Halogen-Free Ciamician-Dennstedt Single-Atom Skeletal Editing DOI Creative Commons
Xihe Bi, Shaopeng Liu, Yong Yang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Abstract Single-atom skeletal editing is an increasingly powerful tool for scaffold hopping-based drug discovery. However, the insertion of a single functionalized carbon atom into heteroarenes remains exceedingly rare, especially when performed in complex chemical settings, due to challenge overcoming aromaticity without uncontrolled degradation. For example, Ciamician–Dennstedt rearrangement, which carbene inserted indole or pyrrole ring, limited halocarbene precursors despite more than century research. Herein, we report general methodology halogen-free Ciamician-Dennstedt reaction, enables direct conversion indoles/pyrroles structurally diverse quinoline/pyridine scaffolds. The generality and applicability this were demonstrated by extensive scope investigation product derivatizations, as well concise syntheses late-stage bioactive compounds. Mechanistic studies reveal pathway that involves intermediacy 1,4-dihydroquinoline intermediate, could undergo oxidative aromatization defluorinative form different carbon-atom products.

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

17
Triftosylhydrazone in Single-Atom Skeletal Editing DOI
Zhaohong Liu, Xiaolong Zhang, Paramasivam Sivaguru

et al.

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

ConspectusIn the past decade, single-atom skeletal editing, which involves precise insertion, deletion, or exchange of single atoms in core skeleton a molecule, has emerged as promising synthetic strategy for rapid construction diversification complex molecules without laborious de novo processes. Among them, carbene-initiated editing is particularly appealing due to ready availability and diverse reactivities carbene species. The initial endeavors modify heteroarenes through carbon-atom insertion could date back 1881, when Ciamician Denstedt described conversion pyrroles pyridines by trapping haloform-derived free carbene. Despite its potential value, general applicability this one-carbon seen limited progress poor yields harsh reaction conditions. Significant advances via were achieved only 3 years Levin, Ball, Xu, Song, Glorius, others. hallmark these approaches facile halocyclopropanation followed regioselective ring opening facilitated expulsion halide ion. Consequently, specially designed α-halocarbene precursors, such haloform derivatives, α-halodiazoacetates, chlorodiazirines, α-chlorodiazo oxime esters, can be employed achieve Ciamician–Denstedt-type editing. This not limits types functional groups installed on expansion products but also prevents their widespread adoption, especially late-stage contexts. enduring quest develop environmentally friendly versatile superior group compatibility, application diversifications investigation mechanistic insights into carbon reactions remain fundamental objective.In our over 5 years, we have developed o-trifluoromethylbenzenesulfonylhydrazones (named Triftosylhydrazones) operationally safe easily decomposable diazo surrogates explored various challenging catalytic transfer reactions. Recently, put great efforts expanding scope unlocking triftosylhydrazones precursors Since 2018, realized range acyclic 1,3-dicarbonyls with silver carbenes access 1,4-dicarbonyls, proceeding cyclopropanation/ring-opening process. Inspired results, recently demonstrated series transition-metal-catalyzed highly selective medicinally interesting like pyrroles, indoles, 1,2-diazoles carbenic insertion. We then strained three-membered nitrogen- oxygen-containing heterocycles single-carbon atoms. In Account, present an overview achievements heterocycles, organized based three situ-generated key intermediates, cyclopropane, N-ylide, O-ylide from focus scopes, features, applications. hope that Account will provide valuable contribute development new methodologies both chemistry fields.

Language: Английский

Citations

14
Asymmetric dearomative single-atom skeletal editing of indoles and pyrroles DOI
Xiaolong Zhang, Qingmin Song, Shaopeng Liu

et al.

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

Published: Nov. 28, 2024

Language: Английский

Citations

12
Precision single-atom editing: new frontiers in nitrogen insertion and substitution for the generation of N-heterocycles DOI
Xue Li, Jia Xu, Zhigang Xu

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(14), P. 4041 - 4053

Published: Jan. 1, 2024

This paper primarily focuses on the editing of nitrogen atoms, encompassing insertion N, substitution C with and utilization 15 N in place 14 for construction N-heterocycles.

