Chemoselective cross-coupling via control of anion metathesis at Pd(II)

通过控制 Pd(II) 阴离子复分解进行化学选择性交叉偶联

• 批准号: EP/R025754/1
• 负责人: Allan Watson
• 金额: $ 49.04万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR025754%2F1
• 关键词: Chemoselective; cross; coupling; via; control

Palladium-catalysed cross-coupling has revolutionised the way molecules are made and are essential to the continued production of myriad products from small bioactive molecules to materials and from small scale to manufacture. A number of these processes have become privileged, with their impact demonstrated from tonne-scale application to the Nobel Prize. Increased mechanistic understanding of catalytic reactions underpins improvements of existing processes while driving development of new methods. By interrogating reactivity and selectivity as a function of the palladium species formed from a key anion exchange (metathesis) event, this proposal aims to bring new understanding to the most important classes of cross-coupling reaction while providing methods for the preparation of novel and synthetically powerful architectures.Our preliminary proof-of-concept experiments in support of this proposal have shown that the anion metathesis event is influenced by different variables specific to catalytic reactions (for example, the substrate, the reaction medium). We have also shown that stoichiometrically prepared palladium complexes with different anions have profoundly different reactivities when assessed using a bifunctional chemical probe. Lastly, we have tentatively shown that this differential reactivity can allow the preparation of highly useful molecules. This proposal will comprehensively investigate this anion metathesis event to allow predictability and the rational application of this unappreciated event as a method for catalytic control of multi-reactive systems and, in this proposal, allow access useful synthetic scaffolds tailored towards application in Medicinal Chemistry.

钯催化的交叉偶联反应彻底改变了分子的制造方式，对于从小的生物活性分子到材料以及从小规模到制造的各种产品的持续生产至关重要。许多这样的过程已经成为特权，它们的影响从吨级应用到诺贝尔奖上得到了体现。对催化反应的机理了解的增加为现有工艺的改进奠定了基础，同时推动了新方法的开发。通过考察阴离子交换(复分解)过程中形成的钯物种的反应活性和选择性，这一建议旨在为最重要的交叉偶联反应类别带来新的理解，同时为制备新的和合成功能强大的结构提供方法。我们支持这一建议的初步概念验证实验表明，阴离子复分解事件受不同的催化反应特定变量(如底物，反应介质)的影响。我们还表明，化学计量比制备的钯与不同的阴离子络合物在使用双功能化学探针进行评估时具有截然不同的反应活性。最后，我们初步证明了这种不同的反应性可以用来制备非常有用的分子。这项建议将全面调查这一阴离子歧化事件，以允许预测和合理应用这一未被认可的事件作为催化控制多反应系统的方法，并在这项建议中，允许访问针对药物化学应用而量身定做的有用的合成支架。

项目成果

Synthesis of 2-BMIDA Indoles via Heteroannulation: Applications in Drug Scaffold and Natural Product Synthesis.

• DOI: 10.1021/acs.orglett.2c00959
• 发表时间: 2022-04-29
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Bell, George E.;Fyfe, James W. B.;Israel, Eva M.;Slawin, Alexandra M. Z.;Campbell, Matthew;Watson, Allan J. B.
• 通讯作者: Watson, Allan J. B.

Cu(OTf) 2 -Mediated Cross-Coupling of Nitriles and N-Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products**

Cu(OTf) 2 -介导腈和 N-杂环与芳基硼酸的交叉偶联生成硝基和吡啶基产品**

• DOI: 10.1002/ange.202016811
• 发表时间: 2021
• 期刊: Angewandte Chemie
• 作者: Bell N

Asymmetric synthesis of heterocyclic chloroamines and aziridines by enantioselective protonation of catalytically generated enamines

通过催化生成烯胺的对映选择性质子化不对称合成杂环氯胺和氮丙啶

• DOI: 10.33774/chemrxiv-2021-d41h5
• 发表时间: 2021
• 作者: McLean L