Regiodivergent Arylation of Pyridines via Zincke Intermediates DOI Creative Commons
Haiwen Wang, Michael F. Greaney

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(8)

Published: Nov. 21, 2023

Abstract An arylation protocol for pyridines is described, via the ring‐opened Zincke intermediate. Treatment of with triflic anhydride and a secondary amine produces an azahexatriene species, which undergoes regioselective Pd‐catalyzed at putative C4 position. Recyclization then provides pyridine products. Alternatively, metal‐free diaryliodonium salt selective meta ‐position, affording regiodivergent approach to biaryls from common

Language: Английский

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing DOI Creative Commons

Tongyu Huo,

Xin-Yi Zhao, Zengrui Cheng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

Citations

26
Precisely succinonitrile-functionalized PEO electrolytes toward room-temperature all-solid-state lithium batteries DOI Creative Commons
Xinyang Li, Zongnan Zhang, Jie Feng

et al.

Science China Materials, Journal Year: 2024, Volume and Issue: 67(5), P. 1412 - 1421

Published: March 20, 2024

Polyethylene oxide) (PEO) polymer electrolytes have the potential for use in all-solid-state lithium-metal batteries (ASSLMBs). However, no effective rules been proposed to prepare PEO that overcome limitation being unusable at room temperature. In this study, based on C–H functionalization strategy, we design a highly ion-conductive electrolyte by directly covalently linking succinonitrile functional-groups with lithium coordination activity chains. The enhance disorder and mobility of chains while acting as sites fast ionic-conduction interchain, thus achieving dual optimization free volume around ions migration behavior. Due precise tuning functional-groups, functionalized exhibits enhanced ionic conductivity (>102 times), high transference number (~0.51) wide electrochemical window (~0.47 V). particular, PEO300k (1.01×10−4 S cm−1 25°C) enables stable operation temperature, providing path development polymer-based practical applications.

Language: Английский

Citations

15
Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch DOI Creative Commons
Pengwei Xu, Zhe Wang, Shu‐Min Guo

et al.

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

Published: May 15, 2024

Abstract Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C−H-difluoromethylation of represents a highly efficient economic way to access these azines. However, the meta-difluoromethylation has remained elusive methods for site-switchable regioselective meta- para-difluoromethylation are unknown. Here, we demonstrate meta-C−H-difluoromethylation through radical process by using oxazino pyridine intermediates, which easily accessed from pyridines. selectivity can be readily switched para situ transformation pyridinium salts upon acid treatment. preparation various para-difluoromethylated this approach is presented. mild conditions used also allow late-stage or containing drugs. Sequential double functionalization presented, further underlines value work.

Language: Английский

Citations

13
Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions DOI
Pengwei Xu, Armido Studer

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

Citations

1
meta-Nitration of Pyridines and Quinolines through Oxazino Azines DOI
Kuruva Balanna, Armido Studer

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7485 - 7495

Published: Feb. 24, 2025

meta-Nitration of azines (pyridines and quinolines) serves as a powerful method for the prompt construction derivatization several pharmaceuticals, agrochemicals, materials. However, due to inherent electronic properties pyridines, achieving direct selective meta-C-H nitration under mild conditions has been long-standing challenge in synthetic chemistry. Currently, there is no adequate strategy late-stage pyridine-containing drugs drug precursors. To address this void, we introduce practical protocol highly regioselective meta-nitration pyridines using dearomatization-rearomatization strategy. The introduced provides diversification platform at meta-position via radical pathway. This mild, open-air, one-pot, scalable, catalyst-free process employed pyridine containing drugs, precursors, ligands limiting reagents. Consecutive C3 C5 difunctionalization also achieved with complete regiocontrol relying on sequential addition, which further highlights potential presented work. Additionally, obtained products could be transformed into meta-amino azine other valuable building blocks. Incorporating N-heterocyclic amine structures through amidation ibuprofen significantly improved drug's clinical success, highlighting importance

Language: Английский

Citations

1
C3‐Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity DOI
Ming Zhang, Qingyang Zhou, Heng Luo

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(6)

Published: Dec. 15, 2022

Methods for C-H cyanation of pyridines are rare. Here, we report a method C3-selective by tandem process with the reaction an in situ generated dihydropyridine cyano electrophile as key step. The is suitable late-stage functionalization pyridine drugs. low reduction potential and effective transfer nitrile group were found to be essential success this method. We studied mechanism detail means control experiments theoretical calculations that combination electronic steric factors determined regioselectivity reactions involving C2-substituted pyridines.

Language: Английский

Citations

30
Regioselective synthesis of 4-functionalized pyridines DOI Creative Commons
Chao Li,

Zixi Yan,

Bingding Wang

et al.

Chem, Journal Year: 2023, Volume and Issue: 10(2), P. 628 - 643

Published: Nov. 21, 2023

Language: Английский

Citations

23
Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities DOI

Sha Hu,

Jiong Chen,

Jin-Xu Cao

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 136, P. 106549 - 106549

Published: April 20, 2023

Language: Английский

Citations

21
A general strategy for the amination of electron-rich and electron-poor heteroaromatics by desaturative catalysis DOI
Javier Corpas, Henry P. Caldora, Ester Maria Di Tommaso

et al.

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(5), P. 593 - 603

Published: April 23, 2024

Language: Английский

Citations

9
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