Relaying radicals for catalytic couplings: Catalysis with SmI2

合成化学是推动科学技术进步的引擎，因为人造分子和材料对全世界成千上万科学家的工作至关重要。合成化学领域最近许多最激动人心的进展都源于自由基化学的复兴；自由基是高度活跃的物质，非常适合于分子构建——当其他化学反应失败时，它们的反应往往成功。电子转移（ET）通常用于生成自由基，众所周知的试剂钐（II）二碘化钐（SmI2）是全球最重要的ET试剂之一，其商业可用性和广泛使用证明了这一点。关键是，SmI2表现出独特的反应性；它可以介导过程，没有其他试剂可以和它的使用证明了关键的许多高调的科学研究在世界各地每年。例如，SmI2已被用于制造著名的抗癌药物紫杉醇，并在工业上以公斤为单位制造药物Halaven。它还被用于制造用于电子应用的聚合物，最近被用于在环境条件下固定氮和产生氨。尽管有成千上万的出版物描述了它的使用，但一个众所周知的缺点掩盖了SmI2；该试剂必须几乎总是过量使用，从而提出了成本和浪费的问题，以及其未来使用的可持续性。SmI2的独特反应性可归因于其在ET之前协调和激活化学原料的能力；这种能力在最先进的自由基化学催化剂中是罕见的。因此，SmI2为催化领域的创新提供了独特而广泛的机会。利用SmI2丰富的化学成分进行催化仍然是一个巨大的挑战，解决方案早就应该出现了。我们将通过SmI2和“自由基继电器”的创新结合，开发一个催化自由基反应工具箱；由催化剂提供的电子被传递回来的化学反应，在所需的化学转化完成后再生催化剂。我们的研究将开启一个新的自由基催化领域，超越目前的最先进技术。此外，我们将利用手性或手性配体来开发罕见的催化自由基偶联的例子，选择性地传递手性产物的单一异构体-左手或右手-并且首次使用SmI2进行这种催化过程。在整个项目中，我们将利用我们在SmI2化学计算建模方面无与伦比的经验来支持我们的研究，我们将通过制备分子或与药物发现相关来展示我们的新催化剂的力量。在我们2019年和2021年的突破性出版物之前，通过自由基接力和SmI2结合的催化作用是未知的；这使我们处于一个独特的位置来承担拟议的项目，并为分子制造者提供强大的新工具，从而使分子使用者受益，并产生重大的科学和社会影响。

Synthetic chemistry is the engine that drives the advance of science and technology as man-made molecules and materials are vital to the work of thousands of scientists around the world. Many of the most exciting recent advances in synthetic chemistry have arisen from a renaissance in the chemistry of free-radicals; radicals are highly reactive species, well suited for molecule-building - their reactions often succeeding when other chemistry fails.Electron transfer (ET) is commonly used to generate radicals and the well-known reagent, samarium(II) diiodide (SmI2), is one of the global community's most important ET reagents, as evidenced by its commercial availability and widespread use. Crucially, SmI2 exhibits unique reactivity; it can mediate processes that no other reagent can and its use proves pivotal in numerous high-profile scientific studies around the world each year. For example, SmI2 has been used to make the famous anti-cancer drug, Taxol, and to manufacture the drug Halaven on kilogram scale in industry. It has also been used to make polymers for electronic applications and was recently used to fix nitrogen and produce ammonia under ambient conditions.Despite 1000s of publications describing its use, a well-known disadvantage shadows SmI2; the reagent must almost always be used in excess thus raising issues of cost and waste, and the sustainability of its future use. The unique reactivity of SmI2 can be ascribed to its ability to coordinate to and activate chemical feedstocks prior to ET; an ability that is rare amongst state-of-the-art catalysts for radical chemistry. SmI2 therefore offers unique and wide-ranging opportunities for innovation in the field of catalysis. Exploiting the rich chemistry of SmI2 in catalysis remains a grand challenge and a solution is long overdue.We will develop a toolbox of catalytic radical reactions through the innovative marriage of SmI2 and 'radical relays'; chemical reactions in which the electron donated by the catalyst is relayed back, regenerating the catalyst after the desired chemical transformation is complete. Our studies will unlock a new field of radical catalysis that goes beyond the current state-of-the-art. Furthermore, we will exploit handed, or chiral, ligands to develop rare examples of catalytic radical couplings that selectively deliver a single isomer of a chiral product - either left or right handed - and the first ever such catalytic processes using SmI2. Throughout the project, we will use our unrivalled experience in the computational modelling of SmI2 chemistry to underpin our studies and we will showcase the power of our new catalysis by preparing molecules or relevance to drug discovery.Prior to our breakthrough publications in 2019 and 2021, catalysis, through the union of radical relays and SmI2, was unknown; this leaves us in a unique position to undertake the proposed project and provide powerful new tools for molecule-makers, thus benefiting molecule-users, and making major scientific and societal impact.