Novel Alternative Approaches to Metallocarbene and Metallonitrene Intermediates and Their Application in Synthesis

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This proposal presents preliminary results and future strategies for a research program based on new applications of hypervalent iodine reagents in synthesis. We will explore the scope of our recently discovered a-difunctionalization strategy, focusing on fluorination reactions. Given the prevalence of fluorine in molecules of medicinal and commercial interest, this strategy could prove appealing to a broad community. Using our a-difluorination protocol for radiotracer compound synthesis would be instantly appealing. ****Development of diazoketone surrogates is also a goal of my research, and we propose to use hypervalent iodine reagents to generate metallocarbenes from Wittig reagents, and from simple carbonyl-containing substrates. Developing alternatives to the potentially hazardous diazo-containing reagents would make these transformations accessible to industrial process chemistry, for which diazoketone chemistry is poorly suited.****We will develop a research program using isocyanates and ketenes as metallonitrene and metallocarbene precursors, respectively. The ability to use stable, commercially available isocyanates as nitrene precursors permit unprecedented investigations into C-H amination and aziridination strategies. Given the prevalence of the diphenyl- subunit in pharmaceutical agents, using stable, monomeric substituted diphenylketenes as carbene precursors would prove appealing to industry. ****Students graduating from this rigorous, comprehensive training environment will possess a solid, well-rounded experimental skill set in organic synthesis, which will be coupled with extensive instrumental experience. The training they receive will make my HQP excellent problem solvers, and they will be highly valuable to potential postdoctoral advisors and future employers.********