Chemodivergent dearomatization of benzene-linked O-oxime esters via EnT-induced radical cross-coupling DOI Creative Commons
Guohui Zeng,

Dongwen Guo,

Huanfeng Jiang

et al.

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

Published: Jan. 1, 2025

Radical-mediated dearomatization strategies offer a blueprint for building value-added and synthetically valuable three-dimensional skeletons from readily available aromatic starting materials.

Language: Английский

Late-Stage C–H Functionalization of Azines DOI

Celena M. Josephitis,

Hillary M. H. Nguyen, Andrew McNally

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7655 - 7691

Published: May 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

Language: Английский

Citations

108
Radical and ionic meta -C–H functionalization of pyridines, quinolines, and isoquinolines DOI
Hui Cao, Qiang Cheng, Armido Studer

et al.

Science, Journal Year: 2022, Volume and Issue: 378(6621), P. 779 - 785

Published: Nov. 17, 2022

Carbon-hydrogen (C−H) functionalization of pyridines is a powerful tool for the rapid construction and derivatization many agrochemicals, pharmaceuticals, materials. Because inherent electronic properties pyridines, selective meta -C−H challenging. Here, we present protocol highly regioselective trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, selenylation through redox-neutral dearomatization-rearomatization process. The introduced dearomative activation mode provides diversification platform meta-selective reactions on other azaarenes radical as well ionic pathways. broad scope high selectivity these catalyst-free render processes applicable late-stage drugs.

Language: Английский

Citations

80
Skeletal editing of pyridines through atom-pair swap from CN to CC DOI Creative Commons
Qiang Cheng,

Debkanta Bhattacharya,

Malte Haring

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(5), P. 741 - 748

Published: Jan. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Language: Английский

Citations

57
Tunable molecular editing of indoles with fluoroalkyl carbenes DOI
Shaopeng Liu, Yong Yang, Qingmin Song

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(6), P. 988 - 997

Published: March 5, 2024

Language: Английский

Citations

44
Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization DOI
Kevin Wu, Nelson Y. S. Lam, Daniel A. Strassfeld

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(19)

Published: Feb. 29, 2024

Abstract In 2001, our curiosity to understand the stereochemistry of C−H metalation with Pd prompted first studies in Pd(II)‐catalyzed asymmetric activation (RSC Research appointment: 020 7451 2545, Grant: RG 36873, Dec. 2002). We identified four central challenges: 1. poor reactivity simple salts native substrates; 2. few strategies control site selectivity for remote bonds; 3. lack chiral catalysts achieve enantioselectivity via metalation, and 4. low practicality due limited coupling partner scope use specialized oxidants. These challenges necessitated new catalyst reaction development. For , we developed approaches enhance substrate–catalyst affinity together novel bifunctional ligands which participate accelerate cleavage step. site‐selectivity introduced concept systematically modulating distance geometry between a directing template, catalyst, substrate selectively access bonds. devised predictable stereomodels catalyst‐controlled enantioselective based on participation ligands. Finally, have varied catalytic manifolds Pd(II) accommodate diverse partners while employing practical oxidants such as peroxides. advances culminated numerous reactions, setting stage broad industrial applications.

Language: Английский

Citations

22
Rational Molecular Editing: A New Paradigm in Drug Discovery DOI Creative Commons
Chunhua Ma, Craig W. Lindsley, Junbiao Chang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(14), P. 11459 - 11466

Published: June 21, 2024

ADVERTISEMENT RETURN TO ARTICLES ASAPPREVEditorialNEXTRational Molecular Editing: A New Paradigm in Drug DiscoveryChunhua MaChunhua MaState Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, NMPA for Research and Evaluation Innovative Drug, School Chemistry Chemical Engineering, Henan Normal University, Xinxiang, 453007, ChinaMore by Chunhua Mahttps://orcid.org/0000-0001-7613-6471, Craig W. Lindsley*Craig LindsleyVanderbilt University Medical Center, Franklin, Tennessee 37027, United States*E-mail: [email protected]More Lindsleyhttps://orcid.org/0000-0003-0168-1445, Junbiao Chang*Junbiao ChangCollege Chemistry, State Zhengzhou 450001, China*E-mail: Chang, Bin Yu*Bin YuCollege Yuhttps://orcid.org/0000-0002-7207-643XCite this: J. Med. Chem. 2024, XXXX, XXX, XXX-XXXPublication Date (Web):June 21, 2024Publication History Received13 June 2024Published online21 2024https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01347https://doi.org/10.1021/acs.jmedchem.4c01347editorialACS PublicationsPublished 2024 American Society. This publication is available under these Terms Use. Request reuse permissions free to access through this site. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (2 MB) Get e-AlertscloseSUBJECTS:Drug discovery,Macrocyclization,Molecules,Pharmaceuticals,Scaffolds e-Alerts

Language: Английский

Citations

22
Remote site-selective arene C–H functionalization enabled by N-heterocyclic carbene organocatalysis DOI
Qing‐Zhu Li,

Wen‐Lin Zou,

Zhaoyuan Yu

et al.

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(8), P. 900 - 911

Published: July 11, 2024

Language: Английский

Citations

17
General (hetero)polyaryl amine synthesis via multicomponent cycloaromatization of amines DOI Creative Commons
Lebin Su, Jianyu Dong, Yangyang Shen

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

Citations

2
Transannular C–H functionalization of cycloalkane carboxylic acids DOI
Guowei Kang, Daniel A. Strassfeld, Tao Sheng

et al.

Nature, Journal Year: 2023, Volume and Issue: 618(7965), P. 519 - 525

Published: May 31, 2023

Language: Английский

Citations

40
Dual-Ligand Catalyst for the Nondirected C–H Olefination of Heteroarenes DOI
Guangrong Meng, Zhen Wang, Hau Sun Sam Chan

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(14), P. 8198 - 8208

Published: March 28, 2023

Pd(II)-catalyzed nondirected C-H functionalization of heteroarenes is a significant challenge for the following reasons: poor reactivity electron-deficient heterocycles and unproductive coordination Lewis basic nitrogen atoms. Existing methodologies using palladium catalysis often employ large excess heterocycle substrates to overcome these hurdles. Despite recent advances in arenes that allow them be used as limiting reagents, reaction conditions are incompatible with heteroarenes. Herein we report dual-ligand catalyst enables olefination without substrate. In general, use 1-2 equiv was sufficient obtain synthetically useful yields. The rationalized by synergy between two types ligands: bidentate pyridine-pyridone ligand promotes cleavage; monodentate substrate acts second form cationic Pd(II) complex has high affinity arenes. proposed cooperation supported combination X-ray, kinetics, control experiments.

Language: Английский

Citations

33