New Reactivity Mediated by Hypervalent Iodine Reagents

高价碘试剂介导的新反应

• 批准号: RGPIN-2019-04086
• 负责人: Murphy, Graham
• 金额: $ 2.62万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748023
• 关键词: New; Reactivity; Mediated; Hypervalent; Iodine

Our research is in the field of synthetic methodology. The great challenge in synthetic organic chemistry is developing new and efficient strategies to build valuable molecular architectures. Organic hypervalent iodine (HVI) reagents are a versatile and multifunctional class of compounds in which iodine's inherent polarity is reversed. In this proposal, I describe how my students and I will advance our research program by developing new HVI-mediated chemistry. Developing new syntheses of fluorine-containing compounds is economically and societally important, and we will investigate new strategies for incorporating fluorine into organic molecules. First, we will develop new molecular rearrangements for preparing fluorinated motifs not easily accessed by traditional reactivity. We will then explore the fluorination of new structural domains, trying to generate new classes of fluorinated ring systems. We plan to also develop HVI-catalyzed cyclizations that could be enhanced to include chiral HVI reagents and lead to asymmetric reactions. We will also develop a series of related domino fluorination and trifluoromethylation reactions. This will be achieved by modifying several related hydrazone oxidation reactions, where the diverse product outcomes would arise from variations in the starting materials used. We will use HVI reagents in new photo-initiated reactions, leading to transition metal-free carbon-carbon bond forming processes. In general, we will use common, commercial light-emitting diodes (LEDs) as replacements for mercury lamps in cyclization reactions of iodonium ylides. A key benefit to LED use is that irradiation is achieved without heating, permitting us to isolate thermally unstable products that would have otherwise reacted further. LED irradiation will enable, for the first time, exploration of thermally unstable iodonium ylides in photo-initiated reactions. We will apply the learned theoretical knowledge to the synthesis of related nitrogen-containing compounds, where the similarly unstable nitrogen-containing intermediates may thrive under LED irradiation. The modern frontier of HVI-mediated chemistry is reactions catalytic in aryliodide, and we will explore these new iodonium ylide reactions as iodoarene-catalyzed processes where the active HVI species is generated in situ. Finally, we will test chiral HVI reagents and chiral iodoarene catalysts in these, with the goal of discovering catalytic, asymmetric, photo-initiated cyclization reactions. The inverted polarity of HVI instills an energetic driving force to undergo reduction and return to normal polarization. We will harness this oxidative potential to develop new strategies for forging carbon-carbon bonds via catalytic oxidative C-H bond couplings. We will develop our catalytic alkene arylation reaction, seeking a better fundamental understanding of it, and then expand this to include heteroatom-containing systems, and pursue new avenues of alkene vinylation reactivity.

我们的研究是在合成方法论领域。合成有机化学的巨大挑战是开发新的有效的策略来建立有价值的分子体系结构。有机高价值碘（HVI）试剂是一种多功能且多功能的化合物类别，其中碘的固有极性被逆转。在此提案中，我描述了我和我的学生如何通过开发新的HVI介导的化学反应来推进我们的研究计划。开发含氟化合物的新合成在经济上和社会上很重要，我们将研究将氟掺入有机分子中的新策略。首先，我们将开发新的分子重排，以制备不容易通过传统反应性访问的氟化基序。然后，我们将探索新结构域的氟化，试图生成新的氟化环系统。我们计划还会开发HVI催化的环化，这些环化可以增强，以包括手性HVI试剂并导致不对称反应。我们还将开发一系列相关的多米诺氟化和三氟甲基化反应。这将通过修改几种相关的氢氧化反应来实现，在这种反应中，各种产品结果将来自使用的起始材料的变化。我们将在新的照片发起的反应中使用HVI试剂，从而导致无金属碳键形成过程。通常，我们将使用常见的商业发光二极管（LED）作为碘碘环境中汞灯的替代。 LED使用的一个关键好处是，可以在不加热的情况下实现辐射，从而使我们能够隔离否则会进一步反应的热不稳定产品。 LED辐照将首次探索光发射反应中热不稳定的碘ylide。我们将把学到的理论知识应用于相关的含氮化合物的合成，在这种化合物中，在LED辐照下，类似不稳定的含氮中间体可能会蓬勃发展。 HVI介导的化学的现代前沿是芳基碘化物中的反应，我们将探索这些新的碘ylide反应，因为碘苯乙烯催化的过程在该过程中产生了活性HVI物种。最后，我们将在其中测试手性HVI试剂和手性iodoarenen催化剂，目的是发现催化，非对称，光引发的环化反应。 HVI的倒极性灌输了一种能量驱动力，以减少并恢复正常极化。我们将利用这种氧化潜力来开发通过催化氧化的C-H键耦合来锻造碳碳键的新策略。我们将发展催化烯烃芳基化反应，寻求对其的基本理解，然后将其扩展到包括含杂原子的系统，并追求烯烃乙烯基化反应性的新途径。