Direct Oxygen Insertion into C-C Bond of Styrenes with Air DOI
Ning Jiao, Qin Q, Liang Zhang

et al.

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

Published: July 16, 2024

Abstract Skeletal editing of single-atom insertion to basic chemicals has been demonstrated as efficient strategy for the discovery structurally novel compounds. Previous endeavors in skeletal have successfully facilitated boron, nitrogen, and carbon atoms. Given prevalence oxygen atoms biologically active molecules, direct oxygenation C-C bonds through single-oxygen-atom like Baeyer-Villiger reaction is particular significance. Herein, we present a approach modification styrenes using O2 via into Ar-C(sp2) σ-bond, resulting formation corresponding aryl ether frameworks under mild conditions. The broad functional-group tolerance excellent chemo- regioselectivity were this protocol. A preliminary mechanistic study indicated potential involvement 1,2-aryl radical migration reaction.

Language: Английский

15NRORC: An Azine Labeling Protocol DOI

Zachary A. Tolchin,

Joel M. Smith

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2939 - 2943

Published: Jan. 12, 2024

A practical method for the synthesis of 15N-labeled azines with a high degree isotopic enrichment is described. Activation azine heterocycles an electron-deficient arene allows facile substitution nitrogen atom specifically designed reagent that undergoes canonical ANRORC-type mechanism. wide range can be converted to their corresponding 15N isotopologs using this method, and it also dearomative access reduced heterocyclic congeners. short formal 15N-solifenacin accomplished as well demonstrate application generating labeled pharmaceuticals.

Language: Английский

Citations

25
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

16
Synthesis of benzenes from pyridines via N to C switch DOI Creative Commons

Aífe Conboy,

Michael F. Greaney

Chem, Journal Year: 2024, Volume and Issue: 10(6), P. 1940 - 1949

Published: June 1, 2024

The skeletal editing of heteroarenes introduces new disconnections to the chemistry lexicon, enabling interconversion ring systems via selective breaking/re-making carbon framework. We describe one-pot transformation pyridines into benzene derivatives, using a nucleophilic addition ring-opening/ring-closing (ANRORC) process with soft nucleophiles such as malonate. Triflic anhydride activates pyridine ANRORC synthesis an isolable amine intermediate, which aromatizes on simple heating. reaction has been exemplified room temperature protocol, along direct syntheses drug-like, tertiary-alkylated, and isotopically labeled benzoates.

Language: Английский

Citations

12
Electrochemical meta-C–H sulfonylation of pyridines with nucleophilic sulfinates DOI Creative Commons

Qin Shi,

Mingkai Yang,

Mingyao Xu

et al.

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

Published: Aug. 28, 2024

Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well materials science, a direct meta-selective C-H functionalization is paramount importance, but such reactions remain limited highly challenging. In general, established methods for meta rely on utilization tailored electrophilic reagents to realize intrinsic polarity match. Herein, we report complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation through redox-neutral dearomatization-rearomatization strategy by tandem dearomative cycloaddition/hydrogen-evolution electrooxidative sulfonation resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, facile late-stage modification, have been demonstrated, which further contributes practicality adaptability this approach.

Language: Английский

Citations

9
Synthesis of naphthalene derivatives via nitrogen-to-carbon transmutation of isoquinolines DOI Creative Commons

Tongtong Zhu,

Xiang Cui, Wenjun Ma

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(5)

Published: Jan. 29, 2025

Heteroarene skeletal editing is gaining popularity in synthetic chemistry. Transmuting single atoms generates molecules that have distinctly varied properties, thereby fostering potent molecular exchanges can be extensively used to synthesize functional molecules. Herein, we present a convenient protocol for nitrogen-carbon single-atom transmutations isoquinolines, which inspired by the Wittig reaction and enables easy access substituted naphthalene derivatives. The uses an inexpensive commercially available phosphonium ylide as carbon source furnish wide range of naphthalenes. key success this transformation formation triene intermediate through ring opening, undergoes 6π-electrocyclization elimination processes afford product. Furthermore, strategy facile synthesis 13 C-labeled naphthalenes using CH 3 PPh I commercial C facilitates modifying directing group C─H functionalization.

Language: Английский

Citations

1
Regioselective Pyridine to Benzene Edit Inspired by Water-Displacement DOI
Benjamin R. Boswell, Zhen‐Sheng Zhao, Ryan L. Gonciarz

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 19660 - 19666

Published: July 12, 2024

Late-stage derivatization of drug-like functional groups can accelerate drug discovery efforts by swiftly exchanging hydrogen-bond donors with acceptors, or modulating key physicochemical properties like logP, solubility, polar surface area. A proven strategy to improve ligand potency is extend the displace water molecules that are mediating interactions a receptor. Inspired this application, we developed method regioselectively transmute nitrogen atom from pyridine into carbon bearing an ester, flexible group handle. We applied variety substituted pyridines, as well late-stage transformation FDA-approved drugs.

Language: Английский

Citations

7
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

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
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

4
Atroposelective [4+1] Annulation for the Synthesis of Isotopic Isoindolinones Bearing both Central and Axial Chirality DOI Creative Commons

Jun Gu,

Lihong Zhang,

Hongfeng Zhuang

et al.

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

Published: Jan. 1, 2025

Isotopically chiral molecules have drawn much attention due to their practical applications in drug discovery. However, existing studies this area are mainly limited centrally and H/D exchange. Herein, we report a phosphoric acid-catalyzed atroposelective [4+1] annulation of ketoaldehydes 1H-indol-1-amines. By means strategy, series D- 18O-labeled atropisomers featuring both central axial chiralities synthesized with high enantioselectivities diastereoselectivities good excellent isotopic incorporation. Experimental density functional theory suggest that the reaction involves sequential condensation, cyclization isomerization cascade, which second step is enantio-determining process.

Language: Английский

Citations

0