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Tag: Organic Chemistry & Synthesis

  • Hydrofluorocarbons can be recycled into useful fluorides

    What the study found

    The study found that hydrofluorocarbons can be converted into anhydrous potassium fluoride, which can then be used to make a range of fluorinated molecules in a one-pot transfer fluorination process. The authors report that this approach applies to several types of fluorochemicals, including industrial refrigerants, hydrofluoroolefins, fluoroethers, perfluorooctanoic acid, and poly(vinylidene) difluoride.

    Why the authors say this matters

    The authors present this as an approach to recycling fluorochemicals. They also note that fluorochemicals improve quality of life, while there is increasing concern over how they are produced and their negative effects on health and the environment.

    What the researchers tested

    The researchers treated hydrofluorocarbons with a potassium base, either KHMDS or KO t Bu, to produce anhydrous potassium fluoride. They then used that fluoride source in one-pot transfer fluorination to prepare fluorinated organic and inorganic molecules, and they also examined aspects of the mechanism with density functional theory calculations. They additionally presented batch scale-up at 50 g and flow chemistry at 1.5 g h−1.

    What worked and what didn't

    Rapid defluorination to anhydrous potassium fluoride was reported with the potassium bases used. That potassium fluoride was then used to prepare sulfonyl fluorides, aryl fluorides, alkyl fluorides, and a range of p-block fluorides. The abstract does not describe specific failures or reactions that did not work.

    What to keep in mind

    The abstract gives a high-level summary and does not provide detailed limitations, yields, or reaction conditions. It also does not state which substrates were less successful, aside from identifying the broad scope of recyclable fluorochemicals and the scale-up examples.

    • Hydrofluorocarbons were converted to anhydrous potassium fluoride by treatment with a potassium base.
    • The potassium fluoride was used in a one-pot transfer fluorination process.
    • The method produced sulfonyl fluorides, aryl fluorides, alkyl fluorides, and p-block fluorides.
    • The reported scope included refrigerants, hydrofluoroolefins, fluoroethers, perfluorooctanoic acid, and poly(vinylidene) difluoride.
    • Mechanistic aspects were studied with density functional theory calculations.
    • Scale-up was demonstrated in batch and flow chemistry.

  • Grushin’s reagent enabled difluoromethylation of complex alcohols

    What the study found

    The study found that Grushin’s reagent, a copper(III) trifluoromethyl complex, can be repurposed as a difluorocarbene source for difluoromethylation. The authors report that this worked for diverse alcohols, including complex saccharides and polyols.

    Why the authors say this matters

    The authors say this matters because the difluoromethoxy motif is valuable in pharmaceuticals and materials, while direct difluoromethylation of complex alcohols is difficult. The study suggests the new strategy may help address those limitations.

    What the researchers tested

    The researchers tested a blue light- and acid-mediated difluoromethylation strategy using Grushin’s reagent. They applied it to primary, secondary, and tertiary alcohols with multiple polar functional groups, and they also examined late-stage modification of complex natural products and bioactive molecules.

    What worked and what didn't

    The method showed broad functional group compatibility and was successfully used on complex alcohols and on late-stage modification targets. A notable result was regioselective difluoromethylation of saccharides and polyols, enabled by Me2SnCl2, which acted as both a hydroxyl activator and a source of hydrogen chloride; the abstract does not describe failures in detail.

    What to keep in mind

    The abstract does not provide detailed limitations, optimization constraints, or substrate scope boundaries beyond the examples mentioned. It also does not describe comparative performance against other difluorocarbene sources.

    • Grushin’s reagent was repurposed from a trifluoromethylation agent to a difluorocarbene source.
    • The strategy used blue light and acid to drive difluoromethylation.
    • The method was reported to work on primary, secondary, and tertiary alcohols with multiple polar functional groups.
    • Regioselective difluoromethylation of saccharides and polyols was achieved with Me2SnCl2.
    • The authors report antifungal activity for compounds 3c and 3n.

  • Difluoroketene rearrangement succeeds with electron-withdrawing substituents

    What the study found

    The study reports a thio-Belluš–Claisen rearrangement using difluoroketene, a very unstable molecule that contains two fluorine atoms and a reactive carbonyl-related group. The authors found that an electron-withdrawing group on the internal alkene site of the allyl thioether was vital for the reaction.

    Why the authors say this matters

    The authors conclude that their protocol enables controlled release of difluoroketene and efficient capture by allyl thioether for the rearrangement. They also say the electron-withdrawing group promotes the rearrangement by stabilizing charge in the transition state, which the study suggests is important for the reaction to work.

