Continuous Flow Decarboxylative Monofluoroalkylation Enabled by Photoredox Catalysis

JACS Au, Год журнала: 2025, Номер 5(2), С. 684 - 692

Опубликована: Фев. 2, 2025

Herein, we report a scalable and mild strategy for the monofluoroalkylation of wide array Giese acceptors via visible-light-mediated photoredox catalysis in continuous flow. The use flow technology significantly enhances productivity scalability, whereas mildness conditions functional group tolerance are ensured by leveraging 4CzIPN, transition-metal-free organic photocatalyst. Structurally diverse secondary tertiary monofluoroalkyl radicals can thus be accessed from readily available α-monofluorocarboxylic acids. Given reaction conditions, this protocol is also amenable to late-stage functionalization biologically relevant molecules such as menthol, amantadine, bepotastine, estrone derivatives, rendering it suitable application drug discovery programs, which introduction fluorinated fragments highly sought after. This method was extended enable reductive multicomponent radical-polar crossover transformation rapidly increase complexity assembled architectures single synthetic operation.

Язык: Английский

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Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(22), С. 15176 - 15185

Опубликована: Май 21, 2024

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation these fundamental steps remain elusive owing largely the typically slow rate instability species. We report herein a novel aryl-radical-enabled stepwise pathway that allows for formation well-defined alkyl–CuIII from CuI complexes. The process is enabled by SET an aryl diazonium salt CuII radical. Subsequent iodine abstraction alkyl iodide radical affords radical, which then reacts with complex. structure resultant [(bpy)CuIII(CF3)2(alkyl)] characterized NMR spectroscopy X-ray crystallography. Competition experiments have revealed at different iodides undergo consistent carbon-centered radicals. intermediate formed during identified as four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. catalytic relevance high-valent organo-CuIII demonstrated C–C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis formal CuIII indicates inverted ligand fields σ(Cu–CH2) bonds. These results demonstrate catalysis provide general strategy investigate

Язык: Английский

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Transition‐Metal‐Mediated Fluoroalkylation of Carbon Electrophiles through Cross‐Electrophile Couplings

Chinese Journal of Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

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 physicochemical biological organic molecules. Transition‐metal‐mediated cross‐electrophile coupling between carbon electrophiles fluoroalkyl has emerged as a straightforward efficient route for synthesis wide range fluoroalkylated because its synthetic convenience without tedious organometallic reagents. Moreover, alkenes or alkynes‐involved three‐component couplings provide rapid effective access carbonfunctionalized alkanes alkenes. Herein, we comprehensively summarize transition‐metal‐mediated reductive fluoroalkylation diverse through historical perspective, including trifluoromethylation, difluoroalkylation, monofluoroalkylation, so on. Different transition metals (Cu, Ni, etc .) strategies are discussed, which nickel‐catalyzed reactions represent an attractive site‐selectively organofluorine compounds. Key Scientists As early 1965, McLoughlin Thrower finished first stoichiometric copper‐mediated aromatic iodides with iodides. However, excess elevated temperature were used this method. In 1969, Kobayashi Kumadaki reported studies on trifluoromethylation halides trifluoromethyl iodide. After more than four decades, Zhang group developed β ‐fluorinated alkylation (hetero)aryl secondary alkyl bromides 2015, difluoromethylation chlorides chlorodifluoromethane ClCF 2 H 2017. The also enantioselective alkyl‐arylation 3,3,3‐trifluoropropene tertiary 2018, MacMillan novel copper/photoredox dual catalytic system aryl ( S )‐(trifluoromethyl) dimesitylsulfonium triflate presence tris‐(trimethylsilyl) silanol. They nickel/photoredox catalyzed silane. During time, Wang monofluoroalkylation monofluoroalkyl halides. From 2021 2023, same further series trifluoroalkylation aryl, alkenyl, acyl nonfluorinated alkynes could be couplings. Chu fluoroalkyl‐acylation Later, they fluoroalkyl‐arylation unactivated tethering pendant chelating group. 2019, Chaładaj palladium‐catalyzed perfluoroalkyl‐arylation perfluoroalkyl

Язык: Английский

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N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides

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

Опубликована: Окт. 16, 2024

Both the pyrroloindoline core and N-CF

Язык: Английский

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N-Atom Deletion Involving Rearrangement of Sulfamoyl Azides or Triazanium Salts

