Synthesis of ¹⁵N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2944 - 2949

Published: Jan. 16, 2024

Methods to incorporate stable radioisotopes are integral pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods 15N atoms within their structures limited. Here, we present a general approach pyridine 15N-labeling that proceeds via ring-opening NTf-Zincke imines then ring-closure with commercially available 15NH4Cl salts. This process functions on range substituted pyridines, from simple building block-type compounds late-stage labeling complex pharmaceuticals, 15N-incorporation is >95% most cases. The reactivity Zincke imine intermediates also enables deuteration C3- C5-positions, resulting higher mass isotopologs required for LCMS analysis biological fluids during drug

Language: Английский

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Photocatalytic furan-to-pyrrole conversion

Science, Journal Year: 2024, Volume and Issue: 386(6717), P. 99 - 105

Published: Oct. 3, 2024

The identity of a heteroatom within an aromatic ring influences the chemical properties that heterocyclic compound. Systematically evaluating effect single atom, however, poses synthetic challenges, primarily as result thermodynamic mismatches in atomic exchange processes. We present photocatalytic strategy swaps oxygen atom furan with nitrogen group, directly converting into pyrrole analog intermolecular reaction. High compatibility was observed various derivatives and nucleophiles commonly used drug discovery, late-stage functionalization furnished otherwise difficult-to-access pyrroles from naturally occurring furans high molecular complexity. Mechanistic analysis suggested polarity inversion through electron transfer initiates redox-neutral processes at room temperature.

Language: Английский

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Recent advances in C(sp³)–N bond formation via metallaphoto-redox catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(50), P. 6340 - 6361

Published: Jan. 1, 2024

In this review, the state-of-the-art advances in radical-involved C(sp 3 )–N bond formation via metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.

Language: Английский

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Photoinduced Nickel-Catalyzed Homolytic C(sp³)–N Bond Activation of Isonitriles for Selective Carbo- and Hydro-Cyanation of Alkynes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(40), P. 27583 - 27593

Published: Sept. 26, 2024

The exploration of strong chemical bonds as synthetic handles offers new disconnection strategies for the synthesis functionalized molecules via transition metal catalysis. However, slow oxidative addition rate these covalent to a center hampers their utility. Here, we report C(sp

Language: Английский

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Low-energy photoredox catalysis

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Language: Английский

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Radical approaches for C(sp³)–N bond cleavage in deaminative transformations

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

Published: Jan. 1, 2025

This review summarizes recent advancements in radical-mediated deaminative transformations, focusing on the mechanisms, substrate compatibility, and emerging applications synthetic organic chemistry.

Language: Английский

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Pyridine-based strategies towards nitrogen isotope exchange and multiple isotope incorporation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 18, 2024

Abstract Isotopic labeling is at the core of health and life science applications such as nuclear imaging, metabolomics plays a central role in drug development. The rapid access to isotopically labeled organic molecules sine qua non condition support these societally vital areas research. Based on rationally driven approach, this study presents an innovative solution pyridines by nitrogen isotope exchange reaction based Zincke activation strategy. technology conceptualizes opportunity field labeling. 15 N-labeling other relevant heterocycles pyrimidines isoquinolines showcases large set derivatives, including pharmaceuticals. Finally, we explore nitrogen-to-carbon strategy order 13 C-labeled phenyl derivatives deuterium mono-substituted benzene from pyridine- 2 H 5 . These results open alternative avenues for multiple aromatic cores.

Language: Английский

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Photocatalytic Generation of Carbocation from Thiols and Application to Cross-Nucleophile Coupling

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4286 - 4291

Published: May 9, 2024

Represented herein is a simple thiol identified as an effective precursor to photochemically form carbocation. Thanks the thiyl radical rapid transformation disulfide, which serves not only stabilize generated but also allow second electron transfer The resulting carbocations, including primary benzylic, secondary, and tertiary can smoothly couple with nitrogen, oxygen, carbon nucleophilic coupling partners well complex drug molecules, accompanied by elemental sulfur formation in air.

Language: Английский

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Silyl Radical as an Isocyanide Transfer Agent for Giese-Type Reactions Involving Aliphatic Amines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(24), P. 5172 - 5176

Published: June 12, 2024

Herein we report silyl radicals serve as isocyanide transfer agents for Giese-type reaction from aliphatic amines and electron-deficient olefins. α-Primary, α-secondary, sterically encumbered α-tertiary primary could be easily converted into isocyanides coupling with olefins by employing latent under visible light irradiation. Notably, the abstraction of silane-mediated not only enables voltage-independent activation strong C-N bonds but also represents a mechanistic alternative in which single electron reduction protonation processes are replaced direct hydrogen atom transfer. This transformation occurs photoinduced catalyst-free conditions exhibits excellent functional group compatibility mild conditions.

Language: Английский

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Pyridine-based Strategy towards Nitrogen Isotope Exchange

Published: Oct. 31, 2023

Isotopic labeling is at the core of health and life science applications such as nuclear imaging, pharmacokinetics bio-distribution studies plays a central role in drug development. The rapid access to isotopically labeled organic molecules sine qua non condition support these societally vital areas research. Despite relevance pyridine biologically active scaffold, nitrogen-13 this scaffold remains elusive an almost prohibited challenge for radio-labelling (+ emitter, T1/2 9.97 min), despite its positron emission tomography. Based on rationally driven approach, study presents innovative solution pyridines by nitrogen isotope exchange reaction based Zincke activation strategy. technology conceptualizes new opportunity field labeling. 15N-labeling other heterocycles pyrimidines isoquinolines was provided large set derivatives including structurally elaborated pharmaceuticals. Using [13N]NH3 primary source, proof-of-concept achieve examples 13N-labeling pyridines. We believe method will play fundamental future developments 13N-based PET radiotracers.

Language: Английский

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