Mechanistic Investigation into Photoredox Catalysis

光氧化还原催化机理研究

• 批准号: 10214239
• 负责人: Jennifer Hirschi
• 金额: $ 46.59万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214239
• 关键词: Address; Alkenes; Amines; Area; Benchmarking; Biological Models; Catalysis; Chemicals; Complement; Complex; Computing Methodologies; Coupled; Coupling; Development; Dyes; Electron Spin Resonance Spectroscopy; Electron Transport; Electrons; Evaluation; Event; Evolution; Geometry; Goals; Growth; Hydrogen Bonding; Industrialization; Investigation; Isotopes; Kinetics; Light; Measurement; Methods; Modeling; Modernization; NMR Spectroscopy; Organic Synthesis; Pathway interactions; Pharmaceutical Chemistry; Pharmacologic Substance; Psychological Techniques; Reaction; Route; Spectrum Analysis; Structure; System; Techniques; Technology; Transition Elements; Translations; Visible Radiation; absorption; base; collaborative approach; design; experimental study; insight; invention; irradiation; new technology; novel; oxidation; scaffold; success; theories; tool

Project Summary: The area of photoredox catalysis has witnessed explosive growth over the past decade and has been established as a central pillar of modern-day organic synthesis. Fundamental to these methods is the use of an organic dye or an organometallic complex as a photocatalyst that is activated by visible-light to trigger a single electron transfer event that generates a highly reactive open- shell radical intermediate. Furthermore, these photoredox events can be coupled with two-electron organocatalysis and traditional transition-metal catalysis to enable novel bond-formations. Detailed mechanistic understanding of these intricate catalytic cycles has emerged at a significantly diminished pace compared to new reaction discovery. This has impacted the translation of these new technologies to industrial settings for the synthesis of high-value pharmaceuticals. The lack of atomistic details of the key-bond forming events has also slowed the development of catalytic asymmetric versions of these reactions. We propose to apply a suite of robust physical organic techniques to address this significant deficiency in this important area of contemporary catalysis. In particular, this proposal outlines both experimental and theoretical approaches that probe the transition state geometry of rate- and stereo- determining steps of some important reactions in photoredox catalysis. Our proposed investigations will complement the current state-of-the-art mechanistic studies of photocatalytic reactions, which focuses on the identification and reactivity of the radical intermediates. The main tool in our proposed investigations is the experimental determination of 2H and 13C kinetic isotope effects under synthetically relevant conditions followed by interpretation of these experiments using high-level theoretical techniques. We expect this collaborative approach between experiment and theory to yield information that will either enhance or provide new insights into the existing mechanistic understanding of these reactions. We focus our efforts on two important classes of reactions enabled by photoredox catalysis – C– H bond functionalization and alkene functionalization. This choice is based on the fact that these two classes of reactions generate new chiral centers. However, since catalytic asymmetric versions of these reactions have been slow to emerge, we believe that our studies will provide an important blueprint for the rational design and optimization of strategies to deliver enantio-enriched products. More importantly, we expect the results from our investigations to establish experiment-validated transition state analysis as a routine tool in the mechanistic description of photoredox catalysis.

项目概述：光氧化还原催化领域在过去经历了爆炸式的增长 十年来，已被确立为现代有机合成的中心支柱。的基础 这些方法是使用有机染料或有机金属配合物作为光催化剂， 由可见光激活，以触发单个电子转移事件，产生高活性的开放- 壳自由基中间体。此外，这些光氧化还原事件可以与双电子 有机催化和传统的过渡金属催化，使新的键形成。详细 对这些复杂的催化循环的机械理解已经出现在一个显着减少 与新反应发现相比，这影响了这些新技术的翻译 用于合成高价值药物的工业环境。缺乏原子的细节， 键键形成事件也减缓了这些催化不对称形式的发展。 反应. 我们建议应用一套强大的物理有机技术来解决这一重大问题 现代催化这一重要领域的不足。特别是，该提案概述了 实验和理论方法，探测率和立体的过渡态几何， 确定了光氧化还原催化中一些重要反应的步骤。我们提议的调查将 补充了目前最先进的光催化反应机理研究，重点是 自由基中间体的鉴定和反应性。我们建议的主要工具 研究是综合条件下2 H和13 C动力学同位素效应的实验测定 相关条件，然后使用高级理论解释这些实验 技术.我们期望这种实验和理论之间的合作方法能够产生信息 这将增强或提供新的见解，现有的机械理解，这些 反应. 我们把精力集中在两个重要类别的反应，使光氧化还原催化- C- 氢键官能化和烯烃官能化。这一选择是基于这两个事实 反应的类别产生新的手性中心。然而，由于这些的催化不对称版本 反应缓慢出现，我们相信我们的研究将提供一个重要的蓝图 合理设计和优化递送对映体富集产物的策略。更重要的是， 我们希望我们的研究结果能够建立实验验证的过渡态分析 作为光氧化还原催化机理描述中的常规工具。

项目成果

Probing the Free Energy Landscape of Organophotoredox-Catalyzed Anti-Markovnikov Hydrofunctionalization of Alkenes.

• DOI: 10.1021/jacs.2c07807
• 发表时间: 2022-09-28
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Mallojjala, Sharath Chandra;Nyagilo, Victor O.;Corio, Stephanie A.;Adili, Alafate;Dagar, Anuradha;Loyer, Kimberly A.;Seidel, Daniel;Hirschi, Jennifer S.
• 通讯作者: Hirschi, Jennifer S.

Probing Catalyst Function - Electronic Modulation of Chiral Polyborate Anionic Catalysts.

• DOI: 10.1021/acs.joc.1c01769
• 发表时间: 2021-12-17
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Osminski, Wynter E. G.;Lu, Zhenjie;Zhao, Wenjun;Mohammadlou, Aliakbar;Yin, Xiaopeng;Matthews, Emily C.;Canestraight, Virginia M.;Staples, Richard J.;Allen, Connor J.;Hirschi, Jennifer S.;Wulff, William D.
• 通讯作者: Wulff, William D.