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

金属碳烯和金属氮烯中间体的新替代方法及其在合成中的应用

• 批准号: 418602-2013
• 负责人: Murphy, Graham
• 金额: $ 2.33万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632826
• 关键词: Novel; Alternative; Approaches; Metallocarbene; Metallonitrene

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.

该提案提出了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策略。我们将探讨我们最近发现的α-双官能化策略的范围，重点是双官能化反应。鉴于氟在具有医学和商业价值的分子中的普遍存在，这一策略可能会吸引广泛的社区。使用我们的α-放射性示踪剂化合物合成方案将立即吸引人。重氮酮替代品的发展也是我的研究的一个目标，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双卡宾。开发潜在危险的含重氮试剂的替代品将使这些转化可用于工业过程化学，其中重氮酮化学不太适合。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氮烯和二氮卡宾的前体。使用稳定的市售异氰酸酯作为氮宾前体的能力允许对C-H胺化和氮丙啶化策略进行前所未有的研究。鉴于二苯基亚基在药剂中的普遍存在，使用稳定的单体取代的二苯基烯酮作为卡宾前体将证明对工业有吸引力。从这个严格、全面的培训环境中毕业的学生将拥有扎实、全面的有机合成实验技能，并具有丰富的仪器经验。他们接受的培训将使我的HQP成为优秀的问题解决者，他们对潜在的博士后顾问和未来的雇主来说将是非常有价值的。