Metal Catalysed Decarboxylative C-C Bond Formation Reactions

不可否认，有机合成在过去的两个世纪里取得了巨大的进步。然而，我们有效合成分子的能力主要局限于结构复杂程度较低的目标。目前，制备更复杂的化合物是可能的；然而，它们的合成效率非常低：它们通常涉及大量的反应和纯化步骤，从而增加废物的产生，并显著降低总产率。因此，这些合成通常不适用于持续生产感兴趣的复杂分子。这一观察结果在科学界达成了普遍共识，即迫切需要新的化学工艺来支持“更绿色”和更可持续的化学工业的发展。传统的合成策略需要存在活性官能团，用作进一步官能化的把手。这一要求是显著增加合成难度的因素之一。此外，这些“把手”通常不是最终分子的一部分，作为废物副产品丢失，可能是有毒的，需要分离和处理。在过去的二十年里，出现了一种更直接的替代方案：C-H键的直接官能化。通过这一策略，有机分子中普遍存在的典型的惰性C-H键可以被过渡金属催化剂激活并随后功能化。第二种方法涉及使用可以通过脱羧基激活的羧酸来非常准确地指导给定分子中的反应性。在我们的研究中，我们希望将这两种新类型的反应性结合起来，开发一系列方法，可以在分子的碳原子之间以非常有限的副产品和高效的方式形成键。这种新转变的发展将对所有应用领域产生影响，例如药物、农用化学品和新材料的合成，因为它提供了廉价和容易获得迄今很难制造(因此没有商业使用)的分子的途径。

Organic synthesis has undeniably made tremendous progress over the past two centuries. Nevertheless, our ability to efficiently synthesise molecules is mostly limited to targets of low structural complexity. Preparing more sophisticated compounds is currently possible; however, their syntheses are highly inefficient: they usually involve a high number of reaction and purification steps, with a consequent increase in waste generation, and a dramatic reduction in overall yields. Consequently, these syntheses are generally not applicable to the sustained production of complex molecules of interest. This observation has led to a general consensus in the scientific community as to the urgent need for new chemical processes supporting the development of a "greener" and more sustainable chemical industry.Traditional synthetic strategies require the presence of reactive functional groups that are used as handles for further functionalisation. This requirement is one of the factors dramatically enhancing the difficulty of syntheses. In addition, often these 'handles' are not part of the final molecule and are lost as waste by-product that may be toxic and needs to be separated and dealt with. The last two decades have seen the emergence of a more straightforward alternative: the direct functionalisation of C-H bonds. Through this strategy the typically inert C-H bonds, ubiquitous in organic molecules, can be activated by transition metal catalysts and subsequently functionalised. A second approach involves the use of carboxylic acids that can be activated via decarboxylation to direct very accurately the reactivity in a given molecule. In our research we want to combine both of these new types of reactivity to develop a series of methodologies that can form bonds between carbon atoms of molecules with a very limited amount of waste by-product and in an efficient manner. The development of such new transformations will impact on all applied areas, such as the synthesis of pharmaceuticals, agrochemicals and new materials, by providing cheap and easy access to molecules that are very difficult to make to date (and therefore not used commercially).