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

CAS：了解和控制催化无金属 C-H 官能化的选择性

• 批准号: 2102267
• 负责人: Forrest Michael
• 金额: $ 47.5万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102267&HistoricalAwards=false
• 关键词: CAS; Understanding; Controlling; Selectivity; Catalytic

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.

在化学系化学催化项目的资助下，华盛顿大学的福雷斯特·迈克尔正在研究如何使用更丰富和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。随着美国向往一个更绿色、更可持续的未来，我们必须为更便宜、更可持续的价值合成转型找到新的催化剂，这一点至关重要。构建新分子的一种有效而有效的方法是选择性地激活这些结构中的一个碳氢键，并用一个新的化学基团取代那个氢键。尽管许多金属催化剂可以用于这一目的，但这项提议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，我们将研究控制单个氢原子选择性取代的基本因素，并将利用这些知识来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的生物、药物和材料特性的新分子。此外，Michael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训有科学天赋的高中生进行化学前沿研究，并在他的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，华盛顿大学的福雷斯特·迈克尔正在研究是什么空间、电子和结构因素控制了由他的实验室开发的新型硒配合物催化的高区域和立体选择性的C-H活化。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使用，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。识别那些强烈指导C-H活化，但也可以很容易地转化为各种新取代基的官能团，可能会使在复杂化合物中安装氮基的新的合成策略成为可能。此外，从这些研究中获得的更完整的机理理解将扩大使用这些反应引入的氮基团的范围，并导致新的反应模式。将通过测试配体和添加剂的影响以及通过多核(1H，31P，77Se)核磁共振检查中间体来研究这些转化中的基本反应机理和关键中间体。Michael博士通过在教育卓越中心和研究科学研究所的工作，参与了指导才华横溢的高中科学家的外展活动。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Metal‐Free Allylic C−H Amination of Vinylsilanes and Vinylboronates using Silicon or Boron as a Regioselectivity Switch

使用硅或硼作为区域选择性开关对乙烯基硅烷和乙烯基硼酸酯进行无金属烯丙基 C-H 胺化

• DOI: 10.1002/anie.202210109
• 发表时间: 2022
• 期刊: Angewandte Chemie International Edition
• 作者: Maloney, T. Parker;Berman, Janna L.;Michael, Forrest E.
• 通讯作者: Michael, Forrest E.

C−H Functionalization and Allylic Amination for Post‐Polymerization Modification of Polynorbornenes

用于聚降冰片烯聚合后改性的 C–H 官能化和烯丙基胺化

• DOI: 10.1002/anie.202303174
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Gitter, Sean R.;Teh, Wei Pin;Yang, Xuejin;Dohoda, Alexander F.;Michael, Forrest E.;Boydston, Andrew J.
• 通讯作者: Boydston, Andrew J.

Metal-Free Intermolecular Allylic C–H Amination of Alkenes Using Primary Carbamates

使用伯氨基甲酸酯对烯烃进行无金属分子间烯丙基 C–H 胺化

• DOI: 10.1021/acscatal.3c00807
• 发表时间: 2023
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Obenschain, Derek C.;Tabor, John R.;Michael, Forrest E.
• 通讯作者: Michael, Forrest E.

Upcycling of Polybutadiene Facilitated by Selenium‐Mediated Allylic Amination

硒介导的烯丙基胺化促进聚丁二烯的升级循环

• DOI: 10.1002/anie.202303115
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Hodges, Mercie N.;Elardo, Matthew J.;Seo, Jinyoung;Dohoda, Alexander F.;Michael, Forrest E.;Golder, Matthew R.
• 通讯作者: Golder, Matthew R.