Wonderful fusion of organofluorine chemistry and decarboxylation strategy

Chemical Society Reviews, Год журнала: 2021, Номер 50(10), С. 6094 - 6151

Опубликована: Янв. 1, 2021

Decarboxylation strategy has been emerging as a powerful tool for the synthesis of fluorine-containing organic compounds that play important roles in various fields such pharmaceuticals, agrochemicals, and materials science. Considerable progress decarboxylation made over past decade towards construction diverse valuable fluorinated fine chemicals which part can be brought two ways. The first way is described reaction non-fluorinated carboxylic acids (and their derivatives) with fluorinating reagents, well building blocks. second dedicated to exploration use decarboxylative transformations. This review aims provide comprehensive summary development applications radical, nucleophilic cross-coupling strategies organofluorine chemistry.

Язык: Английский

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Reactivities of electrophilic N–F fluorinating reagents

Chemical Communications, Год журнала: 2020, Номер 57(6), С. 683 - 712

Опубликована: Дек. 24, 2020

A comprehensive review of past and present approaches towards qualitative quantitative rankings the reactivities electrophilic fluorinating agents.

Язык: Английский

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Visible-Light-Induced Decarboxylative Fluorination of Aliphatic Carboxylic Acids Catalyzed by Iron

Organic Letters, Год журнала: 2022, Номер 24(32), С. 5972 - 5976

Опубликована: Авг. 11, 2022

An efficient and inexpensive protocol for the direct decarboxylative fluorination of aliphatic carboxylic acids catalyzed with iron salts under visible light is presented. This new method allows facile a diverse array even on gram scale using Schlenk flask without loss efficiency. Mechanistic studies suggest that photoinduced ligand-to-metal charge transfer process enables generation key step to generate carboxyl radical intermediates.

Язык: Английский

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Site-Selective Late-Stage C–H Functionalization via Thianthrenium Salts

Synlett, Год журнала: 2021, Номер 33(04), С. 339 - 345

Опубликована: Апрель 13, 2021

Abstract The high abundance of C–H bonds in organic molecules makes functionalization a powerful approach to quickly increase the complexity an molecule. However, also provides challenge reactions: selectivity. While most reactions produce mixtures different products for substrates, we have developed highly selective method aromatic via sulfonium salts. reaction does not require certain directing group be selective. introduced functional is group, which participates various follow-up such as palladium-catalyzed cross-coupling and photoredox catalysis. Here discuss our pathway develop well its scope utility. 1 Introduction 2 Site-Selective Synthesis Sulfonium Salts 3 Palladium-Catalyzed Cross-Coupling 4 Photoredox Catalysis 5 Sulfur(IV) Reductive Elimination 6 Cine Substitution 7 Conclusion

Язык: Английский

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Hydrogen Bonding Phase-Transfer Catalysis with Alkali Metal Fluorides and Beyond

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(12), С. 5200 - 5213

Опубликована: Март 16, 2022

Phase-transfer catalysis (PTC) is one of the most powerful catalytic manifolds for asymmetric synthesis. Chiral cationic or anionic PTC strategies have enabled a variety transformations, yet studies on use insoluble inorganic salts as nucleophiles synthesis enantioenriched molecules remained elusive. A long-standing challenge development methods carbon-fluorine bond formation from readily available and cost-effective alkali metal fluorides. In this Perspective, we describe how H-bond donors can provide solution through fluoride binding. We examples, primarily our own research, to discuss hydrogen bonding interactions impact reactivity role phase-transfer catalysts bring solid-phase fluorides in solution. These led (HB-PTC), new concept PTC, originally crafted but offering opportunities beyond enantioselective fluorination. Looking ahead, unlimited options that consider diversify donor, salt, electrophile, herald era catalysis. Whether abundant lattice energy significantly higher than those studied date could be considered nucleophiles, e.g., CaF2, remains an open question, with solutions may found synergistic PTC.

Язык: Английский

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Handling fluorinated gases as solid reagents using metal-organic frameworks

Science, Год журнала: 2023, Номер 381(6665), С. 1455 - 1461

Опубликована: Сен. 28, 2023

Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for late-stage installation fluorinated groups, but they are generally overlooked require use specialized equipment. We report a general strategy handling as benchtop-stable solid reagents using metal-organic frameworks (MOFs). Gas-MOF prepared on gram-scale used to facilitate fluorovinylation fluoroalkylation reactions. Encapsulation gas-MOF within wax enables stable storage benchtop controlled release into solution upon sonication, which represents safer alternative gas directly. Furthermore, our approach high-throughput reaction development with these gases.

Язык: Английский

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Diastereoselective Synthesis of Monofluorocyclohexenes through Photocatalyzed Cascade Cyclization of gem‐Difluoroalkenes and α,β‐Unsaturated Carbonyl Compounds

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(20)

Опубликована: Март 16, 2023

Monofluoroalkenes are nonhydrolyzable mimetics of amides. Previous work focused on the synthesis non-cyclic monofluoroalkenes. However, diastereoselective monofluorocyclohexenes from substrates is challenging. Herein, we report first photocatalyzed cascade cyclization reactions readily available α,β-unsaturated carbonyl compounds and gem-difluoroalkenes for highly functionalized monofluorocyclohexenes. The reaction shows broad substrate scope with high diastereoselectivity (>30 examples, up to 86 % yield, >20 : 1 dr). post-reaction transformations products demonstrate synthetic potential this methodology.

