New Reactivity Mediated by Hypervalent Iodine Reagents

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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.