Oxidative Coupling in Complexity Building Reactions

化学部的化学合成计划支持宾夕法尼亚大学化学系玛丽莎·科兹洛夫斯基教授的项目。她正在开发将分子片段偶联成更大分子的新方法。这种化学使这些较大的分子能够以一种使其整体结构发生变化的方式快速组装。这反过来又允许研究这些变化如何改变分子的性质。以合成为目标的分子具有广泛的潜在应用，从用作有机电子设备中具有电荷/能量传输特性的半导体和用作液晶材料，到与鸦片生物碱有关的制药应用。该项目的大部分内容涉及有机化学、计算化学和材料化学。因此，所追求的科学的多样性非常适合各级科学家的教育。科兹洛夫斯基教授在宾夕法尼亚大学科学与工程多样性联盟(ADSE)的支持下，特别关注扩大未被充分代表的人群对化学研究的参与。这项研究计划的主要目标是开发片段偶联的氧化方法，以产生更复杂的靶标。这样的路线在非功能化中心引入了功能，从而消除了对复杂的预功能化起始材料的需要。所研究的化学有助于环境友好的化学合成方法：1)在非官能化中心进行工程反应，从而消除了对复杂的预官能化起始材料的需求；2)使用氧气作为终端氧化剂；以及3)使用毒性较低和价格较低的贱金属。正在进行的转化包括氧化苯酚偶联以将三个或更多芳香族亚基聚集在一起，然后进一步氧化以提供具有选择性外围官能化的多环芳烃。正在探索氧化苯酚偶联的动力学拆分，以创建复杂的富含对映体的结构，例如鸦片生物碱的前体。最后，正在探索烷基芳烃的SP3中心与一系列叔亲核试剂的氧化偶联。这些方法的成功开发对许多领域产生了广泛的影响，因为在制药、化学、材料科学和农业以及基础生物和化学研究工作中需要获得这种结构。该教育计划包括培训高中生、本科生、研究生和博士后研究人员，以及推广将代表性不足的社区纳入化学研究企业。该奖项反映了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。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Marisa Kozlowski of the Department of Chemistry at the University of Pennsylvania. She is developing new methods to couple molecular fragments into larger molecules. The chemistry allows for these larger molecules to be rapidly assembled in a manner that enables variations in their overall structure. This in turns allows for the study of how those variation alter the molecules properties. The molecules targeted for synthesis have a wide variety of potential applications ranging from their use as semiconductors with charge/energy transport properties for use in organic electronic devices and as liquid crystal materials to pharmaceutical applications in connection with the opium alkaloids. Much of the project lies at the interface of organic, computational, and materials chemistry. Therefore, the diversity of the science being pursued is well suited for the education of scientists at all levels. Broadening the participation of underrepresented populations in chemistry research is a particular focus of Professor Kozlowski with support for the Alliance for Diversity in Science and Engineering (ADSE) at Penn. The principal goals of this research program entail the development of oxidative methods for the coupling of fragments to generate more complex targets. Such routes introduce functionality at non-functionalized centers, thereby eliminating the need for complex pre-functionalized starting materials. The chemistry studied is contributing to environmentally benign methods for chemical synthesis by 1) engineering reactions at non-functionalized centers, thereby eliminating the need for complex pre-functionalized starting materials, 2) using oxygen is used as the terminal oxidizing agent, and 3) using less toxic and less expensive base metals. Transformations that are being pursued include oxidative phenol coupling to bring together three or more aromatic subunits, which are then oxidized further to provide polycyclic aromatic hydrocarbons with selective peripheral functionalization. Kinetic resolution is being explored with oxidative phenol coupling to create complex enantioenriched architectures, such as precursors to the opium alkaloids. Finally, oxidative coupling of the sp3 centers of alkyl arenes with a range of tertiary nucleophiles are being explored. Successful development of the methods is having a broad impact on a number of areas as there is a need to access such structures in the pharmaceutical, chemical, materials science, and agricultural industries as well as in basic biological and chemical research endeavors. The educational plan involves training high school students, undergraduate students, graduate students and postdoctoral researchers as well as outreach to foster inclusion of underrepresented communities into the chemistry research enterprise.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.