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.

项目概要 开发可持续的分子疗法合成方法对于 药物和药物化学的持续发展和成功。 药物合成涉及过渡金属催化的 C-X（X = C、N、O 等）键形成反应。 虽然钯等贵金属用于这些反应，但第一排过渡金属正在成为 更广泛地采用，因为它们丰富并开辟了涉及一和一的新机械途径 多电子转移反应性，可能与配体非纯真和 多参考电子结构形成变革结构/功能关系。 热催化与光化学的结合也为交叉耦合提供了新的机械可能性 利用光能来驱动在基态下不会发生的成键反应。 然而，无机中间体的性质和重要的超快过渡金属激发态 基态和激发态交叉偶联反应中的弛豫过程尚不清楚。 因此，建议采用物理无机方法来开发基础知识库 Cu- 和 Ni- 中形成的关键无机物质的几何结构和电子结构 催化交叉偶联反应，以及光生电子的时间和能量演化 该知识库最终将指导激发态催化的发展。 我们将带来新的配体开发和催化剂发现的分子工程方法。 场的光谱方法，包括变温变场磁圆 二色性 (VTVH MCD) 和 X 射线吸收和发射光谱，这对于 定量定义过渡金属电子结构，包括超快特征。 光学和 X 射线光谱方法也将用于定义关键的光子能量 定义光催化剂效率并进一步引导配体扰动的分布途径 控制光催化剂的激发态势能表面（PES）的光谱特征。 可分离的物种将用于通过实验校准计算方法来定义临界值 前沿分子轨道和键合相互作用，激活金属中心的反应性，特别是 那些转瞬即逝但对催化至关重要的电子结构计算也将允许进行。 将我们对静息态、中间体和激发态的理解转化为反应 催化协调和控制松弛路径的 PES 与协作一致。 方法论研究，拟议的研究将帮助化学家了解如何利用地面 和第一行过渡金属配合物的激发态电子结构，从而指导学术 以及药物合成中键构建可持续方法的行业研究。