Sustainable Transitions -Metal Catalysts for Radical Reactions

自由基是构建复杂分子的多功能中间体。它们可以在温和的条件下生成，它们的成键反应是可预测的，并且它们对官能团的耐受性高。然而，自由基在可持续合成中的潜力在很大程度上仍未开发。这有两个原因。首先，以传统方式进行链式反应的自由基反应导致产生化学计量的废物，这在环境上是不可接受的;当使用锡铅时，废物具有高度毒性。其次，自由基反应很少在催化下进行。在拟议的工作中，可持续催化的原则将被应用于自由基化学。这将以跨学科的方式完成，将量子化学家（格里姆），机械无机化学家（诺顿）和合成方法化学家（Gansäuer）与通过自由基环化合成生物活性化合物的专家（李）相结合。本提案中研究的第一行过渡金属（V，Ti，Co和Cr）非常适合可持续催化。它们在使用的氧化态下是无毒的，并且将取代使用稀有和昂贵金属Ir和Rh的络合物的旧系统。采用fib作为末端还原剂将解决长期存在的与还原自由基反应相关的环境和毒性问题。将合成新的催化剂，并将量子化学方法用于虚拟催化剂筛选和机理确定。可持续的方法将被开发用于催化氢介导的环氧化物还原为醇，用于催化还原自由基环化与血红蛋白作为唯一的化学计量试剂，和用于催化自由基环异构化的各种二烯，烯炔和环氧。这些方法将被应用于功能化的八元和九元环内酰胺和环胺的高效、通用和立体选择性合成，以及多环Aspidosperma和Kopsia吲哚生物碱如voafinidine和grandilodine A的合成。

Radicals are versatile intermediates for construction of complex molecules. They can be generated under mild conditions, their bond-forming reactions are predictable, and their tolerance of functional groups is high. However, the potential of radicals in sustainable synthesis remains largely untapped. This is so for two reasons. First, conducting radical reactions as chain processes in the traditional way results in the environmentally inacceptable generation of stoichiometric amounts of waste; when tin hydrides are used, the waste is highly toxic. Second, radical reactions have seldom been carried out catalytically. In the proposed work the principles of sustainable catalysis will be applied to radical chemistry. This will be done in an interdisciplinary manner, combining a quantum chemist (Grimme), a mechanistic inorganic chemist (Norton), and a synthetic methods chemist (Gansäuer) with a specialist in the synthesis of biologically active compounds by radical cyclizations (Li). The first-row transition metals investigated in this proposal (V, Ti, Co, and Cr) are ideally suited for sustainable catalysis. They are nontoxic in the Oxidation states to be used, and will replace older Systems employing complexes of the rare and expensive metals Ir and Rh. Employing fib as the terminal reductant will resolve the longstanding environmental and toxicity issues associated with reductive radical reactions. New catalysts will be synthesized and quantum chemical methods used for virtual catalyst screening and mechanism determination. Sustainable methods will be developed for catalyzing the hydrogen-mediated reduction of epoxides to alcohols, for catalyzing reductive radical cyclizations with Hb as the only stoichiometric reagent, and for catalyzing radical cycloisomerizations by various dienes, enynes and epoxyenes. These methods will be applied into the efficient, general and stereoselective synthesis of functionalized eight- and nine-membered ring lactams and cyclic amines, and to the synthesis of polycyclic Aspidosperma and Kopsia indole alkaloids such as voafinidine and grandilodine A.