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

项目摘要 发展可持续的方法来合成分子治疗剂将是重要的， 医药化学的持续发展和成功。的主要组成部分 药物合成涉及过渡金属催化的C-X（X = C、N、O等）。键形成反应 虽然贵金属如Pd用于这些反应，但第一行过渡金属正成为 更广泛地采用，因为它们是丰富的，并开辟了新的机制途径，涉及一个-和 多电子转移反应性，这可能与配体的非无辜性和 多参考电子结构，以形成转化的结构/功能关系。合并 热催化与光化学的结合也为交叉偶联提供了新的机理可能性 利用光能来驱动在基态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还没有很好地理解。这 因此，建议采用物理无机方法来开发基础知识库 的几何和电子结构的关键无机物种形成的Cu-和Ni- 催化的交叉偶联反应，以及光诱导电子的时间和能量演化 参与激发态催化的状态。这一知识库将最终指导 一种分子工程方法来开发配体和发现催化剂。我们将带来新的 光谱方法的领域，包括变温变场磁圆 二色性（VTVH MCD）和X射线吸收和发射光谱，这将是至关重要的 定量定义过渡金属的电子结构，包括多参比性质。超快 光学和X射线光谱学方法也将用于确定关键的光子能量 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面（PES）。光谱特征 可分离的物种将用于实验校准计算方法，以确定关键的 前线分子轨道和键相互作用，激活金属中心的反应性，特别是 那些转瞬即逝但对催化作用至关重要的物质电子结构计算也将允许 将我们对静止态、中间体和激发态的理解转化为反应 协调催化和PES管理松弛途径。与合作的音乐会 方法学研究，拟议的研究将有助于告知化学家如何利用地面 和激发态电子结构的第一行过渡金属配合物，从而指导学术 和工业研究，以实现药物合成中键结构的可持续方法。

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.