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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Synthesis of benzenes from pyridines via N to C switch

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

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Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions

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

Published: Jan. 28, 2025

ConspectusSkeletal editing, which involves adding, deleting, or substituting single multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages synthesis, skeletal editing minimizes need cost- labor-intensive processes often associated with de novo thus accelerating discovery optimization complex architectures. While current efforts predominantly focus on monatomic-scale modifications, molecules through cycloaddition followed cycloreversion offers unique to manipulate double-atomic scale. introduces possibilities chemical transformations enables such double-atom transmutation, formal single-atom atom insertion. Early examples relied inherent high reactivity substrates, needed be sufficiently active undergo possess good leaving groups subsequent fragmentation (cycloreversion) step. Recently, however, structural relatively inert substrates become achievable substrate activation strategies designed enhance either step.Along these lines, we recently developed dearomative process activating pyridines. In simple high-yielding operation, oxazinopyridines are readily obtained activated dearomatized isolable intermediates. method enabled us achieve transformation pyridines into benzenes naphthalenes cycloaddition/cycloreversion sequence. this Account, related recent contributions from other research highlighted well, alongside early involving tetrazines, triazines, diazines, similar heterocycles reaction partners. By offering streamlined route modify structures, approaches have demonstrated their ability interconvert arenes heteroarenes shown significant potential late-stage applications well advancing drug synthesis bioactive molecules.In future, will undoubtedly see broader development field editing. New should devised enable not only incorporation nitrogen heteroatoms rings─rather than deletion─but also contraction expand application non-aromatic rings. We hope that advancements summarized Account inspire chemists explore methodologies. pushing boundaries approaches, researchers can unlock opportunities constructing modifying frameworks, eventually paving way chemistry, biology, science.

Language: Английский

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

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

Published: March 7, 2025

Language: Английский

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Regioselective Pyridine to Benzene Edit Inspired by Water-Displacement

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

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Synthesis of naphthalene derivatives via nitrogen-to-carbon transmutation of isoquinolines

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

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Nitrogen-to-functionalized carbon atom transmutation of pyridine

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

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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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C3 Selective chalcogenation and fluorination of pyridine using classic Zincke imine intermediates

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

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Chemodivergent C-to-N atom swap from benzofurans to benzisoxazoles and benzoxazoles

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

Published: Jan. 1, 2025

We present a chemodivergent net C-to-N atom swap in benzofurans, affording benzoxazoles or benzisoxazoles via photo-mediated oxidative benzofuran cleavage, followed by oxime imine formation, and cyclization using commercially available reagents.

Language: Английский

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