Dearomative 1,4-Difunctionalization of Non-Activated Arenes Enabled by Boryl Radical-Mediated Halogen-Atom Transfer

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 1294 - 1304

Опубликована: Янв. 7, 2025

Given the widespread presence of spirocyclic scaffolds in natural products and pharmacologically relevant synthetic compounds, development efficient methodologies for their construction holds great importance medicinal chemistry pharmaceutical research. In this study, a general photochemical dearomative spirocyclization nonactivated arenes has been established. The key to method lies ability amine-borane radicals activate aryl bromides iodides via halogen-atom transfer, thereby allowing conversion halides into corresponding subsequent chemodivergent transformations. remarkable compatibility versatility 1,4-difunctionalization is showed by rapid assembly structurally diverse 1,4-cyclohexadiene-based spirocycles incorporating oxindole, indoline, or dihydrobenzofuran subunits. Moreover, potential utility protocol exemplified formal total synthesis vasopressin V2 receptor antagonist Satavaptan.

Язык: Английский

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CO₂^•– Enabled Synthesis of Phenanthridinones, Oxindoles, Isoindolinones, and Spirolactams

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

We report herein that photoinduced CO2•– enabled reductive intramolecular radical cyclization of a variety aryl iodide derivatives to the corresponding phenanthridinone, oxindole, isoindolinone, and spirolactam in good yields. Preliminary mechanistic studies suggested generation through homolysis cesium formate presence light, further involvement was directly proved by trapping with diphenyl styrene TEMPO.

Язык: Английский

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Radical Replacement Process for Ligated Boryl Radical-Mediated Activation of Unactivated Alkyl Chlorides for C(sp³)–C(sp³) Bond Formation

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 12, 2024

The ligated boryl radical (LBR) has emerged as a potent tool for activating alkyl halides in transformations through halogen-atom transfer (XAT). However, unactivated chlorides still present an open challenge this strategy. We herein describe new activation mode of the LBR to construct C(sp

Язык: Английский

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Controllable Hydrodebromination of Tribromomethyl Groups via Lewis Base–Borane-Mediated Ionic and Radical Pathways

Synthesis, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract Compounds bearing mono- and dibromomethyl groups are extensively utilized in synthetic medicinal chemistry. In this regard, selective debromination of readily or easily accessible tribromomethyl compounds offers a direct efficient method to access those two moieties. work, we introduced Lewis base–borane-mediated hydrodebromination via ionic radical pathway. Using 4-(dimethylamino)pyridine–borane (DMAP-BH3) as hydride donor, monohydrodebromination was achieved nucleophilic substitution by hydride, delivering groups. On the other hand, treatment with an N-heterocyclic carbene–borane (NHC-BH2CN) boryl precursor presence dilauroyl peroxide (DLP) initiator afforded monobromomethyl through consecutive bromine atom abstractions cleave C–Br bonds. Various group acetamides acetates were applied developed protocol, showcasing good functional tolerance broad substrate scope.

Язык: Английский

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Modular assembly of amines and diborons with photocatalysis enabled halogen atom transfer of organohalides for C(sp³)–C(sp³) bond formation

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A new photocatalytic approach by using the assembly of DABCO A1 and B 2 Nep B1 has been established to enable cross-coupling organohalides alkenes for C(sp 3 )–C(sp ) bond formation.

Язык: Английский

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Monodefluorinative Halogenation of Perfluoroalkyl Ketones via Organophosphorus-Mediated Selective C–F Activation

JACS Au, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Through the prosperity of organofluorine chemistry in modern organic synthesis, perfluorinated compounds are now abundant and widely available. Consequently, these substances become attractive starting materials for production complex, multifunctional fluorinated molecules. However, inherent challenges associated with activation discrimination C–F bonds typically lead to overdefluorination as well functional group incompatibility. To address problems, our utilized a rationally designed organophosphorus reagent that promoted mild selective manipulation single bond trifluoromethyl pentafluoroethyl ketones via an interrupted Perkow-type reaction, which allowed replacement fluorine more labile synthetically versatile congeners such chlorine, bromine, iodine. The resulting α-haloperfluoroketones have two reactive units orthogonal properties would be suitable subsequent structural diversification. DFT calculations identified favorable P–F interaction crucial factor from both thermodynamic kinetic viewpoints.

