The α-trideuteromethylation of arylacetonitriles with deuterated methanol via deuterium autotransfer process catalyzed by a metal-ligand bifunctional iridium catalyst

Journal of Catalysis, Год журнала: 2024, Номер 430, С. 115301 - 115301

Опубликована: Янв. 18, 2024

Язык: Английский

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The development and application of a novel trideuterium methylation reagent

Cell Reports Physical Science, Год журнала: 2024, Номер 5(3), С. 101843 - 101843

Опубликована: Фев. 27, 2024

The incorporation of a trideuteromethyl group in diverse pharmaceutical building blocks and drug-like molecules serves as valuable strategy medicinal industrial chemistry. Trideuteromethylation reactions have gained significant, continuous attention at rapid pace recent years. However, the lack known trideuteromethylated reagents prevents range applications terms substrate reaction type. In this study, we report synthesis application thianthrenium triflate (TT-CD3+OTf−) trideuteromethylating reagent that makes use inexpensive raw material. This performs well nucleophilic, radical, transition-metal-catalyzed C–H trideuteromethylations. Microflow technique can enhance intensify these processes resulting various organic deuterated pharmaceuticals with comparable yields high deuterium content.

Язык: Английский

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Robust, scalable construction of an electrophilic deuterated methylthiolating reagent: facile access to SCD₃-containing scaffolds

Chemical Communications, Год журнала: 2022, Номер 58(18), С. 3015 - 3018

Опубликована: Янв. 1, 2022

We have established a practical and concise method for the straightforward access of universal deuterated methylthiolating reagent through one-pot gram-scale operation under mild conditions. This odourless electrophilic SCD3 was widely applied to react with numerous representative nucleophiles approached various valuable analogues excellent levels deuterium content (>99% D). The divergent further transformations were smoothly carried out obtain significant derivatives different oxidative states in high efficiency.

Язык: Английский

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Hydrodeuteroalkylation of Unactivated Olefins Using Thianthrenium Salts

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(36)

Опубликована: Июнь 13, 2024

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered synthesis corresponding products. In this study, we introduce nickel-catalyzed system that facilitates various deuterium-labeled through hydrodeuteroalkylation d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional reagents, thianthrenium (TT) can effectively selectively deuterium at α position chains using D

Язык: Английский

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Benzyl Deuteriodifluoromethyl Sulfoxide: An Easily Accessible and Stable Reagent for Direct Deuterodifluoromethylthiolation

Organic Letters, Год журнала: 2024, Номер 26(3), С. 687 - 691

Опубликована: Янв. 18, 2024

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The displays excellent reactivities toward Tf2O promoted C–H of electron-rich arenes, indoles, alkenes, intramolecular lactonization 2-alkynylbenzoates. Moreover, high deuteration rates good to yields were achieved under metal-free reaction conditions. As result, wide range deuteriodifluoromethylthilolated compounds prepared, enabling further applications in drug discovery.

Язык: Английский

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Atom- and step-economic 1,3-thiosulfonylation of activated allenes with thiosulfonates to access vinyl sulfones/sulfides

Chemical Communications, Год журнала: 2022, Номер 58(47), С. 6765 - 6768

Опубликована: Янв. 1, 2022

A new type of organocatalyzed 1,3-thiosulfonylation has been developed to straightforwardly access highly functionalized vinyl sulfones, which features mild conditions, atom- and step-economy, practicability, conciseness, environmental friendliness. Moreover, these valuable products can be transformed sulfides via a base-promoted isomerization. The versatile route efficiently rapidly introduce SCD3 groups with excellent levels deuterium content (>99% D) by utilizing our newly reagents. Gram-scale operations further transformations are smoothly carried out, providing promising applications for drug discovery.

