The Ironworks: a mechanistic foundry for iron-catalysed cross-coupling

碳-碳键的形成是社会赖以生存的分子生产的核心，最好的例子包括药品、农用化学品和精细化学品，比如你可能正在看的屏幕上的有机发光二极管。有许多方法可以产生C-C键，但利用催化可以大大提高特定转化的可持续性，因为它减少了所需的能量和产生的废物以及生产中所需的单个步骤的数量。事实上，催化剂用于生产约90%的化学品。过渡金属在催化中起着特殊的作用，铂族金属（PGM）如铂、铑，特别是钯，在许多碳-碳键形成过程中普遍存在，特别是在所谓的催化交叉偶联反应中。然而，与所有铂族金属一样，由于其毒性，钯受到FDA和EAEMP监管控制，目前在药品中的含量低于5-10 ppm，降低了其在大规模生产中的吸引力。此外，由于天然丰度低，所有铂族金属在英国地理学会2011年的52种元素或元素组的风险清单上被定义为“非常高的风险”，这些元素或元素组是维持我们的经济和生活方式所必需的（http：//www.bgs.ac.uk/mineralsuk/aprics/riskList.html）。随着汽车和消费电子行业的竞争日益激烈，铂族金属在催化领域的长期使用是不可持续的。因此，开发基于地球上丰富的第一行过渡元素金属的新催化剂是一个重大的推动力：铁（地壳中第四大常见元素）的低毒性和高可用性使其成为替代钯的理想候选者。因此，在碳-碳键形成研究中使用铁已经有了相当大的全球性努力，然而该领域即将陷入一个主要的僵局：最简单的铁催化交叉偶联反应已经实现，而许多更有吸引力的过程，通常在钯催化中开发，仍然难以捉摸。这是因为我们对铁催化作用的机制充其量只有初步的了解。这些机制比基于钯的机制更难研究。因此，我们建议在四个不同的机构（布里斯托，卡迪夫，巴斯，普林斯顿）开展一项详细的机制研究，利用广泛的互补技术，以揭示真正的活性催化剂的详细性质及其催化作用模式。然后，我们打算利用这些独特的数据为高度理想但尚未满足的催化过程提供铁基催化剂，自下而上构建它们。

The formation of carbon-carbon bonds lies at the very heart of the production of the molecules that society depends on. Prime examples include pharmaceuticals, agrochemicals and fine chemicals such as the oleds in the screen that you are probably looking at. There are many ways of producing C-C bonds, but exploiting catalysis hugely increases the sustainability of a given transformation as it reduces the amount of energy required and waste produced as well as the number of individual steps necessary in the production. Indeed catalysis is used in the manufacture of around 90% of all chemicals. Transition metals play a special role in catalysis and the platinum group metals (PGMs) such as platinum, rhodium and, in particular palladium, are ubiquitous in many carbon-carbon bond-forming processes, especially in so called catalytic cross-coupling reactions. However, like all PGMs, due to its toxicity, palladium is subject to FDA and EAEMP regulatory control, currently to less than 5-10 ppm in pharmaceutical products, reducing its attractiveness in larger-scale manufacture. Furthermore, due to low natural abundance, all PGMs are defined as being at "very high risk" on the British Geographical Society's 2011 Risk List of 52 elements or element groups necessary to maintain our economy and lifestyle (http://www.bgs.ac.uk/mineralsuk/statistics/riskList.html). With ever increasing competition from the automotive and consumer electronics sectors the long-term use of PGMs in catalysis is unsustainable.Therefore there is a major drive to uncover new catalysts based on Earth abundant metals from the first row transition elements: the low toxicity and high availability of iron (fourth most common element in the Earth's crust) make it the ideal candidate to replace palladium. Thus there has been considerable global effort in the use of iron in carbon-carbon bond-formation studies, however the field is about to hit a major impasse: the simplest iron-catalysed cross-coupling reactions have been realised, while many of the more attractive processes, commonly exploited in palladium catalysis, remain elusive. This is because we have at best only a rudimentary grasp of the mechanisms involved in iron catalysis. These mechanisms are far more challenging to study than those based on palladium. Accordingly we propose to launch a detailed mechanistic study exploiting a wide raft of complementary techniques at four different institutions (Bristol, Cardiff, Bath, Princeton) to uncover the detailed nature of the true active catalysts and their modes of catalytic action. Then we intend to use this unique data to deliver iron-based catalysts for highly desirable yet unmet catalytic processes, building them from the bottom up.