Язык: Английский

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Cryogenic Organometallic Carbon–Fluoride Bond Functionalization with Broad Functional Group Tolerance

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

The unique properties of fluorinated organic compounds have received intense interest and conquered a myriad applications in the chemical pharmaceutical sciences. Today, an impressive range alkyl fluorides are commercially available, there many practical methods to make them exist. However, unmatched stability inertness C–F bond largely limited its synthetic value, which is very different from widely accepted utility chlorides, bromides, iodides that serve everyday as "workhorse" building blocks countless carbon–carbon forming reactions. This study demonstrates high-yielding functionalization under mild conditions, i.e., at temperatures low −78 °C, short reaction times with unconventional chemoselectivity. Cryogenic Csp3–F cleavage using fluorophilic organoaluminum together fast nucleophile transfer intermediate ate complexes forge bonds unactivated primary, secondary, tertiary alike. method, exploits Al–F thermodynamic driving force, highly selective toward functionalization, whereas other functional groups including chloride, bromide, iodide, aryl halide, alkenyl, alkynyl, difluoroalkyl, trifluoromethyl, ether, ester, hydroxyl, acetal, heteroaryl, nitrile, nitro, amide tolerated, unexpected reversal long-standing main group organometallic halide cross-coupling reactivity compatibility patterns. As result, strongest single chemistry can now be selectively targeted arylation, alkylation, alkenylation, alkynylation reactions used late-stage complementary currently available methods.

Язык: Английский

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Mechanistic Exploration of N-Heterocyclic Carbene Boranes as the Hydrogen Atom Transfer Reagent in Selective Hydrodefluorination Reactions

ACS Catalysis, Год журнала: 2024, Номер unknown, С. 17547 - 17555

Опубликована: Ноя. 13, 2024

In the modern era of organic synthesis, mechanisms centered on radical intermediates have become increasingly impactful. Among all these, hydrogen atom transfer (HAT) represents one most fundamental chemical reaction steps and has found applications in designing practical transformations. Herein, we present a detailed case study selective hydrodefluorination trifluoromethylarenes utilizing N-heterocyclic carbene boranes (NHC-boranes) as donor. Under optimal conditions featuring an acridine-based photocatalyst, complete selectivity for mono-hydrodefluorination was achieved across wide array substrates. Comprehensive mechanistic studies combining experimental computational approaches disproved chain process involving fluorine but rather pointed to HAT non-chain mechanism, where key step involves difluorobenzylic abstracting from NHC-borane generate boryl polarity-matched fashion. Evaluation selection Lewis base-ligated revealed molecular descriptors critical outcomes this reaction, classification model built explain structure–reactivity relationship how various elementary can be influenced. These results collectively provide valuable information future design increase utility chemistry.

Язык: Английский

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C(sp3)‐F Bond Activation by Lewis Base‐Boryl Radicals via Concerted Electron‐Fluoride Transfer

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Selective C-F bond activation through a radical pathway in the presence of multiple C-H bonds remains formidable challenge, owing to extraordinarily strong strength bond. By aid density functional theory calculations, we disclose an innovative concerted electron-fluoride transfer mechanism, harnessing unique reactivity Lewis base-boryl radicals selectively activate resilient fluoroalkanes. This enables direct abstraction fluorine atom and subsequent generation alkyl radical, thus expanding boundaries halogen reactions.

Язык: Английский

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C(sp3)‐F Bond Activation by Lewis Base‐Boryl Radicals via Concerted Electron‐Fluoride Transfer

Angewandte Chemie, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Abstract Selective C−F bond activation through a radical pathway in the presence of multiple C−H bonds remains formidable challenge, owing to extraordinarily strong strength bond. By aid density functional theory calculations, we disclose an innovative concerted electron‐fluoride transfer mechanism, harnessing unique reactivity Lewis base‐boryl radicals selectively activate resilient fluoroalkanes. This enables direct abstraction fluorine atom and subsequent generation alkyl radical, thus expanding boundaries halogen reactions.

Язык: Английский

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