Understanding Geometric and Electronic Structure Contributions to Ground and Excited State Cu- and Ni-Catalyzed Cross-Coupling Reactions

了解几何和电子结构对基态和激发态铜和镍催化交叉偶联反应的贡献

• 批准号: 10589159
• 负责人: Ryan G Hadt
• 金额: $ 41.88万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589159
• 关键词: Adopted; Calibration; Catalysis; Computing Methodologies; Coupling; Development; Disparate; Electron Transport; Electronics; Engineering; Evolution; Industrialization; Industry; Ligands; Light; Metals; Methodological Studies; Methods; Molecular; Nature; Optics; Pathway interactions; Pharmaceutical Chemistry; Pharmacologic Substance; Photochemistry; Planet Earth; Potential Energy; Process; Property; Reaction; Relaxation; Research; Rest; Roentgen Rays; Spectrum Analysis; Structure; Surface; Temperature; Therapeutic; Time; Transition Elements; Translations; Work; absorption; catalyst; circular magnetic dichroism; drug candidate; drug discovery; drug synthesis; electronic structure; emission spectroscopy; frontier; geometric structure; knowledge base; magnetic field; metal complex; molecular orbital; novel therapeutics; photonics; success

Project Summary Developing sustainable approaches to the synthesis of molecular therapeutics will be important for the continued evolution and success of medicinal and pharmaceutical chemistries. A major component of drug synthesis involves transition metal catalyzed C–X (X = C, N, O, etc.) bond formation reactions. While precious metals such as Pd are used for these reactions, first row transition metals are becoming more widely adopted, as they are abundant and open new mechanistic pathways involving one- and multi-electron transfer reactivity, which can potentially work in concert with ligand noninnocence and multireference electronic structure to form transformative structure/function relationships. The merger of thermal catalysis with photochemistry also provides new mechanistic possibilities for cross-couplings that harness the energy of light to drive bond-formation reactions that would not occur in ground states. However, the nature of inorganic intermediates and the important ultrafast transition metal excited state relaxation processes in ground and excited state cross-coupling reactions are not well understood. This proposal therefore applies physical inorganic approaches to develop a fundamental knowledge base of the geometric and electronic structures of the critical inorganic species formed in Cu- and Ni- catalyzed cross-coupling reactions, as well as the time and energy evolution of photoinduced electronic states involved in excited state catalysis. This knowledge base will ultimately guide the development of a molecular engineering approach to ligand development and catalyst discovery. We will bring new spectroscopic methods to the field, including variable temperature variable field magnetic circular dichroism (VTVH MCD) and X-ray absorption and emission spectroscopies, which will be critical to quantitatively define transition metal electronic structure, including multireference character. Ultrafast optical and X-ray spectroscopic approaches will also be used to define the key photonic energy distribution pathways that define photocatalyst efficiency and further guide ligand perturbations to control the excited state potential energy surfaces (PESs) of photocatalysts. Spectral features of isolable species will be used to experimentally calibrate computational methods to define the critical frontier molecular orbitals and bonding interactions that activate metal centers for reactivity, especially those that are fleeting but critical to catalysis. Electronic structure calculations will also allow for the translation of our understanding of resting states, intermediates, and excited states to reaction coordinates in catalysis and the PESs governing relaxation pathways. In concert with collaborative methodological studies, the proposed research will help inform chemists how to leverage the ground and excited state electronic structures of first-row transition metal complexes and thus guide academic and industry research toward sustainable approaches for bond constructions in drug synthesis.

项目摘要 开发可持续的方法来合成分子疗法对 医学和药物化学的持续进化和成功。一个主要组成部分 药物合成涉及过渡金属催化的C – X（X = C，N，O等）键形反应。 尽管这些反应使用诸如PD之类的贵金属，但第一排过渡金属正在变成 更广泛地采用，因为它们丰富且开放的新机械途径，涉及一种和 多电子转移反应性，它可能与配体非净源性和 多次电子结构形成变革性结构/功能关系。合并 光化学的热催化也为交叉耦合提供了新的机械可能性 利用光的能量驱动基态不会发生的键形反应。 但是，无机中间体和重要的超快金属激发态的性质 地面上的松弛过程和激发态交叉偶联反应尚不清楚。这 因此，建议采用物理无机方法来建立基本知识库 在Cu和Ni形成的关键无机物质的几何和电子结构中 催化的交叉偶联反应，以及光诱导的电子的时间和能量演变 参与激发状态催化的国家。这些知识基础最终将指导 配体开发和催化剂发现的分子工程方法。我们将带来新的 光谱法到该场，包括可变温度可变场磁圆形的方法 二分（VTVH MCD）和X射线抽象和发射光谱，这对 定量定义过渡金属电子结构，包括多差。超快 光学和X射线光谱方法也将用于定义关键光子能量 定义光催化剂效率并进一步指导配体扰动的分布途径 控制光催化剂的激发状态势能表面（PESS）。光谱特征 可隔离物种将用于实验校准计算方法以定义关键 边境分子轨道和键相互作用，激活金属中心以提高反应性，尤其是 那些转瞬即逝但对催化至关重要的人。电子结构计算也将允许 转化我们对静息状态，中间体和激发状态的理解向反应 在催化和佩斯管理松弛途径中进行坐标。与协作协作 方法论研究，拟议的研究将有助于告知化学家如何利用地面 以及第一行过渡金属配合物的激发状态电子结构，从而引导学术 以及针对药物合成中粘结建构的可持续方法的行业研究。