Reactions of Arynes and Other Reactive Intermediates

伊利诺伊大学芝加哥分校（UIC）的李大成教授在化学系化学合成（SYN）项目的支持下，正在研究被称为芳基炔的活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以形成新的化学物质。这些合成方法将允许有效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。探索这些新的反应性芳炔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好处是，本文假设的合成方法，如果成功的话，可以刺激其他系统的相关研究。简单的设计原理和进行反应的模式--在相对较低的温度下的纯热条件下--将允许高中生和本科生参与这个研究项目，这将增加UIC从代表性不足的群体中招收学生的机会（与UIC Faculty Program联系）和芝加哥地区的高中生（史蒂文森高中STEM专业人员资源知识计划）。李大成和他的学生将进一步开发基于六脱氢狄尔斯-阿尔德反应的芳炔化学，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，新的氢键促进策略将被探索并应用于生物活性天然产物的合成，包括selaginellin H，selagintamarin A和selaginpuvilin G。此外，在Alder烯反应，[2+2]环加成之间的炔和丙二烯，Myers-Saito和Bergman环化反应中，额外的炔在1，3-二炔中的活化作用将被检查。炔取代基的活化作用将被进一步利用，在一个新的[4+2]环加成反应的发展，以产生α，3-脱氢甲苯中间体，然后通过它们的捕获作为一个两性离子或双自由基物种。与六脱氢Diels-Alder反应相比，这种新的环芳构化模式预计将显示出不同的反应性，从而显着丰富了多炔化合物的热转化阵列。该项目的更广泛影响将涉及机理研究，天然产物合成以及药物和药物先导化合物开发的各个方面，这些化合物可以作为各级学生培训的理想平台，包括本科生，研究生，该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的评估支持影响审查标准。

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.