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

基本信息

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

项目摘要

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.

使用钯催化的交叉偶联反应，通过结合带有适当化学基团的两个底物分子，可以快速有效地构建某些类别的分子。这项技术的影响力得到了认可，2010 年诺贝尔化学奖授予了三位在该化学发展中发挥重要作用的研究人员：Richard Heck、Ei-ichi Negishi 和 Akira Suzuki。镍能够介导许多相同的反应，目前比钯便宜大约一千倍，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与最终产物分离。例如，这对于药品生产具有实际意义。为了使镍成为具有竞争力的、低成本的钯替代品，或者为了在工业中利用其不同的反应特性，必须降低所需的镍含量。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/或更经济有效的途径来制备当前的目标分子。提高镍催化剂效率的一种方法是改变附着在执行催化作用的镍原子上的基团（配体）。虽然许多研究人员对此进行了研究，但典型的方法是通过“试错”，其中用不同的配体制备一系列镍配合物，并依次测试每种配合物。在某些情况下，催化剂是在反应过程中在反应容器中制备的；一致的部分，例如金属盐和配体前体，与底物结合，并且假设在反应过程中形成某种催化剂络合物。然而，通常不清楚为什么络合物的性能不同，因为在单个时间点仅采取单一测量（转化率和/或分离产率），并且确定活性催化剂的化学结构并非易事。拟议的研究课程旨在制备一组明确的模型配合物，其具有已知的结构和纯度，并使用有机金属化学中最先进的技术进行测定。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，即氧化加成；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：将制备和表征这一步骤的产物，深入了解其结构；将使用不同的反应物测量该步骤发生的速率，以探索底物结构如何影响该步骤的速率；将探索与不同化学基团反应的选择性，以便了解给定分子的何处会发生反应；配合物的整体催化活性将在工业相关的测试反应中进行探索。总之，这些研究将提供对镍催化关键步骤的详细了解，可作为进一步研究底物和催化剂结构对反应活性的影响以及设计新的、更高效的催化反应的基础。这样做还将帮助 PI David Nelson 博士在斯特拉斯克莱德大学建立一个研究小组。