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.

钯催化的交叉偶联反应的使用使某些类型的分子能够通过结合带有适当化学基团的两个底物分子而快速而有效地构建。2010年，这项技术的影响得到了认可，将诺贝尔化学奖授予了三位对这一化学的发展起到重要作用的研究人员：理查德·赫克、Negishi Ei-ichi和Akira Suzuki。镍能够调节许多相同的反应，目前大约比钯便宜一千倍，但表现出略有不同的反应性曲线。镍可以与更广泛的化学基团相互作用，包括常见的碳氧键，因此可以调节更广泛的反应；这就给功能化分子的选择性带来了挑战。当前一代镍催化剂的效率通常比最先进的钯催化剂低得多。进行交叉偶联反应通常需要大量的镍，因此必须将废催化剂和配体从最终产品中分离出来。例如，这对药品生产具有实际意义。为了使镍成为一种具有竞争力的、低成本的钯替代品，或者为了使其不同的反应性特征在工业上得到利用，必须降低所需的镍水平。如果能够做到这一点，它将为工业界和学术界提供一种制备新分子的方法和/或一条更具成本效益的途径来获得当前的目标分子。提高镍催化剂效率的一种方法是改变与执行催化作用的镍原子相连的基团(配体)。虽然许多研究人员已经对此进行了研究，但典型的方法是反复试验，即用不同的配体制备一系列镍络合物，然后依次测试每个络合物。在某些情况下，催化剂在反应本身的反应容器中制备；一致的部分，如金属盐和配体前体，与底物结合，并假设在反应过程中形成了某种催化剂络合物。然而，人们往往不清楚为什么络合物的性能不同，因为在单个时间点(转化率和/或分离收率)只进行了一次测量，并且确定活性催化剂的化学结构并不是一件容易的事情。拟议的研究过程旨在制备一组定义明确的、具有已知结构和纯度的模型络合物，并使用最先进的有机金属化学技术进行测定。然后，这些化合物将被用来研究整个催化循环中的一个单独的步骤，称为氧化加成；这是第一个底物与催化剂反应的地方。这项研究将包括一些组成部分：将制备这一单一步骤的产品并对其进行表征，以洞察其结构；将测量不同反应物发生这一步骤的速度，以探索底物结构如何影响这一步骤的速度；将探索与不同化学基团反应的选择性，以便能够了解在特定分子上将发生反应的位置；以及将在与工业相关的测试反应中探索化合物的总体催化活性。总之，这些研究将提供对镍催化中的关键步骤的详细了解，该步骤可作为进一步研究底物和催化剂结构对反应活性的影响的基础，并可用于设计新的、更高效的催化反应。在这样做的同时，这也将有助于私人侦探大卫·纳尔逊博士在斯特拉斯克莱德大学建立一个研究小组。

项目成果

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

醛和酮会影响镍催化的铃木 - 米洛拉反应的反应性和选择性。

• 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

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-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.