Understanding Mechanism and Selectivity in Oxidative Addition to Nickel(0) for Catalytic Cross Coupling

了解镍 (0) 氧化加成催化交叉偶联的机理和选择性

• 批准号: EP/M027678/1
• 负责人: David Nelson
• 金额: $ 12.31万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM027678%2F1
• 关键词: Understanding; Mechanism; Selectivity; Oxidative; Addition

The use of palladium-catalysed cross-coupling reactions has allowed certain classes of molecules to be constructed in a rapid and efficient manner, by combining two substrate molecules that bear appropriate chemical groups. The impact of this technology was recognised in 2010 by the award of the Nobel Prize in Chemistry to three researchers who were instrumental in the development of this chemistry: Richard Heck, Ei-ichi Negishi, and Akira Suzuki. Nickel is capable of mediating many of the same reactions, and is currently approximately one thousand times cheaper than palladium, but exhibits a somewhat different reactivity profile. Nickel can interact with a wider range of chemical groups, including common carbon-oxygen bonds, and can therefore mediate a wider range of reactions; this then provides challenges in terms of selectivity in functionalised molecules. The current generation of nickel catalysts is typically much less efficient than state-of-the-art palladium catalysts. Larger quantities of nickel are typically required to carry out cross-coupling reactions, and so the spent catalyst and ligand must then be separated from the final products. This has practical implications for the production of pharmaceuticals, for example. For nickel to become a competitive, low-cost alternative to palladium, or for its different reactivity profile to be utilised in industry, the required levels of nickel must be decreased. If this could be done, it would provide industry and academia with a means by which to prepare new molecules and/or a more cost-effective route to current target molecules. One way by which the efficiency of nickel catalysts might be improved is by altering the groups (ligands) that are attached to the nickel atoms that perform the catalysis. While a number of researchers have investigated this, the typical approach is by 'trial-and-error' in which a range of nickel complexes is prepared with different ligands and each complex is tested in turn. In some cases, catalysts are prepared in the reaction vessel during the reaction itself; the consistent parts, such as a metal salt and a ligand precursor, are combined with the substrates and it is assumed that a certain catalyst complex is formed during the reaction. However, it is often not clear why the performance of complexes differ, as only a single measure is taken at a single time point (conversion and/or isolated yield), and it is not trivial to determine what the chemical structure of the active catalyst is.The proposed course of research aims to prepare a set of well-defined model complexes, of known structure and purity, determined using state-of-the-art techniques in organometallic chemistry. These compounds will then be used to study a single, isolated step of the overall catalytic cycle known as oxidative addition; this is where the first substrate reacts with the catalyst. This study will comprise a number of components: the products of this single step will be prepared and characterised, giving insight into their structure; the rate at which this step happens will be measured with different reactants, in order to explore how the substrate structure affects the rate of this step; the selectivity for reaction with different chemical groups will be explored, so that it can be understood where on a given molecule reaction will occur; and the overall catalytic activity of the complexes will be explored in industrially-relevant test reactions. Together, these studies will provide a detailed understanding of a key step in nickel catalysis that can be used as the foundation for further studies on the effect of substrate and catalyst structure on reactivity, and in the design of new and more efficient catalytic reactions. In doing so, this will also aid the PI, Dr David Nelson, in establishing a research group at the University of Strathclyde.

通过结合两个具有适当化学基团的底物分子，使用钯催化的交叉偶联反应的使用可以快速有效地构建某些类别的分子。这项技术的影响在2010年通过诺贝尔化学奖授予了三名在这种化学发展中发挥作用的研究人员：理查德·赫克（Richard Heck），Ei-ichi negishi和Akira Suzuki。镍能够介导许多相同的反应，目前比钯的便宜大约一千倍，但反应性曲线却有些不同。镍可以与更广泛的化学基团相互作用，包括常见的碳氧键，因此可以介导更广泛的反应。然后，这在功能化分子的选择性方面提供了挑战。当前的镍催化剂通常比最先进的钯催化剂效率要低得多。通常需要大量的镍进行交叉偶联反应，因此必须将支出的催化剂和配体与最终产物分开。例如，这对药品的生产具有实际影响。为了使镍成为钯金的竞争性，低成本的替代品，或者要在行业中使用其不同的反应性概况，则必须降低所需镍的水平。如果可以做到这一点，它将为行业和学术界提供准备新分子和/或到当前目标分子的更具成本效益的途径的手段。可以提高镍催化剂效率的一种方法是改变连接到执行催化的镍原子的组（配体）。尽管许多研究人员都对此进行了研究，但典型的方法是通过“试验和纠正”，其中一系列具有不同配体的镍配合物，又依次测试了每个复合物。在某些情况下，在反应本身中，在反应容器中制备催化剂。一致的部分（例如金属盐和配体前体）与底物结合使用，并假定在反应过程中形成某个催化剂络合物。但是，通常不清楚为什么复合物的性能有所不同，因为仅在一个时间点（转换和/或孤立的产率）采取单一措施，并且确定活性催化剂的化学结构是什么。拟议的研究过程旨在使用一组良好的模型结构和纯度，使用状态化的技术来确定的是机构化学技术。然后，这些化合物将用于研究称为氧化添加的总催化循环的单个，分离的步骤。这是第一底物与催化剂反应的地方。这项研究将包括许多组成部分：该单一步骤的产品将得到准备和表征，从而深入了解其结构；为了探索底物结构如何影响此步骤的速率，将使用不同的反应物测量此步骤的速率；将探索与不同化学基团反应的选择性，以便可以理解在给定的分子反应的位置；并且将在与工业相关的测试反应中探索复合物的总体催化活性。总之，这些研究将提供对镍催化的关键步骤的详细理解，该步骤可作为基础，以进一步研究底物和催化剂结构对反应性的影响，以及设计新的，更有效的催化反应的设计。为此，这也将有助于PI，David Nelson博士在Strathclyde大学建立研究小组。

项目成果

Correction to Oxidative Addition of Aryl Electrophiles to a Prototypical Nickel(0) Complex: Mechanism and Structure/Reactivity Relationships

芳基亲电子试剂与典型镍 (0) 配合物氧化加成的修正：机理和结构/反应性关系

• DOI: 10.1021/acs.organomet.7b00307
• 发表时间: 2017
• 期刊: Organometallics
• 影响因子: 2.8
• 作者: Bajo S

Aldehydes and ketones influence reactivity and selectivity in nickel-catalysed Suzuki-Miyaura reactions.

• DOI: 10.1039/c9sc05444h
• 发表时间: 2020-01-06
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Cooper AK;Leonard DK;Bajo S;Burton PM;Nelson DJ
• 通讯作者: Nelson DJ

Aldehydes and Ketones Influence Reactivity and Selectivity in Nickel-Catalyzed Suzuki-Miyaura Reactions

醛和酮影响镍催化 Suzuki-Miyaura 反应的反应性和选择性

• 发表时间: 2019
• 作者: Alasdair Cooper

Oxidative Addition of Aryl Electrophiles to a Prototypical Nickel(0) Complex: Mechanism and Structure/Reactivity Relationships

• DOI: 10.1021/acs.organomet.7b00208
• 发表时间: 2017-04-24
• 期刊: ORGANOMETALLICS
• 影响因子: 2.8
• 作者: Bajo, Sonia;Laidlaw, Gillian;Nelson, David J.
• 通讯作者: Nelson, David J.