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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=737400
• 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学领域。有机合成化学面临的巨大挑战是开发新的和有效的策略来构建有价值的分子结构。有机高价碘（HVI）试剂是一类用途广泛、多功能的化合物，其中碘的固有极性是相反的。在这个建议中，我描述了我的学生和我将如何通过开发新的HVI介导的化学来推进我们的研究计划。开发含氟化合物的新合成方法具有重要的经济和社会意义，我们将研究将氟引入有机分子的新策略。首先，我们将开发新的分子重排制备氟化图案不容易通过传统的反应。然后，我们将探索新的结构域，试图产生新的氟化环系统的类别。我们还计划开发HVI催化的环化反应，可以增强包括手性HVI试剂，并导致不对称反应。我们也将发展一系列相关的多米诺骨牌和三氟甲基化反应。这将通过修改几个相关的腙氧化反应来实现，其中不同的产物结果将由所用起始材料的变化引起。我们将在新的光引发反应中使用HVI试剂，导致无过渡金属的碳-碳键形成过程。一般来说，我们将使用普通的商业发光二极管（LED）作为碘鎓叶立德环化反应中汞灯的替代品。使用LED的一个关键好处是，在不加热的情况下实现辐照，使我们能够隔离热不稳定的产物，否则这些产物会进一步反应。LED照射将首次探索光引发反应中热不稳定的碘叶立德。我们将把所学的理论知识应用于相关含氮化合物的合成，其中类似不稳定的含氮中间体可能在LED照射下茁壮成长。HVI介导的化学的现代前沿是芳基碘的催化反应，我们将探索这些新的碘鎓叶立德反应作为碘芳烃催化的过程，其中活性HVI物种原位生成。最后，我们将测试手性HVI试剂和手性碘代芳烃催化剂在这些，发现催化，不对称，光引发的环化反应的目标。HVI的反向极性灌输了一种充满活力的驱动力，使其经历还原并返回正常极化。我们将利用这种氧化潜力，通过催化氧化C-H键偶联来开发锻造碳-碳键的新策略。我们将发展我们的催化烯烃芳基化反应，寻求更好的基本理解，然后将其扩展到包括含杂原子的系统，并寻求烯烃乙烯化反应性的新途径。