New Reactivity Mediated by Hypervalent Iodine Reagents

我们的研究是在综合方法论领域。合成有机化学的最大挑战是开发新的有效的策略来构建有价值的分子结构。有机高价碘(HVI)试剂是一类多功能的化合物，其中碘的固有极性被颠倒。在这个提案中，我描述了我和我的学生将如何通过开发新的HVI介导性化学来推进我们的研究计划。开发新的含氟化合物的合成具有重要的经济和社会意义，我们将探索将氟结合到有机分子中的新策略。首先，我们将开发新的分子重排来制备传统反应性不易获得的氟化基序。然后，我们将探索新结构域的氟化，试图生成新的氟化环系。我们还计划开发HVI催化的环化反应，可以增强到包括手性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。这将通过修改几个相关的肼类氧化反应来实现，在这些反应中，不同的产品结果将产生于所使用的起始材料的不同。*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。一般而言，我们将在碘叶立德的环化反应中使用普通的商用发光二极管(LED)作为汞灯的替代品。LED使用的一个关键好处是无需加热即可实现辐射，使我们能够隔离热不稳定的产品，否则会发生进一步的反应。LED辐射将首次能够在光引发反应中探索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，在这些化合物中，同样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化合物中的反应催化，我们将把这些新的碘叶立德反应作为碘代芳烃催化的过程来探索，其中活性的HVI物种是原位生成的。最后，我们将在其中测试手性HVI试剂和手性碘芳烃催化剂，目的是发现催化的、不对称的、光引发的环化反应。HVI的反转极性注入了一种能量驱动力，使其发生还原并恢复正常极化。我们将利用这种氧化潜力，开发通过催化氧化C-H键偶联来锻造碳-碳键的新策略。我们将发展我们的催化烯烃芳基化反应，寻求对其更好的基础了解，然后将其扩展到包含杂原子的体系，并探索烯烃乙烯基化反应的新途径。

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.