Harnessing Electron-Donor-Acceptor Complexes to Enable Photo-Induced Metal-Free Cross-Coupling Reactions

利用电子供体-受体配合物实现光诱导无金属交叉偶联反应

• 批准号: 10715256
• 负责人: Sebastien Laulhe
• 金额: $ 35.43万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715256
• 关键词: Acceleration; Address; Alkanes; Alkylating Agents; Attention; Chemicals; Complex; Computer Models; Coupled; Coupling; Development; Electron Transport; Halogens; Health; Human; Hydrogen; Hydrogen Bonding; Improve Access; Investigation; Mediating; Metals; Methods; Modification; Organic Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Process; Reaction; Reagent; Research; Research Proposals; Safety; Site; Societies; Structure; Sustainable Development; Technology; Transition Elements; Work; catalyst; design; electron donor; innovation; interest; manufacturing cost; tool

Project Summary/Abstract The abundance of C(sp3)–H bonds in organic molecules and building blocks, makes the direct functionalization of these structures a very attractive and powerful tool for the synthesis and late-stage functionalization of pharmaceuticals. Unfortunately, current methods to achieve these transformations use metal-catalysts and reagents that do not meet requirements for sustainable development. Similarly, alkyl halides are among the largest groups of commercially available building blocks used in organic chemistry, but bulky tertiary alkyl halides cannot be easily used as alkylating agents because they cannot undergo SN2 processes. Therefore, the development of strategies that are transition-metal-free and orthogonal to current approaches to activate C–H and C–X bonds would be a significant contribution as it addresses an unmet need. Recently, the application of electron-donor-acceptor (EDA) complexes has gained attention as a photo-induced method to perform single electron transfers between otherwise unreactive reagents. Unfortunately, current reactions that proceed via EDA complexes do not take advantage of the formed radicals to perform hydrogen- atom-transfer (HAT) and halogen-atom-transfer (XAT) processes that could enable the use of the abundant chemical feedstock mentioned above. The research objectives of the proposed investigations promise to tackle the above-cited barriers to help establish EDA complexes as a cutting-edge strategy for the photo-induced radical-activation of alkanes and alkyl halides. Our conceptually innovative hypothesis is that sterically and electronically tuned aryl radicals generated from EDA complexes can be used to achieve site-selective HAT and XAT processes. The resulting alkyl radicals generated are then coupled to achieve enantio- and diastereoselective cross-couplings. This work will use computational models to support, guide, and accelerate the design and discovery of EDA complexes of arenes. These explorations will establish new platforms that enable enantio- and regioselective cross-dehydrogenative couplings, and XAT mediated couplings that form challenging C(sp3)–C(sp3) bonds.

项目概要/摘要 有机分子和结构单元中丰富的 C(sp3)–H 键使得直接功能化 这些结构是一种非常有吸引力和强大的工具，用于合成和后期功能化 不幸的是，目前实现这些转化的方法使用金属催化剂和 同样，烷基卤化物也不符合可持续发展的要求。 用于有机化学的最大的市售结构单元，但体积大的叔烷基 卤化物不能轻易用作烷化剂，因为它们不能进行 SN2 过程。 开发不含过渡金属且与当前激活方法正交的策略 C-H 和 C-X 债券将做出重大贡献，因为它解决了未满足的需求。 近年来，电子供体受体（EDA）配合物作为光诱导材料的应用引起了人们的关注。 不幸的是，目前的方法在其他不反应的试剂之间进行单电子转移。 通过 EDA 络合物进行的反应不利用形成的自由基来进行氢- 原子转移（HAT）和卤素原子转移（XAT）过程可以利用丰富的 上述化学原料。 拟议调查的研究目标有望解决上述障碍，以帮助 建立 EDA 复合物作为烷烃光诱导自由基激活的前沿策略 我们在概念上的创新假设是空间和电子调节的芳基自由基。 由 EDA 复合物生成的 HAT 和 XAT 过程可用于实现位点选择性 HAT 和 XAT 过程。 然后将生成的烷基偶联以实现对映选择性和非对映选择性交叉偶联。 工作将使用计算模型来支持、指导和加速 EDA 的设计和发现 这些探索将建立新的平台，实现对映体和区域选择性。 交叉脱氢偶联，以及 XAT 介导的偶联，形成具有挑战性的 C(sp3)–C(sp3) 键。