    What the researchers tested

    The researchers developed a fluoride-initiated desilylative beta-elimination of difluorobromoacetylsilane to generate difluoroketene in a controlled way. They then tested whether the generated difluoroketene could be captured by allyl thioether in a thio-Belluš–Claisen rearrangement.

    What worked and what didn't

    The protocol was successfully developed for controlled release of difluoroketene and its efficient capture by allyl thioether. The abstract says the presence of an electron-withdrawing group on the internal alkene site was proven to be vital; it does not describe successful outcomes without that group.

    What to keep in mind

    The abstract does not provide yield values, substrate scope, or detailed experimental limitations. It also does not describe how broadly the method works beyond the specific rearrangement reported.

    • A thio-Belluš–Claisen rearrangement with difluoroketene is reported.
    • Difluoroketene was generated by fluoride-initiated desilylative beta-elimination of difluorobromoacetylsilane.
    • The protocol was described as enabling controlled release of the unstable difluoroketene.
    • An electron-withdrawing group on the internal alkene site of allyl thioether was vital for the reaction.
    • The authors attribute this effect to charge stabilization in the transition state.

  • Dihydroquinoline sulfonyl fluorides were synthesized without transition metals

    What the study found

    The study reports a modular synthesis of trifluoromethylated and difluoromethylated dihydroquinoline sulfonyl fluorides. It also reports that these compounds can be converted into sulfonamides and sulfonates through sulfur(VI) fluoride exchange, a reaction that replaces a sulfur-bound fluoride with another group.

    Why the authors say this matters

    The authors conclude that the products hold significant potential in medicinal chemistry, chemical biology, and drug discovery. They also note that the reaction avoids transition metal catalysts.

    What the researchers tested

    The researchers tested [4 + 2] cycloadditions, a type of ring-forming reaction, between o-aminotrifluoroacetophenone derivatives or o-aminodifluoroacetophenone derivatives and 2-chloroprop-2-ene-1-sulfonyl fluoride (CESF). They then optimized sulfur(VI) fluoride exchange for nucleophiles based on nitrogen and oxygen.

    What worked and what didn't

    The cycloaddition approach produced the targeted dihydroquinoline sulfonyl fluorides under mild reaction conditions. The optimized sulfur(VI) fluoride exchange furnished sulfonamides from nitrogen-based nucleophiles and sulfonates from oxygen-based nucleophiles. The abstract does not describe any failed conditions or negative results.

    What to keep in mind

    The available summary does not provide detailed yields, comparisons with other methods, or broader testing beyond the reported reaction scope. Limitations are not described in the abstract.

    • The study reports a modular route to trifluoromethylated and difluoromethylated dihydroquinoline sulfonyl fluorides.
    • The synthesis used [4 + 2] cycloadditions with CESF under mild conditions.
    • No transition metal catalysts were used.
    • Sulfur(VI) fluoride exchange was optimized to make sulfonamides and sulfonates.
    • The authors say the products have potential in medicinal chemistry, chemical biology, and drug discovery.

  • Cyclometalated platinum compounds formed through competing bond-activation pathways

    What the study found

    The study found that competing carbon-hydrogen bond activation and carbon-halogen bond oxidative addition pathways can lead to different cyclometalated platinum compounds. When X = Br, the product was a six-coordinate platinum(IV) compound containing an anionic C^N^N ligand, and when X = Cl, both platinum(IV) and platinum(II) products were formed.

    Why the authors say this matters

    The authors suggest that comparing these pathways helps explain how platinum compounds form under different conditions. The findings also connect the observed products with photophysical behavior and with calculations of the competition between carbon-hydrogen activation and carbon-halogen oxidative addition.

    What the researchers tested

    The researchers studied cyclometalated platinum compounds formed from competing carbon-hydrogen bond activation and carbon-halogen bond oxidative addition pathways. They characterized the products with multinuclear nuclear magnetic resonance spectroscopy and single-crystal X-ray diffraction, and they examined photophysical properties using ultraviolet/visible, emission, and transient absorption spectroscopies. They also used density functional theory and time-dependent density functional theory calculations and compared those calculations with experiment.

    What worked and what didn't

    For X = Br, the pathway gave a six-coordinate platinum(IV) compound containing an anionic C^N^N ligand. For X = Cl, both a platinum(IV) product and a platinum(II) product were obtained; the platinum(II) species was formed by carbon-hydrogen activation followed by reductive elimination of methane.

    What to keep in mind

    The abstract does not describe broader limitations or practical applications. It also does not provide quantitative performance data for the photophysical measurements or detailed outcomes of the calculations beyond their comparison with experiment.