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

ConspectusAmines are frequent structural components in natural products, pharmaceuticals, ligands, and catalysts, making their synthesis transformation essential to organic chemistry. While C-N bond formation has become a well-established reliable synthetic strategy, the selective cleavage of bonds remains relatively underexplored. This challenge arises from low heterolytic nucleofugality nitrogen, property that limits practical application cleavage. gap underscores significant area methodology need further development. In this context, N atom deletion─defined as removal nitrogen via cleavage, while preserving integrity remaining framework─has emerged promising approach for skeletal editing. Since Levin's landmark 2021 report, deletion gained attention its potential precisely modify molecular skeletons. Building on editing concepts advanced by Levin Sarpong, particularly strategies modifying cyclic frameworks, we recognized critical developing mild efficient methods enable manipulation systems.This Account summarizes our research since 2017, focusing two approaches with distinct mechanisms: rearrangement sulfamoyl azides conversion triazanium intermediates. Initially, explored optimized thermal derived secondary amines, discovering viable strategy deletion. 2024, introduced an O-diphenylphosphinyl hydroxylamine (DPPH)-promoted deletion, involving generation novel Both polar aliphatic amines into nonpolar scaffolds applicable both linear molecules systems varying sizes. The DPPH-based approach, particular, demonstrated exceptional effectiveness sterically hindered substrates reaction conditions no anhydrous or oxygen-free environments. mechanisms methods─both isodiazene radical intermediates─were elucidated through rigorous experimental investigation. Additionally, observed rapid hydro(deutero)deamination products when primary were exposed DPPH.Beyond role typical crucial approach. Though limitations, it transforms challenging task constructing C-C more manageable sequence: following removal. We have applied hydrocarbon cages, pharmaceuticals. hope work will stimulate interest encourage incorporation methodologies, thereby expanding utility across diverse areas

Язык: Английский

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Electron-Donor-Mediated Divergent Transformation of Br–R_F via EDA Complex for the Synthesis of Fluorine-Containing Oxindoles and Amides

Organic Letters, Год журнала: 2024, Номер 26(46), С. 9990 - 9995

Опубликована: Ноя. 11, 2024

We have developed an unprecedented electron-donor-controlled divergent reaction between

Язык: Английский

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Visible Light Mediated Palladium-Catalyzed Hydrodebromination of Aliphatic α-Bromotrifluoromethyl Compounds

Chinese Journal of Organic Chemistry, Год журнала: 2025, Номер 45(4), С. 1334 - 1334

Опубликована: Янв. 1, 2025

Язык: Английский

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Hydro- and deutero-deamination of primary amines using O-diphenylphosphinylhydroxylamine

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

Опубликована: Ноя. 24, 2024

Abstract While selective defunctionalizations are valuable in organic synthesis, hydrodeamination of primary amines poses challenges. Deuterodeamination, analogous to hydrodeamination, presents even greater difficulties due its frequently slower deuteration rate, interference by hydrogenation and constraints deuterated sources. This study introduces a reliable, robust, scalable hydro- deuterodeamination method capable handling various amines. Defined mild reaction conditions, rapid completion, simplified purification facilitated water-soluble byproducts, the leverages deuterium oxide as source employs commercialized O-diphenylphosphinylhydroxylamine for deamination. Applied diverse range biologically active molecules, it has consistently achieved high yields efficient incorporation. By synergizing with site-selective C–H functionalization aliphatic amines, our reveals synthetic strategies utilizing nitrogen atom traceless directing group, encompassing deaminative alkylation, 1,1-deuteroalkylation, 1,1-dialkylation, 1,1,1-deuterodialkylation, arylation, 1,3-deuteroarylation. Emphasizing this innovation, processes degree-controlled have been developed.

Язык: Английский

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Facile and efficient transformation of thiols to disulfides via a radical pathway with N-anomeric amide

RSC Advances, Год журнала: 2024, Номер 14(25), С. 17780 - 17784

Опубликована: Янв. 1, 2024

Radical coupling of thiols is an attractive route for the synthesis disulfides, but this approach should be promoted by strong oxidants and/or metal salts in combination with additives, which limits its substrate scope and application. In work, N-anomeric amide was first found to able realize conversion sulfur radicals high efficiency absence oxidant or any additives symmetrical disulfides. The protocol features mild reaction conditions, good functional group tolerance, moderate excellent yields.

Язык: Английский

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Well‐Defined Highly‐Coordinated Copper(III) Iodide and Pincer Tris(trifluoromethyl)copper Complexes

Chemistry - A European Journal, Год журнала: 2024, Номер unknown

Опубликована: Июль 8, 2024

Copper(III) iodide and bromide complexes representing a unique combination of highly-coordinated metal soft polarizable anions were synthesized fully characterized, including X-ray crystallography. Ligand substitution in well-defined copper complex PyCu(CF

Язык: Английский

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