Fluorinated Imide for Practical Catalytic Imidations.

Catalytic imidation using NFSI as the nitrogen source has become an emerging tool for oxidative carbon-nitrogen bond formation. However, the less than ideal benzenesulfonimide moiety is incorporated into products, severely detracting its synthetic value. As a solution to this challenge, we report herein the development of a novel -fluorinated imide, -fluoro--(fluorosulfonyl)carbamate (NFC), by which the attached imide moiety acts as a modular synthetic handle for one-step derivatization to amines, sulfonamides, and sulfamides.

Highly Active Cross-Metathesis of Tetrafluoroethylene with a Seven-Membered N-Heterocyclic-Carbene-Ruthenium Catalyst.

A drastic increase in catalyst turnover number (TON) was accomplished in the cross-metathesis of tetrafluoroethylene (TFE) and vinyl ethers. Under a continuous flow of TFE, catalyst , which contains a seven-membered N-heterocyclic carbene (NHC) ligand, reached a TON of 4100; this is 2 orders of magnitude higher than the highest hitherto reported value. Mechanistic studies revealed that the expanded NHC successfully destabilizes the stable intermediates with a difluorocarbene structure, which strongly promotes the reaction.

Methyl to trifluoromethyl substitution as a strategy to increase the membrane permeability of short peptides.

Here, we investigated the effect of CH to CF substitution on the membrane permeability of peptides. We synthesized a series of peptides with CF groups and corresponding nonfluorinated peptides and measured the membrane permeability of the peptides. As a result, we demonstrated that CH to CF substitution is useful for increasing the membrane permeability of di-/tri-peptides.

Photo-on-Demand Base-Catalyzed Phosgenation Reactions with Chloroform: Synthesis of Arylcarbonate and Halocarbonate Esters.

Carbonate esters are utilized as solvents and reagents for C1 building blocks in organic synthesis. This study reports a novel photo-on-demand in situ synthesis of carbonate esters with CHCl solutions containing a mixture of an aromatic or haloalkyl alcohol having relatively high acidity, and an organic base. We found that the acid-base interaction of the alcohol and base in the CHCl solution plays a key role in enabling the photochemical reaction.

Bench-Stable Electrophilic Fluorinating Reagents for Highly Selective Mono- and Difluorination of Silyl Enol Ethers.

Efficient methods for the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench-stable electrophilic fluorinating reagents were synthesized as N-fluorobenzenesulfonimide (NFSI) substitutes.

Photo-on-Demand Synthesis of Vilsmeier Reagents with Chloroform and Their Applications to One-Pot Organic Syntheses.

The Vilsmeier reagent (VR), first reported a century ago, is a versatile reagent in a variety of organic reactions. It is used extensively in formylation reactions. However, the synthesis of VR generally requires highly toxic and corrosive reagents such as POCl, SOCl, or COCl.

Synthesis of Fluorinated Dialkyl Carbonates from Carbon Dioxide as a Carbonyl Source.

Fluorinated dialkyl carbonates (DACs), which serve as environmentally benign phosgene substitutes, were produced successfully from carbon dioxide either directly or indirectly. Nucleophilic addition of 2,2,2-trifluoroethanol to carbon dioxide and subsequent reaction with 2,2,2-trifluoroethyltriflate (3 a) afforded bis(2,2,2-trifluoroethyl) carbonate (1) in up to 79 % yield. Additionally, carbonate 1 was obtained through the stoichiometric reaction of 3 a and cesium carbonate.

Cyanide-Free One-Pot Synthesis of Methacrylic Esters from Acetone.

Methacrylic esters, represented by methyl methacrylate (MMA), are widely used as commodity chemicals. Here, the one-pot synthesis of methacrylic esters from acetone, a haloform and alcohols in the presence of an organic base is described. Using DBU as the organic base for the reaction of acetone, chloroform and methanol in acetonitrile afforded MMA in 66 % yield.

Overview on the history of organofluorine chemistry from the viewpoint of material industry.

Fluorine (from "le fluor", meaning "to flow") is a second row element of Group 17 in the periodic table. When bound to carbon it forms the strongest bond in organic chemistry to give organofluorine compounds. The scientific field treating them, organofluorine chemistry, started before elemental fluorine itself was isolated.