Understanding the Platinum-Catalysed Reaction of Allenes with Nucleophiles: Towards New Reactivities and Novel Structures

新的催化反应的发展和不寻常的反应机制的研究是科学的基本组成部分，对推动新的化学反应的发展至关重要。这个重要的领域旨在提高和完善我们对化学反应如何工作的理解，不仅满足我们对周围世界的好奇心，而且帮助合成和工业化学家合理化结果，预测结果，并设计更好，更实用的方法，通过避免麻烦的副反应来创造新的化合物。通过过渡金属配合物活化不饱和键是生成新的C-C和C-X的非常有用的工具（X =杂原子）键以非常选择性和有效的方式连接。虽然过渡金属催化的烯烃和炔烃的反应已经被广泛研究，但联烯（具有两个连续碳-碳双键的分子）的配位化学才刚刚开始探索，与亲核试剂的反应是最重要的例子之一。涉及联烯的催化循环提供了对一个双键或另一个双键进行选择性反应的可能性。金属的选择（Pd，Rh，Ir，Au，Pt）对控制反应的结果起着关键作用，不同的配位模式被提出来解释所遇到的新的反应性.在本项目中，我们提出了一种机理方法来研究最近报道的Pt催化的联烯和亲核试剂的反应，以及利用所获得的知识来发现新的反应性，并解开所提出的关键反应中间体背后的合成潜力，以得到可用作新药的复杂结构。我们实验室的最新发现表明，在铂催化条件下，与更常规的金催化相反，联烯和亲核试剂的反应通过涉及稀有Pt-联烯配位的发散机理途径进行，这允许形成新的反应产物：在铂络合物的存在下发生亲核试剂在丙二烯的末端碳上的双加成和丙二烯体系的第二个双键的完全饱和，与单加成和与其它金属如金形成E-烯丙基化产物相反。我们已经证明了该反应用于合成缩醛和双吲哚基烷烃的适用性，这是具有不同生物活性的重要产物。了解主要的反应途径，各个步骤的参数，并确定可能的中间体参与这个催化循环，是至关重要的控制反应，发现新的催化循环和新的一锅多步转化来自关键中间体的反应对复杂的分子，纳入重要的结构基序观察到的天然产物。我们提出了一种互动的方法，即从机理研究中获得的知识将用于开发新的反应性和不同的催化循环，并根据新反应性的需要和收集的机理信息设计改进的催化剂。所有化学学科之间以及与工业界的合作将得到利用。

The development of new catalytic reactions and the study of unusual reaction mechanisms is a fundamental part of science, crucial to drive the development of new chemical reactions. This essential field aims to enhance and refine our understanding of how chemical reactions work, not only to satisfy our curiosity about the world surrounding us, but also to help the synthetic and industrial chemists to rationalise results, predict outcomes and design better and more practical ways of creating new compounds by avoiding troublesome side reactions, identifying new transformations and devising safer reaction conditions.Activation of unsaturated bonds by transition metal complexes is a very useful tool to create new C-C and C-X (X = heteroatom) bonds in a very selective and efficient way. Although transition-metal catalysed reactions of alkenes and alkynes have been widely studied, the coordination chemistry of allenes (molecules with two consecutive carbon-carbon double bonds) has only started to be explored, being the reaction with nucleophiles one of the most important examples. Catalytic cycles involving allenes give the possibility of selective reactions towards one double bond or the other. The selection of the metal (Pd, Rh, Ir, Au, Pt) employed in the reaction is critical to control the outcome of the reaction, and different coordination modes have been proposed to explain the new reactivities encountered.In this project we propose a mechanistic approach to the study of a recently reported Pt-catalysed reaction of allenes and nucleophiles, and the use of the knowledge gained to discover new reactivities and unravel the synthetic potential behind the proposed key reaction intermediates to give complex structures that could be exploited as new drugs.Recent discoveries in our laboratory indicate that, under platinum-catalysed conditions, and in contrast to more conventional gold catalysis, the reaction of allenes and nucleophiles proceeds by a divergent mechanistic pathway involving a rare Pt-allene coordination, which allow the formation of new reaction products: double addition of the nucleophiles on to the terminal carbon of the allene and complete saturation of the second double bond of the allenic system occurs in the presence of platinum complexes, in contrast to the mono addition and formation of E-allylated products with other metals, like gold. We have already shown the applicability of this reaction for the synthesis of acetals and bisindolylalkanes, important products with varied biological activity. Understanding the main reaction pathway, the parameters of the individual steps, and identification of the possible intermediates involved in this catalytic cycle, are crucial for the control of the reaction, the discovery of new catalytic cycles and new one-pot multistep transformations derived from key intermediates of the reaction towards complex molecules that incorporate important structural motifs observed in natural products. We proposed an interactive approach were the knowledge gain form the mechanistic study will be use to exploit new reactivities and divergent catalytic cycles, and improved catalytsts will be design according to the needs of the new reactivities and the mechanistic information gathered.The work described in this proposal has the potential to influence science research in a broad sense, as it falls in a very multidisciplinary environment, and collaborations between all the chemistry disciplines and with industry will be exploited.