(4+3) Cycloadditions of Oxidopyridinium and Oxidopyrylium Ions

在化学系化学合成(SYN)计划的支持下，密苏里-哥伦比亚大学的迈克尔·哈马塔教授正在研究一系列产生碳原子七元环的化学反应。正在研究的转化涉及所谓的[4+3]-环加成反应，其中，在包含氮原子(氧化吡啶离子)或氧原子(氧化吡啶离子)的反应物种中，跨越三个原子的区域以有组织的方式添加到四个原子跨越的组分(二烯)。这项研究很重要，因为它将促进七元环环状亚结构的产生，这些亚结构通常存在于生物活性分子中，包括天然产品和药物制剂。此外，关于分子反应性和成键等问题的基本新见解可能会从这些研究中出现。更广泛的影响将包括一项高中推广计划，该计划包括来自科学、技术、工程和数学(STEM)领域传统上代表性较低的群体的学生，并通过实验室暑期实习提供高级化学体验。Harmata教授还将组织一场名为“周六早晨科学”的活动，来自密苏里大学哥伦比亚分校的教职员工将以一种能够激发和培养各个年龄段社区成员对科学的兴趣的方式，向公众展示他们的研究成果。受资助的研究集中在标题物种的[4+3]-环加成化学的重大进一步发展上，重点是确定实现高水平区域和立体控制的可行策略。此外，将复杂的双环环加合物转化为最终感兴趣的目标，包括生物活性生物碱的定制过程也在研究中。为了实现区域控制，本研究的一个主要目的是研究含硫或含硅取代基的共轭双烯环加成反应中的动力学和热力学效应。在其他工作中，将探索环加合物桥头位置的官能化，以进一步扩大所追求的化学的用途。最后，将环加合物转化为环七[b]-吡咯和环七[b]吲哚。这些杂环被认为是特权结构，因为它们出现在许多具有生物和药用价值的生物碱中。这些研究建立在PI实验室的大量工作基础上，以确定通过[4+3]-环加成化学构建复杂环状结构的可能性，并因此有望更完整地定义合成有机化学的这一有趣维度。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。

With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Michael Harmata of the University of Missouri-Columbia is studying a family of chemical reactions that generate seven-membered rings of carbon atoms. The transformations being investigated involve so-called [4+3]-cycloadditions, wherein a domain spanning three atoms within a reactive species containing either a nitrogen atom (oxidopyridinium ion) or an oxygen atom (oxidopyrylium ion), adds in an organized fashion to a four atom-spanning component (a diene). This research is important because it will facilitate the generation of seven-membered ring cyclic substructures that occur commonly in biologically active molecules, including natural products and pharmaceutical agents. In addition, fundamental new insights concerning issues such as molecular reactivity and bonding are likely to emerge from these studies. The broader impacts will include a high school outreach program that includes students from groups traditionally underrepresented in science, technology, engineering, and mathematics (STEM) fields and provides advanced chemistry experiences through laboratory-based summer internships. Professor Harmata will also organize an event called “Saturday Morning Science,” at which faculty from across the University of Missouri-Columbia will present their research to the general public in a manner that will excite and cultivate an interest in science among members of the community of all ages.The funded research focuses on significant further development of the [4+3]-cycloaddition chemistry of the title species with an emphasis on the identification of viable strategies to effect high levels of regio- and stereocontrol. In addition, tailoring processes to convert the complex bicyclic cycloadducts into targets of ultimate interest, including bioactive alkaloids, are likewise under investigation. In a major aim of the research, kinetic and thermodynamic effects in the cycloadditions of conjugated dienes bearing sulfur or silicon substituents will be studied for the purpose of achieving regiocontrol. In other work, functionalization of the bridgehead positions of the cycloadducts will be explored to further extend the utility of the chemistry being pursued. Finally, the conversion of the cycloadducts to cyclohepta[b]-pyrroles and cyclohepta[b]indoles will be developed. Such heterocycles are considered privileged structures as they appear in many alkaloids of biological and pharmaceutical interest. These studies build upon a substantial body of work in the PI's laboratory to define the potential for complex cyclic ring structure construction through [4+3]-cycloaddition chemistry and, as such, are expected to define more completely this interesting dimension of synthetic organic chemistry.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.