Merging Computation and Experiment to Understand and Develop Asymmetric Open-Shell Radical Cross-Couplings

结合计算和实验来理解和开发非对称开壳径向交叉耦合

• 批准号: 10025776
• 负责人: Osvaldo Gutierrez
• 金额: $ 38.23万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10025776
• 关键词: Area; Carbon; Catalysis; Chemicals; Communities; Complex; Coupling; Data; Development; Electron Transport; Goals; Health; Human; Iron; Knowledge; Mechanics; Methods; Molecular; Potential Energy; Property; Reaction; Reagent; Research; Surface; Transition Elements; catalyst; chemical reaction; computerized tools; design; experimental study; high throughput screening; improved; molecular modeling; predictive modeling; prevent; programs; quantum

PROJECT SUMMARY/ABSTRACT Despite advances in high-throughput screening methods leading to a surge in the discovery of catalytic reactions, our knowledge of the molecular-level interactions in the rate- and selectivity-determining steps of catalytic reactions involving highly unstable and reactive open-shell intermediates is rudimentary. These knowledge gaps prevent control, suppression or enhancement, of competing reaction channels that can drive development of new catalytic reactions. Built on strong computational and experimental preliminary results, this program seeks to understand and guide design of new sustainable, catalytic, and asymmetric transformations. Overall, our goals are to develop predictive models of reactivity and selectivity of first-row, open-shell transition metal-catalyzed carbon-carbon bond formations that can be adapted by the organic, organometallic, and bio(in)organic community in the synthesis of medicinally-active compounds. To accomplish this overarching goal, we have identified two areas of research for the next 5 years and plans for beyond. In the first area, we will use combined experimental and computational tools to understand and develop new asymmetric iron-catalyzed radical cascade/cross-coupling reactions. In the second area, through collaborative efforts, we will target the synthesis of quaternary centers via metallophotoredox-catalyzed cross-couplings. These reactions proceed through carbon-centered radical intermediates, open-shell organometallic species, and photoexcited electronic state species where evaluating the mechanisms has been historically hampered by the inherent complexity associated with the high reactivity and instability of these species. High-level quantum mechanical calculations, rigorously calibrated against experimental data, will be used to interrogate the mechanisms and to guide the development of new catalysts and reagents for currently sluggish or unselective reactions. In addition, we will exploit selected potential energy surfaces susceptible to dynamic effects, single-electron transfers, and intersystem crossings to gain a deeper understanding of the factors determining product selectivity and inform catalyst and reaction design. Overall, these efforts will push the limits of accurate molecular modeling of increasing complex catalytic reactions and potentially impact the fields of organic, bio(in)organic, and transition-metal catalysis.

项目概要/摘要 尽管高通量筛选方法的进步导致催化活性的发现激增 反应，我们对速率和选择性决定步骤中分子水平相互作用的了解 涉及高度不稳定和反应性开壳中间体的催化反应还处于初级阶段。这些 知识差距阻碍了对可驱动的竞争反应通道的控制、抑制或增强 开发新的催化反应。基于强大的计算和实验初步结果，这 该计划旨在理解和指导新的可持续、催化和不对称转型的设计。 总体而言，我们的目标是开发第一排开壳反应性和选择性的预测模型 过渡金属催化的碳-碳键形成，可以通过有机、有机金属、 和生物（内）有机群落在药物活性化合物的合成中的作用。为了实现这一点 为了实现总体目标，我们确定了未来 5 年的两个研究领域以及未来的计划。在 第一个领域，我们将使用组合的实验和计算工具来理解和开发新的 不对称铁催化自由基级联/交叉偶联反应。在第二个领域，通过协作 我们的努力目标是通过金属光氧化还原催化的交叉偶联合成四元中心。 这些反应通过以碳为中心的自由基中间体、开壳有机金属物质、 和光激发电子态物质，其机制的评估历来受到阻碍 与这些物种的高反应性和不稳定性相关的固有复杂性。高级别 根据实验数据严格校准的量子力学计算将用于询问 机制并指导新催化剂和试剂的开发，以解决当前缓慢或 非选择性反应。此外，我们将利用选定的易受动态影响的势能表面 效应、单电子转移和系间交叉，以更深入地了解这些因素 确定产物选择性并为催化剂和反应设计提供信息。总体而言，这些努力将推动 日益复杂的催化反应的精确分子建模的局限性并可能影响该领域 有机、生物（无机）有机和过渡金属催化。