Development of excited-state bond homolysis as a key step for Ni catalysis

激发态键均裂的发展作为镍催化的关键步骤

• 批准号: 10753322
• 负责人: Alexander Cusumano
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753322
• 关键词: Address; Catalysis; Chemicals; Chemistry; Chlorides; Complex; Coupling; Cyclization; Development; Drug Industry; Electron Transport; Electrons; Equipment; Generations; Goals; Libraries; Light; Literature; Medicine; Methods; Molecular; Outcome; Phenols; Photochemistry; Process; Reaction; Research; Resources; System; Transition Elements; Universities; improved; interest; irradiation; novel; oxidation; quantum; rational design; scaffold; small molecule; success; tool

Methods for bond construction enabling the synthesis of complex molecular scaffold are of key interest to the pharmaceutical industry. To this end, Ni catalysis has emerged as a versatile tool for the construction of C(sp2)– C(sp2), C(sp3)–C(sp2), and C(sp3)–C(sp3) bonds. The success of Ni in accomplishing these transformations lies in the ability of Ni to engage in both single- and two-electron processes – cycling through 0, I, II, and III oxidation states. As a result, in addition to canonical two-electron processes (migratory insertion, b-hydride elimination, etc.), fundamental steps such as abstractions, radical captures, and electron transfers are often encountered in Ni catalysis. Ni catalysis has also served as a fruitful platform for the integration of photochemistry in transition- metal catalysis. Recently, our group found that upon irradiation with light, aryl NiII(bpy) complexes can undergo excited-state bond homolysis to generate C(sp2) radicals. These initial stoichiometric studies demonstrate that light energy can be selectively directed to Ni to generate highly reactive intermediates from feedstock chemical precursors. We propose leveraging photoelimination from NiII as a general step to be employed in Ni catalysis. Traditional development of cross-coupling reactions focuses around achieving new outcomes from sequences of known fundamental processes. This proposal is unique as it is based on the development of a new fundamental step for Ni catalysis. Our efforts will capitalize on the interplay between single- and two- electron processes accessible to Ni to address limitations in selectivity and reactivity in the present literature. The research described herein will be comprised of three aims: (1) developing approaches for improving quantum yield of excited-state Ni bond homolysis processes, (2) explore and extend the scope of organic radical centers accessed by photoelimination, and (3) employing photoelimination as fundamental step in Ni catalysis. All three aspects will be explored concurrently and together represent an exciting new direction in the field of first-row transition metal catalysis.

实现复杂分子支架合成的键构建方法是关键的关键兴趣 制药行业。为此，NI催化已成为用于构建C（SP2） - c（sp2），c（sp3）–c（sp2）和c（sp3）–c（sp3）键。 NI完成这些转变的成功在于 在Ni参与单电子和两电子过程的能力中 - 循环通过0，I，II和III氧化 国家。结果，除了规范的两电子过程（迁移插入，b-氢消除， 等），通常会遇到抽象，激进捕获和电子传输等基本步骤 NI催化。 NI催化也是一个富有成果的平台，用于整合过渡中的光化学 - 金属催化。最近，我们的小组发现，在用光照射后，芳基NIII（BPY）复合物可以经历 激发态键同伊分析产生C（SP2）自由基。这些最初的化学计量研究表明 轻能可以选择性地引导到Ni，以产生来自原料化学物质的高反应性中间体 前体。我们建议将NIII的光启发性作为NI催化的一般步骤。 交叉耦合反应的传统发展围绕取得序列的新结果 已知的基本过程。该建议是独一无二的，因为它基于新的发展 NI催化的基本步骤。我们的努力将利用单电子和两电子之间的相互作用 NI可以访问的过程以解决演讲文献中选择性和反应性的局限性。这 本文所述的研究将完成三个目标：（1）开发改善量子的方法 激发态NI键同溶解过程的产率，（2）探索和扩展有机根中心的范围 通过光启发访问，（3）采用光启示作为NI催化的基本步骤。这三个 方面将同时探索，并共同代表了第一排领域的一个令人兴奋的新方向 过渡金属催化。