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已经允许通过结合带有适当化学基团的两种底物分子以快速和有效的方式构建某些类别的分子。这项技术的影响在2010年被诺贝尔化学奖授予三位在这项化学发展中发挥作用的研究人员：Richard Heck，Ei-ichi Negishi和Akira Suzuki。镍能够介导许多相同的反应，并且目前比钯便宜约一千倍，但表现出稍微不同的反应性特征。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;这就为功能化分子的选择性带来了挑战。目前这一代镍催化剂的效率通常比现有技术的钯催化剂低得多。通常需要更大量的镍来进行交叉偶联反应，因此必须将废催化剂和配体与最终产物分离。例如，这对药品生产具有实际意义。为了使镍成为钯的有竞争力的低成本替代品，或者为了使其不同的反应性特征在工业中得到利用，必须降低镍的所需水平。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/或一种更具成本效益的方法来制备当前的靶分子。可以提高镍催化剂效率的一种方式是通过改变连接到进行催化的镍原子上的基团（配体）。虽然许多研究人员已经对此进行了研究，但典型的方法是通过“试错法”，即用不同的配体制备一系列镍络合物，并依次测试每种络合物。在一些情况下，催化剂在反应本身期间在反应容器中制备;一致的部分，如金属盐和配体前体，与底物结合，并且假定在反应期间形成某种催化剂络合物。然而，通常不清楚为什么复合物的性能不同，因为在单个时间点仅进行单个测量（转化率和/或分离产率），并且确定活性催化剂的化学结构是什么并不是微不足道的。所提出的研究过程旨在制备一组定义明确的模型络合物，其具有已知的结构和纯度，使用有机金属化学中最先进的技术测定。然后，这些化合物将用于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。这项研究将包括若干组成部分：将对这一单一步骤的产物进行制备和表征，以了解其结构;将用不同的反应物测量这一步骤发生的速率，以探索底物结构如何影响这一步骤的速率;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分子上反应将发生的位置;并将在工业相关的测试反应中探索络合物的总体催化活性。总之，这些研究将提供镍催化的关键步骤的详细了解，可用作进一步研究的基础上的基板和催化剂结构对反应性的影响，并在新的和更有效的催化反应的设计。这样做，这也将有助于PI，大卫博士纳尔逊，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.