Nickel Meets Aryl Thianthrenium Salts: Ni(I)-Catalyzed Halogenation of Arenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(18), С. 9988 - 9993

Опубликована: Май 1, 2023

Herein, a regioselective, late-stage two-step arene halogenation method is reported. We propose how unusual Ni(I)/(III) catalysis enabled by combination of aryl thianthrenium and Ni redox properties that hitherto unachieved with other (pseudo)halides. The catalyst accessed in situ from inexpensive NiCl2·6(H2O) zinc without the need supporting ligands.

Язык: Английский

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Light-promoted aromatic denitrative chlorination

Nature Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Язык: Английский

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Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 14(3), С. 1030 - 1076

Опубликована: Ноя. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Язык: Английский

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Diversification of pharmaceutical molecules via late-stage C(sp2)–H functionalization

Green Synthesis and Catalysis, Год журнала: 2023, Номер 4(2), С. 104 - 123

Опубликована: Янв. 2, 2023

C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds' bioactivity. Significant advances in this field have been achieved past few years, mainly, system (hetero)aryl activation owing to importance moiety pharmaceutical. In review, we described selected recent examples how developed intermolecular C(sp2)–H methodologies involving diverse techniques diversify pharmaceutical molecules late stage.

Язык: Английский

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Aromatic halogenation using carborane catalyst

Chem, Год журнала: 2023, Номер 10(1), С. 402 - 413

Опубликована: Ноя. 6, 2023

Язык: Английский

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Late-Stage C–H Nitration of Unactivated Arenes by Fe(NO₃)₃·9H₂O in Hexafluoroisopropanol

Organic Letters, Год журнала: 2024, Номер 26(15), С. 3316 - 3320

Опубликована: Апрель 10, 2024

Operationally simple and generally applicable arene nitration with cheap easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized goal nontoxic inexpensive Fe(NO3)3·9H2O as nitro source recyclable solvent hexafluoroisopropanol promotor via network of hydrogen-bonding interactions. As result relative mildness high reliability protocol, late-stage various highly functionalized natural products commercially available drugs was realized.

Язык: Английский

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Selective C−H Halogenation of Alkenes and Alkynes Using Flavin‐Dependent Halogenases

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(13)

Опубликована: Янв. 27, 2024

Abstract Single component flavin‐dependent halogenases (FDHs) possess both flavin reductase and FDH activity in a single enzyme. We recently reported that the AetF catalyzes site‐selective bromination iodination of variety aromatic substrates enantioselective bromolactonization iodoetherification styrenes bearing pendant carboxylic acid or alcohol substituents. Given this inherent reactivity selectivity, we explored utility as catalyst for alkene alkyne C−H halogenation. find halogenation range 1,1‐disubstituted styrenes, often with high stereoselectivity. Despite haloalkenes cross‐coupling other applications, accessing these compounds stereoselective manner typically requires functional group interconversion processes, selective 1,1′‐disubstituted olefins remains rare. also establish homologues enzyme can halogenate terminal alkynes. Mutagenesis studies deuterium kinetic isotope effects are used to support mechanistic proposal involving covalent catalysis unactivated alkynes by homologues. These findings expand scope continue show unique FDHs biocatalysis.

Язык: Английский

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Direct C–H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(14), С. 9755 - 9767

Опубликована: Март 26, 2024

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development reactions that complement address limitations existing methods for introduction aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable direct C–H hydroxylation mildly acidic N-heteroarenes benzenes. This protocol employs alkoxide base catalyze X-transfer from sacrificial 2-halothiophene oxidants aryl substrates, forming SNAr-active intermediates undergo nucleophilic hydroxylation. Key process use 2-phenylethanol inexpensive hydroxide surrogate that, after substitution rapid elimination, provides hydroxylated arene styrene byproduct. Use simple 2-halothiophenes allows 6-membered 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends scope electron-deficient benzene substrates. Mechanistic studies indicate reversible, suggesting deprotonation, halogenation, steps operate synergy, manifesting unique selectivity trends not necessarily dependent on most position. The utility method further demonstrated through streamlined target molecule syntheses, examples regioselectivity contrast alternative methods, scalable recycling thiophene oxidants.

Язык: Английский

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Cavity Quantum Electrodynamics Enables para- and ortho-Selective Electrophilic Bromination of Nitrobenzene

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(23), С. 16184 - 16193

Опубликована: Май 30, 2024

Coupling molecules to a quantized radiation field inside an optical cavity has shown great promise modify chemical reactivity. In this work, we show that the ground-state selectivity of electrophilic bromination nitrobenzene can be fundamentally changed by strongly coupling reaction cavity, generating ortho- or para-substituted products instead meta product. Importantly, these are not obtained from same outside cavity. A recently developed ab initio approach was used theoretically compute relative energies cationic Wheland intermediates, which indicate kinetically preferred site for all products. Performing analysis electron density intermediates and demonstrate how strong induces reorganization molecular charge distribution, in turn leads different sites directly dependent on conditions. Overall, results presented here understand induced changes reactivity mechanistic perspective as well connect frontier theoretical simulations state-of-the-art, but realistic, experimental

Язык: Английский

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Zwitterionic Dual Halogen Bond-Catalyzed Electrophilic Bromination of Electron-Deficient Arenes under Mild Conditions

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 4270 - 4279

Опубликована: Фев. 25, 2025

Язык: Английский

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