Sustainable Electron-Transfer Processes for the Synthesis and Functionalization of Nitrogen-Containing Compounds

有机化学在化学科学中占据中心地位，因为通过它的发展，它赠款获得对其他科学的进步和最终社会福祉至关重要的新分子系统和材料。产生碳-氮键的能力是有机合成中最重要的目标之一，因为含氮化合物广泛用作治疗剂，农用化学品，有机染料和材料：例如，20种最畅销的药物都含有C-N键。从这个角度来看，现在变得越来越重要的不仅是能够创造新的和复杂的分子，而且还要确定可以以更有效，选择性和可持续的方式获得它们的新方法。事实上，化学合成中的成本、毒性和废物产生等因素迫切需要解决。联合国大会第68届会议宣布2015年为国际光和光基技术年。这次大会的一个重要结论是认识到“必须提高全球对光基技术如何促进可持续发展和为能源、教育、农业和卫生领域的全球挑战提供解决方案的认识”。我的研究金的总体目标是通过开发全新的催化方法来解决这一关键问题，这些方法能够利用可见光作为能源来构建C-N键。通过这种方式，我们将提供独特的反应，通过方便地获得N-自由基来简化含N分子的合成。该项目分为4个不同但互补的部分，旨在解决与化学合成，生物学和材料中应用的C-N键形成相关的特定挑战。1.我们将使用可见光，使新的电子转移反应，将产生胺基和酰胺基自由基。在这里，我们将开发不同的方法添加N和H，以及N和O原子在烯烃形成环胺和酰胺。然后，我们将使用这些活化模式来产生一系列广泛的多官能化分子，如具有定义的3D形状的二胺，氨基（二）醇，氨基硫醇，二氨基醇和硫代氨基醇。2.这些可见光介导的转化将通过开发多组分反应来扩展。在这里，我们将开发的过程中，各种反应伙伴将顺序反应周围的关键电子转移歧管，以提供多官能化的N-化合物。因此，我们将提供创新的流形，将结合联合收割机高原子，步骤和时间经济性与分子多样化的巨大可能性3。促进立体限定的C-N键形成的催化方案的开发是非常重要的，特别是在其中3D分子被认为具有更高的临床成功机会的治疗背景下。我们提出了一种新的策略，使用手性催化剂的基础上使用氮自由基的不对称合成。目前还没有实现所提出的那种转换的方法。非活化C-H键的受控官能化是当前有机化学中最具挑战性的任务之一，但具有简化许多化合物合成的潜力。在此，我们将开发未活化的C-H键的远程功能化，通过利用氮中心自由基进行C-H提取反应的能力。该研究计划的成功实施将提供新颖和可持续的方法，使含氮化合物的合成更快，更环保，更高效。促进小分子药物、生物探针、农用化学品和材料的鉴定和制备的方法的开发将影响英国社会的健康和福祉。

Organic chemistry occupies a central position within the chemical sciences because through its development it grants access to new molecular systems and materials that are vital to the advancement of other sciences and ultimately the wellbeing of society. The ability to create carbon-nitrogen bonds is one of the most important goals in organic synthesis as nitrogen-containing compounds are widespread as therapeutic agents, agrochemicals, organic dyes and materials: as an example, the 20 top-selling drugs all contain C-N bonds. From this perspective, it is now becoming increasingly important not just to be able to create new and complex molecules but also to identify novel methods that can access them in a more efficient, selective and sustainable way. In fact, factors such as cost, toxicity and waste production in chemical synthesis urgently needs to be addressed. The United Nations General Assembly 68th Session has proclaimed 2015 as the International Year of Light and Light-based Technologies. A key conclusion of this assembly was the recognition about "the importance of raising global awareness about how light-based technologies promote sustainable development and provide solutions to global challenges in energy, education, agriculture and health". The overarching aim of my Fellowship is to address this crucial problem by developing fundamentally new catalytic methods that enable the construction of C-N bonds harnessing visible-light as the source of energy. In this way we will provide unique reactions that will streamline the synthesis of N-containing molecules by enabling easy access to N-radicals.The project is divided in 4 different but complementary parts aimed at addressing specific challenges relevant to the formation of C-N bonds with applications in chemical synthesis, biology and materials.1. We will use visible-light to enable novel electron transfer reactions that will generate aminyl and amidyl radicals. Here we will develop divergent methods for the addition of N and H, as well as N and O atoms across alkenes to form cyclic amines and amides. Then, we will use these activation modes for the generation of a broad series of poly functionalised molecules like diamines, amino (di)alcohol, aminothiols, diamino alcohols and thio-aminoalcohols with defined 3D shapes. 2. These visible-light-mediated transformations will be expanded by developing multicomponent reactions. Here we will develop processes where various reaction partners will sequentially react around the key electron transfer manifold to deliver polyfunctionalised N-compounds. Thus we will provide innovative manifolds that will combine high atom-, step-, and time-economy with great possibilities for molecular diversification3. The development of catalytic protocols that facilitate the formation of stereo defined C-N bonds is of great importance, especially in a therapeutic context in which 3D molecules are acknowledged to have a higher chance of clinical success. We propose to develop a novel strategy based on the use of chiral catalysts to use nitrogen-radicals in asymmetric synthesis. There is no method for carrying out the kind of transformation which is proposed.4. The controlled functionalization of non-activated C-H bonds is one of the most challenging tasks in current organic chemistry but has the potential to streamline the synthesis of many compounds. Here, we will develop remote functionalizations of unactivated C-H bonds by harnessing the ability of nitrogen-centered radicals to undergo C-H abstraction reactions.The successful implementation of this research program will deliver novel and sustainable methods that can make the synthesis of nitrogen-containing compounds quicker, greener and more efficient. The development of methods that facilitate the identification as well as the preparation of small molecule drugs, biological probes, agrochemicals and materials will impact the health and wellbeing UK society.