Reactions of Arynes and Other Reactive Intermediates

芳炔和其他反应中间体的反应

• 批准号: 2055055
• 负责人: Daesung Lee
• 金额: $ 50万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2055055&HistoricalAwards=false
• 关键词: Reactions; Arynes; Other; Reactive; Intermediates

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Daesung Lee of University of Illinois at Chicago (UIC) is studying new reactivity of reactive intermediates known as arynes and developing new synthetic methods for forming these intermediates. Suitably designed organic compounds can undergo structural reorganization by heating to form new chemical species. These synthetic methods will allow for efficient synthesis of organic compounds that have potential value in chemical biology and medicinal chemistry. Exploring these new reactive aryne species and their subsequent chemical transformations will help chemists better understand the factors and principles that facilitate the formation of these high energy species and their reactivity patterns. An additional potential benefit of this research is that the synthetic approaches postulated herein, if successful, could spur related investigations in other systems. The simple design principles and mode of performing the reaction--under purely thermal conditions at relatively low temperatures--will allow participation of high school and undergraduate students in this research project, which will increase the opportunity of recruiting students from under-represented groups at UIC (Connect with UIC Faculty program) and high school students in Chicago area (STEM Professionals as Resource Knowledge Program of Stevenson High School).Daesung Lee and his students will further develop hexadehydro Diels-Alder reaction-based aryne chemistry and expand the scope of transformations of other thermally generated reactive intermediates. To facilitate these thermal reactions, novel hydrogen bonding-promoted strategies will be explored and applied to the synthesis of biologically active natural products including selaginellin H, selagintamarin A, and selaginpuvilin G. Also, the activating effect of an extra alkyne in 1,3-diynes will be examined in Alder-ene reactions, [2+2] cycloadditions between alkyne and allene, Myers-Saito and Bergman cyclizations. The activating effect of an alkyne substituent will be further exploited in the development of a new [4+2] cycloadditions to generate alpha,3-dehydrotoluene intermediates followed by their trapping as a zwitterionic or a diradical species. This new mode of cycloaromatization is expected to display different reactivity compared to that of hexadehydro Diels-Alder reaction, thereby significantly enriching the array of thermal transformations available to multiynes. Broader impacts of this project will involve various aspects of mechanistic study, natural product synthesis, and development of medicinal and pharmaceutical lead compounds that can serve as an ideal platform for student training at various levels, including undergraduates, graduate students, and postdocs.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，伊利诺伊大学芝加哥分校（UIC）的李大成教授正在研究被称为芳烃的反应性中间体的新反应性，并开发形成这些中间体的新合成方法。适当设计的有机化合物可以通过加热进行结构重组，形成新的化学物质。这些合成方法将允许有效地合成在化学生物学和药物化学中具有潜在价值的有机化合物。探索这些新的活性aryne物种及其随后的化学转化将有助于化学家更好地理解促进这些高能量物种及其反应模式形成的因素和原理。这项研究的另一个潜在的好处是，这里假设的合成方法，如果成功，可以刺激其他系统的相关研究。简单的设计原则和执行反应的模式-在相对较低的温度下纯热条件下-将允许高中生和本科生参与该研究项目，这将增加从UIC（连接UIC教师计划）和芝加哥地区高中生（史蒂文森高中STEM专业人士资源知识计划）中招募代表性不足的学生的机会。Daesung Lee和他的学生将进一步发展基于六氢Diels-Alder反应的炔化学，并扩大其他热生成反应中间体的转化范围。为了促进这些热反应，将探索新的氢键促进策略，并将其应用于合成具有生物活性的天然产物，包括selaginellin H、selaginamarin A和selaginpuvilin g。此外，将在醛烯反应、[2+2]炔与烯之间的环加成、Myers-Saito和Bergman环化中研究1,3-二炔中额外炔的激活作用。炔取代基的活化作用将在新的[4+2]环加成物的开发中得到进一步利用，以生成α，3-脱氢甲苯中间体，然后它们被捕获为两性离子或双自由基。这种新的环芳构化模式预计将显示出与六氢diols - alder反应不同的反应活性，从而显著丰富了多炔热转化的阵列。该项目的广泛影响将涉及机制研究、天然产物合成以及药用和药物先导化合物开发的各个方面，这些方面可以作为本科生、研究生和博士后等各级学生培训的理想平台。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。

项目成果

Synthesis of N-Acyl Pyrroles and Isoindoles from Oxime Ester Precursors via Transition-Metal-Catalyzed Iminocarboxylation

肟酯前体通过过渡金属催化亚氨基羧化合成 N-酰基吡咯和异吲哚

• DOI: 10.1055/s-0042-1751377
• 发表时间: 2023
• 期刊: Synlett
• 影响因子: 2
• 作者: Su, Siyuan;Lee, Daesung
• 通讯作者: Lee, Daesung