Язык: Английский

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Iron photocatalysis via Brønsted acid-unlocked ligand-to-metal charge transfer

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 20, 2024

Abstract Reforming sustainable 3d-metal-based visible light catalytic platforms for inert bulk chemical activation is highly desirable. Herein, we demonstrate the use of a Brønsted acid to unlock robust and practical iron ligand-to-metal charge transfer (LMCT) photocatalysis multifarious haloalkylcarboxylates (C n X m COO − , = F or Cl) produce C radicals. This process enables fluoro-polyhaloalkylation non-activated alkenes by combining easily available Selectfluor as fluorine source. Valuable alkyl fluorides including potential drug molecules can be obtained through this protocol. Mechanistic studies indicate that real light-harvesting species may derive from in situ-assembly Fe 3+ H + acetonitrile solvent, which indeed increases efficiency LMCT between center via hydrogen-bond interactions. We anticipate acid-unlocked platform would an intriguing option execute compounds.

Язык: Английский

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Development of S_NAr Nucleophilic Fluorination: A Fruitful Academia-Industry Collaboration

Accounts of Chemical Research, Год журнала: 2020, Номер 53(10), С. 2372 - 2383

Опубликована: Сен. 24, 2020

ConspectusThe identification of reliable, general, and high yielding methods for the formation C(sp2)–fluorine bonds remains a major challenge synthetic organic chemists. A very common approach involves nucleophilic aromatic fluorination (SNAr fluorination) reactions aryl chlorides or nitroarenes. Despite being known more than century, traditional SNAr suffer from significant limitations, particularly on process scale. These include cost reagents [e.g., cesium fluoride (CsF)], requirement elevated temperatures long reaction times, poor functional group tolerance, need rigorous exclusion water. This Account summarizes our collaboration with Corteva Agriscience (previously Dow Agrosciences) to address many these challenges. has provided platform fundamental scientific advances involving development new methods, reagents, substrates mild reactions.Our early studies established that combination potassium (KF) superstoichiometric tetrabutylammonium chloride (Bu4NCl) serves as cost-effective alternative CsF chloropicolinate substrates. However, still require (>130 °C) afford moderate yields due competing decomposition substrate product. The temperature is largely slow rates resulting low concentration active fluorinating reagent [anhydrous (Bu4NF)] under conditions. To this issue, we developed several strategies generating solutions anhydrous tetraalkylammonium in situ by combining fluorine-containing electrophiles (e.g., hexafluorobenzene, acyl fluorides, sulfonyl fluorides) nucleophiles (R4NCN R4NOR). systems enable unusually conditions, affording nearly quantitative yield at room temperature. generation large quantities byproducts R4NF-forming step render unsuitable scale applications. As an alternative, next explored tetramethylammonium (Me4NF) transformations. highly reactive source can be synthesized directly inexpensive KF Me4NCl then dried heating vacuum. Unlike Bu4NF, it not susceptible Hofmann elimination. such, Me4NF stable isolable, well effective chloropicolinates other electron deficient substrates.The R4NF drew attention another associated reactions: their limitation bearing resonance electron-withdrawing groups. We hypothesized could addressed circumventing Meisenheimer intermediate, canonical mechanistic feature fluorination. By designing involve concerted delivery ipso C(sp2) center, deoxyfluorination arylfluorosulfonates using Me4NF. exhibits broad scope respect electrophile, both (CN, ester, CF3, Cl) moderately donating (phenyl, alkyl) substituents participating deoxyfluorination. conditions were also expanded nonaromatic substrates, including aldehydes benzylic/aliphatic alcohols.This concludes delineating ongoing challenges opportunities fast-moving field. For instance, one important future direction will moisture sensitivity In addition, application synthesis pharmaceuticals, agrochemicals, PET imaging agents continue test versatility compatibility methods.

Язык: Английский

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Photocatalytic C−F Bond Activation of Fluoroarenes, gem‐Difluoroalkenes and Trifluoromethylarenes

Asian Journal of Organic Chemistry, Год журнала: 2021, Номер 10(10), С. 2454 - 2472

Опубликована: Авг. 18, 2021

Abstract Fluorine‐containing compounds have been widely applied on pharmaceuticals, agrochemicals, and materials. The synthetic methodology for the introduction of fluorine into organic motifs has witnessed dramatically development recently. Selective C−F bond activation functionalization easily accessible fluorinated provided an efficient way to synthesize novel products degradate extremely stable pollutants. As photocatalytic transformations, light induced direct under mild conditions leading production various functionalities become one most advanced methodologies available. This minireview summarizes recent activations compounds, including fluoroarenes, gem ‐difluoroalkenes trifluoromethylarenes, intends illustrate readers a comprehensive this research topic via demonstrating representative examples detailed mechanism according reaction types transformations.

Язык: Английский

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