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

在化学部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、更经济的元素来替代昂贵的过渡金属催化剂，从而在复杂的有机分子中引入新的功能。随着国家追求更绿色、更可持续的未来，我们必须找到新的催化剂，以更便宜、更可持续的方式实现价值的综合转化。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众多碳氢键中的一个，并用新的化学基团取代那个氢。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，基于硒的新催化剂正在开发中，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拥有许多不同类型的碳氢键，控制单个氢原子选择性替换的基本因素将被研究，这些知识将用于设计制造分子的新方法。这项工作的更广泛的影响包括更可持续地获得具有新的生物、制药和材料特性的新分子。此外，Michael教授还在美国和世界各地培养有科学天赋的高中生，进行尖端化学研究，并通过他与卓越教育中心和研究科学研究所的合作，在他的实验室指导他们进行研究项目。在化学部化学催化项目的资助下，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由他实验室开发的新型硒复合物催化的碳氢活化的高区域和立体选择性。通过对这些因素的系统探索，可以提前预测和设计具有高选择性的底物和催化剂，从而可能使这些催化剂在合成中得到更广泛的应用。鉴定出强烈引导C-H活化，但也可以很容易地转化为各种新的取代基的官能团，可能会为在复杂化合物中安装氮基团提供新的合成策略。此外，从这些研究中获得的更完整的机理理解将扩大利用这些反应引入的氮基团的范围，并导致新的反应模式。通过测试配体和添加剂的作用，以及通过多核（1H, 31P, 77Se）核磁共振波谱检测中间体，将研究这些转化的基本反应机制和关键中间体。迈克尔博士通过他在卓越教育中心和科学研究所的工作，从事外联活动，指导极具天赋和才华的高中科学家。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 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.