Applications of Oxidatively Generated Carbocations in Organic Synthesis

氧化生成的碳正离子在有机合成中的应用

• 批准号: 2154551
• 负责人: Paul Floreancig
• 金额: $ 50.69万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154551&HistoricalAwards=false
• 关键词: Applications; Oxidatively; Generated; Carbocations; Organic

With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Paul Floreancig of the University of Pittsburgh is studying new methods to prepare value-added materials from simple precursors via oxidative transformations. The approaches being developed are based on carbon-hydrogen bond cleavage reactions and include the use of electricity as an energy source in combination with an electrocatalyst to generate synthetically useful positively charged intermediates called carbocations. The pathways by which these intermediates emerge are being studied in detail and their inherent reactivity will be exploited to produce structurally complex molecules that are of potential utility as pharmaceutical agents, agrochemicals, and other materials of value to science, engineering, and commerce. The broader impacts of the funded project extend to the benefits accrued to society as Professor Floreancig and his coworkers engage in a variety of educational and outreach activities in the greater Pittsburgh area. In a signature effort designed to support future leaders in the chemical sciences, Professor Floreancig will lead workshops to prepare senior graduate students and post-doctoral associates at the University of Pittsburgh for possible transitions to independent careers as junior academics. Support for this project is also aiding Professor Floreancig's ongoing efforts to increase the diversity of the graduate student body at the University of Pittsburgh by the establishment of protocols designed to remove implicit biases during the graduate admissions process.The funded research is focused on fundamental mechanistic studies of oxidative carbon–hydrogen bond cleavage processes from allylic ethers and application of the insights gained to the design of new chemical reactions. A primary goal of the study is to understand the impact of remote functional groups on the kinetics of hydride-abstraction reactions with quinone (e.g., DDQ) and oxoammonium ion (e.g., Bobbitt's salt) oxidants. Understanding these effects will aid in the design of oxidative transformations that proceed at a sufficient rate to be applicable to an environmentally benign electrocatalytic protocol recently reported by the Floreancig group. Remote conformational effects impacting the oxidatively-generated oxocarbenium ions through electrostatic interactions will be investigated with the objective of enhancing stereocontrol in cationic cycloaddition reactions. Acyliminium ion formation will also be studied with the expectation of devising new oxidative processes for the synthesis of nitrogen-containing compounds. This objective is founded on understanding the conformational preferences of highly substituted acyliminium ions and exploiting the results for stereocontrolled heterocycle formation through rearrangement processes. Conformational preferences will also be used to instruct on the design of optimal substrates for stereoselective quaternary carbon formation with applications to complex alkaloid synthesis. The findings of the research are anticipated to provide the synthetic chemistry community with new transformations, valuable mechanistic insights, and blueprints for designing additional oxidative functionalization reactions going forward.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学合成（SYN）项目的支持下，匹兹堡大学的Paul Floreancig教授正在研究通过氧化转化从简单前体制备增值材料的新方法。正在开发的方法是基于碳-氢键裂解反应，包括使用电力作为能源与电催化剂相结合，以产生合成有用的带正电荷的中间体，称为碳阳离子。正在详细研究这些中间体出现的途径，并且将利用它们的固有反应性来产生结构复杂的分子，这些分子具有作为药剂、农用化学品和其他对科学、工程和商业有价值的材料的潜在效用。资助项目的更广泛的影响延伸到累积到社会的好处教授Floreancig和他的同事在大匹兹堡地区从事各种教育和推广活动。在旨在支持化学科学未来领导者的标志性努力中，Floreancig教授将领导研讨会，为匹兹堡大学的高级研究生和博士后研究员做好准备，以便他们可能过渡到独立的职业生涯作为初级学者。对该项目的支持也有助于Floreancig教授通过建立旨在消除研究生入学过程中隐性偏见的协议来增加匹兹堡大学研究生群体的多样性。烯丙基醚的氢键断裂过程以及将所获得的见解应用于新化学反应的设计。该研究的主要目标是了解远程官能团对与醌的缩合-提取反应动力学的影响（例如，DDQ）和氧代铵离子（例如，Bobbons盐）氧化剂。了解这些影响将有助于设计的氧化转化，进行足够的速度，适用于环境友好的电催化协议最近报道的Floreancig集团。通过静电相互作用影响氧化生成的oxocarbenium离子的远程构象效应将进行研究，目的是增强阳离子环加成反应中的立体控制。酰亚胺离子的形成也将进行研究，以期为含氮化合物的合成设计新的氧化过程。这一目标是建立在理解高度取代的酰基杂环离子的构象偏好，并利用通过重排过程的立体控制的杂环形成的结果。构象偏好也将用于指导立体选择性季碳形成的最佳底物的设计与复杂的生物碱合成的应用。该研究的发现有望为合成化学界提供新的转变、有价值的机理见解和设计未来其他氧化官能化反应的蓝图。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。