Mechanistic Investigation into Photoredox Catalysis

项目概述：光氧化还原催化领域在过去经历了爆炸性的增长 十年，并已被确立为现代有机合成的中心支柱。基础到 这些方法是使用有机染料或有机金属络合物作为光催化剂，即 被可见光激活以触发单电子转移事件，该事件产生高反应性的开路- 壳基中间体。此外，这些光氧化还原事件可以与两个电子耦合 有机催化和传统的过渡金属催化，以实现新的成键。详细 对这些错综复杂的催化循环的机械理解已经出现了显著的减少 与新反应发现相比，速度更快。这影响了这些新技术的翻译 到用于合成高价值药物的工业环境。缺乏原子化的细节 键键形成事件也减缓了这些催化不对称版本的发展 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 当代催化这一重要领域的不足。特别是，这项提案概述了这两个方面 用实验和理论方法探索了速率和立体声的过渡态几何结构。 确定了光氧化还原催化中几个重要反应的步骤。我们提议的调查将 补充目前最先进的光催化反应机理研究，其重点是 关于自由基中间体的鉴定和反应活性。我们建议的主要工具 研究了在合成条件下2H和13C动力学同位素效应的实验测定。 使用高级理论解释这些实验所遵循的相关条件 技巧。我们期望这种实验和理论之间的协作方法能够产生信息 这将增强或提供对这些问题的现有机械性理解的新见解 反应。 我们把精力集中在两类由光氧化还原催化实现的重要反应上--C- 氢键官能化和烯烃官能化。这一选择是基于这样一个事实：这两个 各类反应会产生新的手性中心。然而，由于这些化合物的催化不对称版本 反应迟缓，我们相信我们的研究将为 合理设计和优化投放对映体产品的策略。更重要的是， 我们期望我们的研究结果能够建立起经过实验验证的过渡态分析。 作为光氧化还原催化机理描述的常规工具。

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.