Applications of Oxidatively Generated Carbocations in Organic Synthesis

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，包括使用电作为能源与电催化剂相结合，以产生合成有用的带正电的中间产物，称为碳阳离子。这些中间体产生的途径正在被详细研究，它们固有的反应性将被利用来生产结构复杂的分子，这些分子作为药物制剂、农用化学品和其他对科学、工程和商业有价值的材料具有潜在的用途。由于弗洛伦奇教授和他的同事在大匹兹堡地区从事各种教育和推广活动，资助项目的更广泛影响延伸到社会积累的利益。在一项旨在支持化学科学领域未来领导者的标志性努力中，弗洛朗西格教授将主持研讨会，为匹兹堡大学的高级研究生和博士后准备可能过渡到独立的初级学者职业生涯。对该项目的支持也有助于弗洛朗西格教授通过建立旨在消除研究生录取过程中隐性偏见的协议，不断努力增加匹兹堡大学研究生群体的多样性。该基金的研究重点是对烯丙醚氧化碳氢键裂解过程的基本机理研究，并将所获得的见解应用于设计新的化学反应。该研究的主要目标是了解远端官能团对醌（如DDQ）和氧铵离子（如博比特盐）氧化剂的氢化物提取反应动力学的影响。了解这些影响将有助于以足够的速度进行氧化转化的设计，以适用于最近由Floreancig小组报道的无害环境的电催化方案。通过静电相互作用研究影响氧化生成的氧羰基离子的远程构象效应，以增强阳离子环加成反应中的立体控制。酰基铵离子的形成也将被研究，期望设计新的氧化工艺来合成含氮化合物。这一目标是建立在了解高取代酰基铵离子的构象偏好和利用结果立体控制杂环形成通过重排过程。构象偏好也将用于指导设计立体选择性季碳形成的最佳底物，并应用于复杂生物碱的合成。该研究结果有望为合成化学界提供新的转化，有价值的机理见解，并为未来设计其他氧化官能化反应提供蓝图。该奖项反映了美国国家科学基金会的法定使命，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。

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.