CAS: Catalytic Stereoselective Fragment Coupling Reactions of Feedstock Chemicals

将丰富的化学原料有效地转化为具有生物学重要性的手性分子的新转化的发展对生物学和医学的未来发展至关重要。在这个项目中，米克博士正在开发催化的多组分碳-碳键形成反应，将碳氢化合物与普通分子片段连接起来。这种转变为合成新的复杂分子提供了一种创新的策略，此外还提供了比现有方法更经济和制造的优势。米克博士和他的团队正在证明，通过使用富含地球元素的过渡金属催化剂，现成的起始材料可以转化为合成用途广泛的反应性中间体，从而提供具有医学意义的非常特定的产品结构。Meek博士积极参与建立在他的研究基础上的外展活动，并专注于展示化学合成和催化对社会的有利影响的主题。这些活动包括增加各种背景的本科生的参与，并将广泛的教育内容纳入各级课程，旨在加强所有学生的STEM教育，并为培养下一代科学家创造有利的环境。该团队还计划整合和扩大他们已建立的外展活动（例如，AM-WISE，北卡罗来纳大学（UNC）科学博览会，全国黑人化学家和化学工程师专业发展组织（NOBCChE），以及他们的nsf资助的北卡罗来纳大学本科生研究经验（REU）计划）。在这个由化学部化学合成计划资助的项目中，Meek博士和他的北卡罗来纳大学教堂山分校的研究生和本科生团队开发了立体选择性镍催化的烯烃片段偶联反应。这些转化表现出高水平的对映选择性和非对映选择性，这对于合成难以获得的分子实体具有更大的时间和成本效益至关重要，这些特性对学术和工业合成化学都很重要。一般来说，这些多组分工艺包括通过氧化过程催化立体选择性生成手性烷基镍，然后与各种碳亲核试剂偶联以提供一系列产品。反应生成两个新键和最多三个新的立体中心，除了醇、胺和羰基官能团外，还可以生成叔、季立体中心。该研究将影响手性配体设计领域，并将刺激富过渡金属催化和方法开发领域。Meek博士积极参与外展活动，重点是提高学生对STEM教育的接触，增加代表性不足群体对科学的参与，并扩大科学知识的传播。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。

The development of new transformations that convert abundant chemical feedstocks efficiently into chiral molecules of biological importance is essential to the future advances in biology and medicine. In this project, Dr. Meek is developing catalytic, multicomponent carbon-carbon bond-forming reactions that link hydrocarbons with common molecular fragments. Such transformations provide an innovative strategy for synthesizing new complex molecules, in addition to providing economic and manufactural advantages over current methods. By using earth abundant transition metal catalysts, Dr. Meek and his team are demonstrating that readily available starting materials can be converted into synthetically-versatile, reactive intermediates to deliver very specific product structures with medical-relevance. Dr. Meek is actively engaged in outreach activities that build upon his research and focus on topics that demonstrate the enabling impact chemical synthesis and catalysis have on society. These activities, which include increasing participation of undergraduate students of all backgrounds and incorporating broad educational components into courses at various levels, are aimed towards enhancing all students’ STEM education and creating supportive environments for fostering next-generation scientists. This team also plans to integrate and expand their established outreach activities (e.g., AM-WISE, University of North Carolina (UNC) Science Expo, National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE), and their NSF-funded UNC Research Experiences for Undergraduates (REU)program).In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Dr. Meek and his team of graduate and undergraduate students at the University of North Carolina at Chapel Hill, develop stereoselective nickel-catalyzed fragment coupling reactions of olefins. These transformations exhibit high levels of enantio- and diastereoselectivity essential for rendering the syntheses of difficult-to-access molecular entities substantially more time and cost effective – properties that are of importance to both academic and industrial synthetic chemistry. In general, these multicomponent processes involve the catalytic stereoselective generation of chiral nickel–alkyl species through an oxidative process, followed by coupling with a variety of carbon nucleophiles to afford a range of products. Reactions result in the formation of two new bonds and up to three new stereocenters, and allow for the generation of tertiary and quaternary stereocenters in addition to alcohol, amine, and carbonyl functionality. This research impacts areas of chiral ligand design and will stimulate areas of catalysis and method development with earth abundant transition metals. Dr. Meek is actively engaged in outreach activities that focus on enhancing students’ exposure to STEM education, increasing the participation of underrepresented groups in science, and broadening the dissemination of scientific knowledge.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.