Language: Английский

Citations

10
Carbene-Assisted Arene Ring-Opening DOI
Zengrui Cheng, Haoran Xu, Zhibin Hu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 16963 - 16970

Published: May 1, 2024

Despite the significant achievements in dearomatization and C–H functionalization of arenes, arene ring-opening remains a largely unmet challenge is underdeveloped due to high bond dissociation energy strong resonance stabilization inherent aromatic compounds. Herein, we demonstrate novel carbene assisted strategy for ring-opening. The understanding mechanism by our DFT calculations will stimulate wide application bulk chemicals synthesis value-added polyconjugated chain molecules. Various aryl azide derivatives now can be directly converted into valuable enynes, avoiding traditional including multistep unsaturated precursors, poor selectivity control, subsequent transition-metal catalyzed cross-coupling reactions. simple conditions required were demonstrated late-stage modification complex molecules fused ring This chemistry expands horizons provides pathway

Language: Английский

Citations

7
Rh-Catalyzed Enantioselective Single-Carbon Insertion of Alkenes DOI Creative Commons
Wei Jie Teo,

Josep Esteve Guasch,

Liyin Jiang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(31), P. 21837 - 21846

Published: July 26, 2024

The interest in the discovery and development of skeletal editing processes that selectively insert, exchange, or delete an atom organic molecules has significantly increased over last few years. However, this class proceed through creation a chiral center with high asymmetric induction have been largely unexplored. Herein, we report enantioselective single-carbon insertion aryl- alkyl-substituted alkenes mediated by catalytically generated Rh-carbynoid phosphate nucleophiles produce enantioenriched allylic phosphates (enantiomeric ratio (e.r.) = 89.5:10.5-99.5:0.5). key to process was diastereo- cyclopropanation alkene formation transient cyclopropyl-I

Language: Английский

Citations

7
Formal meta-C–H-Fluorination of Pyridines and Isoquinolines through Dearomatized Oxazinopyridine Intermediates DOI
Malte Haring, Kuruva Balanna, Qiang Cheng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 30758 - 30763

Published: Nov. 1, 2024

Organofluorine compounds, including fluorinated pyridines and isoquinolines, play a crucial role in pharmaceuticals, agrochemicals, materials science. However, step-economic selective C-H-functionalization to access these azaarenes is still underexplored, with

Language: Английский

Citations

6
C—F Bond Insertion into Indoles with CHBr2F: An Efficient Method to Synthesize Fluorinated Quinolines and Quinolones DOI
Chao Li, Lei Chen, Hongye Wang

et al.

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(10), P. 1128 - 1132

Published: Feb. 6, 2024

Comprehensive Summary A mild and practical method for synthesizing fluorinated quinoline derivatives, which have a wide range of applications in pharmaceuticals, materials, organic synthesis, was described through C—F bond insertion into indoles using CHBr 2 F. The simple conditions, readily availability F, as well the versatility transformations make this strategy very powerful 3‐fluoroquinoline 3‐fluoroquinolone. mechanistic studies reveal that bromofluorocarbene generated in‐situ under basic condition key intermediate.

Language: Английский

Citations

5
Skeletal Editing Through Single Atom Insertion and Transmutation: An Insight into A New Era of Synthetic Organic Chemistry DOI
Chandi C. Malakar, Chandresh K. Patel, Kamal Kant

et al.

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

Citations

4
Selective 6π‐Electrocyclization of N‐Vinyl‐α,β‐Unsaturated Nitrones to Prepare Polysubstituted Pyridine Derivatives DOI Open Access

Li‐Yao Ding,

Yan‐Jiao Lu,

Jung-Hyun Pang

et al.

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

Published: March 7, 2025

Comprehensive Summary Herein, we have developed a facile method for the synthesis of various polysubstituted pyridine derivatives through selective 6π‐electrocyclization N ‐vinyl‐ α , β ‐unsaturated nitrones. It was found that gold catalysts promoted carbon‐6π‐electrocyclization nitrones to afford 6‐alkenyl ‐oxides in 43%—75% yields, whereas copper facilitated oxygen‐6π‐electrocyclization give 6‐epoxy pyridines 41%—83% yields. The present features broad substrate scope, good functional group tolerance, high cyclization selectivity, and diversity scaffolds.

Language: Английский

Citations

0