Mechanistically guided improvement in radical alkene coupling by base metal catalysts

项目摘要/摘要 HAT(氢原子转移)烯烃反应提供了未活化的官能化的机会 在温和的条件下生成高度取代的碳中心，这些碳中心在 生物活性分子。但是，烷烃反应催化剂的合理设计 更高的产量、更快的速度和更少的浪费目前由于缺乏机械而受到阻碍 信息。一个特别的挑战是发现结构和反应性趋势 执行关键HAT步骤的氢化物络合物。拟议的项目旨在改善 催化剂中金属氢化物和自由基中间体的研究 HAT-烯烃反应的循环，从烯烃交叉偶联开始，继续到其他 烯烃加氢功能化反应。这些研究的预期结果是，帽子 在室温或更低的温度下，烯烃反应将成为可能，具有高的化学选择性， 区域选择性和立体选择性。这将包括对映体选择性的第一个例子。 这是烯烃反应。私家侦探帕特里克·霍兰德是机械研究方面的专家， 顺磁性铁-烷基和铁-氢化物，该项目将提供严格的 鉴定与之相关的结构、光谱、反应和机理 催化循环。第一个资助期的一个特别焦点将是铁催化的还原剂 烯烃的交叉偶联，我们将利用我们发现的重要但尚未实现的 该机制的一些方面，如从金属-质子耦合电子转移的存在- 酒精种类。学到的经验教训将适用于激进的C-C和C-N大家族 由锰、钴、铁催化的键偶联反应。这些进步将使帽子 烯烃反应更温和和更高产率，将最大限度地减少副产品/废物，并将 为制备与生物相关的产品提供更广泛的底物。 烯烃交叉偶联反应的对映选择性形式将提供一条新的路线 在天然产品和生物活性中有用的大量取代的、固定定义的碳位置 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.