Mechanistically guided improvement in radical alkene coupling by base metal catalysts

项目总结/摘要 HAT（氢原子转移）烯烃反应提供了将未活化的 烯烃在温和条件下，产生高度取代的碳位点， 生物活性分子。然而，HAT烯烃反应催化剂的合理设计 更高的产量，更快的速度，更少的浪费，目前阻碍了缺乏机械 信息.一个特别的挑战是发现的结构和反应性的趋势， 氢化物络合物，执行关键的HAT步骤。拟议项目旨在改善 通过研究HAT烯烃反应中金属离子和自由基中间体的催化作用， HAT烯烃反应的循环，从烯烃交叉偶联开始并继续到其它 烯烃氢官能化反应。这些研究的预期结果是， 烯烃反应将在室温或低于室温下进行，具有高的化学选择性， 区域选择性和立体选择性。这将包括对映选择性的第一个例子 HAT烯烃反应。PI，帕特里克荷兰，是一个专家，在机械研究与 顺磁性铁烷基和铁氢化物化合物，该项目将提供严格的 结构、光谱、反应和机制的鉴定， 催化循环第一个融资期的一个特别重点将是铁催化还原剂 烯烃的交叉偶联，我们将利用我们的发现，重要的，但未实现的 该机制的各个方面，如从金属质子耦合电子转移的存在， 酒精种类所吸取的教训将适用于一个广泛的家庭激进的C-C和C-N Mn、Co和Fe催化的键偶联反应。这些进步将使HAT 烯烃反应更温和和更高产率，将使副产物/废物最小化，并将 适用于制备生物相关产品的更广泛的基质。 烯烃交叉偶联反应的对映选择性版本将提供一种新的途径， 可用于天然产物和生物活性物质中的高度取代的立体定向的碳位点， 分子。

Project Summary/Abstract HAT (hydrogen atom transfer) alkene reactions offer the opportunity to functionalize unactivated alkenes under mild conditions, creating highly substituted carbon sites that are prevalent in biologically active molecules. However, the rational design of catalysts for HAT alkene reactions with higher yield, faster rates, and less waste is currently held back by a lack of mechanistic information. A particular challenge is the discovery of structure and reactivity trends for the hydride complexes that perform the key HAT step. The proposed project aims to improve the HAT alkene reactions through study of metal-hydrides and radical intermediates in the catalytic cycle of HAT alkene reactions, starting with alkene cross-coupling and continuing to other alkene hydrofunctionalization reactions. The expected outcome of these studies is that the HAT alkene reactions will become possible at or below room temperature, with high chemoselectivity, regioselectivity, and stereoselectivity. This will include the first examples of enantioselective HAT alkene reactions. The PI, Patrick Holland, is an expert in mechanistic studies with paramagnetic iron-alkyl and iron-hydride compounds, and the project will provide rigorous identification of the structures, spectroscopy, reactions and mechanisms that are relevant to the catalytic cycle. A special focus in the first funding period will be the iron-catalyzed reductive cross-coupling of alkenes, where we will leverage our discovery of important but unrealized aspects of the mechanism such as the presence of proton-coupled electron transfer from metal- alcohol species. The lessons learned will be applied to a broad family of radical C-C and C-N bond coupling reactions catalyzed by Mn, Co, and Fe. These advances will make the HAT alkene reactions milder and higher-yielding, will minimize byproducts/waste, and will accommodate a broader range of substrates for preparation of biologically relevant products. The enantioselective versions of the alkene cross-coupling reactions will provide a new route to heavily substituted, stereodefined carbon sites that are useful in natural products and bioactive molecules.