Nickel-Catalyzed Three-Component Cross-Coupling with Unactivated Alkenes

高效地将可再生化学原料转化为有价值的产品，如药品、农用化学品和其他材料，是现代合成化学研究的核心挑战。烯烃(含有碳-碳双键(C=C)键的分子)是一类普遍存在、价格低廉、可大规模获得的原料。虽然烯烃长期以来一直被认为是合成有价值物质的重要起始原料，但目前化学家仍然很难将烯烃转化为许多类型的理想产品。在这个项目中，基里·M·恩格尔博士正在开发新的反应来填补这一空白。具体地说，通过使用少量廉价、无毒和富含稀土的镍催化剂，恩格尔博士的反应允许将烯烃用作连接到另外两种反应物的连接销，从而允许在反应物和烯烃之间形成本来难以形成的碳-碳单键。恩格尔博士和他的研究团队高度参与与他的研究协同的外展活动，以促进不同人群对科学、工程和数学(STEM)学科的参与。具体地说，这些努力包括为高中生和本科生提供实习机会，为科学家和普通公众开放获取与研究相关的信息，以及实施课堂教学的主动学习战略。这一研究项目有助于提高化学工业的可持续性和创新性，同时增加美国的技术劳动力。在化学部化学催化计划的资助下，斯克里普斯研究所的Keary M.Engle博士正在开发一种镍催化的三组分交叉偶联反应工具包，将烯烃转化为结构复杂的产品，这些产品在学术和工业中具有潜在的实用价值。特别是，恩格尔实验室正在开发战略性地使用近端螯合官能团来控制关键基本步骤并提高烯烃1，2-双官能化选择性的转化。结合反应动力学、有机金属合成和密度泛函理论(DFT)的详细机理研究正在进行，以阐明参与这些催化过程的关键有机镍中间体的反应性。通过利用这些机械论的见解，恩格尔博士正在将现有的基于辅助剂的方法转化为新的策略，这些策略利用天然官能团的方向性，以提高此类反应的效率、实用性和原子经济性。正在审查各种反应伙伴，包括那些能够形成具有挑战性的C(SP3)-C(SP3)和C(SP3)-杂原子键的反应伙伴。恩格尔博士和他的研究小组积极参与STEM推广计划，包括高中和本科实习计划，并通过各种媒体平台和创新的课堂教学计划向不同受众传播科学知识。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。

The efficient conversion of renewable chemical feedstocks into valuable products, such as medicines, agricultural chemicals, and other materials, is a central challenge in modern synthetic chemistry research. Alkenes (molecules that contain a carbon-carbon double bond (C=C) bond) are one class of feedstocks that are ubiquitous, inexpensive, and available on large scale. While alkenes have been long appreciated as important starting materials for the synthesis of valuable substances, at present it remains difficult for chemists to convert alkenes into many types of desirable products. In this project, Dr. Keary M. Engle is developing new reactions to fill this gap. Specifically, by using small quantities of an inexpensive, non-toxic, and earth-abundant nickel catalyst, Dr. Engle's reactions are allowing alkenes to be used as lynchpins to connect to two additional reactants, allowing for the formation of otherwise difficult to form carbon-carbon single bonds bonds between the reactants and the alkenes. Dr. Engle and his research team are highly engaged in outreach activities that are synergistic with his research in order to promote engagement with science, engineering, and mathematics (STEM) disciplines among diverse populations. Specifically, these efforts include internships for high school and undergraduate students, open-access sharing of research-relevant information for scientists and for the general public, and implementation of active-learning strategies for classroom teaching. This research project helps to improve the sustainability and innovation of the chemical industry while increasing the technical workforce of the United States.With funding from the Chemical Catalysis Program of the Chemistry Division, Dr. Keary M. Engle of The Scripps Research Institute is developing a toolkit of nickel-catalyzed, three-component, cross-coupling reactions to convert alkenes into structurally complex products that have potential utility in academia and industry. In particular, the Engle lab is developing transformations that strategically employ proximal chelating functional groups to control the key elementary steps and enhance selectivity for a desired 1,2-difunctionalization of alkenes. Detailed mechanistic studies combining reaction kinetics, organometallic synthesis, and density functional theory (DFT) are being carried out to elucidate the reactivity of key organonickel intermediates involved in these catalytic processes. By drawing on these mechanistic insights, Dr. Engle is translating existing auxiliary-based approaches to new strategies that take advantage of native functional groups for directivity, in order to improve the efficiency, utility, and atom-economy of such reactions. A diverse collection of reaction partners are being examined, including those capable of forming challenging C(sp3)-C(sp3) and C(sp3)-heteroatom linkages. Dr. Engle and his research group are actively engaged in STEM outreach programs, including high school and undergraduate internship programs, as well as disseminating scientific knowledge to diverse audiences through various media platforms and through innovative classroom teaching initiatives.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.