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

这项建议提出了一个基于高价碘试剂在合成中的新应用的研究计划的初步结果和未来战略。我们将探索我们最近发现的a-去功能化策略的范围，重点是氟化反应。鉴于氟在具有医疗和商业价值的分子中的普遍存在，这一策略可能会被证明对广泛的社区具有吸引力。使用我们的a-二氟化方案合成放射性示踪剂化合物将立即吸引人。开发重氮酮替代品也是我的研究目标之一，我们建议使用高价碘试剂从Wittig试剂和简单的含酮基底物生成金属卡宾。开发潜在危险的重氮试剂的替代品将使工业过程化学能够实现这些转化，而重氮酮化学不太适合重氮酮化学。我们将开发一个研究计划，分别使用异氰酸酯和烯酮作为金属氰化物和金属卡宾的前体。使用稳定的、商业上可获得的异氰酸酯作为氮化物前体的能力使人们能够对C-H胺化和氮杂环化策略进行前所未有的研究。鉴于二苯亚基在药剂中的普遍存在，使用稳定的单体取代的二苯基酮作为卡宾前体将被证明对工业有吸引力。从这种严谨、全面的培训环境中毕业的学生将拥有扎实的、全面的有机合成实验技能，并将伴随着广泛的仪器经验。他们所接受的培训将使我的HQP成为优秀的问题解决者，他们对潜在的博士后导师和未来的雇主将非常有价值。

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.