Site-Selective and Late-Stage Deuteration of (Hetero)arenes with Supported Iridium Nanoparticles

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2822 - 2826

Published: Jan. 31, 2025

Deuterated compounds have emerged as critical tools across diverse research areas, including pharmaceuticals, where deuterium incorporation can modulate the absorption, distribution, metabolism, and excretion (ADME) properties of drugs. In this study, we report development a new hydrogen/deuterium (H/D) exchange catalyst based on supported iridium nanoparticles that enables selective deuteration arenes heteroarenes under mild conditions. Using C6D6 source, our catalytic system achieves high chemo- regioselectivity, avoiding common side reactions such hydrogenation dehalogenation observed with traditional heterogeneous catalysts. Notably, occurs selectively at para- meta-C(sp2)–H bonds, leaving ortho-C(sp2)–H C(sp3)–H bonds intact, exhibits broad functional group tolerance, ketones, amides, alkenes, aryl ethers, acidic protons. The nature was confirmed via filtration mercury drop tests. This work presents for regioselective complex molecules, offering complementary site selectivity to existing homogeneous methods possibility being used in late-stage pharmaceuticals.

Language: Английский

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Late-Stage C–H Deuteration of Organic Compounds via Ligand-Enabled Palladium-Catalyzed Hydrogen Isotope Exchange

Synlett, Journal Year: 2024, Volume and Issue: 35(19), P. 2191 - 2200

Published: March 22, 2024

Abstract Over the past years our lab has established a research program towards late-stage introduction of deuterium into organic molecules using Pd-catalyzed reversible C–H activation as means to affect hydrogen isotope exchange. Through catalyst design, including novel ligand scaffolds, well use strategically chosen optimization and screening approaches, e.g., exploiting microscopic reversibility by first optimizing de-deuteration processes or multi-substrate approach, studies have resulted in number synthetically useful labelling protocols are described herein from personal perspective. 1 Introduction 2 β-C(sp3)–H Deuteration Free Carboxylic Acids 3 Nondirected Arenes 4 Heteroarenes 5 Conclusion

Language: Английский

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Merging directed sp³ and nondirected sp² C–H functionalization for Pd-catalyzed polydeuteration of (hetero)arenes

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A ligand-enabled strategy achieves deuteration with high deuterium enrichment through both directed sp 3 and nondirected 2 C–H deuteration.

Language: Английский

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Pd-catalyzed deuteration of aryl halides with deuterium oxide

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 16, 2025

Late-stage deuteration of aryl halides with deuterium oxide is a highly desirable but challenging transformation, primarily due to the difficulty activating inert carbon-halogen bonds and umpolung in presence various functional groups. To achieve this efforts have been made develop photo-chemical, electro-chemical, or mechano-chemical strategies. However, these approaches often require specialized setups activated substrates. Despite well-known group tolerance palladium catalysis, which makes it valuable late-stage functionalization, palladium-catalyzed has remained elusive. Herein, reaction bromides, chlorides, triflates developed, through catalysis. Chemical equivalent amount D2O required for substrates like chlorides. The features high tolerance, making suitable deuteration. authors report catalyzed oxide.

Language: Английский

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Au(I)-catalysis Enables Regioselective Hydrogen Isotope Labeling of Indoles

Published: June 11, 2024

The gold(I)-catalyzed hydrogen isotope exchange reaction on indoles and related heterocycles is described, under mild conditions low catalyst loadings, using CD3OD D2O as readily available deuterium sources. C3-unsubstituted are labeled at the C3 position with an exquisite regioselectivity, while C3-substituted C2 position. tolerates a number of chemical functions including amines, alcohols, aldehydes, in addition to most classical functional groups. This method has been applied label-ing densely functionalized bioactive compounds synthesis tritiated analogue pindolol water isotopic source. Mechanistic study revealed involvement aurated indole key intermediates.

Language: Английский

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Organophotoredox Pd‐Catalyzed C–H Arylation at Room Temperature using Diaryliodonium Salts

ChemPhotoChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract Direct functionalization of C−H bonds is the most expeditious strategy to build complexity into organic molecules. Unfortunately, Pd‐catalyzed arylation strategies require high temperatures and/or stoichiometric oxidants. The discovery metallaphotoredox in 2011 forged a new approach achieve metal catalyzed at room temperature. Since this discovery, reports still use explosive diazonium salts as aryl radical precursors. Alternatively, single report uses bench‐stable diaryliodonium salts, albeit with an Ir‐based photocatalyst. In study, we develop organophotoredox manifold that enables numerous N ‐aryl amide substrates. results present are expected revitalize temperature arylations wide‐ranging classes bonds.

Language: Английский

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