{"title":"Direct C–H functionalisation of azoles via Minisci reactions","authors":"Ai-Lan Lee , David T. Mooney , Heather McKee","doi":"10.1039/d4ob01526f","DOIUrl":null,"url":null,"abstract":"<div><div>Azoles have widespread applications in medicinal chemistry; for example, thiazoles, imidazoles, benzimidazoles, isoxazoles, tetrazoles and triazoles appear in the top 25 most frequently used N-heterocycles in FDA-approved drugs. Efficient routes for the late-stage C–H functionalisation of azole cores would therefore be highly desirable. The Minisci reaction, a nucleophilic radical addition reaction onto N-heterocyclic bases, is a direct C–H functionalisation reaction that has the potential to be a powerful method for C–H functionalisations of azole scaffolds. However, azoles have not been as widely studied as substrates for modern Minisci-type reactions as they are often more electron-rich and thus more challenging substrates compared to electron-poor 6-membered N-heterocycles such as quinolines, pyrazines and pyridines typically used in Minisci reactions. Nevertheless, with the prevalence of azole scaffolds in drug design, the Minisci reaction has the potential to be a transformative tool for late-stage C–H functionalisations to efficiently access decorated azole motifs. This review thus aims to give an overview of the C–H functionalisation of azoles <em>via</em> Minisci-type reactions, highlighting recent progress, existing limitations and potential areas for growth.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":"22 47","pages":"Pages 9145-9164"},"PeriodicalIF":2.9000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/ob/d4ob01526f?page=search","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1477052024009455","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Azoles have widespread applications in medicinal chemistry; for example, thiazoles, imidazoles, benzimidazoles, isoxazoles, tetrazoles and triazoles appear in the top 25 most frequently used N-heterocycles in FDA-approved drugs. Efficient routes for the late-stage C–H functionalisation of azole cores would therefore be highly desirable. The Minisci reaction, a nucleophilic radical addition reaction onto N-heterocyclic bases, is a direct C–H functionalisation reaction that has the potential to be a powerful method for C–H functionalisations of azole scaffolds. However, azoles have not been as widely studied as substrates for modern Minisci-type reactions as they are often more electron-rich and thus more challenging substrates compared to electron-poor 6-membered N-heterocycles such as quinolines, pyrazines and pyridines typically used in Minisci reactions. Nevertheless, with the prevalence of azole scaffolds in drug design, the Minisci reaction has the potential to be a transformative tool for late-stage C–H functionalisations to efficiently access decorated azole motifs. This review thus aims to give an overview of the C–H functionalisation of azoles via Minisci-type reactions, highlighting recent progress, existing limitations and potential areas for growth.
期刊介绍:
Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.