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

本文提出了基于高价碘试剂在合成中的新应用的初步研究结果和未来的研究策略。我们将探讨我们最近发现的a-双官能化策略的范围，重点是氟化反应。鉴于氟普遍存在于具有药用和商业价值的分子中，这一策略可能会吸引广泛的社区。使用我们的a-二氟化方案合成放射性示踪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，我们建议使用高价碘试剂从Wittig试剂和简单的含羰基底物中生成金属卡宾。开发潜在危险的含重氮试剂的替代品将使这些转化能够用于工业过程化学，而重氮酮化学不太适合。开展以异氰酸酯和烯酮分别作为金属腈和金属苯前体的研究。使用稳定的，商业上可用的异氰酸酯作为亚硝基前体的能力允许对C-H胺化和叠氮化策略进行前所未有的研究。鉴于二苯基亚基在药物制剂中的普遍存在，使用稳定的、单体取代的二苯基烯酮作为碳前体对工业具有吸引力。在这种严格、全面的训练环境中毕业的学生将拥有扎实、全面的有机合成实验技能，并将拥有丰富的仪器经验。他们接受的培训将使我的HQP成为优秀的问题解决者，他们将对潜在的博士后导师和未来的雇主非常有价值。

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.