    • Competing carbon-hydrogen activation and carbon-halogen oxidative addition pathways produced different platinum compounds.
    • With bromine, the product was a six-coordinate platinum(IV) compound containing an anionic C^N^N ligand.
    • With chlorine, both platinum(IV) and platinum(II) products were formed.
    • The platinum(II) species came from carbon-hydrogen activation followed by methane elimination.
    • The products were characterized by multinuclear NMR and single-crystal X-ray diffraction.

  • Tertiary trifluoroacetamide stereochemistry can be assigned by NMR

    What the study found

    The study found that E/Z stereochemistry of N,N-dialkyl trifluoroacetamides can be assigned by considering both through-space 1H–19F spin–spin couplings and anisotropic solvent-induced shifts. The authors report that this combined approach is effective for these isomers.

    Why the authors say this matters

    The authors conclude that this approach is useful because 1H–19F HOESY, a specialized 1H–19F heteronuclear Overhauser enhancement spectroscopy experiment, is somewhat specialized and uncommon. They present the combined use of through-space couplings and solvent-induced shifts as a reliable and convenient way to determine stereochemistry.

    What the researchers tested

    The researchers examined N,N-dialkyl trifluoroacetamides 1–8 using 1H nuclear magnetic resonance spectroscopy. They used data on through-space spin–spin couplings and aromatic solvent-induced shifts, and also used 1D 1H–19F HOESY to distinguish through-space couplings from through-bond couplings.

    What worked and what didn't

    Through-space couplings alone may be useful for determining E/Z isomers, but through-bond couplings were also observed when a proton was five bonds away from the fluorine in the CF3 group. The ASIS results for all compounds were consistent with the general observation that C6D6 preferentially shifts trans-methyl/methylene protons toward the carbonyl oxygen atom over cis-methyl/methylene protons, and ASISs with C6F6 for compounds 4–8 were analyzed to support the method's reliability.

    What to keep in mind

    The abstract does not describe broader limitations beyond noting that 1H–19F HOESY is specialized and uncommon. The summary is limited to N,N-dialkyl trifluoroacetamides 1–8 and the methods described in the abstract.

    • The study addresses E/Z-isomer assignment in N,N-dialkyl trifluoroacetamides.
    • Both through-space 1H–19F couplings and aromatic solvent-induced shifts were used.
    • 1H–19F HOESY was needed to separate through-space couplings from through-bond couplings.
    • C6D6 shifted trans-methyl/methylene protons more than cis ones, as reported.
    • ASIS data with C6F6 for compounds 4–8 were analyzed to support reliability.

  • Pentafluoroethyl sulfoximine enables styrene difunctionalization

    What the study found

    The study reports a pentafluoroethyl sulfoximine reagent that can act as a source of pentafluoroethyl radical. Under mild photocatalytic conditions, it was used to add a pentafluoroethyl group to styrene derivatives while forming additional C-O, C-N, C-S, or C-C bonds.

    Why the authors say this matters

    The authors say this significantly broadens the difunctionalization scope involving pentafluoroethylation compared with previous copper-based methods. The study suggests the reagent expands the range of simple nucleophiles that can be used in these reactions.

    What the researchers tested

    The researchers synthesized a pentafluoroethyl sulfoximine and tested it in pentafluoroethylation-difunctionalization reactions of styrene derivatives. They used photocatalytic conditions and simple nucleophiles to evaluate whether the reagent could transfer the pentafluoroethyl group.

    What worked and what didn't

    What worked was the use of the sulfoximine reagent as a pentafluoroethyl radical source for styrene derivatives under mild photocatalytic conditions. The abstract states that this approach allowed formation of C-O/C-N/C-S/C-C bonds, but it does not provide detailed examples of failures or side-by-side performance data.

    What to keep in mind

    The available summary does not describe specific reaction yields, substrate limits, or failed cases. It also does not give detailed experimental conditions beyond the note that the process is photocatalytic and mild.

    • A pentafluoroethyl sulfoximine reagent was synthesized and applied to styrene derivatives.
    • The reagent acts as a source of pentafluoroethyl radical.
    • The reactions were carried out under mild photocatalytic conditions.
    • Pentafluoroethylation was accompanied by formation of C-O, C-N, C-S, or C-C bonds.
    • The authors say the method broadens pentafluoroethylation difunctionalization beyond previous copper-based methods.

  • Chiral carbon-bonding donors induced asymmetric selectivity

    What the study found

    The study found that chiral carbon-bonding donors can produce asymmetric induction, which means they can favor one mirror-image product over another in a reaction. In the reported benchmark reaction, this effect was observed for oxocarbenium ion intermediates.

