CAS: Understanding and Controlling the Selectivity of Catalytic Metal-Free C-H Functionalizations

在化学系化学催化项目的资助下，华盛顿大学的Forrest Michael正在研究如何使用更丰富、更经济的元素作为昂贵的过渡金属催化剂的替代品，在复杂的有机分子中引入新的功能。随着国家渴望实现更绿色、更可持续的未来，我们必须找到新的催化剂，以实现成本更低、更可持续的价值综合转化。构建新分子的一种强大而有效的方法是选择性地激活这些结构中的许多碳-氢键之一，并用新的化学基团取代该氢。虽然许多金属基催化剂可用于此目的，但该提案解决了两个主要挑战。首先，正在开发基于硒的新催化剂，作为现有金属基方法的潜在更经济的替代品。其次，由于复杂的有机分子具有许多不同类型的碳-氢键，因此将研究控制单个氢原子选择性取代的基本因素，并将利用这些知识设计制造分子的新方法。这项工作的更广泛影响包括更可持续地获得具有新生物，药物和材料特性的新分子。此外，迈克尔教授还通过与卓越教育中心和研究科学研究所的合作，在美国和世界各地培养有科学天赋的高中生，进行化学前沿研究，并在实验室的研究项目中指导他们。 在化学系化学催化计划的资助下，华盛顿大学的Forrest Michael正在研究是什么空间、电子和结构因素控制了他实验室开发的新型硒络合物催化的C-H活化的高区域和立体选择性。对这些因素的系统探索将可能使这些催化剂在合成中得到更广泛的应用，因为它允许提前预测和设计具有高选择性的底物和催化剂。鉴定强烈指导C-H活化但也可以容易地转化为各种新取代基的官能团将可能使在复杂化合物中安装氮基团的新合成策略成为可能。此外，从这些研究中获得的更完整的机理理解将扩大可以使用这些反应引入的氮基团的范围，并导致新的反应模式。在这些转换的基本反应机制和关键中间体将通过测试的配体和添加剂的影响，并通过检查中间体的多核（1H，31 P，77 Se）NMR光谱进行研究。迈克尔博士通过与卓越教育中心和研究科学研究所的合作，参与了一些外展活动，指导具有高度天赋和才华的高中科学家。该奖项反映了NSF的法定使命，并通过使用基金会的智力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 funding from the Chemical Catalysis Program of the Chemistry Division, Forrest Michael of the University of Washington is studying how to use more abundant and economical elements as replacements for expensive transition metal catalysts to introduce new functionality in complex organic molecules. As the nation aspires toward a greener, more sustainable future, it is critical that we find new catalysts for synthetic transformations of value that are less expensive and more sustainable. One powerful and efficient way to build new molecules is by selective activation of one of the many carbon-hydrogen bonds in these structures and substitution of that hydrogen with a new chemical group. Though many metal-based catalysts can be used for this purpose, this proposal addresses two major challenges. First, new catalysts based on selenium are being developed as potentially more economical alternatives to existing metal-based methods. Second, because complex organic molecules possess many different types of carbon-hydrogen bonds, the fundamental factors that control the selective replacement of individual hydrogen atoms will be studied and this knowledge will be used to design new ways to make molecules. The broader impacts of this work include more sustainable access to new molecules with novel biological, pharmaceutical, and materials properties. Additionally, Prof. Michael trains scientifically-talented high school students in the US and around the world about cutting-edge research in chemistry and mentors them in research projects in his laboratory, through his work with the Center for Excellence in Education and the Research Science Institute. With funding from the Chemical Catalysis Program of the Chemistry Division, Forrest Michael of the University of Washington is studying what steric, electronic, and structural factors control the high regio- and stereoselectivity of C-H activation catalyzed by novel complexes of selenium developed in his laboratory. Systematic exploration of these factors will likely enable the more widespread use of these catalysts in synthesis by allowing substrates and catalysts that give high selectivity to be predicted and designed ahead of time. Identification of functional groups that strongly direct C-H activation, but which also can be easily transformed into a wide variety of new substituents will likely enable new synthetic strategies for installation of nitrogen groups in complex compounds. Furthermore, the more complete mechanistic understanding obtained from these studies will expand the scope of nitrogen groups that can be introduced using these reactions and lead to new modes of reactivity. The fundamental reaction mechanisms and key intermediates in these transformations will be studied by testing the effects of ligands and additives and by examining intermediates by multi-nuclear (1H, 31P, 77Se) NMR spectroscopy. Dr. Michael is engaged in outreach activities that mentor highly gifted and talented high school scientists through his work with the Center for Excellence in Education and the Research Science Institute.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.