Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Chemical Reviews, Год журнала: 2022, Номер 122(6), С. 6634 - 6718

Опубликована: Фев. 18, 2022

Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of by deuterium gives rise improved absorption, distribution, metabolism, and excretion (ADME) properties drugs enables preparation internal standards for analytical mass spectrometry, use tritium-labeled is key technique all along drug discovery development pharmaceutical industry. For these reasons, interest new methodologies isotopic enrichment organic molecules extent their applications are equally rising. In this regard, Review intends comprehensively discuss developments area over last years (2017–2021). Notably, besides fundamental isotope exchange (HIE) reactions isotopically analogues common reagents, plethora reductive dehalogenative deuteration techniques other transformations incorporation emerging now part labeling toolkit.

Язык: Английский

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Deuterium in drug discovery: progress, opportunities and challenges

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(7), С. 562 - 584

Опубликована: Июнь 5, 2023

Язык: Английский

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Synthesis of tri- and tetrasubstituted stereocentres by nickel-catalysed enantioselective olefin cross-couplings

Nature Catalysis, Год журнала: 2022, Номер 5(10), С. 934 - 942

Опубликована: Окт. 19, 2022

Язык: Английский

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Photocatalytic Deuterium Atom Transfer Deuteration of Electron‐Deficient Alkenes with High Functional Group Tolerance

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(3)

Опубликована: Ноя. 17, 2022

Abstract Due to its mild reaction conditions and unique chemoselectivity, hydrogen atom transfer (HAT) hydrogenation represents an indispensable method for the synthesis of complex molecules. Its analog using deuterium, deuterium (DAT) deuteration, is expected enable access deuterium‐labeled compounds. However, DAT deuteration has been scarcely studied synthetic purposes, a that possesses favorable characteristics HAT hydrogenations remained elusive. Herein, we report protocol photocatalytic electron‐deficient alkenes. In contrast previous this tolerates variety synthetically useful functional groups including haloarenes. The late‐stage also allows deuterated amino acids as well donepezil‐ d 2 . Thus, work demonstrates potential chemistry become alternative choice preparing deuterium‐containing

Язык: Английский

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Hydrogen Bond Donor and Unbalanced Ion Pair Promoter-Assisted Gold-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Iodides with Alcohols

ACS Catalysis, Год журнала: 2023, Номер 13(3), С. 1823 - 1829

Опубликована: Янв. 17, 2023

We have developed an efficient gold-catalyzed C–O cross-coupling reaction of (hetero)aryl iodides with primary and secondary alcohols via AuI–AuIII catalytic cycle. This protocol featured moisture/air insensitivity, simple operation, excellent functional group tolerance. Good yields were obtained regardless steric hindrance electronic factor (electron-rich or poor) substrates, the chirality chiral alcohol starting materials could be preserved. Our worked well for both intermolecular intramolecular couplings. In addition, RuPhos ligand was applied to cross-couplings. An unbalanced ion pair promoter hydrogen bond donor solvent might crucial in this transformation.

Язык: Английский

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Trifluoromethyl Rhodium‐Carbynoid in [2+1+2] Cycloadditions

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

Опубликована: Янв. 18, 2024

Abstract Trifluoromethyl cationic carbyne (CF 3 C + :) possessing dual carbene‐carbocation behavior emulated as trifluoromethyl metal‐carbynoid =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α‐diazotrifluoroethyl sulfonium salt was prepared used in Rh‐catalyzed three‐component [2+1+2] cycloadditions for the first time with commercially available N ‐fused heteroarenes nitriles, yielding series of imidazo[1,5‐ ] ‐heterocycles that interest medicinal chemistry, which insertion Rh‐carbynoid =Rh) into C=N bonds involved. This strategy demonstrates synthetic applications late‐stage modification pharmaceuticals, construction CD ‐containing ‐heterocycles, gram‐scale experiments, synthesis phosphodiesterase 10A inhibitor analog. These highly valuable modifiable exhibit good antitumor activity vitro, thus demonstrating their potential chemistry.

Язык: Английский

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Manganese‐Catalyzed Mono‐N‐Methylation of Aliphatic Primary Amines without the Requirement of External High‐Hydrogen Pressure

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

Опубликована: Фев. 1, 2024

Abstract The synthesis of mono‐ N ‐methylated aliphatic primary amines has traditionally been challenging, requiring noble metal catalysts and high‐pressure H 2 for achieving satisfactory yields selectivity. Herein, we developed an approach the selective coupling methanol amines, without hydrogen, using a manganese‐based catalyst. Remarkably, up to 98 % with broad substrate scope were achieved at low catalyst loadings. Notably, due weak base‐catalyzed alcoholysis formamide intermediates, our novel protocol not only obviates addition but also prevents side secondary ‐methylation, supported by control experiments density functional theory calculations.

Язык: Английский

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Catalytic ortho C–H methylation and trideuteromethylation of arylthianthrenium salts via the Catellani strategy

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(12), С. 3333 - 3340

Опубликована: Янв. 1, 2024

We report a Pd/NBE cooperative catalyzed ortho C–H methylation and trideuteromethylation of arylthianthrenium salts, enabling the efficient synthesis wide variety (trideutero)methylated arenes in moderate to good yields.

Язык: Английский

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Metallaphotoredox deuteroalkylation utilizing thianthrenium salts

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

Опубликована: Июнь 13, 2024

Abstract Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such typically involves deuterated building blocks, allowing for the incorporation deuterium atoms functional groups into target molecule single step. Unfortunately, limited availability synthetic approaches to synthons has impeded progress this field. Here, we present an approach utilizing alkyl-substituted thianthrenium salts that efficiently selectively introduce at α position alkyl chains through pH-dependent HIE process, using D 2 O as source. resulting α-deuterated salts, which bear two atoms, exhibit excellent selectivity electrophilic substitution reactions. Through situ formation isotopically labelled halides, these demonstrate compatibility series metallaphotoredox cross-electrophile coupling with (hetero)aryl, alkenyl, bromides, other salts. Our technique allows wide range substrates, high incorporation, precise control over site insertion within benzyl position, allylic or any chain between, well neighboring heteroatoms. This makes it invaluable synthesizing various deuterium-labeled compounds, especially those significance.

Язык: Английский

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Recent advances in the catalytic N-methylation and N-trideuteromethylation reactions using methanol and deuterated methanol

Coordination Chemistry Reviews, Год журнала: 2022, Номер 474, С. 214827 - 214827

Опубликована: Окт. 11, 2022

Язык: Английский

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