Electrochemical generation of oxygen and nitrogen centred radicals

电化学产生氧和氮中心自由基

• 批准号: EP/S017097/1
• 负责人: Kevin Lam
• 金额: $ 26.94万
• 依托单位: University of Greenwich
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS017097%2F1
• 关键词: Electrochemical; generation; oxygen; nitrogen; centred

The need to design libraries of compounds is essential across a wide diversity of fields such as drug design, new material development or environmental chemistry. Radical chemistry is a unique tool for achieving this goal, via the construction of complex molecular scaffolds under mild conditions, due to the broad array of radical transformation available. Yet one of the major issues remains the generation of those radicals, which very often require the use of toxic metals or unstable and hazardous compounds. For instance, such conditions are incompatible with pharmaceutical applications, where the product has to be produced safely on a large scale and without any trace of toxic contaminant.Electrosynthesis is a powerful tool in organic chemistry that circumvents the afore-mentioned issues by allowing the generation of radicals under mild and green conditions. Even though a plethora of transformations have been developed and many of them have been successfully used in several industrial processes, the potential of preparative organic electrochemistry remains largely underestimated. The growing impetus to look for greener and cheaper alternatives to classic synthetic methodologies has further prompted us to investigate new electrochemical methodologies. Based on very encouraging preliminary results, we envision using electrochemistry to develop a novel way to generate aroyloxy/acryloyl (RCOO*) and amidyl radicals (R2N*) under mild, green, economical and safe conditions. The project proposed is interdisciplinary since, besides the extensive organic synthetic studies, a comprehensive electroanalytical study using high-speed voltammetry will be performed in order to study the electrode mechanisms and establish the mechanism of the reaction.Finally, as a proof of concept, the newly developed synthetic methodologies will be used to generate libraries of bioactive compounds (phthalides, isochromanones, isoindolinones, etc. ). This will lay the ground for future medicinal chemistry grant proposals.Through this research, we will work in close collaboration with IKA which recently released "Electrasyn 2.0", the first commercial electrosynthesis setup. This proposal will lead to constructive feedback that will be shared with IKA in order to develop new applications for Electrasyn 2.0. to further aid research in this area.

在药物设计、新材料开发或环境化学等广泛不同的领域，设计化合物库的需求是必不可少的。自由基化学是实现这一目标的独特工具，通过在温和的条件下构建复杂的分子支架，由于有广泛的自由基转化可用。然而，主要问题之一仍然是这些自由基的产生，这往往需要使用有毒金属或不稳定和危险的化合物。例如，这样的条件与制药应用不相容，在制药应用中，产品必须大规模安全生产，并且没有任何有毒污染物的痕迹。电合成是有机化学中的一种强大工具，它允许在温和和绿色的条件下产生自由基，从而绕过了上述问题。尽管已经开发了过多的转化，其中许多已经成功地用于几个工业过程，但制备有机电化学的潜力仍然被大大低估。寻找更环保、更便宜的传统合成方法替代品的动力越来越大，这进一步促使我们研究新的电化学方法。基于非常令人鼓舞的初步结果，我们设想利用电化学开发一种新的方法，在温和、绿色、经济和安全的条件下生成芳氧基/丙烯酰基(RCOO*)和酰胺基(R2N*)。该项目是跨学科的，因为除了广泛的有机合成研究外，还将利用高速伏安法进行全面的电分析研究，以研究电极机制和建立反应机理。最后，作为概念验证，新开发的合成方法将用于生成生物活性化合物(邻苯二甲酸酯、异色满酮、异吲哚等)的库。这将为未来的药物化学拨款申请奠定基础。通过这项研究，我们将与IKA密切合作，该公司最近发布了第一个商业化电合成装置--Electrasyn2.0。这项提议将产生建设性的反馈，并将与宜家分享，以便为Electrasyn2.0开发新的应用程序。以进一步帮助这一领域的研究。

项目成果

Anodic Oxidation of Dithiane Carboxylic Acids: A Rapid, Mild and Practical Way to Access Functionalised Orthoesters

二噻烷羧酸的阳极氧化：一种快速、温和且实用的获得功能化原酸酯的方法

• DOI: 10.26434/chemrxiv.12137550.v1
• 发表时间: 2020
• 作者: Garcia A

Supporting-Electrolyte-Free Anodic Oxidation of Oxamic Acids into Isocyanates: An Expedient Way to Access Ureas, Carbamates, and Thiocarbamates

• DOI: 10.1021/acs.oprd.1c00112
• 发表时间: 2021-05
• 期刊: Organic Process Research & Development
• 影响因子: 3.4
• 作者: Alessia Petti;Corentin Fagnan;Carlo G. W. van Melis;Nour Tanbouza;Anthony D. Garcia;Andrea Mastrodonato;M. Leech;I. Goodall;A. Dobbs;Thierry Ollevier;K. Lam

Electrosynthesis: A Practical Way to Access Highly Reactive Intermediates

电合成：获取高反应性中间体的实用方法

• DOI: 10.1055/a-1890-9162
• 发表时间: 2022
• 期刊: Synlett
• 影响因子: 2
• 作者: Lam K

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

通过阳极生成氧羰基自由基实现取代内酯的经济、绿色和安全路线

• DOI: 10.1002/ange.201909922
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: Petti A

Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides.

氨基四唑的阳极氧化：温和且安全的异氰化物途径。

• DOI: 10.1021/acs.orglett.1c03475
• 发表时间: 2021
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Leech MC