Nickel Catalyzed Electrochemical C-C Cross-Coupling Reactions

项目摘要。本提案描述了刘(Pi)和Ess(co-Pi)的合作研究活动 发展高效、可持续、绿色的镍(Ni)催化的电化学交叉偶联 药物和生物活性分子制造中的合成应用反应和综合教育 旨在促进本科生和研究生研究经验的活动。特别强调 将被放在吸引和培训代表不足的美洲原住民学生上。新知识 从这项拟议的研究中获得的结果将为发展有竞争力和原子经济性的产品提供指导 电合成方法及其在药物和生物活性分子开发中的应用 增进人类健康，促进社会可持续发展。 在此，我们提出可以实现氧化还原中性的电化学C？C交叉偶联反应 在使用工作台稳定的亲电体(芳基卤化物、烯基卤化物和炔基)的未分割单元构型中 卤化物)和亲核试剂(有机三氟硼酸盐、羧酸盐和胺)，非贵重的，稳定的 在环境条件下由NiII前催化剂和聚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范围广、产率高。 通过50个芳基/β-苯乙烯基氯/溴和三氟硼酸苄酯的例子。它们的潜在应用是 药物、天然氨基酸的电合成和后期功能化 使用流动电池电解槽进行改性和可扩展合成。 在未来，我们计划扩大亲电性和亲核性的底物范围，并进一步 开发流动槽电解槽技术，以实现最佳反应效率和可扩展的合成。在……里面 此外，我们将进行全面的实验和计算研究，以获得深入的机理 理解。这种电化学C？C交叉耦合范例预计将是高效的和 原子经济，并将在开发药物和生物活性方面得到广泛应用 分子。所获得的知识将对开发其他金属基(如铁和钴)产生广泛影响 以及甚至无金属的电化学反应C-C、C-N和C-O，以及C-S偶联等电化学反应 有机的转变。此外，这项建议还将为本科生提供丰富的研究机会 学生(尤其是美国原住民本科生)，这将扩大他们在健康领域的职业视野 科学。这一领域的拨款对PI的实验室以及为以下方面提供研究和指导机会至关重要 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.