Язык: Английский

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Sulfonium Salt Reagents for the Introduction of Deuterated Alkyl Groups in Drug Discovery

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Сен. 20, 2023

Abstract The pharmacokinetics of pharmaceutical drugs can be improved by replacing C−H bonds with the more stable C−D at α‐position to heteroatoms, which is a typical metabolic site for cytochrome P450 enzymes. However, application deuterated synthons limited. Herein, we established novel concept preparing reagents successful synthesis complex drug skeletons deuterium atoms heteroatoms. ( d n ‐Alkyl)diphenylsulfonium salts prepared from corresponding nondeuterated forms using inexpensive and abundant D 2 O as source base, were used electrophilic alkylating reagents. Additionally, these sulfonium efficiently transformed into ‐alkyl halides azide coupling amine nucleophile. Furthermore, liver microsomal metabolism studies revealed kinetic isotope effects (KIE) in 7‐( ‐ethoxy)flavone. present first demonstration KIE ‐ethoxy group will contribute discovery research based on chemistry.

Язык: Английский

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Thianthrenium-Enabled Chromium-Catalyzed Deuterated Alkyl Addition to Aldehydes via a Photoactive Electron Donor–Acceptor Complex

Organic Letters, Год журнала: 2025, Номер 27(5), С. 1112 - 1117

Опубликована: Янв. 23, 2025

The Nozaki-Hiyama-Kishi reaction offers effective and reliable strategies for the preparation of alcohols via carbon-carbon bond formation. Typical methods usually require stoichiometric amounts chromium salts, co-transition metals, auxiliary reagents, which limits their practical application in industrial chemistry. To mitigate these limitations, substantial efforts have been made to develop chromium-catalytic approaches. However, an excess metal reductants or expensive photocatalysts played essential roles during catalytic cycles. Here, we present a photoactive electron donor-acceptor (EDA) complex-induced chromium-catalyzed route, accomplishing alkyl addition aldehydes without requirement photocatalysts. Furthermore, on basis pH-dependent site-selective hydrogen isotope exchange thianthrenium range β-deuterated secondary could be prepared with high efficiency excellent deuterium incorporation. Mechanistic studies revealed that photoinduced intramolecular single-electron transfer EDA complex happened provide radicals are captured by Cr(II) species facilitate subsequent Meanwhile, excited Hantzsch ester act as terminal reductant turnover catalyst.

Язык: Английский

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S-(Methyl-d₃) Arylsulfonothioates: A Family of Robust, Shelf-Stable, and Easily Scalable Reagents for Direct Trideuteromethylthiolation

Organic Letters, Год журнала: 2022, Номер 24(37), С. 6794 - 6799

Опубликована: Сен. 14, 2022

A family of electrophilic deuterated methylthiolating reagents, S-(methyl-d3) arylsulfonothioates, was developed in two or three steps from cheap d4-MeOH high yields. S-(Methyl-d3) arylsulfonothioates represent a kind powerful reagent and allow modular trideuteromethylthiolation with variety nucleophiles electrophiles including aryl(hetero) iodides, boronic acids esters, terminal alkynes, diazonium salts, β-ketoester, oxindole under mild reaction conditions. structure–reactivity research (SAR) study conducted provided new avenue for the development reagents efficient methodology trideuteromethylthiolation.

Язык: Английский

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Tunable Unsymmetrical Ferrocene Ligands Bearing a Bulky Di-1-adamantylphosphino Motif for Many Kinds of C_sp²–C_sp³ Couplings

ACS Catalysis, Год журнала: 2022, Номер 12(9), С. 5123 - 5135

Опубликована: Апрель 15, 2022

A class of ferrocene-based unsymmetrical bidentate ligands containing a di(1-adamantyl)phosphino group, Fc(PAd2)(PR2) (R = Ph, Cy, iPr, tBu) abbreviated as MPhos ligands, and their corresponding (MPhos)PdCl2 pre-catalysts were synthesized in very good yields fully characterized using techniques including single-crystal X-ray crystallography. These utilized for Csp2–Csp3 couplings many kinds name reactions such Murahashi–Feringa, Kumada–Corriu, Negishi, Suzuki–Miyaura with substrate scope isolated yields. About nine "drug-like" molecules also tested successfully to demonstrate potential applications active pharmaceutical ingredient (API) synthesis. The tunability the catalyst system enabled matching sterics electronics ligand that substrates have desirable results over five dozen systems selectivity.

Язык: Английский

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