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.

能够合成复杂分子支架的键构建方法是人们的主要兴趣 制药业。为此，Ni 催化已成为构建 C(sp2)– 的通用工具。 C(sp2)、C(sp3)–C(sp2) 和 C(sp3)–C(sp3) 键。 Ni成功完成这些转变的关键在于 Ni 参与单电子和双电子过程的能力 - 通过 0、I、II 和 III 氧化循环 州。因此，除了典型的双电子过程（迁移插入、b-氢化物消除、 等），抽象、自由基捕获和电子转移等基本步骤经常遇到 镍催化。镍催化也为光化学在转变过程中的整合提供了一个富有成效的平台。 金属催化。最近，我们课题组发现，在光照射下，芳基NiII(bpy)配合物可以发生 激发态键均裂产生 C(sp2) 自由基。这些最初的化学计量研究表明 光能可以选择性地导向镍，从原料化学品中产生高活性中间体 前体。我们建议利用 NiII 的光消除作为 Ni 催化的一般步骤。 交叉偶联反应的传统发展侧重于从序列中获得新结果 已知的基本过程。该提案是独一无二的，因为它基于新的开发 Ni催化的基本步骤。我们的努力将利用单电子和双电子之间的相互作用 Ni 可利用的工艺来解决现有文献中选择性和反应性的局限性。这 本文描述的研究将包括三个目标：（1）开发改进量子的方法 激发态Ni键均裂过程的产率，（2）探索和扩展有机自由基中心的范围 通过光消除获得，以及(3)采用光消除作为Ni催化的基本步骤。全部三个 各方面将同时进行探索，并共同代表第一排领域令人兴奋的新方向 过渡金属催化。