Catalytic Ambiphilic C-H Activation: Mechanism and Exploitation

催化双亲 C-H 激活：机制和开发

• 批准号: EP/J002917/1
• 负责人: David Davies
• 金额: $ 40.77万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FJ002917%2F1
• 关键词: Catalytic; Ambiphilic; Activation; Mechanism; Exploitation

Methods for the formation of C-C and C-Y (Y = O, N) bonds are crucial for the synthesis of new molecules. In the last 20 years there have been huge advances in Pd-catalysed cross-coupling reactions and this was recognized in the award of the 2011 Nobel Prize. These reactions involve joining together two organic molecules, one of which features a bond between carbon and a halogen (a C-X bond) while the other coupling partner may feature a non-carbon centre such as tin, boron or zinc (a C-M bond). The coupling of these two partners to give a new C-C bond usually involves a palladium catalyst. Later versions involved forming C-N or C-O bonds. This coupling reaction generally works well, however the efficiency of this individual step masks significant waste of time and energy as well problems with environmental sustainability. These problems arise because both coupling partners ultimately derive from precursors that only contain C-H bonds and therefore require prior synthesis that usually involves several steps each with costly energy and purification implications. Moreover the final coupling process itself eliminates salts that must first of all be separated from the reaction products (a further costly and expensive process) before disposal, often with significant environmental impact. A far more desirable approach would be to use the unactivated C-H containing precursors directly as the coupling partners. Such compounds are readily available and cheap. This approach would circumvent the need for the costly and wasteful preactivation that is required to make C-X and M-C species, as well as the post processing clean up of M-X by-products. Until very recently this approach has not been adopted as C-H based precursors are usually rather chemically inert. However, catalysis based on such C-H species (catalytic C-H activation) is now within reach, mainly due to recent advances where the means to activate the C-H bond with a transition metal catalyst have been understood. A key point in C-H activation is to have a directing group elsewhere on the feedstock molecule so that it can interact with the metal catalyst and so bring the C-H bond close enough to react. The M-C bond that is thus formed can then undergo reactions with other substrates to produce the desired C-C, C-N or C-O bond. Moreover, if instead this new bond is formed with another atom in the same molecule then a ring is formed. Such cyclic compounds containing an N or O atom are heterocyclic compounds and these play a key role as major constituents of pharmaceuticals and agrochemicals. In addition they often have interesting optical and electrical properties in their own right that are important in a range of technological applications. It is therefore crucial that the synthesis of heterocyclic compounds is as efficient as possible; moreover the need for a wide range of heterocycles with different properties depends upon the development of new, efficient methods for their synthesis.There are several precedents for this type of catalytic C-H activation in the scientific literature, however to date there is little understanding of what controls this reactivity. Thus the range of species that can be made is limited, the catalysis is not yet efficient and the selectivity of the reaction is poorly understood. To improve this situation requires a deeper understanding of how these systems work. We aim to provide this here through a combination of experimental studies and computational modeling. By understanding the factors that control reactivity and selectivity we will be able to design new, more efficient catalysts and also to widen the scope of the catalytic C-H activation methodology. The ultimate aim is to provide a flexible set of efficient synthetic tools that chemists will be able to use to make a wide range of important heterocycles in an environmentally sustainable manner.

C-C和C-Y （Y = O， N）键的形成方法对新分子的合成至关重要。在过去的20年里，钯催化的交叉偶联反应取得了巨大的进步，这在2011年的诺贝尔奖中得到了认可。这些反应包括将两个有机分子连接在一起，其中一个以碳和卤素之间的键（C-X键）为特征，而另一个偶联伙伴可能以非碳中心为特征，如锡、硼或锌（C-M键）。这两个伙伴的偶联形成新的C-C键通常需要钯催化剂。后来的版本涉及到形成碳氮键或碳氧键。这种偶联反应通常效果良好，然而，这一个别步骤的效率掩盖了大量的时间和能源浪费以及环境可持续性问题。这些问题的出现是因为这两个偶联伙伴最终都来源于只含有C-H键的前体，因此需要预先合成，通常需要几个步骤，每个步骤都需要昂贵的能量和纯化。此外，最后的偶联过程本身消除了在处理之前必须首先从反应产物中分离出来的盐（另一个昂贵的过程），通常会对环境产生重大影响。更理想的方法是直接使用未活化的含碳氢化合物前体作为偶联伙伴。这种化合物很容易获得，而且价格便宜。这种方法将避免制造C-X和M-C物种所需的昂贵和浪费的预激活，以及M-X副产品的后处理清理。直到最近，这种方法还没有被采用，因为基于碳氢化合物的前体通常是相当惰性的。然而，基于C-H的催化（催化C-H活化）现在已经触手可及，这主要是由于最近的进展，用过渡金属催化剂激活C-H键的方法已经被理解。碳氢键活化的一个关键点是在原料分子的其他地方有一个导向基团，这样它就可以与金属催化剂相互作用，从而使碳氢键足够接近以发生反应。这样形成的M-C键可以与其他底物反应生成所需的C-C、C-N或C-O键。此外，如果这个新键与同一分子中的另一个原子形成，那么就会形成一个环。这种含有N或O原子的环状化合物是杂环化合物，它们作为药物和农用化学品的主要成分起着关键作用。此外，它们通常具有有趣的光学和电学特性，这些特性在一系列技术应用中很重要。因此，杂环化合物的合成必须尽可能高效；此外，对各种性质的杂环化合物的需求取决于新的、有效的合成方法的发展。在科学文献中，这种类型的催化C-H活化有几个先例，然而迄今为止，人们对控制这种反应性的原因知之甚少。因此，可以制造的物种范围有限，催化效率尚不高，反应的选择性也知之甚少。要改善这种情况，需要更深入地了解这些系统是如何工作的。我们的目标是通过实验研究和计算建模的结合来提供这一点。通过了解控制反应活性和选择性的因素，我们将能够设计出新的、更有效的催化剂，并扩大催化C-H活化方法的范围。最终目标是提供一套灵活有效的合成工具，化学家们将能够用环境可持续的方式制造各种重要的杂环。

项目成果

Tetraphenylcyclopentadienyl rhodium complexes in stoichiometric and catalytic CH functionalization

• DOI: 10.1016/j.jorganchem.2018.09.005
• 发表时间: 2019-01
• 期刊: Journal of Organometallic Chemistry
• 影响因子: 2.3
• 作者: D. Davies;Charles E. Ellul;Kuldip Singh

Steric effects on acetate-assisted cyclometallation of meta-substituted N-phenyl and N-benzyl imidazolium salts at [MCl2Cp*]2 (M = Ir, Rh).

间位取代的 N-苯基和 N-苄基咪唑鎓盐在 [MCl2Cp*]2 (M = Ir, Rh) 上的乙酸辅助环金属化的空间效应。

• DOI: 10.1039/d1dt02677a
• 发表时间: 2021
• 期刊: 2003)
• 作者: Davies DL

Combined experimental and computational investigations of rhodium-catalysed C - H functionalisation of pyrazoles with alkenes.

• DOI: 10.1002/chem.201405550
• 发表时间: 2015-02-09
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Algarra AG;Davies DL;Khamker Q;Macgregor SA;McMullin CL;Singh K;Villa-Marcos B
• 通讯作者: Villa-Marcos B