    Why the authors say this matters

    The authors conclude that carbon bonding is a feasible method for asymmetric induction. They say this opens a path for future development in more efficient asymmetric synthesis.

    What the researchers tested

    The researchers synthesized chiral carbon-bonding donors and tested them in a proof-of-concept study. They used the oxa-Pictet-Spengler reaction as a benchmark reaction to examine whether this weak noncovalent interaction could induce chirality.

    What worked and what didn't

    The experimental results showed that the chiral carbon-bonding donors did exert asymmetric induction over oxocarbenium ion intermediates. However, the enantioselectivity, meaning the preference for one enantiomer or mirror-image product, was modest in this first attempt.

    What to keep in mind

    This was a first proof-of-concept study, so the reported performance was limited to a modest level of enantioselectivity. The abstract does not provide further limitations beyond that scope.

    • Chiral carbon-bonding donors were synthesized and tested for asymmetric induction.
    • The benchmark reaction was the oxa-Pictet-Spengler reaction.
    • The study reports asymmetric induction over oxocarbenium ion intermediates.
    • The initial enantioselectivity was modest.
    • The authors say carbon bonding is a feasible method for asymmetric induction.

  • Fluoronitromethane addition to tetrahydroisoquinolines was achieved by CDC

    What the study found

    The study reports an organocatalytic cascade that enables the formal addition of fluoronitromethane to tetrahydroisoquinolines, which are nitrogen-containing ring compounds. The reaction gives fluorinated compounds in good yields.

    Why the authors say this matters

    The authors frame the work in the context of green chemistry, which aims to reduce waste generation and energy consumption. The study suggests that cross-dehydrogenative coupling, or CDC, can be a useful strategy for carbon-carbon bond formation under these conditions.

    What the researchers tested

    The researchers tested a novel organocatalytic cascade based on CDC activation of tetrahydroisoquinolines followed by formal fluoronitromethane addition. They used the organic dye Rose Bengal as the catalyst, green LEDs as the light source, and molecular oxygen as the stoichiometric oxidant.

    What worked and what didn't

    The reported reaction worked under the stated conditions and enabled synthesis of fluorinated compounds in good yields. The abstract does not describe failed substrates, comparison conditions, or cases where the method did not work.

    What to keep in mind

    The available summary does not provide detailed limitations, substrate scope, or mechanistic evidence. It also does not state how broadly the method applies beyond the compounds and conditions described.

    • The paper reports a formal addition of fluoronitromethane to tetrahydroisoquinolines.
    • The method uses an organocatalytic cascade based on CDC activation.
    • Rose Bengal, green LEDs, and molecular oxygen were used in the reaction.
    • The abstract says the fluorinated products were obtained in good yields.
    • The abstract presents the work in the context of green chemistry.

  • THF increased tetraketone yield in reactions with alkyl ketones

    What the study found

    The study found that reacting dialkyl esters of perfluoroadipic and perfluoropimelic acids with alkyl ketones produced diketoesters. It also found that tetrahydrofuran (THF) increased the yield of polyfluorinated tetraketones made from dimethyl perfluorododecanedioate and alkyl ketones.

    Why the authors say this matters

    The authors suggest that understanding how to improve the synthesis of polyfluorinated tetraketones is important for this chemistry. They also conclude that the proposed reaction mechanism can be discussed using non-empirical MP2/6-31G* calculations, which are quantum-chemical calculations based on molecular structure and energy.

    What the researchers tested

    The researchers examined reactions between dialkyl esters of perfluoroadipic and perfluoropimelic acids and alkyl ketones. They also studied the synthesis of polyfluorinated tetraketones from dimethyl perfluorododecanedioate and alkyl ketones, and used MP2/6-31G* calculations to analyze possible stages of the process.

    What worked and what didn't

    The reaction produced diketoesters from the perfluorodicarboxylic acid esters and alkyl ketones. In the tetraketone synthesis, THF increased the yield. The abstract does not report any conditions that failed or any negative results.

    What to keep in mind

    The abstract provides only a brief summary and does not give numerical yields, reaction conditions, or detailed mechanism steps. It also does not describe limitations of the study beyond the scope of the calculations and reactions tested.

    • Dialkyl esters of perfluoroadipic and perfluoropimelic acids reacted with alkyl ketones to form diketoesters.
    • Dimethyl perfluorododecanedioate was used to study synthesis of polyfluorinated tetraketones.
    • Tetrahydrofuran (THF) increased the yield of tetraketones.
    • The authors discussed the reaction mechanism using MP2/6-31G* calculations.
    • The abstract does not report numerical yields or detailed limitations.