Applications of Oxidatively Generated Carbocations in Organic Synthesis

在化学系化学合成(SYN)计划的支持下，匹兹堡大学的Paul Floreancig教授正在研究通过氧化转化从简单的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，结合电催化剂产生合成有用的正电中间体，称为碳正离子。人们正在详细研究这些中间体的产生途径，并将利用它们固有的反应性来生产具有潜在用途的结构复杂的分子，如医药制剂、农用化学品和其他对科学、工程和商业有价值的材料。随着Floreancig教授和他的同事在大匹兹堡地区开展各种教育和外联活动，资助项目的更广泛影响延伸到为社会带来的好处。在一项旨在支持化学科学未来领导者的标志性努力中，弗洛雷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助理做好准备，为可能过渡到独立的职业生涯做准备，成为初级学者。对该项目的支持也有助于弗洛雷西格教授继续努力，通过建立旨在消除研究生招生过程中隐含偏见的协议，来增加匹兹堡大学研究生群体的多样性。资助的研究集中在烯丙基醚氧化碳氢键断裂过程的基础机制研究，以及将所获得的见解应用于设计新的化学反应。这项研究的一个主要目标是了解远程官能团对苯二酚(例如DDQ)和氧铵离子(例如Bobbitt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设计以足够的速度进行的氧化转化，以适用于Floreancig小组最近报告的环境友好的电催化方案。将研究通过静电相互作用影响氧化生成的氧碳正离子的远程构象效应，目的是加强阳离子环加成反应中的立体控制。还将研究丙烯酸锂离子的形成，以期为合成含氮化合物设计新的氧化工艺。这一目标建立在了解高取代的酰亚胺离子的构象偏好和利用通过重排过程形成立体控制的杂环的结果的基础上。构象偏好还将用于指导立体选择性季碳形成的最佳底物的设计，并将其应用于复杂生物碱的合成。这项研究的结果有望为合成化学界提供新的转变、有价值的机制见解和未来设计更多氧化官能化反应的蓝图。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.