¹⁴N to ¹⁵N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2950 - 2958

Published: Jan. 29, 2024

The selective modification of nitrogen heteroaromatics enables the development new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting skeletal structures are emerging, for direct exchange single core atoms remain limited. Here, we present a method 14N → 15N isotopic several aromatic heterocycles. This isotope transmutation occurs through activation heteroaromatic substrate by triflylation atom, followed ring-opening/ring-closure sequence mediated 15N-aspartate to effect atom. Key success this transformation is formation an isolable 15N-succinyl intermediate, which undergoes elimination give isotopically labeled heterocycle. These transformations occur under mild conditions in high yields.

Language: Английский

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Formation of C(sp²)–C(sp³) Bonds Instead of Amide C–N Bonds from Carboxylic Acid and Amine Substrate Pools by Decarbonylative Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 9951 - 9958

Published: May 1, 2023

Carbon-heteroatom bonds, most often amide and ester are the standard method to link together two complex fragments because carboxylic acids, amines, alcohols ubiquitous reactions reliable. However, C-N C-O linkages a metabolic liability they prone hydrolysis. While C(sp

Language: Английский

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Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22829 - 22839

Published: Aug. 1, 2024

The molecular editing of ketones represents an appealing strategy due to its ability maximize the structural diversity ketone compounds in a straightforward manner. However, developing efficient methods for arbitrary modification ketonic molecules, particularly those integrated within complex skeletons, remains significant challenge. Herein, we present unique recasting that involves radical acylation

Language: Английский

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Nitrogen atom insertion into arenols to access benzazepines

Chemical Science, Journal Year: 2024, Volume and Issue: 15(7), P. 2612 - 2617

Published: Jan. 1, 2024

Advances in site-selective molecular editing have enabled structural modification on complex molecules.

Language: Английский

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Asymmetric dearomative single-atom skeletal editing of indoles and pyrroles

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

Published: Nov. 28, 2024

Language: Английский

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Carbon–nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes

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

Published: May 4, 2024

Abstract Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in ring system without altering size even more challenging. Here, we introduce strategy that enables polycyclic arenols, highly prevalent motif bioactive molecules, to be readily converted into N -heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion C–C bond of arenol frameworks by azidative dearomatization aryl migration, followed ring-opening, ring-closing (ANRORC) achieve carbon-to-nitrogen aromatic framework arenol. Using widely available arenols as -heteroarene precursors, this alternative approach allows streamlined assembly complex heteroaromatics with broad functional group tolerance. Finally, pertinent transformations products, including synthesis biheteroarene skeletons, were conducted exhibited significant potential materials chemistry.

Language: Английский

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Unimolecular Fragment Coupling: A New Bond-Forming Methodology via the Deletion of Atom(s)

JACS Au, Journal Year: 2024, Volume and Issue: 4(5), P. 1676 - 1695

Published: April 23, 2024

Unimolecular fragment coupling (UFC) is defined as a reaction format, wherein atom(s) located in the middle of molecule are extruded, and remaining fragments coupled. UFC potentially powerful strategy that an alternative to transition-metal-catalyzed cross-coupling because target chemical bond formed intramolecular fashion, which inherently beneficial for chemoselectivity stereoselectivity issues. In this Perspective, we will present overview recent advances reactions, encompass those proceeding through elimination CO

Language: Английский

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Halogencarbene-free Ciamician-Dennstedt single-atom skeletal editing

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

Published: Nov. 19, 2024

Single-atom skeletal editing is an increasingly powerful tool for scaffold hopping-based drug discovery. However, the insertion of a functionalized carbon atom into heteroarenes remains rare, especially when performed in complex chemical settings. Despite more than century research, Ciamician-Dennstedt (C-D) rearrangement limited to halocarbene precursors. Herein, we report general methodology reaction using α-halogen-free carbenes generated situ from N-triftosylhydrazones. This one-pot, two-step protocol enables various carbenes, including those previously unexplored C-D chemistry, indoles/pyrroles scaffolds access 3-functionalized quinolines/pyridines. Mechanistic studies reveal pathway involving intermediacy 1,4-dihydroquinoline intermediate, which could undergo oxidative aromatization or defluorinative form different carbon-atom products. Ciamician–Dennstedt authors

Language: Английский

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One‐Carbon Ring Expansion of Indoles and Pyrroles: A Straightforward Access to 3‐Fluorinated Quinolines and Pyridines

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 12, 2023

Abstract 3‐Fluorinated quinolines and pyridines are prevalent pharmacophores, yet their synthesis is often challenging. Herein, we demonstrate that dibromofluoromethane as bromofluorocarbene source enables the one‐carbon ring expansion of readily available indoles pyrroles to structurally diverse 3‐fluorinated pyridines. This straightforward protocol requires only a short reaction time ten minutes can be performed under air atmosphere. Preliminary investigations reveal this strategy also applied other valuable azines by using different 1,1‐dibromoalkanes bromocarbene sources.

Language: Английский

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Skeletal Editing Through Single Atom Insertion and Transmutation: An Insight into A New Era of Synthetic Organic Chemistry

Synthesis, Journal Year: 2024, Volume and Issue: 56(24), P. 3793 - 3814

Published: Aug. 20, 2024

Abstract Considering the importance of heterocycles, significantly represented in medicinal chemistry and drug development, single-atom insertion technique transmutation strategy provide productive approaches towards complicated molecular structures through heterocycle diversification. It shows a potentially powerful approach for modifying complex substrates concisely chemospecifically. Although skeletal editing applies to cyclic acyclic compounds, this review focuses on diversification carbo- heterocyclic compounds synthesizing various medicinally important molecules via technique. The classification system is based recent critical historical methods as applied aromatic rings. 1 Introduction 2 Skeletal Editing Carbon-Atom Insertion 2.1 Indoles Pyrroles Derivatives: into C=C Bond 2.2 Pyrazole Indazole an N–N 2.3 CF3 Group Heteroarenes 2.4 Imidazole C–N 2.5 Atom-to-Atom Transmutation 3 N-Atom 3.1 Nitrogen-Atom Carbocycles 3.2 Heterocycles 3.3 Carbon Nitrogen Molecular Isotopic 4 Conclusion

Language: Английский

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