Nickel Catalyzed Electrochemical C-C Cross-Coupling Reactions

项目摘要。该提案描述了Liu（PI）和Ess（co-PI）的合作研究活动 致力于开发高效、可持续、绿色镍催化的电化学交叉偶联 用于制造药物和生物活性分子的合成应用的反应，以及综合教育 旨在促进本科生和研究生研究经验的活动。特别重点 将被放置在吸引和培训代表性不足的美洲原住民学生。新知识 从这项拟议的研究中获得的信息将为开发有能力的原子经济型 用于开发药物和生物活性分子的电合成方法， 促进人类健康，促进社会的可持续发展。 在此，我们建议，氧化还原中性电化学C？C交叉偶联反应可以完成 在使用工作台稳定的亲电试剂（芳基卤、烯基卤和炔基卤）的未分隔的电池配置中， 卤化物）和亲核试剂（有机三氟硼酸盐、羧酸盐和胺），非贵金属，工作台稳定 由Ni II预催化剂和多吡啶配体组成的催化剂。初步研究 证实了镍催化的电化学偶联反应具有较宽的反应范围和较好的产率 芳基/β-苯乙烯基氯/溴和苄基三氟硼酸酯的50个实例。它们的潜在应用是 通过电合成和后期功能化药物，天然氨基酸 改性和使用流动池电解槽的规模化合成。 在未来，我们计划扩大亲电试剂和亲核试剂的底物范围，并进一步 开发流动电池电解槽技术，以实现最佳反应效率和可扩展的合成。在 此外，我们将进行全面的实验和计算研究，以获得深入的机制， 理解。这种电化学C？C交叉耦合范例预计将是高生产力的， 原子经济，并将在开发药物和生物活性物质方面获得广泛的应用。 分子。所获得的知识将对开发其他金属基（如铁和钴）产生广泛的影响。 以及甚至无金属的电化学C-C、C-N和C-O以及C-S偶联反应和其它电化学反应。 有机转化。此外，该提案将为本科生提供丰富的研究机会， 学生（特别是美洲原住民本科生），这将扩大他们的职业视野，在健康 以理工科为重该地区赠款是必不可少的PI的实验室，并提供研究和指导的机会， 本科生和研究生。

Project Summary. This proposal describes the collaborative research activities by Liu (PI) and Ess (co-PI) towards developing highly effective, sustainable, green Nickel (Ni) catalyzed electrochemical cross-coupling reactions for synthetic applications in making pharmaceuticals and bioactive molecules, and integrated education activities aimed at promoting research experiences of undergraduate, and graduate students. Special emphases will be placed on attracting and training underrepresented Native American students. The new knowledge obtained from this proposed research will provide guidance in developing competent and atomically economic electrosynthesis approaches for their utilization in developing pharmaceuticals and bioactive molecules, thereby enhancing human health and enabling the sustainable development of our society. Herein, we propose that redox neutral electrochemical C?C cross-coupling reactions can be accomplished in an undivided cell configuration using bench-stable electrophiles (aryl halide, alkenyl halides, and alkynyl halides) and nucleophiles (organic trifluoroborate, carboxylates, and amines), non-precious, bench-stable catalysts consisting of a NiII pre-catalyst and polypyridine ligands under ambient conditions. Preliminary studies have confirmed the broad reaction scope and good yields of the Ni-catalyzed electrochemical coupling reactions by 50 examples of aryl/β-styrenyl chloride/bromide and benzyl trifluoroborates. Their potential applications were demonstrated by electrosynthesis and late-stage functionalization of pharmaceuticals, natural amino acid modification, and scalable synthesis using a flow-cell electrolyzer. In the future, we plan to expand the substrate scopes of both electrophiles and nucleophiles and further develop the flow-cell electrolyzer technology to achieve optimal reaction efficiency and scalable synthesis. In addition, we will conduct comprehensive experimental and computational studies to gain in-depth mechanistic understandings. This electrochemical C?C cross-coupling paradigm is expected to be highly productive and atomically economic and will find wide-spread applications in developing pharmaceuticals and bioactive molecules. The knowledge gained will have broad impacts on developing other metal based (e.g. Fe, and Co) and even metal free electrochemical C-C, C-N, and C-O, and C-S coupling reactions and other electrochemical organic transformations. In addition, this proposal will provide rich research opportunities for undergraduate students (particularly for Native American undergraduate students) that will enlarge their career vision in health sciences. This AREA grant is essential to the PI’s lab and to providing research and mentoring opportunities for undergraduate and graduate students.