Sustainable Transitions -Metal Catalysts for Radical Reactions

自由基是构建复杂分子的多种中间体。它们可以在温和的条件下生成，其成键反应是可预测的，并且它们对官能团的耐受性很高。然而，自由基在可持续合成中的潜力在很大程度上仍未被开发。这是有两个原因的。首先，以传统方式进行连锁反应会产生化学计量比的废物，这在环境上是不可接受的；当使用锡氢化物时，废物是剧毒的。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应用于基础化学。这将以跨学科的方式完成，将一名量子化学家(Grimme)、一名机械论无机化学家(Norton)和一名合成方法化学家(Gansäuer)与一名通过自由基环化合成生物活性化合物的专家(Li)结合在一起。本方案中研究的第一排过渡金属(V、钛、钴和铬)非常适合用于可持续催化。它们在将要使用的氧化态下是无毒的，并将取代使用稀有和昂贵金属Ir和Rh的络合物的旧系统。使用FIB作为末端还原剂将解决与还原自由基反应相关的长期存在的环境和毒性问题。将合成新的催化剂，并利用量子化学方法进行虚拟催化剂的筛选和机理确定。可持续的方法将被开发用于催化氢催化的环氧化物还原为醇，用于催化以Hb为唯一化学计量比试剂的还原自由基环化反应，以及用于催化各种二烯、烯炔和环氧烯的自由基环异构化。这些方法将被应用于功能化八元环和九元环内酰胺和环胺的高效、通用和立体选择性的合成，以及多环无精子植物和Kopsia indole生物碱的合成，如伏非尼定和格列罗定A。

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.