Mechanism-driven Development of Mo catalysts for Z-selective Isomerization of Terminal Olefins

在化学学部化学催化项目的支持下，天普大学的Graham Dobereiner正在研究如何利用催化剂重新排列有机分子中的特定化学键。重新排列的分子在制造药物和其他精细化学品方面具有潜在的用途。除了寻求对催化现象的更大控制外，项目团队正在努力用更富土的替代品取代通常用作催化剂的稀有铂族金属。该项目将加强学术化学与工业之间的互动，并通过天普大学和葛兰素史克的研究人员之间的合作，帮助培养学生从事药物化学的职业。PI将通过让学生参加定期的无机化学家区域会议来促进费城地区STEM（科学、技术、工程和数学）的参与。PI还将通过与费城学区（SPD）高中学生的互动活动来支持中学STEM教育。天普大学的这个项目正在为末端烯烃的z选择性异构化构建有机钼催化剂，这是迄今为止罕见的合成转化。假设是，钼配合物与立体要求半可溶配体可以用来控制立体化学结果比最先进的催化剂更有效。为了验证这一假设，将比较具有不同配体空间性质的配合物的异构化选择性、作用范围和活性。催化机理将通过实验和计算进行探索，以完善z选择性的工作模型。正在开发的新型催化剂将用于串联转化，目标是具有工业意义的高价值有机化合物。化学计量学研究、计算设计和动力学分析的混合将为异构化选择性模型提供信息，从而为均相催化提出合理的设计概念。这些模型的发展将作为控制以烯烃为中心的反应的立体化学结果的框架，这是合成有机化学的一个至关重要的领域。除了对催化剂设计产生重大影响外，所开发的方法在顺式烯烃及其衍生物的生产中也很有价值，通过与葛兰素史克公司之前建立的合作，在药物开发中有潜在的重要应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Catalysis program in the Division of Chemistry, Graham Dobereiner of Temple University is studying how to rearrange specific chemical bonds in organic molecules using catalysts. The rearranged molecules are potentially useful for making pharmaceuticals and other fine chemicals. Besides seeking greater control of the phenomenon of catalysis, the project team is working to replace rare platinum-group metals typically used as catalysts with more earth abundant alternatives. The project will strengthen interactions between academic chemistry and industry and help train students for careers in medicinal chemistry via collaboration between investigators at Temple University and GlaxoSmithKline. The PI will bolster STEM (science, technology, engineering and mathematics) participation in the Philadelphia region by involving students in a regular, regional meeting for inorganic chemists. The PI will also support secondary STEM education through interactive activities with students from School District of Philadelphia (SPD) high schools.This project at Temple University is building organomolybdenum catalysts for the Z-selective isomerization of terminal alkenes - to date a rare synthetic transformation. The hypothesis is that molybdenum complexes with sterically demanding hemilabile ligands can be used to control stereochemical outcomes more effectively than state-of-the-art catalysts. To test the hypothesis, complexes with varying ligand steric properties will be compared in their isomerization selectivity, scope, and activity. Catalytic mechanisms will be probed experimentally and computationally to refine the working model of Z-selectivity. New catalysts under development will be employed in tandem transformations, targeting high-value organic compounds with industrial relevance. The blending of stoichiometric studies, computational design and kinetic analysis will inform models for isomerization selectivity to advance a rational design concept for homogeneous catalysis. The development of these models will serve as a framework for controlling stereochemical outcomes of alkene-focused reactions, an area of critical importance to synthetic organic chemistry. Besides having a significant impact on catalyst design, the methods developed will be valuable in the production of cis-alkenes and their derivatives, with potentially important applications in drug development to be exploited via a previously established collaboration with GlaxoSmithKline.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.