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Pd(II)/Pd(IV) Catalytic Cycles involving Pseudohalides in Cross-Coupling Processes: Mechanistic Studies and Synthetic Applications

交叉偶联过程中涉及拟卤化物的 Pd(II)/Pd(IV) 催化循环：机理研究和合成应用

基本信息

批准号：
EP/D078776/1
负责人：
Ian Fairlamb
金额：
$ 40.35万
依托单位：
University of York
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FD078776%2F1
关键词：
Pd II IV Catalytic Cycles

项目摘要

Transition metals can act as catalysts, effecting the reactions of many types of substrates to provide important products that display extraordinary complexity and structural diversity. Such enhanced reactions often proceed rapidly, are higher yielding and give fewer by-products than the related non-catalysed reaction. Indeed, there are many cases where reactions do not occur at all in the absence of a catalyst and it is this what makes transition metal-catalysed reactions important. The metal centre is essentially the active site for catalysis, the activity of which can be modulated using ligands that are capable of binding metals to varying degrees, depending on their size and electronic properties. One can envisage changing the catalytic properties just like a tunable dial on a radio receiver. The precise property required, whether that is high activity, selectivity or catalyst lifetime, can be tuned by alteration of these ligands, to each specific reaction of interest. One of the most versatile transition metals available to synthetic chemists is palladium. It has attracted significant interest for use in many reactions applied to the preparation of valuable synthetic targets such as natural products and therapeutic agents, that possess unique medicinal and biological properties (anti-cancer etc.), and advanced materials.In this proposal, we wish to study the mechanism of an important palladium-catalysed reaction known as Stille cross-coupling, employing the catalyst (PPh3)2Pd(N-Succ)Br, recently developed by our research groups. Many palladium catalysts have been found for this reaction, although the majority of researchers have focussed on preparing catalysts that are more active, something accomplished through alteration of the type of donor neutral ligand for palladium. However, alteration of anionic ligands e.g. halides and pseudohalides, is an area that has been relatively neglected, which is surprising given that these ligands are likely to involve the global catalyst reactivity arguably more so than neutral donor ligands. We have found that an unusual pseudohalide, succinimide and related pseudohalides, exerts intriguing substrate selectivity effects in Stille coupling (for allylic and benzylic substrates); effects that are unprecedented for any other known palladium catalyst. Generally, product selectivity is something which has been overlooked in this field, particularly when two outcomes are possible (from two reactive centres). Being able to direct one outcome is an important goal, as the second reactive centre can be used for other synthetic transformations, making overall synthetic routes more efficient. The selectivity origin is likely to derive from an unusual mechanistic pathway. We wish to gather insights and understanding into the precise mechanism by which (PPh3)2Pd(N-Succ)Br operates by using classical and state-of-the-art tools to assist mechanism elucidation. The identification of clear reaction pathways allows us to exploit this knowledge in the rational design of more efficient, selective and environmentally friendly catalysts, as well as taking advantage of novel mechanistic implications that have been established. The latter point is important, as this often facilitates the development of new synthetic transformations. The substrate scope and reaction types, using our catalyst and related derivatives, will be significantly expanded.We plan to identify and develop new synthetic transformations using the proposed technology. An efficient synthetic route to an exciting target, phacelocarpus-pyrone A, using (PPh3)2Pd(N-Succ)Br in Stille cross-coupling and related cross-coupling processes, is outlined. The overall aim is to demonstrate the versatility of this and related catalysts in a target compound containing a fascinating arrangement of functionality as part of a macrocyclic ring.

过渡金属可以作为催化剂，影响许多类型的底物的反应，以提供显示出非凡的复杂性和结构多样性的重要产物。这种增强的反应通常进行迅速，产率更高，并且比相关的非催化反应产生更少的副产物。事实上，在许多情况下，在没有催化剂的情况下，反应根本不发生，这就是过渡金属催化反应的重要性。金属中心基本上是催化的活性位点，其活性可以使用能够结合金属到不同程度的配体来调节，这取决于它们的大小和电子性质。人们可以设想改变催化剂的性质，就像无线电接收器上的可调谐刻度盘一样。所需的精确性质，无论是高活性、选择性还是催化剂寿命，都可以通过改变这些配体来调整，以适应每个特定的反应。钯是合成化学家可用的最通用的过渡金属之一。它在许多反应中的应用引起了人们的极大兴趣，这些反应应用于制备有价值的合成靶点，如天然产物和治疗剂，这些靶点具有独特的医学和生物学特性（抗癌等），在本研究中，我们希望研究一个重要的钯催化反应Stille交叉偶联反应的机理，该反应使用我们的研究小组最近开发的催化剂（PPh_3）_2Pd（N-Succ）Br。许多钯催化剂已被发现用于该反应，尽管大多数研究人员专注于制备更活性的催化剂，通过改变钯的供体中性配体的类型来实现。然而，阴离子配体例如卤化物和拟卤化物的改变是相对被忽视的领域，这是令人惊讶的，因为这些配体可能涉及全局催化剂反应性，可以说比中性供体配体更多。我们已经发现，一种不寻常的拟卤化物，琥珀酰亚胺和相关的拟卤化物，发挥有趣的底物选择性的影响，在斯蒂尔耦合（烯丙基和苄基底物），效果是前所未有的任何其他已知的钯催化剂。一般来说，产品的选择性是在这一领域被忽视的东西，特别是当两个结果是可能的（从两个反应中心）。能够引导一个结果是一个重要的目标，因为第二个反应中心可以用于其他合成转化，使整个合成路线更有效。选择性起源可能来自一个不寻常的机制途径。我们希望通过使用经典和最先进的工具来帮助阐明机制，从而收集对（PPh 3）2 Pd（N-Succ）Br操作的精确机制的见解和理解。明确的反应途径的识别使我们能够利用这一知识，更有效的，选择性和环境友好的催化剂的合理设计，以及利用新的机制的影响，已经建立。后一点是重要的，因为这往往有利于新的合成转化的发展。使用我们的催化剂和相关衍生物的底物范围和反应类型将显著扩大。我们计划使用拟议的技术识别和开发新的合成转化。本文介绍了一种利用（PPh 3）2 Pd（N-Succ）Br进行Stille交叉偶联及相关交叉偶联反应的方法，合成了一个激动人心的目标化合物phacelocarpus-pyrone A。总体目标是证明这种催化剂和相关催化剂在目标化合物中的多功能性，所述目标化合物包含作为大环的一部分的功能性的迷人排列。