Heterocyclic Surgery for Isotopic Labeling DOI
Joel M. Smith

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

Published: Sept. 26, 2024

Abstract Recent developments in the isotopic labeling of heteroarenes may prove to be useful realms biomedical science, materials chemistry, and fundamental organic chemistry. The use age-old Zincke reaction, or tactical variants thereof, has become particularly utilitarian effecting single-atom nitrogen replacement various azines generate their desired isotopologues. This chemistry can synthetically leveraged at an early stage for diversity-oriented heterocyclic pharmaceuticals and/or natural products. Additionally, given prevalence saturated azacycles biologically relevant molecules, access these isotopologues becomes through dearomative retrosynthetic analysis from corresponding 15N-labeled heteroarenes. 1 Introduction 2 Our Lab’s Development 15NRORC Reaction 3 Other Azine-Labeling Methods 4 Expanded ANRORC Utilization 5 Conclusion Outlook

Language: Английский

Photocatalytic furan-to-pyrrole conversion DOI

D.B. Kim,

Jaehyun You,

D. H. Lee

et al.

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

Citations

19

Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis DOI
Qing‐Zhu Li,

Mei-Hao He,

Rong Zeng

et al.

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

Citations

17

A three-step strategy for the conversion of pyridines into benzonitriles DOI Creative Commons

Reyhan Güdük,

Niklas Kehl,

Chiara Stavagna

et al.

Nature Synthesis, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Language: Английский

Citations

2

Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles DOI
Hong Lu, Jie Chang, Hao Wei

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ConspectusN-Heterocycles are essential in pharmaceutical engineering, materials science, and synthetic chemistry. Recently, skeletal editing, which involves making specific point changes to the core of a molecule through single-atom insertion, deletion, or transmutation, has gained attention for its potential modify complex substrates. In this context, insertion nitrogen atoms into carbocycles form N-heterocycles emerged as significant research focus modern chemistry owing novel logic. This distinctive retrosynthetic approach enables late-stage modification molecular skeletons provides different pathway synthesizing multiply substituted N-heterocycles. Nevertheless, atom proven challenging because inherent inertness carbon-based difficulty cleaving C-C bonds. Therefore, selective editing remains growing field Account primarily highlights contributions our laboratory active acknowledges key from other researchers. It is organized two sections based on type carbocycle. The first section explores cycloalkenes. Recent Co-catalyzed oxidative azidation strategies have enabled cyclobutenes, cyclopentenes, cyclohexenes, facilitating synthesis polysubstituted pyridines, been conventionally pyridine cross-coupling. subsequent discovery realm arenes. site-selective stable arenes We developed method intramolecular benzene rings 2-amino biaryls by suppressing competing C-H process using paddlewheel dirhodium catalyst. addition, address issues we employed arenols substrates, could act controlling elements editing. reported Cu-catalyzed arenols, proceeds dearomative azidation/aryl migration process, enabling incorporation Inspired result, recently extended reaction model Fe-catalyst facilitate ring contraction nitrogen-inserted product, achieving carbon-to-nitrogen transmutation arenols. Various polyaromatic effectively undergo desired atom's presenting considerable various applications Account, present an overview achievements reactions, with scopes, mechanistic features, applications. anticipate that will provide valuable insights propel development innovative methodologies both N-heterocycle synthesis.

Language: Английский

Citations

1

Combining (CH2O)n and (NH4)2CO3 as a Formamidine Equivalent for “Four-in-One” Synthesis of Fluoroalkylated 2-H-Pyrimidines DOI
Wei Han,

Yuanyuan Ren,

Ming-Yao Tang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(33), P. 7078 - 7082

Published: Aug. 9, 2024

Multicomponent reactions hold the potential to maximize synthetic efficiency in preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for one-step synthesis fluoroalkylated 2-H-pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, ammonium carbonate is described. By harnessing readily accessible (CH2O)n cheap (NH4)2CO3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with pyrimidine assembly. The multicomponent reaction proceeds step-economical, operationally simple, metal-free, additive-free manner, featuring broad substrate scope, excellent functional group compatibility, scalability. elaboration obtained 2-H-pyrimidine further demonstrated alkylation vinylation its C2 position.

Language: Английский

Citations

7

Cheminformatic Analysis of Core-Atom Transformations in Pharmaceutically Relevant Heteroaromatics DOI
G. Logan Bartholomew, Lucas J. Karas,

Reilly M. Eason

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Heteroaromatics are the basis for many pharmaceuticals. The ability to modify these structures through selective core-atom transformations, or "skeletal edits", can dramatically expand landscape drug discovery and development. However, despite importance of modifications, quantitative impact such transformations on accessible chemical space remains undefined. Here, we report a cheminformatic platform analyze which skeletal edits would most increase access novel space. This study underscores significance emerging single multiple heteroaromatics in enhancing diversity, example, at late-stage campaign. Our findings provide framework prioritizing modifications heteroaromatic structural motifs, calling development new methods achieve types transformations.

Language: Английский

Citations

1

Switchable skeletal editing of quinolines enabled by cyclizative sequential rearrangements DOI
Di Tian,

Yu‐Ping He,

Yang Li

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

1

Nitrogen-to-functionalized carbon atom transmutation of pyridine DOI Creative Commons
Fu‐Peng Wu,

Madina Lenz,

Adhya Suresh

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(37), P. 15205 - 15211

Published: Jan. 1, 2024

The targeted and selective replacement of a single atom in an aromatic system represents powerful strategy for the rapid interconversion molecular scaffolds. Herein, we report pyridine-to-benzene transformation

Language: Английский

Citations

6

C3 Selective chalcogenation and fluorination of pyridine using classic Zincke imine intermediates DOI Creative Commons
Shun Li, Juan Tang,

Yonglin Shi

et al.

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

Published: Aug. 28, 2024

Regioselective C-H functionalization of pyridines remains a persistent challenge due to their inherent electronically deficient properties. In this report, we present strategy for the selective pyridine C3-H thiolation, selenylation, and fluorination under mild conditions via classic N-2,4-dinitrophenyl Zincke imine intermediates. Radical inhibition trapping experiments, as well DFT theoretical calculations, indicated that thiolation selenylation proceeds through radical addition-elimination pathway, whereas two-electron electrophilic substitution pathway. The pre-installed electron-deficient activating N-DNP group plays crucial positive role, with additional benefit recyclability. practicability protocol was demonstrated in gram-scale synthesis late-stage modification pharmaceutically relevant pyridines.

Language: Английский

Citations

6

Diversified ring expansion of saturated cyclic amines enabled by azlactone insertion DOI
Licheng Wu,

Hanyu Xia,

Jin Bai

et al.

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

Published: Nov. 21, 2024

Language: Английский

Citations

6